HK40094450A - Nucleoside phosphoramidate prodrugs - Google Patents

Description

Nucleoside aminophosphate prodrug

This application is a divisional application of Chinese Patent Application No. 200880018024.2, entitled “Nucleoside aminophosphate prodrug”, filed on March 26, 2008.

This application was filed on March 25, 2008, as a PCT international patent application. The designated applicant in all countries except the United States is Pharmasset, Inc., a U.S. company. The designated applicants in the United States are Michael Joseph Sofia (U.S. citizen), Jinfa Du (U.S. citizen), Peiyuan Wang (Citizen of the People's Republic of China), and Dhanapalan Nagarathnam (U.S. citizen). This application claims priority to U.S. Provisional Application No. 60/909,315, filed March 30, 2007; U.S. Provisional Application No. 60/982,309, filed October 24, 2007; and U.S. Non-Provisional Application No. 12/053,015, filed March 21, 2008. The contents of all the above applications are hereby incorporated by reference in their entirety.

Invention Field

This invention relates to nucleoside aminophosphates and their use as medicaments for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA virus replication and can be used as inhibitors of HCV NS5B polymerase, inhibitors of HCV replication, and for treating hepatitis C infection in mammals. This invention provides novel compounds and their use, alone or in combination with other antiviral agents for treating HCV infection.

background

Hepatitis C virus (HCV) infection is a serious health problem, causing chronic liver diseases such as cirrhosis and hepatocellular carcinoma in a large number of infected individuals (estimated at 2-15% of the world's population). The U.S. Centers for Disease Control and Prevention estimates that 4.5 million people are infected in the United States alone. According to the World Health Organization, there are over 200 million infected individuals worldwide, with at least 3 to 4 million new infections each year. Once infected, approximately 20% of people clear the virus, but the rest may carry HCV for the rest of their lives. 10% to 20% of chronically infected individuals eventually develop devastating liver cirrhosis or cancer. This viral disease is transmitted extragastally through contaminated blood and blood products, contaminated needles, sexual contact, and vertical transmission from an infected mother or carrier mother to their offspring. Current treatment for HCV infection is limited to immunotherapy with recombinant interferon-alpha alone or in combination with the nucleoside analog ribavirin, which has limited clinical benefit. Furthermore, there is no well-developed vaccine against HCV. Therefore, there is an urgent need for improved treatments to effectively combat chronic HCV infection.

HCV virions are enveloped, positive-sense RNA viruses with a single oligonucleotide genome sequence of approximately 9,600 bases, encoding a multi-protein complex of about 3,010 amino acids. The protein products of the HCV gene consist of structural proteins C, E1, and E2, and non-structural proteins NS2, NS3, NS4A, NS4B, and NS5A and NS5B. The non-structural (NS) proteins are considered to provide the catalytic structure for viral replication. The NS3 protease releases NS5B, an RNA-dependent RNA polymerase derived from the multi-protein chain. The synthesis of double-stranded RNA from single-stranded viral RNA, used as a template in the HCV replication cycle, requires the HCV NS5B polymerase. Therefore, the NS5B polymerase is considered an essential component of the HCV replication complex (K. Ishi et al., Heptology, 1999, 29:1227-1235; V. Lohmann et al., Virology, 1998, 249:108-118). Inhibition of HCV NS5B polymerase prevents the formation of double-stranded HCV RNA, thus posing an attractive pathway for developing HCV-specific antiviral therapies.

HCV belongs to a fairly large family of viruses that share many common characteristics.

Flaviviridae viruses

The Flaviviridae family of viruses comprises at least three distinct genera: *pestiviruses*, which cause disease in cattle and pigs; *flavivruses*, which are the primary causes of diseases such as dengue fever and yellow fever; and *hepaciviruses*, whose only member is HCV. The genus *Flavavirus* includes more than 68 members, grouped based on serological phylogenetic relationships (Calisher et al., J. Gen. Virol, 1993, 70, 37-43). Clinical symptoms vary and include fever, encephalitis, and hemorrhagic fever (Fields Virology, eds.: Fields, B.N., Knipe, D.M., and Howley, P.M., Lippincott-Raven Press, Philadelphia, PA, 1996, Chapter 31, 931-959). Globally recognized flaviviruses associated with human diseases include dengue hemorrhagic fever virus (DHF), yellow fever virus, shock syndrome virus, and Japanese encephalitis virus (Halstead, S.B., Rev. Infect. Dis., 1984, 6, 251-264; Halstead, S.B., Science, 239: 476-481, 1988; Monath, T.P., New Eng. J. Med, 1988, 319, 64 1-643).

The genus *Pleurotus* includes bovine viral diarrhea virus (BVDV), typical swine fever virus (CSFV, also known as swine cholera virus), and sheep border disease virus (BDV) (Moennig, V. et al., Adv. Vir. Res. 1992, 41, 53-98). Infections with *Pleurotus* viruses in domestic livestock (cattle, pigs, and sheep) cause significant economic losses worldwide. BVDV causes mucosal disease in cattle and is of significant economic importance to livestock farming (Meyers, G. and Thiel, H.J., Advances in Virus Research, 1996, 47, 53-118; Moennig, V. et al., Adv. Vir. Res. 1992, 41, 53-98). Human *Pleurotus* viruses have not been characterized as extensively as animal *Pleurotus* viruses. However, serological tests indicate considerable exposure to *Pleurotus* viruses in humans.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are closely related virologies within the flavivirus family. Other closely related viruses in this family include GBV A, GBV A-like material, GBV B, and GBV C (also known as hepatitis G virus, HGV). The hepatitis C virus group (HCV) consists of a large number of closely related but genotype-distinguishable viruses that infect humans. There are at least six HCV genotypes and more than 50 subtypes. Due to the similarity between HBV and HCV and the weak ability of HCV to grow efficiently in cell culture, bovine viral diarrhea virus (BVDV) is often used as a substitute for HCV in research.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share a very similar genetic composition. These positive-sense RNA viruses possess a large open reading frame (ORF) encoding all the viral proteins required for viral replication. These proteins can be expressed as polyproteins, which undergo co-translation and post-translational processing via cellular proteases and viral-encoded proteases to obtain mature viral proteins. The viral proteins responsible for viral genome RNA replication reside near the carboxyl terminus. Two-thirds of the ORF is referred to as non-structural (NS) proteins. The genetic composition and polyprotein processing of the non-structural protein portions of the ORF are remarkably similar between HBV and HCV. For both HBV and HCV, the mature non-structural (NS) proteins, in a continuous sequence from the amino terminus of the non-structural protein coding region to the carboxyl terminus of the ORF, consist of p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B.

The NS proteins of hepatitis B virus (HBV) and hepatitis C virus (HCV) share sequence domains characterized by specific protein functions. For example, the NS3 proteins of both viruses possess amino acid sequence motifs characterized by serine proteases and helicases (Gorbalenya et al., Nature, 1988, 333, 22; Bazan and Fletterick Virology, 1989, 171, 637-639; Gorbalenya et al., Nucleic Acid Res., 1989, 17, 3889-3897). Similarly, the NS5B proteins of HBV and HCV possess motifs characterized by RNA-directed RNA polymerases (Koonin, E.V. and Dolja, V.V., Crir. Rev. Biochem. Molec. Biol. 1993, 28, 375-430).

The actual roles and functions of NS proteins in the viral life cycle of hepatitis B virus (HBV) and hepatitis C virus (HCV) are completely similar. In both cases, the NS3 serine protease is responsible for all proteolytic processing of its multi-protein precursor downstream of the ORF position (Wiskerchen and Collett, Virology, 1991, 184, 341-350; Bartenschlager et al., J. Virol. 1993, 67, 3835-3844; Eckart et al. Biochem. Biophys. Res. Comm. 1993, 192,399-406; Grakoui et al., J.Virol. 1993,67,2832-2843; Grakoui et al., Proc. Natl. Acad Sci. USA 1993,90,10583-10587; Hijikata et al., J.Virol. 1993,67,4665-4675; Tome et al., J.Virol., 1993,67,4017-4026. In both cases, the NS4A protein acts as a cofactor for the NS3 serine protease (Bartenschlager et al., J.Virol. 1994,68,5045-5055; Failla et al., J.Virol. 1994,68,3753-3760; Xu et al., J.Virol., 1997,71:53 12-5322). The NS3 protein of both viruses also acts as a helicase (Kim et al., Biochem. Biophys. Res. Comm., 1995, 215, 160-166; Jin and Peterson, Arch. Biochem. Biophys., 1995, 323, 47-53; Warrener and Collett, J. Virol. 1995, 69, 1720-1726). Finally, the NS5B protein of hepatitis virus and hepatitis C virus has the expected RNA-directed RNA polymerase activity (Behrens et al., EMBO, 1996, 15, 12-22; Lechmann et al., J. Virol., 1997, 71, 8416-8428; Yuan et al., Biochem. Biophys. Res. Comm. 1997, 232, 231-235; Hagedorn, PCT WO 97/12033; Zhong et al., J. Virol., 1998, 72, 9365-9369).

Currently, there are limited treatment options for individuals infected with hepatitis C virus (HCV). The currently approved treatment option is immunotherapy using recombinant interferon-alpha alone or in combination with the nucleoside analog ribavirin. This therapy is limited by its clinical efficacy, and only 50% of treated patients respond to it. Therefore, there is a significant need for more effective and novel therapies to address the unmet medical needs arising from HCV infection.

Numerous potential molecular targets have been identified for drug development using direct-acting antiviral agents as anti-HCV therapeutics, including but not limited to NS2-NS3 autoproteases, N3 proteases, N3 helicases, and NS5B polymerases. RNA-dependent RNA polymerases are absolutely essential for the replication of single-stranded sense RNA genomes, and these enzymes have attracted significant interest from medicinal chemists.

Inhibitors of HCV NS5B as a potential therapy for HCV infection have been reviewed in the following journals: Tan, S.-L., et al., Nature Rev. Drug Discov., 2002, 1, 867-881; Walker, M.P., et al., Exp. Opin. Investigational Drugs, 2003, 12, 1269-1280; Ni, Z-J., et al., Current Opinion in Drug Discovery and Development, 2004, 7, 446-459; Beaulieu, P.L., et al., Current Opinion in Drug Discovery and Development, 2004, 7, 446-459; Opinion in Investigational Drugs, 2004, 5, 838-850; Wu, J. et al., Current Drug Targets-Infectious Disorders, 2003, 3, 207-219; Griffith, R.C. et al., Annual Reports in Medicinal Chemistry, 2004, 39, 223-237; Carrol, S. et al., Infectious Disorders-Drug Targets, 2006, 6, 17-29. The possibility of the emergence of resistant HCV strains and the need to identify agents with a broad genotypic range support the need for continued efforts to identify novel and more effective nucleosides as HCV NS5B inhibitors.

Nucleoside inhibitors of NS5B polymerase can serve as non-natural substrates leading to chain termination, or as competitive inhibitors competing with nucleotides for binding to the polymerase. To act as chain terminators, nucleoside analogs must be taken up by cells and converted in vivo to triphosphates to compete for the polymerase's nucleotide binding site. This conversion to triphosphates is typically mediated by cellular kinases that impose additional structural requirements on potential nucleoside polymerase inhibitors. Unfortunately, this limits the direct evaluation of nucleosides as HCV replication inhibitors to cell-based assays capable of in situ phosphorylation.

In some cases, the biological activity of nucleosides is hindered by their poor substrate properties for one or more kinases, which are required to convert the nucleoside to its active triphosphate form. The formation of monophosphates via nucleoside kinases is generally considered the rate-limiting step in the triphosphate event. To avoid the required initiation phosphorylation step in the metabolism of nucleosides to active triphosphate analogs, stable phosphate prodrug preparations have been reported. Nucleoside aminophosphate prodrugs have been shown to be precursors to active nucleoside triphosphates and to inhibit viral replication when administered to virus-infected whole cells (McGuigan, C. et al., J. Med. Chem., 1996, 39, 1748-1753; Valette, G. et al., J. Med. Chem., 1996, 39, 1981-1990; Balzarini, J. et al., Proc. National Acad Sci USA, 1996, 93, 7295-7299; Siddiqui, A.). Q. et al., J. Med. Chem., 1999, 42, 4122-4128; Eisenberg, E. J. et al., Nucleosides, Nucleotides and Nucleic Acids, 2001, 20, 1 091-1098; Lee, W.A. et al., Antimicrobial Agents and Chemotherapy, 2005, 49, 1898); US 2006/0241064 and WO 2007/095269.

Furthermore, the time-varying physicochemical and pharmacokinetic properties of nucleosides also limit their use as viable therapeutic agents. These differential properties can restrict intestinal absorption and uptake into target tissues or cells. To improve these properties, nucleoside prodrugs have been employed. Nucleoside aminophosphate preparations have been shown to improve the systemic absorption of nucleosides, and furthermore, the aminophosphate moiety of these “pronucleotides” is masked by a neutral lipophilic group to achieve a suitable partition coefficient to optimize uptake and transport into cells, thereby significantly increasing the intracellular concentration of nucleoside monophosphate analogs relative to administration of the parent nucleoside alone. The enzymatic hydrolysis of the phosphate moiety yields the nucleoside monophosphate, where rate-limiting initiation phosphorylation is not necessary.

Invention Overview

This invention relates to novel aminophosphate prodrugs of nucleoside derivatives for treating viral infections in mammals, wherein the aminophosphate prodrug is a compound represented by the following structures, its stereoisomers, its salts (acid or base addition salts), hydrates, solvates, or crystalline forms:

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

The base is a naturally occurring or modified purine or pyrimidine base, represented by the following structure:

in

Z is N or CR ¹² ;

^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R',

Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ .

definition

As used herein, the term "a(a)" or "an(an)" refers to one or more of the aforementioned entities; for example, "a compound" refers to one or more compounds or at least one compound. Similarly, the terms "a(a)" (or "an(an)"), "one or more," and "at least one" are used interchangeably herein.

The phrase "as defined above" refers to the initial definition provided in the invention overview.

As used herein, the terms "optional" or "optionally" mean that the event or condition described thereafter may occur but is not required to occur, and the description includes examples of the event or condition occurring and examples of the condition not occurring. For example, "optional key" means that the key may or may not exist, and the description includes single keys, double keys, or triple keys.

The term "independently" as used in this paper means that the variable can be applied to any situation, regardless of the presence or absence of variables with the same or different definitions within the same compound. Therefore, in a compound where R appears twice and is defined as "independently carbon or nitrogen," both Rs can be carbon, both Rs can be nitrogen, or one R can be carbon and the other nitrogen.

The term "alkenyl" refers to an unsubstituted hydrocarbon chain group having 2 to 10 carbon atoms, the hydrocarbon chain group having one or two alkene double bonds, preferably having one alkene double bond. The term "C2 _-N alkenyl" refers to an alkenyl group comprising 2 to N carbon atoms, where N is an integer having the following values: 3, 4, 5, 6, 7, 8, 9, or 10. The term " _C2-10 alkenyl" refers to an alkenyl group comprising 2 to 10 carbon atoms. The term " _C2-4 alkenyl" refers to an alkenyl group comprising 2 to 4 carbon atoms. Examples include, but are not limited to, vinyl, 1-propenyl, 2-propenyl (allyl), or 2-butenyl (crotonyl).

The term "halogenated alkenyl" refers to an alkenyl group that includes at least one of F, Cl, Br, and I.

The term "alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon residue containing 1 to 30 carbon atoms. The term "C1 _-M alkyl" refers to an alkyl group comprising 1 to M carbon atoms, where M is an integer having the following values: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. The term " _C1-4 alkyl" refers to an alkyl group containing 1 to 4 carbon atoms. The term "lower alkyl" refers to a straight-chain or branched hydrocarbon residue comprising 1 to 6 carbon atoms. As used herein, " _C1-20 alkyl" refers to an alkyl group comprising 1 to 20 carbon atoms. As used herein, " _C1-10 alkyl" refers to an alkyl group comprising 1 to 10 carbon atoms. Examples of alkyl groups include, but are not limited to, lower alkyl groups, including methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl. The terms (aromatic)alkyl or (heteroaryl)alkyl refer to alkyl groups optionally substituted with aryl or heteroaryl groups, respectively.

The term "cycloalkyl" refers to an unsubstituted or substituted carbon ring containing 3 to 10 carbon atoms, preferably 3 to 8 carbon atoms, more preferably 3 to 6 carbon atoms (i.e., a lower cycloalkyl group). Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

The term "cycloalkylalkyl" refers to another unsubstituted alkyl group or a substituted alkyl group substituted with a lower cycloalkyl group. Examples of cycloalkylalkyl groups include, but are not limited to, any of the following: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl substituted with cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

The term "cycloheteroalkyl" refers to an unsubstituted or substituted heterocycle containing 2 to 9 carbon atoms, preferably 2 to 7 carbon atoms, more preferably 2 to 5 carbon atoms. Examples of cycloheteroalkyl include, but are not limited to, acridine-2-yl, NC _1-3 -alkyl-acrididine-2-yl, acridine-yl, NC _1-3 -alkyl-acrididine-m'-yl, pyrrolidine-m'-yl, NC _1-3 -alkyl-pyrrolidine-m'-yl, piperidin-m'-yl, and NC _1-3 -alkyl-piperidine-m'-yl, wherein m' is 2, 3, or 4 depending on the cycloheteroalkyl group. Specific examples of NC _1-3 -alkyl-cycloheteroalkyl groups include, but are not limited to, N-methyl-acetidin-2-yl, N-methyl-acetidin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-2-yl, N-methyl-piperidin-3-yl, and N-methyl-piperidin-4-yl. In the case of R ⁴ , the connection point between the cycloheteroalkyl ring carbon and oxygen appears in any m'.

The term "heterocycle" refers to an unsubstituted or substituted heterocycle containing carbon, hydrogen, and at least one N, O, and S, wherein C and N can be trivalent or tetravalent, i.e., sp ^2- or sp ^3- hybridized. Examples of heterocycles include, but are not limited to, acridine, acridine, pyrrolidine, piperidine, imidazole, oxazole, piperazine, etc. In the case of piperazine, as associated with R ¹⁰ of NR' ₂ , the corresponding para-nitrogen atom on the piperazine group is substituted with a lower alkyl group represented by the following structure:

Preferably, the para-nitrogen of the piperazine group is replaced by a methyl group.

The term "halogenated alkyl" (or "halogenated alkyl") refers to a straight-chain or branched alkyl group comprising at least one F, Cl, Br, and I atom. The term " _C1-M haloalkyl" refers to an alkyl group comprising 1 to M carbon atoms, comprising at least one F, Cl, Br, and I atom, where M is an integer having the following values: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. " _C1-3 haloalkyl" refers to a haloalkyl group comprising 1 to 3 carbon atoms and at least one F, Cl, Br, and I atom. The term "halogenated lower alkyl" (or "lower haloalkyl") refers to a haloalkyl group comprising 1 to 6 carbon atoms and at least one F, Cl, Br, and I atom. Examples include, but are not limited to, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, diiodomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 1-iodoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2-dichloroethyl, 2,2-dibromomethyl, 2,2-diiodomethyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 2,2,2-trifluoroethyl, or 1,1,2,2,2-pentafluoroethyl.

The term "alkynyl" refers to a straight-chain or branched hydrocarbon group having 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms, and a triple bond. The term "C2 _-N alkynyl" refers to an alkynyl group comprising 2 to N carbon atoms, where N is an integer having the following values: 3, 4, 5, 6, 7, 8, 9, or 10. The term " _C2-4 alkynyl" refers to an alkynyl group comprising 2 to 4 carbon atoms. The term " _C2-10 alkynyl" refers to an alkynyl group comprising 2 to 10 carbon atoms. Examples include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, or 3-butynyl.

The term "halogenated alkynyl" refers to a hydrocarbon chain group having 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms, and having a triple bond and at least one straight or branched F, Cl, Br and I.

The term "cycloalkyl" refers to a saturated carbon ring comprising 3 to 8 carbon atoms, namely cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl. As used herein, the term "C _3-7 cycloalkyl" refers to a cycloalkyl ring comprising 3 to 7 carbon atoms.

The term "alkoxy" refers to -O-alkyl or –O-cycloalkyl, where alkyl and cycloalkyl are as defined above. Examples of –O-alkyl include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy. As used herein, "lower alkoxy" refers to an alkoxy group having a "lower alkyl" group as defined above. "C _1-10 alkoxy" refers to -O-alkyl, where the alkyl group is C _1-10 . Examples of –O-cycloalkyl include, but are not limited to, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl, and –O-cyclohexyl.

The term "halogenated alkoxy" refers to –O-alkyl, wherein the alkyl group includes at least one F, Cl, Br and I.

The term "halogenated lower alkoxy" refers to an –O- (lower alkyl) group, wherein the lower alkyl group includes at least one F, Cl, Br and I.

The term "amino acid" includes naturally occurring and synthetic α, β, γ, or δ amino acids, and includes, but is not limited to, amino acids present in proteins, namely glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, and histidine. In a preferred embodiment, the amino acid is L-configured. Optionally, the amino acid can be a derivative of: alanyl, valine, leucyl, isoleucyl, proline, phenylalanyl, tryptophanyl, methionyl, glycyl, serine, threonyl, cysteyl, tyrosine, asparagine, glutamine, asparagine, glutamine, lysine, arginine, histidine, β-alanyl, β-valine. Acyl, β-leucyl, β-isoleucyl, β-prolyl, β-phenylalanyl, β-tryptophanyl, β-methionyl, β-glycyl, β-seryl, β-threonyl, β-cysteyl, β-tyrosyl, β-asparagine acyl, β-glutamine acyl, β-asparagine, β-glutamine, β-lysyl, β-arginine acyl, or β-histidine acyl. When the term amino acid is used, various esters of the following amino acids in D and L configurations are considered to be specifically and independently disclosed: α, β, γ, or δ glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, and histidine.

The term "aminoacyl" includes naturally occurring and synthetic derivatives of α,N-unsubstituted, N,N-monsubstituted, and N,N-disubstituted α,N-aminoacyl groups derived from amino acids. The amino nitrogen can be substituted or unsubstituted. When the amino nitrogen is substituted, it is monosubstituted or disubstituted, wherein the substituent bonded to the amino nitrogen is a lower alkyl or alkylaryl group. In its application to Y, the expression "O (aminoacyl)" is used. It should be understood that the C3' carbon of the ribose is bonded to oxygen "O" and then to the carbonyl carbon of the aminoacyl group.

The terms "alkylamino" or "aromaticamino" refer to amino groups having one or two alkyl or aryl substituents, respectively.

As used herein, the term "protected" unless otherwise specified means a group added to an oxygen, nitrogen, or phosphorus atom to prevent further reaction or for other purposes. A variety of oxygen and nitrogen protecting groups are known to those skilled in the art of organic synthesis. Non-limiting examples include: C(O)-alkyl, C(O)Ph, C(O)aryl, _CH3 , _CH2 -alkyl, _{CH2 -} alkenyl, _CH2Ph , _CH2 -aryl, CH2O _- alkyl, _CH2O -aryl, _SO2 -alkyl, SO2-aryl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, and 1,3-(1,1,3,3-tetraisopropyldisiloxane).

As used herein, the term "aryl" unless otherwise specified means a substituted or unsubstituted phenyl (Ph), diphenyl, or naphthyl group, and preferably refers to a substituted or unsubstituted phenyl group. The aryl group may be substituted with one or more of the following moieties: hydroxyl, F, Cl, Br, I, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphoric acid, phosphate ester, and phosphonate; it may be unprotected or protected as required, as known to those skilled in the art, for example, as taught in T.W. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis," 3rd ed., John Wiley & Sons, 1999.

The terms "alkylaryl" or "alkylaryl" refer to alkyl groups with aryl substituents, such as benzyl. The terms "aralkyl" or "arylalkyl" refer to aryl groups with alkyl substituents.

The term "di(lower alkyl)amino-lower alkyl" refers to a lower alkyl group substituted with an amino group that _is itself replaced by two lower alkyl groups. Examples include, but are not limited to _, ( _CH3 ) _2NCH2 , ( _{CH3 )2NCH2CH2 ,} ( _CH3 ) _2NCH2CH2CH2 , _etc. The examples above show lower alkyl groups in which the terminal carbon atom is substituted with an N,N _{- dimethyl} -amino substituent. These are intended only as examples and are not intended to limit the meaning of the term "di(lower alkyl)amino-lower alkyl" to the meaning of the term being the same as the examples described. It is understood that the lower alkyl chain can be substituted with N,N-di(lower alkyl)-amino at any point along the chain, such as _CH3CH (N-(lower alkyl) _{2 ) CH2CH2} .

As used in this article, the term "halogen" includes chlorine, bromine, iodine, and fluorine.

The term "acyl" refers to a substituent containing a carbonyl moiety and a non-carbonyl moiety. The carbonyl moiety contains a double bond between a carbonyl carbon and a heteroatom selected from O, N, and S. When the heteroatom is N, N is substituted with a lower alkyl group. The non-carbonyl moiety is selected from: straight-chain, branched, and cyclic alkyl groups, including but not limited to straight-chain, branched, or cyclic _C1-20 alkyl, _C1-10 alkyl, or lower alkyl groups; alkoxyalkyl groups, including methoxymethyl; aralkyl groups, including benzyl; aroxyalkyl groups such as phenoxymethyl; or aryl groups, including phenyl groups optionally substituted with: halogens (F, Cl, Br, I), hydroxyl groups, _C1 to _C4 alkyl or _C1 to _C4 alkoxy groups, sulfonates such as alkyl or aralkylsulfonyl groups, including methanesulfonyl, mono, di, or triphosphates, triphenylmethyl or monomethoxytriphenylmethyl, substituted benzyl, trialkylsilyl (such as dimethyl tert-butylsilyl) or diphenylmethylsilyl. When at least one aryl group is present in the non-carbonyl moiety, the aryl group preferably includes a phenyl group.

The term "lower acyl" refers to an acyl group in which the non-carbonyl portion is a lower alkyl group.

The term "purine" or "pyrimidine" includes, but is not limited to, adenine, ^N6 -alkylpurine, ^N6 -acylpurine (where the acyl group is C(O)) (alkyl, aryl, alkylaryl, or arylalkyl), ^N6 -benzylpurine, ^N6 -halopurine, ^N6 -vinylpurine, N6-acetylenic purine, ^N6 -acylpurine, ^N6 -hydroxyalkylpurine, ^N6 -alkylaminopurine, ^N6 -thioallcylpurine, ^N2 -alkylpurine, N2-alkyl- ⁶ -thiopurine, thymine, cytosine, ⁵ -fluorocytosine, 5-methylcytosine, 6-azapyrimidine including 6-azacytosine, 2- and/or 4-mercaptopyrmidine, uracil, 5-halouracil including 5-fluorouracil, ^C5 C5-alkylpyrimidines, ^C5 -benzylpyrimidines, ^C5 -halogenpyrimidines, C5-vinylpyrimidines, ^C5 -alkynylpyrimidines, ^C5 -acylpyrimidines, ^C5 -hydroxyalkylpurines, ^C5 -amidepyrimidines, ^C5 -cyanopyrimidines, C5-iodopyrimidines, ^C6 -iodopyrimidines, ^C5 -Br-vinylpyrimidines, ^{C6 -} Br-vinylpyrimidines, ^{C5 -} nitropyrimidines, ^C5 -aminopyrimidines, ^N2 -alkylpurines, ^N2 -alkyl-6-thiopurine, 5-azacytosine nucleoside, 5-azauracil, triazolanopyridyl, imidazopyridyl, pyrrolopyrimidinyl, and pyrazolopyrimidinyl. Purine bases include, but are not limited to, guanine, adenine, hypoxanthine, 2,6-diaminopurine, and 6-chloropurine. The functional oxygen and nitrogen groups on the bases may be protected as needed or desired. Suitable protecting groups are well known to those skilled in the art and include trimethylsilyl, dimethylhexylsilyl, tert-butyldimethylsilyl and tert-butyldiphenylsilyl, triphenylmethyl, alkyl, and acyl groups, such as acetyl and propionyl, methanesulfonyl and p-toluenesulfonyl.

The terms “tautomer” and “tautomer” have their accepted and clear meanings.

The term "P*" indicates that the phosphorus atom is chiral and has the corresponding Cahn-Ingold-Prelog designation "R" or "S", which has the clear meaning for which they are accepted. Compounds of formula I are expected to be racemic due to the chirality of phosphorus. The applicant has considered the use of racemic and/or resolved enantiomers. In some cases, an asterisk is not shown near the phosphorus atom of the aminophosphate. In these cases, it should be understood that the phosphorus atom is chiral, and that a person skilled in the art should also understand this, unless the substituents bonded to phosphorus exclude the possibility that phosphorus is chiral, such as P(O) _Cl3 .

Invention Details

This invention relates, in one respect to compounds represented by formula I, and their salts, hydrates, solvates, crystalline forms, and analogs:

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

The base is a naturally occurring or modified purine or pyrimidine base, represented by the following structure:

in

Z is N or CR ¹² ;

^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R',

Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, _C2 - _C6 optionally substituted alkynyl, _C2 - _C6 optionally substituted lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ .

As understood from the structure represented by Formula I above, there are numerous ways to represent several embodiments of the invention and several aspects of each embodiment. As shown below, the inventors disclose certain embodiments relating to compounds of Formula I, each embodiment having several aspects based on the identity of the modified purine or pyrimidine bases. This is not intended to expressly or implicitly acknowledge that the three embodiments are independent or distinct, nor should it be interpreted as such. Rather, it is intended to convey information so that the full scope of the invention can be understood. Furthermore, the following embodiments and aspects are not intended to limit the full scope of the invention as enumerated by the structure of Formula I.

The first embodiment of the present invention relates to a compound represented by formula I-1:

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, _cyclohexyl , aminoacyl, di(lower alkyl)-amino, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, Cl, Br, I, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

(i) ^R7 , ^R8 , and ^R9 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, _C2 - _C6 lower alkenyl, _CO2H , CO2R', _CONH2 , CONHR _' , _CONR'2 , wherein R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, or _C2 - _C6 alkynyl.

A first aspect of the first implementation plan relates to a compound represented by formula I-1.

in

(a) R ¹ is hydrogen, n-alkyl or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a and ^R3b are independently (i) ^R3a is hydrogen, while ^R3b and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _{CH3 ) CH2CH3} , _CH2Ph , CH ₂ -Indole-3-yl, -CH₂CH₂SCH₃, _CH₂CO₂H , _CH₂C (O) _NH₂ , _{CH₂CH₂COOH} , _CH₂CH₂C ( _O ) _NH₂ , CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC _{(NH) NH₂ , CH₂ - imidazol} - ₄ -yl, _CH₂OH , _CH (OH _{) CH₃ , CH₂ (} (4'-OH)-Ph), _{CH₂SH or} a _lower cycloalkyl group; or (viii) ^R₃a is _CH₃ , _CH ( _CH₃ ) _₂ , _CH₂CH ( _CH₃ ) _₂ , CH( _CH₃ ) _CH₂CH₃ , _CH₂Ph , _{CH₂ -} Indole _{- 3 - yl} , _{-CH₂CH₂SCH₃} , _CH₂CO₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph) or CH ₂ SH, R ^3b is H;

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, _CN , _CH3 , vinyl, _OCH3 , _OCH2CH3 , _CH2OH , _CH2 (halogen) such as _CH2F , _N3 , _CH2CN , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _CH2N ( _CH3 ) _{2 ,} halogens, including F, Cl, _Br or I, provided that when X is OH, the base is cytosine and ^R6 is H, _and ^R5 is not _N3 ;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, Cl, Br, I, _NH2 or _N3 ;

(h)Y is OH, H, _C1-4 alkyl, vinyl, _N3 , CN, Cl, Br, F, I, O ( _C1-6 acyl), O ( _C1-4 alkyl), _NH2 , NH ( _{C1-4 alkyl), NH (C2-4} alkenyl), NH ( _C2-4 alkynyl), NH ( _C1-4 acyl), N ( _{C1-4 alkyl} ) ₂ , N ( _C1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl, and vinyl groups are optionally substituted with: _N3 , CN, 1-3 halogens (Cl, Br, F, I), _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 alkynyl), OC(O)O ( _C2-4 alkenyl), _{OC1-4 haloalkyl, O (aminoacyl), O (C1-18 acyl)2,} etc. _1-4 acyl), O (C _1-4 alkyl), O (C _2-4 alkenyl), S (C _1-4 acyl), S (C _1-4 alkyl), S (C _2-4 alkynyl), S (C _2-4 alkenyl), SO (C _1-4 acyl), SO (C _1-4 alkyl), SO (C _2-4 alkynyl), SO (C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C _2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ or N(C _1-4 acyl) ₂ ;

(i) ^R7 , ^R8 , and ^R9 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, _C2 - _C6 lower alkenyl, _CO2H , CO2R', _CONH2 , CONHR _' , _CONR'2 , wherein R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, or _C2 - _C6 alkynyl.

The second aspect of the first implementation plan relates to a compound represented by formula I-1.

in

(a) R ¹ is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: _C1-3 alkyl, _C1-3 alkoxy, F, Cl, Br, I, nitro, cyano, and _C1-3 haloalkyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a and ^R3b are independently (i) ^R3a is hydrogen, while ^R3b and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _{CH3 ) CH2CH3} , _CH2Ph , CH ₂ -Indole-3-yl, -CH₂CH₂SCH₃, _CH₂CO₂H , _CH₂C (O) _NH₂ , _{CH₂CH₂COOH} , _CH₂CH₂C ( _O ) _NH₂ , CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC _{(NH) NH₂ , CH₂ - imidazol} - ₄ -yl, _CH₂OH , _CH (OH _{) CH₃ , CH₂ (} (4'-OH)-Ph), _{CH₂SH or} a _lower cycloalkyl group; or (viii) ^R₃a is _CH₃ , _CH ( _CH₃ ) _₂ , _CH₂CH ( _CH₃ ) _₂ , CH( _CH₃ ) _CH₂CH₃ , _CH₂Ph , _{CH₂ -} Indole _{- 3 - yl} , _{-CH₂CH₂SCH₃} , _CH₂CO₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph) or CH ₂ SH, R ^3b is H;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl or aminoacyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2 (halogen) such as _CH2F , _N3 , _CH2CN , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 )2 ,} halogens, including F, Cl, Br or _I , provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _{N3 ;}

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH (vinyl), NH (acetyl), NH (C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ or O (aminoacyl);

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , CH3 _{- qXq} , where X is F, Cl, Br or I and q is 1 to 3, vinyl, _CO2H , _CO2CH3 , _{CONH2 , CONHCH3} or CON _{( CH3} ) ₂ ; and

(j)R ⁹ is selected from the following: OH, OCH ₃ , SH, SCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O)(C1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O)(C1-20 alkyl), including but not limited to NHC(O)(CH 2 ) s CH 3; and N(C(O)(CH ₂ ) _s CH ₃ ) 2, including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , _where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, ₈ , 9, ₁₀ , ₁₁ , 12, 13, 14, 15, 16, 17, 18 and 19.

The third aspect of the first embodiment relates to a compound represented by formula I-1.

in

(a) R ¹ is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: CH ₃ , OCH ₃ , F, Cl, Br, I, nitro, cyano and CH _3-q X _q , wherein X is F, Cl, Br or I and q is 1-3;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH (CH3) ₂ , CH( _{CH3 ) CH2CH3} , CH2Ph, _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , _CH2C ( _O ) _NH2 , _CH2CH2COOH , _{CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC ( NH ) NH2 , CH2 - imidazol - 4} -yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} (4'-OH)-Ph), _{CH2SH ,} or _a lower cycloalkyl ^group , or _R3a is _CH3 , CH( _CH3 ) _{2 CH2CH} ( _CH3 ) ₂ , CH( _CH3 )CH2CH3, _CH2Ph , _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , CH2C( _O ) _NH2 , _CH2CH2COOH , _CH2CH2C (O) _NH2 , _{CH2CH2CH2CH2NH2} , _{-CH2CH2CH2NH2 , CH2 -} imidazol _{- 4 -} yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} ( _4' -OH) _-Ph ), _{CH2SH or lower} ^cycloalkyl , _R3b is H;

(d) ^R4 is hydrogen, _CH3 , Et, ^iPr , ^nPr , ^nBu , 2-butyl, ^tBu , benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl or aminoacyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2 (halogen) such as _CH2F , _N3 , _CH2CN , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 )2 ,} halogens, including F, Cl, Br or _I , provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _{N3 ;}

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH (vinyl), NH (acetyl), NH (C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ or O (aminoacyl);

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I and q is 1 to ₃ , vinyl, CO2H, _CO2CH3 , _{CONH2 , CONHCH3} or CON( _CH3 ) ₂ , where R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, _C2 - _C6 ynyl; and

(j)R ⁹ is selected from the following: OH, OCH ₃ , SH, SCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O)(C1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O)(C1-20 alkyl), including but not limited to NHC(O)(CH 2 ) s CH 3; and N(C(O)(CH ₂ ) _s CH ₃ ) 2, including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , _where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, ₈ , 9, ₁₀ , ₁₁ , 12, 13, 14, 15, 16, 17, 18 and 19.

The fourth aspect of the first embodiment relates to a compound represented by formula I-2.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: CH ₃ , OCH ₃ , F, Cl, Br, I, nitro, cyano and CH _3-q X _q , wherein X is F, Cl, Br or I and q is 1-3;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH (CH3) ₂ , CH( _{CH3 ) CH2CH3} , CH2Ph, _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , _CH2C ( _O ) _NH2 , _CH2CH2COOH , _CH2CH2C (O) _NH2 , _{CH2CH2CH2CH2NH2} , _{-CH2CH2CH2NHC} ( _{NH ) NH2} , _{CH2 -} imidazol _{- 4} -yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} (4'-OH)-Ph), _{CH2SH ,} or _a lower cycloalkyl ^group , or _R3a is _CH3 , CH( _CH3 ) _{2 CH2CH} ( _CH3 ) ₂ , CH( _CH3 )CH2CH3, _CH2Ph , _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , CH2C( _O ) _NH2 , _CH2CH2COOH , _CH2CH2C (O) _NH2 , _{CH2CH2CH2CH2NH2} , _{-CH2CH2CH2NH2 , CH2 -} imidazol _{- 4 -} yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} ( _4' -OH) _-Ph ), _{CH2SH or lower} ^cycloalkyl , _R3b is H;

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , CH2F, _N3 , _CH2CN , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _CH2N ( _CH3 ) ₂ , or a halogen, including F, Cl, _{Br ,} or I, provided that when X is OH, the base is cytosine and ^R6 is H, _and ^R5 is _{not N3} .

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH (vinyl), NH (acetyl), NH (C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ or O (aminoacyl);

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I and q is 1 to ₃ , vinyl, CO2H, _CO2CH3 , _{CONH2 , CONHCH3} or CON( _CH3 ) ₂ , where R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, _C2 - _C6 ynyl; and

(j)R ⁹ is selected from the following: OH, OCH ₃ , SH, SCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O)(C1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O)(C1-20 alkyl), including but not limited to NHC(O)(CH 2 ) s CH 3; and N(C(O)(CH ₂ ) _s CH ₃ , including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 _{, 11} , ₁₂ , 13, 14, 15, 16, 17, 18 and 19.

The fifth aspect of the first embodiment relates to a compound represented by formula I-2.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) ^R4 is hydrogen, _CH3 , Et, ^iPr , ^nPr , ^nBu , 2-butyl, ^tBu , benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl or aminoacyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 or O (aminoacyl);

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I and q is 1 to ₃ , vinyl, CO2H, _CO2CH3 , _{CONH2 , CONHCH3} or CON( _CH3 ) ₂ , where R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, _C2 - _C6 ynyl; and

(j)R ⁹ is selected from the following: OH, OCH ₃ , SH, SCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O) (C _1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O) (C 1-20 alkyl), including but not limited to NHC(O)(CH ₂ ) s CH 3; and N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , where s is an integer selected from 0, 1, 2, 3, ₄ , 5, 6, 7, 8, ₉ , ₁₀ , 11, 12, 13, 14, 15, 16, 17, 18 and 19.

The sixth aspect of the first embodiment relates to a compound represented by formula I-2.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e)R ⁵ is H, OMe, CN, CH _2F , F, Cl, Br or I;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I or _N3 , _OCH3 , OC(O) _CH3 or O (amino acyl);

(i) ^R7 and ^R8 are independently H, F, Br, _SCH3 , _CH3 , _{CH3-qXq ,} where X is F, Cl, Br or I and q is 1 to 3, _vinyl , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ ; and

(j)R ⁹ is selected from the following: OH, OCH ₃ , SH, SCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O) (C _1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O) (C 1-20 alkyl), including but not limited to NHC(O)(CH ₂ ) s CH 3; and N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , where s is an integer selected from 0, 1, 2, 3, ₄ , 5, 6, 7, 8, ₉ , ₁₀ , 11, 12, 13, 14, 15, 16, 17, 18 and 19.

The seventh aspect of the first embodiment relates to a compound represented by formula I-2.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e)R ⁵ is H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F or _N3 ;

(h)Y is OH, _OCH3 , OC(O) _CH3 or O (aminoacyl);

(i) ^R7 and ^R8 are independently H, F, Br, _SCH3 , _CH3 , _{CH3-qXq ,} where X is F, Cl, Br or I and q is 1 to 3, _vinyl , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ ; and

(j)R ⁹ is selected from the following: OH, OCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O) (C _1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O) (C _1-20 alkyl), including but not limited to NHC(O)(CH 2) s CH ₃ ; and N(C(O)(CH ₂ ) _s CH 3) ₂ , including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ₁₁ , _{12 ,} 13, 14, 15, 16, 17, 18 and 19.

The eighth aspect of the first embodiment relates to a compound represented by formula I-2.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e)R ⁵ is H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F or _N3 ;

(h)Y is OH, _OCH3 , OC(O) _CH3 or O (aminoacyl);

(i) ^R7 and ^R8 are independently H, F, Br, _SCH3 , _CH3 , _{CH3-qXq ,} where X is F, Cl, Br or I and q is 1 to 3, _vinyl , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ ;

(j)R ⁹ is selected from the following: OH, OCH ₃ , NH ₂ , NHCH ₃ , N(CH ₃ ) ₂ , OC(O) (C _1-20 alkyl), including but not limited to OC(O)(CH ₂ ) _s CH ₃ ; NHC(O) (C _1-20 alkyl), including but not limited to NHC(O)(CH 2) s CH ₃ ; and N(C(O)(CH ₂ ) _s CH 3) ₂ , including but not limited to N(C(O)(CH ₂ ) _s CH ₃ ) ₂ , where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ₁₁ , _{12 ,} 13, 14, 15, 16, 17, 18 and 19.

A second embodiment of the invention relates to a compound represented by Formula I, wherein the bases are in the structure represented by Formula b above, wherein ^R1 , ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , ^R6 , X, Y, ^R7 and ^R8 are defined in the invention overview section above.

The first aspect of the second implementation scheme relates to the compound shown in Formula I-3.

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, Cl, Br, I, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ or N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ or N(C _1-4 acyl) ₂ ;

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , lower alkyl, lower alkyl of halogenated (F, Cl, Br, I), _C2 - _C6 lower alkenyl, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , wherein R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, or _C2 - _C6 alkynyl.

The second aspect of the second implementation scheme relates to the compound shown in Formula I-3.

in

(a) R ¹ is hydrogen, n-alkyl or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a and ^R3b are independently (i) ^R3a is hydrogen, while ^R3b and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _{CH3 ) CH2CH3} , _CH2Ph , CH ₂ -Indole-3-yl, -CH₂CH₂SCH₃, _CH₂CO₂H , _CH₂C (O) _NH₂ , _{CH₂CH₂COOH} , _CH₂CH₂C ( _O ) _NH₂ , CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC _{(NH) NH₂ , CH₂ - imidazol} - ₄ -yl, _CH₂OH , _CH (OH _{) CH₃ , CH₂ (} (4'-OH)-Ph), _CH₂SH or a _lower cycloalkyl group; or (viii) ^R₃a is _CH₃ , _CH ( _CH₃ ) _₂ , _CH₂CH ( _CH₃ ) _₂ , CH( _CH₃ ) _CH₂CH₃ , _CH₂Ph , _{CH₂ -} Indole _{- 3 - yl} , _{-CH₂CH₂SCH₃ , CH₂CO₂} H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph) or CH ₂ SH, R ^3b is H;

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) R ⁵ is H, CN, CH ₃ , vinyl, OCH ₃ , OCH ₂ CH ₃ , CH ₂ OH, CH ₂ (halogen) such as CH ₂ F, N ₃ , CH ₂ CN, CH ₂ N ₃ , CH ₂ NH ₂ , CH ₂ NHCH ₃ , CH ₂ N(CH ₃ ) ₂ , halogens, including F, Cl, Br or I;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y is OH, H, _C1-4 alkyl, vinyl, _N3 , CN, Cl, Br, F, I, O ( _C1-6 acyl), O ( _C1-4 alkyl), _NH2 , NH ( _C1-4 alkyl), NH ( _C2-4 alkenyl), NH ( _C2-4 alkynyl), NH ( _C1-4 acyl), N ( _C1-4 alkyl) ₂ , N ( _C1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl, and vinyl groups are optionally substituted with: _N3 , CN, 1-3 halogens (Cl, Br, F, I), _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 alkynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O (C _1-4 acyl), O (C _1-4 alkyl), O (C _2-4 alkenyl), S (C _1-4 acyl), S (C _1-4 alkyl), S (C _2-4 alkynyl), S (C _2-4 alkenyl), SO (C _1-4 acyl), SO (C _1-4 alkyl), SO (C _2-4 alkynyl), SO (C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C _2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, _C2 - _C6 lower alkenyl, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , wherein R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, or _C2 - _C6 alkynyl.

The third aspect of the second implementation scheme relates to compounds represented by formula I-3.

(a) R ¹ is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: _C1-3 alkyl, _C1-3 alkoxy, F, Cl, Br, I, nitro, cyano and _C1-3 haloalkyl;

(b) ^R2 is hydrogen, _CH3 , and ^R3a or ^R3b and ^R2 together are ( _CH2 ) ₃ , in order to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, where n is 2 ^to 4, ^{and R1} , ^R3a and ^R3b are as defined herein;

(c) ^R3a and ^R3b are independently (i) ^R3a is hydrogen, while ^R3b and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together are ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _{CH3 ) CH2CH3} , _CH2Ph , CH ₂ -Indole-3-yl, -CH₂CH₂SCH₃, _CH₂CO₂H , _CH₂C (O) _NH₂ , _{CH₂CH₂COOH} , _CH₂CH₂C ( _O ) _NH₂ , CH₂CH₂CH₂NH₂, -CH₂CH₂CH₂NHC _{(NH) NH₂ , CH₂ - imidazol} - ₄ -yl, _CH₂OH , _CH (OH _{) CH₃ , CH₂ (} (4'-OH)-Ph), _{CH₂SH or} a _lower cycloalkyl group; or (viii) ^R₃a is _CH₃ , _CH ( _CH₃ ) _₂ , _CH₂CH ( _CH₃ ) _₂ , CH( _CH₃ ) _CH₂CH₃ , _CH₂Ph , _{CH₂ -} Indole _{- 3 - yl} , _{-CH₂CH₂SCH₃} , _CH₂CO₂ H, _CH₂C (O) _NH₂ , _{CH₂CH₂COOH} , _CH₂CH₂C ( _{O )} NH₂, _{CH₂CH₂CH₂NH₂} , _{-CH₂CH₂CH₂NHC} (NH) _NH₂ , _{CH₂ -} imidazol-4-yl _{, CH₂OH} , _CH (OH) _{CH₃ , CH₂ (} (4'-OH)-Ph), _CH₂SH or _lower cycloalkyl groups, where _R₃b is H ^;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2 (halogen) such as _CH2F , _N3 , _CH2CN , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _{CH2N ( CH3} ) _{2 ,} halogens, including F, Cl, Br or _I ;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , halogen, _NH2 , or _N3.

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH (vinyl), NH (acetyl), NH (C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ ;

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I and q is 1 to ₃ , vinyl, _CO2H , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ .

The fourth aspect of the second implementation scheme relates to the compound represented by formula I-3.

in

(a) R ¹ is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: CH ₃ , OCH ₃ , F, Cl, Br, I, nitro, cyano and CH _3-q X _q , wherein X is F, Cl, Br or I and q is 1-3;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH (CH3) ₂ , CH( _{CH3 ) CH2CH3} , CH2Ph, _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , _CH2C ( _O ) _NH2 , _CH2CH2COOH , _{CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC ( NH ) NH2 , CH2 - imidazol - 4} -yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} (4'-OH)-Ph), _{CH2SH ,} or _a lower cycloalkyl ^group , or _R3a is _CH3 , CH( _CH3 ) _{2 CH2CH} ( _CH3 ) ₂ , CH( _CH3 )CH2CH3, _CH2Ph , _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , CH2C( _O ) _NH2 , _CH2CH2COOH , _CH2CH2C (O) _NH2 , _{CH2CH2CH2CH2NH2} , _{-CH2CH2CH2NH2 , CH2 -} imidazol _{- 4 -} yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} ( _4' -OH) _-Ph ), _{CH2SH or lower} ^cycloalkyl , _R3b is H;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2 (halogen) such as _CH2F , _N3 , _CH2CN , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _{CH2N ( CH3} ) _{2 ,} halogens, including F, Cl, Br or _I ;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH (vinyl), NH (acetyl), NH (C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ ;

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I, and q is 1 to ₃ , vinyl, _CO2H , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ , where R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, _C2 - _C6 alkynyl.

The fifth aspect of the second implementation scheme relates to the compound represented by formula I-4.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: CH ₃ , OCH ₃ , F, Cl, Br, I, nitro, cyano and CH _3-q X _q , wherein X is F, Cl, Br or I and q is 1-3;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH (CH3) ₂ , CH( _{CH3 ) CH2CH3} , CH2Ph, _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , _CH2C ( _O ) _NH2 , _CH2CH2COOH , _{CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC ( NH ) NH2 , CH2 - imidazol - 4} -yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} (4'-OH)-Ph), _{CH2SH ,} or _a lower cycloalkyl ^group , or _R3a is _CH3 , CH( _CH3 ) _{2 CH2CH} ( _CH3 ) ₂ , CH( _CH3 )CH2CH3, _CH2Ph , _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , CH2C( _O ) _NH2 , _CH2CH2COOH , _CH2CH2C (O) _NH2 , _{CH2CH2CH2CH2NH2} , _{-CH2CH2CH2NH2 , CH2 -} imidazol _{- 4 -} yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} ( _4' -OH) _-Ph ), _{CH2SH or lower} ^cycloalkyl , _R3b is H;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , CH2F, _{N3 , CH2CN} , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2} , or a halogen, including F, Cl, _{Br ,} or I;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH (vinyl), NH (acetyl), NH (C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ ;

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I and q is 1 to ₃ , vinyl, CO2H, _CO2CH3 , _{CONH2 , CONHCH3} or CON( _CH3 ) ₂ , where R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, _C2 - _C6 ynyl.

The sixth aspect of the second implementation scheme relates to the compound represented by formula I-4.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, _NH2 , _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) ^R7 and ^R8 are independently H, F, Cl, Br, I, OH, _OCH3 , SH, _SCH3 , _NH2 , _NHCH3 , N( _CH3 ) ₂ , _CH3 , _{CH3 - qXq} , where X is F, Cl, Br or I and q is 1 to ₃ , vinyl, CO2H, _CO2CH3 , _{CONH2 , CONHCH3} or CON( _CH3 ) ₂ , where R' is _C1-20 alkyl, _C1-20 cycloalkyl, _C2 - _C6 alkenyl, _C2 - _C6 ynyl.

The seventh aspect of the second implementation scheme relates to the compound represented by formula I-4.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e)R ⁵ is H, OMe, CN, CH _2F , F, Cl, Br or I;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , OCH3 or OC(O) _CH3 ;

(i) ^R7 and ^R8 are independently H, F, Br, _SCH3 , _CH3 , _{CH3-qXq ,} where X is F, Cl, Br or I and q is 1 to 3, _vinyl , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ ;

The eighth aspect of the second implementation scheme relates to the compound represented by formula I-4.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e)R ⁵ is H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R7 and ^R8 are independently H, F, Br, _SCH3 , _CH3 , _{CH3-qXq ,} where X is F, Cl, Br or I and q is 1 to 3, _vinyl , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ .

The ninth aspect of the second implementation scheme relates to the compound represented by formula I-4.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e)R ⁵ is H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F or _N3 ;

(h) Y is OH, OCH ₃ or OC(O)CH ₃ ;

(i) ^R7 and ^R8 are independently H, F, Br, _SCH3 , _CH3 , _{CH3-qXq ,} where X is F, Cl, Br or I and q is 1 to 3, _vinyl , _CO2CH3 , _CONH2 , _CONHCH3 or CON( _CH3 ) ₂ .

A third embodiment of the invention relates to a compound represented by Formula I, wherein the bases in the compound have the structure represented by Formula c above, wherein ^R1 , ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , ^R6 , X, Y, Z, ^R10 , ^R11 and ^R12 are defined in the invention summary section above; provided that ^R11 is not H.

The first aspect of the third implementation scheme relates to the compound shown in Formula I-5.

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R (v) ^R3b is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; where c is ¹ to 6, d is 0 to 2, e is 0 to 3, f is 2 to ₅ , n is 2 to ⁴ , and where ^R3 ' is independently hydrogen or ^C1-6 alkyl, and _R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is _H and ^R3b is derived from H, _CH3 , CH2CH3, CH( _CH3 ) _{2 , CH2CH} (CH3) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _CH2 -indole- _{3 -} yl, _{-CH 2} CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

(i) ^R10 and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2 R', the condition is that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The second aspect of the third implementation scheme relates to the compound shown in Formula I-5.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) ^R4 is hydrogen, _CH3 , Et, ^iPr , ^nPr , ^nBu , 2-butyl, ^tBu , benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, NH2 _{, N3} , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The third aspect of the third implementation scheme relates to the compound represented by formula I-5.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The fourth aspect of the third implementation scheme relates to compounds represented by formula I-5.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The fifth aspect of the third implementation scheme relates to compounds represented by formula I-5.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The sixth aspect of the third implementation scheme relates to the compound represented by formula I-5.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, _NH2 , _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The seventh aspect of the third implementation scheme relates to the compound represented by formula I-5.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The eighth aspect of the third implementation scheme relates to the compound represented by formula I-5.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, or a lower haloalkyl group;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The ninth aspect of the third implementation scheme relates to the compound represented by formula I-5.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) ^R4 is hydrogen, _CH3 , Et, ^iPr , ^nPr , ^nBu , 2-butyl, ^tBu , benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl or N-methyl-pyrrolidine-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The tenth aspect of the third implementation scheme relates to compounds represented by formula I-6.

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, Cl, Br, I, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The eleventh aspect of the third embodiment relates to the compound represented by formula I-6.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, _NH2 , _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The twelfth aspect of the third implementation scheme relates to a compound represented by formula I-6.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The thirteenth aspect of the third implementation scheme relates to the compound shown in Formula I-6.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The fourteenth aspect of the third implementation scheme relates to the compound shown in Formula I-6.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are independently H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ', provided that ^R11 is not _NH2 when ^R10 is OH;

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The fifteenth aspect of the third implementation scheme relates to the compound shown in Formula I-6.

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The sixteenth aspect of the third implementation scheme relates to the compound shown in Formula I-6.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, _NH2 , _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The seventeenth aspect of the third implementation scheme relates to a compound represented by formula I-6.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The eighteenth aspect of the third implementation scheme relates to a compound represented by formula I-6.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 is _NH2 , while ^R11 is H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The nineteenth aspect of the third implementation scheme relates to the compound shown in Formula I-6.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) R ¹⁰ is NH ₂ , while R ¹¹ is independently H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R';

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The fourth embodiment of the present invention relates to a compound represented by Formula I, wherein the bases are in the structure represented by Formula c above, wherein ^R11 is H, and ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , ^R6 , X and Y are defined in the invention overview section above.

The first aspect of the fourth embodiment relates to compounds represented by formula I-7.

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a and ^R3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ', aryl and _aryl ^C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) ^R3a and ^R3b are both _C1-6 alkyl; (iii) ^R3a and ^R3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while ^R3 ' is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ;

(i) ^R10 is H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkoxy such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkoxy, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ',

Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is R ¹² are not: (i) –C≡C–H, (ii) –C＝CH ₂ or (iii) –NO ₂ .

The second aspect of the fourth embodiment relates to compounds represented by formula I-7.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen (including F, Cl, Br, or I), provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , halogen, _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, _NH2 , _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The third aspect of the third implementation scheme relates to the compound represented by formula I-7.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The fourth aspect of the fourth embodiment relates to compounds represented by formula I-7.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) ^R10 and ^R11 are H, F, Br, I, OH, OR', _NH2 , NHR', _NR'2 , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2H or CH＝ _CHCO2R ',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The fifth aspect of the fourth embodiment relates to compounds represented by formula I-7.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 can be H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '.

The sixth aspect of the fourth embodiment relates to compounds represented by formula I-8.

                        

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _C2-4 alkenyl), SO (C1-4 acyl), SO ( _C1-4 alkyl), SO ( _C2-4 ynyl), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 ( _C1-4 alkyl), _SO2 ( _C2-4 alkenyl) _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C _2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkenyl), O (C _1-4 acyl), O ...1-4 alkyl _1-4 alkyl), O (C _2-4 alkenyl), S (C _1-4 acyl), S (C _1-4 alkyl), S (C _2-4 ynyl), S (C _2-4 alkenyl), SO (C _1-4 acyl), SO (C _1-4 alkyl), SO (C _2-4 ynyl), SO (C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C _2-4 ynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-4 acyl) ₂ ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that when the base is represented by the structure c where ^R11 is hydrogen, ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The seventh aspect of the fourth embodiment relates to compounds represented by formulas I-8.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , halogen, _NH2 or _N3 ;

(h)Y can be OH, H, _CH3 , vinyl, _NH2 , _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , or _OCH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The eighth aspect of the fourth embodiment relates to compounds represented by formula I-8.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The ninth aspect of the fourth embodiment relates to compounds represented by formula I-8.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The tenth aspect of the fourth embodiment relates to compounds represented by formulas I-8.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 ;

(i) R ¹⁰ is H, F, Br, I, OH, OR', NH ₂ , NHR', NR' ₂ , CO ₂ R', CONH ₂ , CONHR', CONR' ₂ , CH＝CHCO ₂ H or CH＝CHCO ₂ R',

Wherein R' is a lower alkyl, lower cycloalkyl, or C(O) (lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and

(j) Z is N or CR ¹² ; and

^R12 is H, halogen (including F, Cl, Br, I), OR', _NH2 , NHR', _NR'2 , _NO2 , _C1 - _C6 lower alkyl, _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; provided that ^R12 is not: (i)–C≡C–H, (ii)–C= _CH2 or (iii) _–NO2 .

The fifth embodiment of the present invention relates to a compound represented by Formula I, wherein the bases in the compound have the structure represented by Formula d above, wherein ^R1 , ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , ^R6 , X and Y are defined in the invention overview section above.

The first aspect of the fifth implementation scheme relates to compounds represented by formula I-9.

in

(a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N(R1 ^' ) ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N(R1 ^' ) ₂ );

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ );

(d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, _C1-10 haloalkyl, _{C3-10 cycloalkyl} , cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ;

(h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ .

The second aspect of the fifth implementation scheme relates to compounds represented by formula I-9.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , halogen, _NH2 or _N3 ;

_{(h)Y is OH, H, CH3, vinyl, NH2, N3 , CN} , Cl, Br, F, I, OC(O) _CH3 , _OCH3 .

The third aspect of the fifth embodiment relates to compounds represented by formula I-9.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h) Y is H, OH, CH ₃ , F, Cl, Br, I, NH ₂ , N ₃ , OCH ₃ or OC(O)CH ₃ .

The fourth aspect of the fifth embodiment relates to compounds represented by formula I-9.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 .

The fifth aspect of the fifth embodiment relates to compounds represented by formula I-9.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 .

The sixth aspect of the fifth embodiment relates to the compound represented by formula I-10.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl or substituted or unsubstituted phenyl, wherein the substituent of the substituted phenyl is at least one of the following: CH ₃ , OCH ₃ , F, Cl, Br, I, nitro, cyano and CH _3-q X _q , wherein X is F, Cl, Br or I and q is 1-3;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH (CH3) ₂ , CH( _{CH3 ) CH2CH3} , CH2Ph, _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , _CH2C ( _O ) _NH2 , _CH2CH2COOH , _{CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC ( NH ) NH2 , CH2 - imidazol - 4} -yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} ⁽ 4'-OH)-Ph), _CH2SH , or _{a lower} cycloalkyl group; or _R3a is _CH3 , CH( _CH3 ) _{2 CH2CH} ( _CH3 ) ₂ , CH( _CH3 )CH2CH3, _CH2Ph , _CH2 -indole-3-yl, _-CH2CH2SCH3 , _CH2CO2H , CH2C( _O ) _NH2 , _CH2CH2COOH , _CH2CH2C (O) _NH2 , _{CH2CH2CH2CH2NH2} , _{-CH2CH2CH2NH2 , CH2 -} imidazol _{- 4 -} yl, _CH2OH , _CH ( _{OH ) CH3} , _{CH2 (} ( _4' -OH) _-Ph ), _{CH2SH or lower} ^cycloalkyl , _R3b is H;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , CH2F, _{N3 , CH2CN} , _CH2N3 , _CH2NH2 , _CH2NHCH3 , _{CH2N ( CH3} ) ₂ , or a halogen, including F, Cl, _{Br ,} or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 or _N3 ;

(h)Y is OH, H, _CH3 , vinyl, _N3 , CN, Cl, Br, F, I, OC(O) _CH3 , _OCH3 , _NH2 , _NHCH3 , NH(vinyl), NH(acetyl), NH(C(O) _CH3 ), N( _CH3 ) ₂ , N(C(O) _CH3 ) ₂ .

The seventh aspect of the fifth embodiment relates to the compound represented by formula I-10.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) R ^3a is H, while R ^3b is H, CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph, CH ₂ -indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H, CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH _{2 CH 2 NH 2} , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH3 , _OCH3 , _CH2OH , _CH2F , or a halogen, including F, Cl, Br, or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN;

(g)X is H, OH, F, _OCH3 , Cl, Br, I, _NH2 , or _N3 ; and

_{(h)Y is OH, H, CH3, vinyl, NH2, N3 , CN} , Cl, Br, F, I, OC(O) _CH3 , _OCH3 .

The eighth aspect of the fifth embodiment relates to the compound represented by formula I-10.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen or _CH3 ;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, CN, _CH2F , F, Cl, Br or I, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, F, _OCH3 , F, Cl, Br, I, _NH2 or _N3 ;

(h)Y is H, OH, _CH3 , F, Cl, Br, I, _NH2 or _N3 , _OCH3 or OC(O) _CH3 .

The ninth aspect of the fifth embodiment relates to the compound represented by formula I-10.

in

(a) R ¹ is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromophenyl, p-chlorophenyl, p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 .

The tenth aspect of the fifth embodiment relates to a compound represented by formula I-10.

in

(a) ^R1 is hydrogen, methyl, phenyl, p-bromophenyl, p-chlorophenyl, or p-fluorophenyl;

(b) ^R2 is hydrogen;

(c) ^R3a is H, while ^R3b is H, _CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph or _a lower cycloalkyl group;

(d) R ⁴ is hydrogen, CH ₃ , Et, ⁱ Pr, ⁿ Pr, ⁿ Bu, 2-butyl, ^t Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-acprodin-2-yl, N-methyl-acprodin-3-yl, N-methyl-pyrrolidine-3-yl, N-methyl-pyrrolidine-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di(lower alkyl)amino-lower alkyl;

(e) ^R5 is H, provided that when X is OH, ^R6 is _CH3 or _CH2F , and ^R5 is not H;

(f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , or F;

(g)X is H, OH, _OCH3 , F, _NH2 or _N3 ;

(h)Y is OH, _NH2 , _OCH3 or OC(O) _CH3 .

The following table includes numerical identifiers associated with various substituent identifiers, which should be observed in relation to the attached structures. These structures are intended substances representing different aspects of the disclosed embodiments and are not intended to limit the full range of compounds represented by the structures of Formula I. However, it is also contemplated that any of the example nucleoside bases may be used in combination with any of the intended substances in specific combinations of the specified ^R1 , ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , ^R6 , X, and Y. In each of the given tables, aminophosphate substituents including substituents ^R3a and ^R3b are depicted without mentioning stereochemical structures (refer to: structures I-1, I-3, I-5, I-7, and I-9 above). The compounds listed below are contemplated to include compounds in which ^R3a bulges toward the observer and ^R3b bulges away from the observer (refer to structures I-2, I-4, I-6, I-8, and I-10). Furthermore, the compounds listed below are also expected to include those where R ^3a bulges away from the observer and R ^3b bulges towards the observer. However, without limitation, preferred compounds are those where R ^3a bulges towards the observer and R ^3b bulges away from the observer, in order to present the (S) configuration of the native L amino acid. Furthermore, the inventors recognize that the phosphorus atom in the aminophosphate moiety is another source of chirality. Although the following structures do not specifically depict the chirality of phosphorus, the inventors recognize that stereochemical configurations are possible such that in staggered (or zigzag) linear structures, the oxygen-substituent bulges towards the observer and the OR ¹ substituent bulges away from the observer, and vice versa; that is, the Cahn-Ingold-Prelog stereochemical identifier for phosphorus is R or S. Therefore, the following structures encompass all plausible stereochemical configurations for phosphorus.

Table II-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table II-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table III-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IV-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table V-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VI-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table VIII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table IX-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table X-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XI-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIV-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XV-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVI-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-30.

*R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-31.

* ^R2 and R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-33.

*R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XVIII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XIX-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XX-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXI-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIV-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXV-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVI-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXVIII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXIX-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXX-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXI-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-1.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-2.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-3.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-4.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-5.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-6.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-7.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-8.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-9.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-10.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-11.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-12.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-13.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-14.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-15.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-16.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-17.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-18.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-19.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-20.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-21.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-22.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-23.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-24.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-25.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-26.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-27.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-28.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-29.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-30.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-31.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-32.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-33.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-34.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-35.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-36.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-37.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-38.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-39.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-40.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-41.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-42.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-43.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-44.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-45.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-46.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-47.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-48.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-49.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Table XXXII-50.

* ^R2 and ^R3b are connected together by ( _CH2 ) ₃ to form a pentagonal ring.

Dosage, administration and use

A sixth embodiment of the invention relates to a composition for treating any of the viral agents disclosed herein, the composition comprising a pharmaceutically acceptable medium selected from excipients, carriers, diluents and equivalent media, and a compound represented by Formula I, the compound being intended to include its available salts (acid or base addition salts), hydrates, solvates and crystalline forms.

The formulation of the sixth embodiment is intended to include any of the compounds included in any aspect of the first, second, third, fourth and fifth embodiments, or any of those specifically described in the table above or exemplified herein, either alone or in combination with another compound of the invention.

The compounds of this invention can be formulated with carriers into a variety of oral dosage forms. Oral administration can be in the form of tablets, coated tablets, hard gelatin capsules and soft gelatin capsules, solutions, emulsions, syrups, or suspensions. The compounds of this invention are effective when administered via suppositories and other routes of administration. The most convenient route of administration is typically oral administration using a convenient daily dosing regimen that can be adjusted according to the severity of the disease and the patient's response to antiviral drugs.

The compounds of the present invention, along with their pharmaceutically acceptable salts, can be incorporated into pharmaceutical compositions and unit doses, together with one or more conventional excipients, carriers, or diluents. The pharmaceutical composition and unit dose form may include conventional proportions of conventional ingredients, with or without other active compounds, and the unit dose form may contain any suitable effective amount of active ingredient commensurate with the intended daily dose range. The pharmaceutical composition may be in the form of solids such as tablets or filled capsules, semi-solids, powders, sustained-release formulations, or liquids such as suspensions, emulsions, or filled capsules for oral use; or in the form of suppositories for rectal or vaginal administration. Typical formulations contain about 5% to about 95% (w/w) of the active compound. The terms “formulation” or “dosage form” are intended to include solid and liquid formulations of the active compound, and those skilled in the art will understand that the active ingredient may be present in different formulations depending on the desired dose and pharmacokinetic parameters.

As used herein, the term "excipient" refers to a compound used to prepare a pharmaceutical composition that is generally safe, non-toxic, and biologically or otherwise acceptable, and includes excipients acceptable for veterinary and human pharmaceutical use. The compounds of the present invention may be administered alone, but are typically administered in combination with one or more suitable pharmaceutical excipients, diluents, or carriers selected based on the intended route of administration and standard pharmaceutical practice.

The "pharmaceutically acceptable salt" form of an active ingredient can initially impart desired pharmacokinetic properties not present in its non-salt form, and may even positively influence the pharmacodynamics of the active ingredient in terms of its therapeutic activity in vivo. As used herein, a "pharmaceutically acceptable salt" of a compound refers to a salt that is pharmaceutically acceptable and possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or with organic acids such as glycolic acid, pyruvic acid, lactic acid, malonic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, dodecyl sulfate, gluconic acid, glutamic acid, salicylic acid, mucoconic acid, etc.; or (2) base addition salts, which are formed with the conjugate base of any of the inorganic acids listed above, wherein the conjugate base includes those selected from Na ⁺ , K ⁺ , Mg2 ⁺ , Ca2 ⁺ and _{NH4 +.} ⁺ cationic component, where R”' is a _C1-3 alkyl group and g is a number selected from 0, 1, 2, 3 or 4. It should be understood that all pharmaceutically acceptable salts mentioned include solvation forms (solvates) or crystalline forms (polymorphs) of the same acid addition salts as defined herein.

Solid dosage forms include powders, tablets, pills, capsules, suppositories, and dispersible granules. The solid carrier can be one or more substances, which can also be used as a diluent, flavoring agent, solubilizer, lubricant, suspending agent, binder, preservative, tablet disintegrant, or encapsulation material. In powders, the carrier is typically an extremely fine solid, a mixture with an extremely fine active ingredient. In tablets, the active ingredient is typically mixed with a carrier having the necessary binding capacity in a suitable proportion and compressed into the desired shape and size. Suitable carriers include, but are not limited to, magnesium carbonate, magnesium stearate, talc, sucrose, lactose, pectin, dextrin, starch, gelatin, tragacanth gum, methylcellulose, sodium carboxymethyl cellulose, low-melting-point waxes, cocoa butter, etc. In addition to the active ingredient, solid dosage forms may contain colorants, flavoring agents, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizers, etc.

Liquid formulations also suitable for oral administration include emulsions, syrups, elixirs, and aqueous suspensions. These include solid formulations that are intended to be converted into a liquid form shortly before use. Emulsions can be prepared in solution, such as in an aqueous propylene glycol solution, or may contain emulsifiers such as lecithin, sorbitan monooleate, or gum arabic. Aqueous suspensions can be prepared by dispersing a very fine active ingredient with a viscous material in water, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethyl cellulose, and other known suspending agents.

The compounds of this invention can be formulated as suppositories. First, a mixture of low-melting-point waxes, such as fatty acid glycerides or cocoa butter, is melted, and then the active ingredients are uniformly dispersed by, for example, stirring. The molten, homogeneous mixture is then poured into a mold of suitable size, allowing it to cool and solidify.

The compounds of the present invention can be formulated for vaginal administration. In addition to the active ingredient, vaginal suppositories, tampons, creams, gels, pastes, foams or sprays containing carriers such as those known in the art are suitable.

Suitable formulations, together with drug carriers, diluents, and excipients, are described in Remington: The Science and Practice of Pharmacy 1995, edited by E.W. Martin, Mack Publishing Company, 19th edition, Easton, Pennsylvania, which is hereby incorporated by reference. The compounds of the present invention can also be encapsulated in liposomes, as disclosed in U.S. Patents 6,180,134, 5,192,549, 5,376,380, 6,060,080, and 6,132,763, each of which is incorporated by reference. Experienced formulation physicists may modify formulations within the teachings of this specification to provide numerous formulations for specific routes of administration without causing instability or impairing the therapeutic activity of the compositions of the present invention.

For example, modifying the compounds of the present invention to increase their solubility in water or other carriers can be readily achieved through minor modifications (e.g., saline formulations), which are entirely within the scope of ordinary techniques in the art. Modifying the route of administration and dosage regimen of specific compounds to maximize the beneficial effects in patients by utilizing the pharmacokinetics of the compounds of the present invention is also entirely within the scope of ordinary techniques in the art.

The seventh embodiment of the present invention relates to the use of a medicament prepared from the compound represented by Formula I for treating any symptoms caused by any of the following viral infections: hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, poliovirus, hepatitis A virus, bovine viral diarrhea virus, and Japanese encephalitis virus.

The term "medicine" refers to a substance used in methods of treating and/or preventing a patient in need of it, wherein such substance includes, but is not limited to, compositions, formulations, dosage forms, etc., comprising compounds of Formula I. The compound contemplated for use in the seventh embodiment, representing the use of a compound of Formula I in the preparation of a medicament for treating any of the antiviral symptoms disclosed herein, may be a compound included in any aspect of the first, second, third, fourth, or fifth embodiments, or any of those specifically described in the table above or exemplified herein, alone or in combination with another compound of the invention. A medicament includes, but is not limited to, any of the compositions contemplated in the sixth embodiment of the invention.

An eighth embodiment of the present invention relates to a method for treating and/or preventing a subject in need of such treatment, the method comprising administering to the subject a therapeutically effective amount of a compound of formula I.

The first aspect of the eighth embodiment relates to a method for treating and/or preventing a subject in need of treatment, the method comprising administering to the subject at least two or more different compounds falling within the range of compounds represented by Formula I that are effective in treating the subject.

The second aspect of the eighth embodiment relates to a method for treating and/or preventing a subject in need of treatment, the method comprising alternately or simultaneously administering to the subject at least two compounds that are therapeutically effective and fall within the range of compounds represented by Formula I.

The term "required patient" refers to a patient who has any symptoms caused by infection with any of the viral agents disclosed herein, including, but not limited to, hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, poliovirus, hepatitis A virus, bovine viral diarrhea virus, Japanese encephalitis virus, flavivirus or swine fever virus or hepatitis C virus, or viral agents that cause symptoms equivalent to or comparable to those caused by any of the viruses listed above.

The term "treated subject" refers to a mammal, including but not limited to cattle, pigs, sheep, chickens, turkeys, buffalo, llamas, ostriches, dogs, cats, and humans, preferably humans. The method of treating its treated subject according to the sixth embodiment is contemplated to include compounds included in any aspect of the first, second, and third embodiments, or any of the compounds specifically described in the table above, alone or in combination with another compound of the invention.

As used herein, the term "therapeuticly effective dose" refers to the amount required to reduce disease symptoms in an individual. In each specific case, the dose should be adjusted to the individual's needs. This dose can vary within a wide range based on many factors, such as the severity of the disease to be treated, the patient's age and general health condition, other medications used to treat the patient, the route and form of administration, and the preferences and experience of the relevant physician. For oral administration, the appropriate daily dose in monotherapy and/or combination therapy is between about 0.1 g and about 10 g, including all values such as 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, and 9.5. A preferred daily dose is between about 0.5 g/day and about 7.5 g/day, more preferably between 1.5 g/day and about 6.0 g/day. Generally, a large initial "loading dose" is used to begin treatment in order to rapidly reduce or eliminate the virus, and then the dose is reduced to a level sufficient to prevent recurrence of infection. Without extensive experimentation and relying on personal knowledge, experience, and the disclosure of this application, a person skilled in the art in treating the diseases described herein should be able to determine the therapeutically effective amount of the compounds of this invention for a given disease and patient.

Treatment efficacy can be determined based on the following laboratory tests: liver function, including but not limited to protein levels such as serum proteins (e.g., albumin, coagulation factors, alkaline phosphatase, aminotransferases (e.g., alanine aminotransferase, aspartate aminotransferase), 5'-nucleosidase, gamma-glutamyl transpeptidase, etc.), bilirubin synthesis, cholesterol synthesis, and bile acid synthesis; and liver metabolic function, including but not limited to carbohydrate metabolism, amino acid metabolism, and ammonia metabolism. Optionally, treatment efficacy can be monitored by measuring HCV-RNA. The results of these tests allow for optimization of the dosage.

The third aspect of the eighth embodiment relates to a method for treating and/or preventing a subject in need of the treatment, the method comprising administering to the subject a therapeutically effective compound of Formula I and a therapeutically effective amount of another antiviral agent, wherein the administration is simultaneous or alternating. It should be understood that the time range between alternating administrations can be between 1 and 24 hours, including any subrange between 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours. Examples of “another antiviral agent” include, but are not limited to: HCV NS3 protease inhibitors (see WO2008010921, WO 2008010921, EP 1881001, WO 2007015824, WO 2007014925, WO2007014926, WO 2007014921, WO 2007014920, WO 2007014922, US 2005267018, WO2005095403, WO 2005037214, WO 2004094452, US 2003187018, WO 200364456, WO2005028502 and WO 2003006490); HCV NS5B inhibitors (see US 2007275947, US20072759300, WO2007095269, WO 2007092000, WO 2007076034, WO 200702602, US 2005-98125, WO2006093801, US 2006166964, W) O 2006065590, WO 2006065335, US 2006040927, US2006040890, WO 2006020082 , WO 2006012078, WO 2005123087, US 2005154056, US2004229840, WO 200406536 7. WO 2004003138, WO 2004002977, WO 2004002944, WO2004002940, WO 2004000 858. WO 2003105770, WO 2003010141, WO 2002057425, WO2002057287, WO 200502 1568、WO 2004041201、US 20060293306、US 20060194749、US20060241064、US 6 784166、WO 2007088148、WO 2007039142、WO 2005103045、WO2007039145、WO 200 4096210 and WO 2003037895); HCV NS4 inhibitors (see WO 2007070556 and WO2005067900); HCV NS5a inhibitors (see US 2006276511, WO 2006120252, WO 2006120251, WO2006100310, WO 2006035061); Toll-like receptor agonists (see WO 2007093901); and other inhibitors (see WO 2004035571, WO 2004014852, WO 2004014313, WO 2004009020, WO 2003101993, WO2000006529).

The fourth aspect of the eighth embodiment relates to a method for treating a subject who requires treatment, the method comprising alternately or simultaneously administering to the subject a therapeutically effective compound of Formula I and another antiviral agent. It should be understood that the time range between alternating administrations can be between 1 and 24 hours, including any subrange between 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours.

The fifth aspect of the eighth embodiment relates to a method for treating and/or preventing a subject in need of the treatment, the method comprising administering to the subject at least one therapeutically effective compound of Formula I and a therapeutically effective amount of another antiviral agent, wherein the administration is simultaneous or alternating. It should be understood that the time range between alternating administrations can be between 1 and 24 hours, including any subrange between 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours.

The sixth aspect of the eighth embodiment relates to a method for treating a subject in need of treatment, the method comprising alternating or simultaneous administration to the subject of at least one therapeutically effective compound of Formula I and another antiviral agent. It should be understood that the time range between alternating administrations can be between 1 and 24 hours, including any subrange between 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours.

Another antiviral agent may be envisioned, including, but not limited to, interferon alpha, interferon beta, pegylated interferon alpha, ribavirin, levamisole, viramidine, another nucleoside HCV polymerase inhibitor, HCV non-nucleoside polymerase inhibitor, HCV protease inhibitor, HCV helicase inhibitor, or HCV fusion inhibitor. When an active compound or its derivative or salt is administered in combination with another antiviral agent, its activity may be increased beyond that of the parent compound. When the treatment is combination therapy, such administration may be simultaneous or sequential with respect to the administration of the nucleoside derivative. Therefore, as used herein, “simultaneous administration” includes administration of the agents at the same time or at different times. Simultaneous administration of two or more agents may be achieved by a single formulation containing two or more active ingredients, or by the substantially simultaneous administration of two or more dosage forms with one active agent.

It should be understood that the treatment mentioned in this article extends to the prevention and treatment of existing symptoms. Furthermore, the term "treatment" for HCV infection, as used herein, also includes the treatment or prevention of disease or symptoms or clinical signs associated with or mediated by HCV infection.

Preparation method

A ninth embodiment of the present invention relates to a method for preparing a compound of formula I, comprising reacting a suitably substituted phosphochloridate compound 4 with a nucleoside analog 5.

The substituents ^R1 , ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , X, Y, ^R6 and the base have the meanings disclosed in the detailed description of the invention, and X' is a leaving group, such as Cl, Br, I, toluenesulfonate, methanesulfonate, trifluoroacetate, trifluorosulfonate, pentafluorophenyloxide, p- _NO2 -phenyloxide, or other commonly used leaving groups as disclosed in the fourth edition of Advanced Organic Chemistry in March. Leaving groups and methods that can influence the formation of aminophosphate nucleoside conjugates are found in US20060142238 and WO 2007095269. Preferably, the leaving group is Cl.

The reaction is carried out in an anhydrous aprotic solvent such as tetrahydrofuran, dioxane, or both tetrahydrofuran and dioxane, or any functional equivalent thereof, with tetrahydrofuran being the preferred solvent. The reaction typically begins in a temperature range of -78°C to 40°C, with a preferred reaction temperature between 0°C and room temperature. First, the nucleoside is stirred with a base (5 to 12 equivalents), such as N-methylimidazolium, ceftriaxone, pyridine, 2,6-rutidine, 2,6- ^tBu -pyridine, etc.; tertiary amine bases, such as triethylamine, diisopropylethylamine, etc.; or alkyl Grignard reagents, such as tBuMgCl, tBuMgBr, MeMgCl, MeMgBr, etc. Phosphoryl chloride (3-10 equivalents) is dissolved in the reaction solvent and added to the nucleoside and base mixture. The reactants are then allowed to stir at a temperature between room temperature and 40°C for 30 min to 24 hr, with room temperature being the preferred temperature and 24 hr being the preferred time. The solvent is removed from the reaction mixture, and the product is purified by silica gel chromatography.

The tenth embodiment of the present invention relates to a product obtained by a method comprising reacting a suitably substituted phosphorus chloride compound 4 with a nucleoside analog 5.

The substituents ^R1 , ^R2 , ^R3a , ^R3b , ^R4 , ^R5 , X, Y, ^R6 , X' and the bases have the meanings disclosed in the detailed description of the invention.

The reaction is carried out in an anhydrous aprotic solvent such as tetrahydrofuran, dioxane, or a mixture of tetrahydrofuran and dioxane, or other suitable solvents, with tetrahydrofuran being the preferred solvent. The reaction is typically initiated in a temperature range of -78°C to 40°C, with a preferred reaction temperature between 0°C and room temperature. The nucleoside is first stirred with a base (5 to 12 equivalents), such as N-methylimidazolium, a tertiary amine base, or tert-butylmagnesium chloride. Phosphoryl chloride (3-10 equivalents (or a suitable "phosphoryl-(leaving group)- compound")) is dissolved in the reaction solvent and added to the nucleoside-base mixture. The reactants are then allowed to stir at a temperature between room temperature and 40°C for 30 min to 24 hr, with room temperature being the preferred temperature and 24 hr being the preferred time. The solvent is removed from the reaction mixture, and the product is purified by silica gel chromatography.

Compounds and preparations

The aminophosphate compounds of the present invention can be prepared by condensation of nucleoside analog 5 with a suitably substituted phosphorus chloride compound 4 (Figure 1). The nucleoside analogs are prepared by any of the conventional steps disclosed in U.S. Publications Nos. 2005/0009737, 2006/0199783, 2006/0122146, and 2007/0197463, the entire contents of each of which are incorporated herein by reference.

The disclosed 1H-NMR values were recorded on a Varian AS-400 instrument. Mass spectrometry data were acquired using Micromass-QuattromicroAPI or Waters Acquity.

Therefore, by way of example only, a suitably substituted phenol can be reacted with phosphorus chloride oxide (1) to give aryloxyphosphoryl dichloride 2 (see Example 1), which is then treated with an acid addition salt of an α-amino acid ester in the presence of TEA to give aryloxyphosphoryl chloride 4. This arylalkoxy-amino acid aminophosphate ester reacts with a nucleoside analog to give product I (for the steps, see, e.g. C. McGuigan et al. Antitiviral Res. 1992 17:311-321; D. Curley et al. Antitiviral Res. 1990 14:345-356; McGuigan et al. Antitiviral Chem. Chemother 1990 1(2):107-113).

Diagram 1

The preparation of nucleoside aminophosphates requires the reaction of a suitably substituted phosphoric acid chloride with a nucleoside containing a free 5'-hydroxyl moiety. In the presence of only one hydroxyl group, the preparation of aminophosphates generally proceeds smoothly when the phosphoric acid chloride reacts with the desired nucleoside. In cases where the nucleoside contains more than one free hydroxyl group, it may be necessary to prepare a suitably protected nucleoside. Silicylates, acetone compounds, or other alcohol protecting groups known in the art can ensure the protection of the sugar moiety. Regarding the protection of the nucleoside bases, an amidine protection strategy is required to protect the free amino group.

The condensation of phosphochlorides can be carried out on unprotected nucleosides. Because the 5'-OH group of a nucleoside is much less hindrance than the 3'-OH group, selective aminophosphorylation is possible under carefully controlled conditions. After the condensation to form a protected aminophosphonucleotide, deprotection to obtain the free aminophosphonucleotide can be performed using standard procedures in nucleic acid chemistry. In most cases, the desired product can be readily separated from the starting material using silica gel column chromatography. A schematic diagram of the synthesis is summarized in Figure 1.

A further understanding of the disclosed embodiments will be gained by considering the following examples, which are intended to be illustrative only and not to limit the disclosed invention.

Example 1

General steps for preparing phosphoryl dichloride

A suitable anhydrous ether solution of phenol ^R1 -OH (1 equivalent) and triethylamine (1 equivalent) was added dropwise to a stirred solution of phosphoryl trichloride 1 (1 equivalent) under nitrogen atmosphere at 0°C for 3 hours. The temperature was then raised to room temperature, and the reaction mixture was stirred overnight. The triethylamine salt was rapidly removed by suction filtration, and the filtrate was concentrated under vacuum until dry to obtain oil 2, which was used without further purification.

Example 2

General steps for preparing phosphoryl chloride

A solution of triethylamine (2 equivalents) in anhydrous dichloromethane was added dropwise over 30 to 120 minutes at -78°C with vigorous stirring to a solution of aryloxy-phosphorus dichloride 2 (1 equivalent) and a suitable amino ester 3 (1 equivalent). The reaction was then allowed to rise to room temperature and stirred overnight. The solvent was removed. The residue was washed with diethyl ether and filtered. The filtrate was dried under reduced pressure to obtain 4.

Example 3

General steps for nucleoside aminophosphate derivatives

A suitable solution of anhydrous tetrahydrofuran (THF) of phosphoryl chloride 4 (6.5 equivalents) was added to a mixture of anhydrous THF of nucleoside 5 (1 equivalent) and N-methylimidazole (8 equivalents) under vigorous stirring at room temperature, and the reaction mixture was stirred overnight. The solvent was removed under vacuum, and the crude product was purified by column chromatography and/or preparative thin-layer chromatography to obtain I.

Example 4

Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine

2'-Deoxy-2'-fluoro-2'-C-methylcytidine (1.0 g, 1 equivalent) (Clark, J. et al., J. Med. Chem., 2005, 48, 5504-5508) was dissolved in 10 mL of anhydrous pyridine and concentrated to dryness under vacuum. The resulting slurry was dissolved in 20 mL of anhydrous pyridine under nitrogen atmosphere and stirred and cooled to 0 °C. The brown solution was treated dropwise with benzoyl chloride (1.63 g, 3 equivalent) over 10 min. The ice bath was removed and stirring continued for 1.5 h, resulting in no starting material remaining by thin-layer chromatography (TLC). The mixture was quenched by adding water (0.5 mL) and concentrated to dryness. The residue was dissolved in 50 mL of dichloromethane (DCM) and washed with saturated aqueous _NaHCO3 solution and _H2O . The organic phase was dried over _NaSO4 , filtered, and concentrated to dryness to obtain ^N4,3 ',5'-tribenzoyl-2'-deoxy-2'-fluoro-2'-C-methylcytidine (2.0 g, yield: 91%).

N, ^4,3 ',5'-tribenzoyl-2'-deoxy-2'-fluoro-2'-C-methylcytidine (2.0 g, 1 equivalent) was refluxed overnight in 80% aqueous AcOH. After cooling and standing at room temperature (15 °C), most of the product precipitated and was then filtered through a sintered funnel. The white precipitate was washed with water and co-evaporated with toluene to give a white solid. The filtrate was concentrated and co-evaporated with toluene to give another product, which was washed with water to give a white solid. The two batches of white solid were combined to give 1.50 g of 3',5'-dibenzoyl-2'-deoxy-2'-fluoro-2'-C-methyluridine (yield: 91%).

A saturated solution of ammonia in 20 mL of MeOH was added to a 10 mL solution of 3',5'-dibenzoyl-2'-deoxy-2'-fluoro-2'-C-methyluridine (1.5 g, 1 equivalent) in MeOH. The reaction mixture was stirred at 0 °C for 30 min, and then slowly brought to room temperature. After stirring the reaction mixture for another 18 hours, the reaction mixture was evaporated under reduced pressure to obtain a residue, which was purified by column chromatography to give pure 2'-deoxy-2'-fluoro-2'-C-methyluridine (500 mg, yield: 60%).

Example 5

Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate)

Alaninyl phenylmethoxypropionic acid (1 g, 6.5 equivalents) dissolved in 3 mL of THF was added at room temperature with vigorous stirring to a mixture of 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.15 g, 1 equivalent) and N-methylimidazole (0.3 g, 8 equivalents) in 3 mL of THF. The reaction mixture was then stirred overnight. The solvent was removed under reduced pressure. The resulting crude product was dissolved in methanol and purified on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under reduced pressure to give the desired product (50.1 mg, 15.6%). ¹ H NMR (DMSO-d ₆ )δ1.20-1.27(m,6H),3.58(d,J＝16.0Hz,3H),3.75-3.92(m,2H),4.015-4.379(m,2H),5.54(t,J＝10.2Hz,1H),5.83-5.91 (m,1H),6.00-6.16(m,1H),7.18(d,J＝8.0Hz,2H),7.22(s,1H),7.35(t,J＝4.4Hz,2H),7.55(s,1H),11.52(s,1H);MS,m/e 502(M+1) ⁺ .

Example 6

Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate)

Phenylmethoxy-valinephosphoryl chloride (0.6 g, 3.6 equivalents) dissolved in 3 mL THF was added at room temperature with vigorous stirring to a mixture of 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.15 g, 1 equivalent) and N-methylimidazole (0.44 g, 9 equivalents) in 3 mL THF, and the reaction mixture was stirred overnight. The solvent was removed by vacuum. The resulting crude product was dissolved in methanol and purified on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under vacuum to give the desired product (60 mg, 20%). ^¹H NMR (DMSO-d6 ₎ )δ0.74-0.847(m,6H),1.20-1.28(m,3H),1.89-1.92(m,1H),3.50-3.54(m, 1H),3.58(d,J＝10.4Hz,3H),3.72-3.95(m,1H),4.03-4.05(m,1H),4.23-4.4 3(m,2H),5.56(t,J＝16.0Hz,1H),5.85-5.92(m,1H),6.01-6.07(m,1H),7.1 6-7.21(m,3H),7.37(t,J＝8Hz,2H),7.55-7.60(m,1H),11.52(s,1H); MS,m/e 530(M+1) ⁺ .

Example 7

Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate)

4-Bromophenylmethoxy-valine phosphoryl chloride (1 g, 3.4 equivalents) dissolved in 3 mL THF was added at room temperature with vigorous stirring to a mixture of 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.2 g, 1 equivalent) and N-methylimidazole (0.35 g, 6 equivalents) in 3 mL THF, and the reaction mixture was stirred overnight. The solvent was removed under reduced pressure. The resulting crude product was dissolved in methanol and purified on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under reduced pressure to give the desired product (120 mg, 26%). ¹ H NMR (DMSO-d ₆ )δ0.72-0.82(m,6H),1.19-1.26(m,3H),1.86-1.92(m,1H),3.48-3.50(m,1H),3.56(d,J＝12.0Hz,3H),3.72-3.89(m,1H),3.96-4.03(m,1H) ,4.22-4.37(m,2H),5.54-5.60(m,1H),5.85-5.91(m,1H),5.98-6.13( m,1H),7.15(d,J＝8.0Hz,2H),7.49-7.56(m,3H),11.53(s,1H);MS,m/e 608(M+1) ⁺ .

Example 8

Preparation of 2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate)

4-Bromophenylmethoxy-alanylphosphoryl chloride (0.6 g, 5 equivalents) dissolved in 3 mL THF was added at room temperature with vigorous stirring to a mixture of 2'-deoxy-2'-fluoro-2'-C-methyluridine (0.15 g, 1 equivalent) and N-methylimidazole (0.3 g, 7.8 equivalents) in 3 mL THF, and the reaction mixture was stirred overnight. The solvent was removed by vacuum. The resulting crude product was dissolved in methanol and purified by elution on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under reduced pressure to obtain the desired product (40 mg, 12%); ^¹H NMR (DMSO- _d⁶ ) δ 1.20–1.26 (m, 6H), 3.57 (d, J = 2.8 Hz, 3H), 3.84 (s, 1H), 3.97–4.03 (m, 1H), 4.21–4.25 (m, 1H), 4.33–4.37 (m, 2H), 5.54–5.60 (m, 1H), 5.83–5.89 (m, 1H), 5.98–6.19 (m, 1H), 7.16 (t, J = 10.2 Hz, 2H), 7.52–7.57 (m, 3H), 11.52 (s, 1H); MS, m/e 580 (M+1) ^⁺ .

Example 9

Preparation of N, ^4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine

2'-Deoxy-2'-fluoro-2'-C-methylcytidine (500 mg, 1.9 mmol) was stirred together with a DMF (10 mL) solution of dimethylformamide dimethyl acetal. The resulting mixture was stirred overnight at room temperature. After solvent removal, the crude product was used in the next step without further purification.

Example 10

Preparation of 2'-deoxy-2'-fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate)

Phenylacetylphosphonate chloride (0.6 g, 6 equivalents) dissolved in 3 mL THF was added at room temperature with vigorous stirring to a mixture of ^N4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine (0.15 g, 1 equivalent) and N-methylimidazolium (0.3 g, 7.8 equivalents) in 3 mL THF. The reaction mixture was then stirred overnight. The solvent was removed under reduced pressure. The resulting crude product was dissolved in methanol and purified on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under reduced pressure to give the desired product (62 mg, 20.6%). ¹ H NMR (DMSO-d ₆ )δ1.16(d,J＝23.2Hz,3H),1.22(d,J＝7.2Hz,3H),3.56(S,3H),3.69-3.75(d ,J＝25.6Hz,1H),3.82-3.86(m,1H),3.96-3.98(m,1H),4.21-4.34(m,2H),5. 68(d,J＝7.2Hz,1H),5.75-5.77(m,1H),6.07-6.16(m,1H),7.15-7.19(m,3H ),7.2(d,J＝9.2Hz,2H),7.39(t,J＝7.8Hz,2H),7.48(d,J＝9.2Hz,1H); MS,m/e 501(M+1) ⁺ .

Example 11

Preparation of 2'-deoxy-2'-fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate)

4-Bromophenylmethoxy-valine phosphonate chloride (1.0 g, 3.4 equivalents) dissolved in 3 mL THF was added at room temperature with vigorous stirring to a mixture of ^N4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine (0.2 g, 1 equivalent) and N-methylimidazolium (0.35 g, 6 equivalents) in 3 mL THF, and the reaction mixture was stirred overnight. The solvent was removed by vacuum. The resulting crude product was dissolved in methanol and purified on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under vacuum to give the desired product (59 mg, 13%) as a white solid; ^1H NMR (DMSO- _d6) )δ0.74-0.83(m,6H),1.12-1.20(m,3H),1.89-1.92(m,1H),3.49-3.51(m,1H ),3.55(s,3H),3.59-3.68(m,1H),3.72-.383(m,1H),4.21-4.39(m,2H),5.7 0-5.72(m,1H),5.76-5.83(m,1H),6.04-6.16(m,1H),7.15(d,J＝13.0Hz,2H) ,7.26(s,1H),7.33(s,1H),7.46-7.55(m,1H),7.56(d,J＝4.4Hz,2H);MS,m/e 607(M+1) ⁺ .

Example 12

Preparation of 2'-deoxy-2'-fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate)

Phenylmethoxy-valinephosphoryl chloride (0.6 g, 6 equivalents) dissolved in 3 mL THF was added at room temperature with vigorous stirring to a mixture of ^N4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine (0.15 g, 1 equivalent) and N-methylimidazolium (0.3 g, 7.8 equivalents) in 3 mL THF. The reaction mixture was then stirred overnight. The solvent was removed under reduced pressure. The resulting crude product was dissolved in methanol and purified on a YMC 25x30x2 mm column for preparative HPLC using a water/acetonitrile gradient elution mobile phase. Acetonitrile and water were removed under reduced pressure to give the desired product (86 mg, 42.9%) as a white solid. ¹ H NMR (DMSO-d ₆ )δ0.72-0.80(m,6H),1.09-1.18(m,3H),1.87-1.92(m,1H),3.47-3.51(m, 1H),3.58(s,3H),3.71-3.75(m,1H),3.97(t,J＝11.2Hz,1H),4.22-4.37(m ,2H),5.70(d,J＝8.0Hz,1H),5.76-5.84(m,1H),6.01-6.15(m,1H),7.13-7 .18(m,3H),7.27(s,2H),7.34(d,J＝4.0Hz,2H),7.46-7.50(m,1H); MS,m/e 529(M+1) ⁺ .

Example

Examples 13-54 and 56-66 were prepared using steps similar to those described in Examples 5-8. Example numbers, compound identification, and NMR/MS details are shown below:

* ^R2 and ^R3b together form –( _CH2 ) ₃ – obtained from L-proline.

Purification steps performed by preparative HPLC:

The crude product was dissolved in methanol. The injection volume of these solutions was 5 mL.

The preparative HPLC system consisted of two Gilson 306 pumps, a Gilson 156 UV/Vis detector, a Gilson 215 injector and fraction collector, and Unipoint control software. A Ymc 25×30×2mm column was used. The mobile phase was HPLC-grade water (A) and HPLC-grade acetonitrile (B). Fractions were collected in 100*15mm glass tubes.

The HPLC gradients are shown in Table 1. After selecting the gradient, acetonitrile solution was injected into the HPLC system, and fractions were collected based on the UV peaks. After separation, each glass tube was subjected to MS analysis to collect the desired compound. Fractions with target MS were combined in precisely weighed flasks. Most of the acetonitrile was removed under reduced pressure, and the remaining solution was lyophilized to obtain the desired compound.

Table 1:

Preparation of Example 66

Diagram

Preparation of compound (b)

A 1M solution of LiAl(OBu-t) _3H in THF (2.69 mL, 2.69 mmol) was added dropwise at -20 °C to an anhydrous THF (30 mL) solution of compound a (1 g, 2.69 mmol). The reaction mixture was stirred at the same temperature for 2–3 h. EtOAc (100 mL) was added, followed by saturated _NH4Cl solution (10 mL), and the reaction mixture was slowly brought to room temperature. The reaction mixture was extracted with EtOAc and washed with 1N HCl and water. The combined organic phases were evaporated to give 0.8 g of crude compound b as a clear oil, which was used directly in the next reaction.

Preparation of compound (d)

DEAD (1.8 mL) was added to a solution of compound b (0.8 g, 2.1 mmol), compound c (0.45 g, 2.5 mmol), and Ph ₃ P (0.56 g, 2.1 mmol) in 20 mL of anhydrous THF under a nitrogen atmosphere. The reaction mixture was stirred overnight at room temperature. The reaction solution was concentrated under reduced pressure. The residue was separated by preparative chromatography (hexane:EtOAc = 3:1) to give crude compound d (0.8 g). Crude compound d was used in the next step without further purification.

Preparation of compound (e)

Compound d (0.8 g, 1.57 mmol) was dissolved in THF (2 mL), and then ammonia-saturated THF (5 mL) was added to the solution. The reaction mixture was heated to 90 °C overnight. After 18 hours, the solution was cooled to room temperature with ice water, and then the solvent was removed under reduced pressure. The residue was purified by column chromatography to give compound e (0.75 g) for the next step.

Preparation of compound (f)

Compound e (0.5 g, 1.01 mmol) was dissolved in methanol (2 mL), and then ammonia-saturated methanol (5 mL) was added to the solution. The reaction mixture was stirred overnight at room temperature. After 18 hours, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give crude compound f (0.15 g) for the next step.

Preparation of compound (i)

A solution of triethylamine (1.07 g, 10.6 mmol) in anhydrous dichloromethane (15 mL) was added dropwise to a solution of compound g (1.16 g, 5.3 mmol) and compound h (1.31 g, 5.3 mmol) in dichloromethane (10 mL) over 2 hours at -78 °C with vigorous stirring. After the addition was complete, the reaction temperature was allowed to gradually rise to room temperature and stirred overnight. The solvent was then removed under vacuum, 20 mL of anhydrous ether was added, the precipitated salt was filtered off, and the precipitate was washed with ether. The combined organic phases were concentrated to give a colorless oil (1.0 g) of compound i.

Preparation of compound 66

0.4 g NMI was added to compound j (0.1 g, 0.35 mmol) dissolved in 10 mL of anhydrous THF with stirring until the solution became clear. Compound i (0.8 g, 2.89 mmol) was added dropwise to 10 mL of THF solution, and the mixture was stirred overnight at room temperature. The purity of the compounds was confirmed and identified by LCMS. The solvent was evaporated and purified by preparative HPLC to obtain 66 (25 mg, Yield: 13.6%). ¹ H NMR (DMSO-d ₆ )δ1.08(d,J＝22.8Hz,3H),1.17-1.24(m,3H),3.50-3.52(m,3H),3.78-3.83(m,1H),4.10-4.13(m,1H),4.24-4.44(m,2H),5.8 5-5.92(m,1H),6.01-6.11(m,1H),6.2.-6.27(m,1H),7.08-7.19(m,4H),7.31-7.38(m,3H),8.15(s,1H),8.26(s,1H); MS,m/e 525(M+1) ⁺ .

The embodiments numbered 67-74 below were prepared using steps similar to those disclosed in Embodiment 66 above.

Examples numbered 75-80 were prepared using steps similar to those disclosed in Example 66 above.

Example 81

Due to the chirality of phosphorus, some example compounds were obtained as mixtures of diastereomers. These diastereomers were separated by supercritical fluid chromatography (SFC) on a Chiralpak-AS-H (2 x 25 cm) column using 20% methanol/carbon dioxide as the solvent. The absolute stereochemistry of the P-chiral center of the diastereomers was not determined. However, the chromatographic separation of these two diastereomers provided isomers characterized by rapid elution and slow elution. Some examples are shown below.

Example 82

HCV Replicon Assay. Huh7 cells (clone A cells; Apath, LLC, St. Louis, Mo.) containing HCV replicon RNA were kept at an exponential growth rate in Dalberg Modified Eagle Medium (high glucose) containing 10% fetal bovine serum, 4 mM L-glutamine, 1 mM sodium pyruvate, 1× non-essential amino acids, and G418 (1,000 μg/ml). Antiviral assays were performed in the same medium without G418. Cells were seeded at 1,500 cells/well in 96-well plates, and the test compound was added immediately after seeding. Incubation was performed for 4 days. At the end of the incubation step, total cellular RNA was isolated (RNeasy 96 kit; Qiagen). Replicon RNA and an internal control (TaqMan rRNA control reagent; Applied Biosystems) were amplified using the manufacturer's recommended one-step multiplex RT-PCR assay protocol. HCV primers and probes were designed using primer expression software (Applied Biosystems) and covered highly conserved 5′-untranslated region (UTR) sequences (sense 5′-AGCCATGGCGTTAGTA(T)GAGTGT-3′ and antisense 5′-TTCCGCAGACCACTATGG-3′; probe 5′-FAM-CCTCCAGGACCCCCCCTCCC-TAMRA-3′).

To represent the antiviral efficacy of the compounds, the average RT-PCR cycle threshold of the drug-free control was subtracted from the RT-PCR cycle threshold of the test compound (ΔCt _HCV ). ΔCt 3.3 corresponds to a 1-log 10 reduction in replicon RNA levels (equivalent to 90% of the effective concentration [EC ₉₀ ]). The cytotoxicity of the test compounds can also be represented by calculating the ΔCt _rRNA value. The ΔCt-specific parameter was then substituted into (ΔCt _HCV - ΔCt _rRNA ), where HCV RNA levels were normalized to rRNA levels and corrected relative to the drug-free control.

¹ (4-BrPh): 4-Bromo-phenyl.

Therefore, the entire contents of 60/909,315, filed March 30, 2007, 60/982,309, filed October 24, 2007, and 12/053,015, filed March 21, 2008, are incorporated herein by reference to supplement this disclosure and/or correct any errors as necessary. Furthermore, patent and non-patent documents disclosed herein are incorporated by reference. Where the introduced patent and non-patent documents contain terms that conflict with those disclosed in one of the two provisional applications or in the text of this application, the meanings of the terms contained in the text of this application and the two provisional applications shall prevail, provided that the overall meaning of the incorporated subject matter is not lost.

Claims (12)

1. A compound represented by Formula I, its stereoisomers, salts, hydrates, solvates, or crystalline forms: in (a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N( ^R1 ') ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1 ' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N( ^R1 ') ₂ ); (b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ; (c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ ); (d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl; (e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H; (f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN; (g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ; (h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ; The bases are naturally occurring or modified purine or pyrimidine bases, represented by the following structures: in Z is N or CR ¹² ; ^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R', Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and ^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ . 2. A compound selected from the following, its stereoisomers, its salts, hydrates, solvates, or crystalline forms: 5 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 6 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 7 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 8 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate (((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate); 9N ^4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine; 10 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate (((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 11 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate (2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 12 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 13(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-ethyl propionate; 14(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-benzoic acid ester; 15{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl acetate; 16(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 17(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-methyl propionate; 18(S)-1-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyrrolidine-2-carboxylic acid methyl ester; 19(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 20(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 21(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-methyl propionate; 22(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 23(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 24(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-sec-butyl propionate; 25(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 26(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-butyl propionate; 27(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-ethyl propionate; 28(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-isopropyl propionate; 29(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-benzoic acid ester; 30(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-isopropyl propionate; 31(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-benzoyl propionate; 32(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 33(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-isopropyl propionate; 34(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-butyl propionate; 35(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 36(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 37(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-benzoic acid ester; 38(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-pentyl propionate; 39(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 40(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 41(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 42(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-butyl propionate; 43(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-benzoyl propionate; 44(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl butyrate; 45(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 4-fluoro-benzoyl ester; 46(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 47(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl-butyl propionate; 48(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 49(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl propionate; 50(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 51(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 52(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 53(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 54(S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 55(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl propionate; 56(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosphorylamino]-cyclohexyl propionate; 57(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl butyrate; 58(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl butyrate; 59(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl butyrate; 60(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl butyrate; 61(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2-difluoro-ethyl ester; 62(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; 63(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; 64(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopropyl methyl propionate; 65(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopentyl butyrate; 66(S)-2-{[(2R,3R,4R,5R)-5-(6-amino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 67(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-hydroxy-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 68(S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,6-diamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 69(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclopentylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 70(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-acetidin-1-yl-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 71(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-diethylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 72(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-propylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 73(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclobutylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 74(S)-2-({(2R,3R,4R,5R)-5-[2-amino-6-(4-methyl-piperazin-1-yl)-purine-9-yl]-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy}-phenoxy-phosphorylamino)-methyl propionate; 75(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(propylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 76(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclobutylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 77(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclopentylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 78(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acrididin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 79(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(piperidin-1-yl)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; and 80(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acididin-1-yl)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate. 3. A composition for the treatment and/or prevention of any of the viruses disclosed herein, the composition comprising a pharmaceutically acceptable medium selected from excipients, carriers, diluents and equivalent media, and a compound represented by Formula I, its stereoisomers, its salts, hydrates, solvates or crystalline forms: in (a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N( ^R1 ') ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1 ' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N( ^R1 ') ₂ ); (b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ; (c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ ); (d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl; (e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H; (f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN; (g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ; (h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ; The bases are naturally occurring or modified purine or pyrimidine bases, represented by the following structures: in Z is N or CR ¹² ; ^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R', Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and ^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ . 4. A composition for the treatment and/or prevention of any of the viruses disclosed herein, the composition comprising a pharmaceutically acceptable medium selected from excipients, carriers, diluents and equivalent media, and a compound selected from, stereoisomers thereof, salts thereof, hydrates thereof, solvates thereof or crystalline forms thereof: 5 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 6 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 7 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 8 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate (((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate); 9N ^4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine; 10 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate (((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 11 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate (2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 12 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 13(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-ethyl propionate; 14(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-benzoic acid ester; 15{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl acetate; 16(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 17(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-methyl propionate; 18(S)-1-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyrrolidine-2-carboxylic acid methyl ester; 19(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 20(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 21(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-methyl propionate; 22(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 23(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 24(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-sec-butyl propionate; 25(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 26(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-butyl propionate; 27(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-ethyl propionate; 28(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-isopropyl propionate; 29(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-benzoic acid ester; 30(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-isopropyl propionate; 31(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-benzoyl propionate; 32(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 33(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-isopropyl propionate; 34(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-butyl propionate; 35(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 36(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 37(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-benzoic acid ester; 38(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-pentyl propionate; 39(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 40(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 41(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 42(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-butyl propionate; 43(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-benzoyl propionate; 44(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl butyrate; 45(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 4-fluoro-benzoyl ester; 46(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 47(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl-butyl propionate; 48(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 49(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl propionate; 50(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 51(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 52(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 53(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 54(S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 55(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl propionate; 56(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosphorylamino]-cyclohexyl propionate; 57(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl butyrate; 58(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl butyrate; 59(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl butyrate; 60(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl butyrate; 61(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2-difluoro-ethyl ester; 62(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; 63(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; 64(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopropyl methyl propionate; 65(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopentyl butyrate; 66(S)-2-{[(2R,3R,4R,5R)-5-(6-amino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 67(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-hydroxy-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 68(S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,6-diamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 69(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclopentylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 70(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-acetidin-1-yl-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 71(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-diethylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 72(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-propylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 73(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclobutylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 74(S)-2-({(2R,3R,4R,5R)-5-[2-amino-6-(4-methyl-piperazin-1-yl)-purine-9-yl]-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy}-phenoxy-phosphorylamino)-methyl propionate; 75(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(propylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 76(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclobutylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 77(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclopentylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 78(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acrididin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 79(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(piperidin-1-yl)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; and 80(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acididin-1-yl)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate. 5. Use of the compound shown in Formula I in the preparation of a medicament for treating any symptoms caused by infection with hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, poliovirus, hepatitis A virus, bovine viral diarrhea virus, or Japanese encephalitis virus: The compound, its stereoisomers, its salts, hydrates, solvates, or crystalline forms are represented by Formula I: in (a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N( ^R1 ') ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1 ' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N( ^R1 ') ₂ ); (b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ; (c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ ); (d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl; (e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H; (f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN; (g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ; (h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ; The bases are naturally occurring or modified purine or pyrimidine bases, represented by the following structures: in Z is N or CR ¹² ; ^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R', Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and ^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ . 6. Use of a medicine for treating any symptoms caused by infection with hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, poliovirus, hepatitis A virus, bovine viral diarrhea virus, or Japanese encephalitis virus, selected from the following compounds, their stereoisomers, their salts, hydrates, solvates, or crystalline forms: 5 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 6 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 7 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 8 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate (((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate); 9N ^4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine; 10 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate (((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 11 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate (2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 12 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 13(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-ethyl propionate; 14(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-benzoic acid ester; 15{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl acetate; 16(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 17(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-methyl propionate; 18(S)-1-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyrrolidine-2-carboxylic acid methyl ester; 19(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 20(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 21(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-methyl propionate; 22(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 23(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 24(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-sec-butyl propionate; 25(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 26(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-butyl propionate; 27(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-ethyl propionate; 28(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-isopropyl propionate; 29(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-benzoic acid ester; 30(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-isopropyl propionate; 31(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-benzoyl propionate; 32(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 33(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-isopropyl propionate; 34(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-butyl propionate; 35(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 36(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 37(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-benzoic acid ester; 38(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-pentyl propionate; 39(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 40(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 41(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 42(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-butyl propionate; 43(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-benzoyl propionate; 44(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl butyrate; 45(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 4-fluoro-benzoyl ester; 46(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 47(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl-butyl propionate; 48(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 49(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl propionate; 50(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 51(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 52(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 53(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 54(S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 55(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl propionate; 56(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosphorylamino]-cyclohexyl propionate; 57(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl butyrate; 58(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl butyrate; 59(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl butyrate; 60(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl butyrate; 61(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2-difluoro-ethyl ester; 62(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; 63(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; 64(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopropyl methyl propionate; 65(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopentyl butyrate; 66(S)-2-{[(2R,3R,4R,5R)-5-(6-amino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 67(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-hydroxy-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 68(S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,6-diamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 69(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclopentylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 70(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-acetidin-1-yl-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 71(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-diethylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 72(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-propylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 73(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclobutylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 74(S)-2-({(2R,3R,4R,5R)-5-[2-amino-6-(4-methyl-piperazin-1-yl)-purine-9-yl]-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy}-phenoxy-phosphorylamino)-methyl propionate; 75(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(propylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 76(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclobutylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 77(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclopentylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 78(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acrididin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 79(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(piperidin-1-yl)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; and 80(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acididin-1-yl)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate. 7. A method for treating a subject who requires treatment, comprising: The therapeutically effective amount of the compound represented by Formula I was administered to the patient. The compound or its stereoisomers, salts, hydrates, solvates, or crystalline forms are represented by Formula I: in (a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N( ^R1 ') ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1 ' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N( ^R1 ') ₂ ); (b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ; (c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ ); (d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl; (e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H; (f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN; (g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ; (h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ; The bases are naturally occurring or modified purine or pyrimidine bases, represented by the following structures: in Z is N or CR ¹² ; ^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R', Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and ^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ . 8. A method for treating a subject who requires treatment, comprising: The therapeutically effective amount is selected from the following compounds, their stereoisomers, their salts, hydrates, solvates, or crystalline forms: 5 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 6 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 7 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 8 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate (((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate); 9N ^4- (N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine; 10 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate (((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 11 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate (2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 12 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 13(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-ethyl propionate; 14(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-benzoic acid ester; 15{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl acetate; 16(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 17(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-methyl propionate; 18(S)-1-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyrrolidine-2-carboxylic acid methyl ester; 19(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 20(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 21(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-methyl propionate; 22(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 23(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 24(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-sec-butyl propionate; 25(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 26(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-butyl propionate; 27(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-ethyl propionate; 28(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-isopropyl propionate; 29(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-benzoic acid ester; 30(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-isopropyl propionate; 31(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-benzoyl propionate; 32(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 33(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-isopropyl propionate; 34(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-butyl propionate; 35(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 36(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 37(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-benzoic acid ester; 38(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-pentyl propionate; 39(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 40(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 41(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 42(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-butyl propionate; 43(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-benzoyl propionate; 44(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl butyrate; 45(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 4-fluoro-benzoyl ester; 46(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 47(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl-butyl propionate; 48(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 49(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl propionate; 50(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 51(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 52(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 53(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 54(S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 55(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl propionate; 56(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosphorylamino]-cyclohexyl propionate; 57(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl butyrate; 58(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl butyrate; 59(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl butyrate; 60(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl butyrate; 61(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2-difluoro-ethyl ester; 62(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; 63(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; 64(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopropyl methyl propionate; 65(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopentyl butyrate; 66(S)-2-{[(2R,3R,4R,5R)-5-(6-amino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 67(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-hydroxy-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 68(S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,6-diamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 69(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclopentylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 70(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-acetidin-1-yl-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 71(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-diethylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 72(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-propylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 73(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclobutylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 74(S)-2-({(2R,3R,4R,5R)-5-[2-amino-6-(4-methyl-piperazin-1-yl)-purine-9-yl]-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy}-phenoxy-phosphorylamino)-methyl propionate; 75(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(propylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 76(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclobutylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 77(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclopentylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 78(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acrididin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 79(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(piperidin-1-yl)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; and 80(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acididin-1-yl)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate. 9. A method for preparing a compound of formula I, its stereoisomers, its salts, hydrates, solvates, or crystalline forms: in (a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N( ^R1 ') ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1 ' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N( ^R1 ') ₂ ); (b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ; (c) R ^3a and R ^3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) R ^3a and R ^3b are both _C1-6 alkyl; (iii) R ^3a and R ^3b together are ( _CH2 ) _f to form a spirocycle; (iv) R ^R3a is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; (v) ^R3b is hydrogen, while ^R3a and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms, wherein c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and wherein ^R3 ' is independently hydrogen or _C1-6 alkyl, while R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is _H , _CH3 , _CH2CH3 , CH( _CH3 ) ₂ , _CH2CH ( _CH3 ) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole-3-yl, -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ ); (d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl; (e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H; (f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN; (g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ; (h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ; The bases are naturally occurring or modified purine or pyrimidine bases, represented by the following structures: in Z is N or CR ¹² ; ^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R', Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and ^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ ; The method includes: The substituted phosphorus chloride compound 4 is reacted with nucleoside analog 5. 10. A method for preparing compounds selected from the group consisting of, their stereoisomers, their salts, hydrates, solvates or crystalline forms. 5 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 6 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 7 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 8 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate (((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate); 9 N ⁴ -(N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine; 10 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate (((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 11 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate (2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 12 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 13(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-ethyl propionate; 14(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-benzoic acid ester; 15{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl acetate; 16(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 17(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-methyl propionate; 18(S)-1-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyrrolidine-2-carboxylic acid methyl ester; 19(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 20(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 21(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-methyl propionate; 22(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 23(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 24(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-sec-butyl propionate; 25(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 26(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-butyl propionate; 27(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-ethyl propionate; 28(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-isopropyl propionate; 29(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-benzoic acid ester; 30(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-isopropyl propionate; 31(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-benzoyl propionate; 32(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 33(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-isopropyl propionate; 34(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-butyl propionate; 35(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 36(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 37(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-benzoic acid ester; 38(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-pentyl propionate; 39(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 40(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 41(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 42(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-butyl propionate; 43(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-benzoyl propionate; 44(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl butyrate; 45(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 4-fluoro-benzoyl ester; 46(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 47(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl-butyl propionate; 48(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 49(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl propionate; 50(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 51(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 52(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 53(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 54(S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 55(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl propionate; 56(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosphorylamino]-cyclohexyl propionate; 57(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl butyrate; 58(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl butyrate; 59(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl butyrate; 60(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl butyrate; 61(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2-difluoro-ethyl ester; 62(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; 63(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; 64(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopropyl methyl propionate; 65(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopentyl butyrate; 66(S)-2-{[(2R,3R,4R,5R)-5-(6-amino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 67(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-hydroxy-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 68(S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,6-diamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 69(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclopentylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 70(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-acetidin-1-yl-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 71(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-diethylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 72(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-propylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 73(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclobutylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 74(S)-2-({(2R,3R,4R,5R)-5-[2-amino-6-(4-methyl-piperazin-1-yl)-purine-9-yl]-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy}-phenoxy-phosphorylamino)-methyl propionate; 75(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(propylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 76(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclobutylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 77(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclopentylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 78(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acrididin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 79(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(piperidin-1-yl)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; and 80(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; The method includes: The substituted phosphorus chloride compound 4 is reacted with nucleoside analog 5. 11. A product, its stereoisomer, its salt, hydrate, solvate, or crystalline form, prepared by a method comprising: The substituted phosphorus chloride compound 4 is reacted with nucleoside analog 5. in (a) ^R1 is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, the aryl group including but not limited to phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted by at least one of the following: _C1-6 alkyl, _C2-6 alkenyl, _C2-6 alkynyl, _C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, _C1-6 haloalkyl, -N( ^R1 ') ₂ , _C1-6 amide, _-NHSO2C1-6 alkyl, _-SO2N ( _R1 ^' ) ₂ , COR1 ^" and _-SO2C1-6 alkyl; ( ^R1 ' is independently hydrogen _or alkyl, the alkyl group including but not limited to _C1-20 alkyl, _C1-10 alkyl or _C1-6 alkyl, R1 ^" being –OR' or -N( ^R1 ') ₂ ); (b) ^R2 is hydrogen, _C1-10 alkyl, and ^R3a or ^R3b and ^R2 together are ( _CH2 ) _n , so ^as to form a cyclic ring C(O) ^CR3aR3bNHR1 including adjacent N and C atoms, wherein n is 2 to ⁴ , ^R1 , ^R3a and ^R3b ; (c) ^R3a and ^R3b (i) are independently selected from hydrogen, _C1-10 alkyl, cycloalkyl, -( _CH2 ) _c ( ^NR3 ') ₂ , _C1-6 hydroxyalkyl, _-CH2SH , -( _CH2 ) _2S (O) _dMe , -( _CH2 ) _3NHC (=NH) _NH2 , (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, -( _CH2 ) _eCOR3 ^" , aryl and aryl _C1-3 alkyl, wherein the aryl group is optionally substituted with a group selected from hydroxyl, _C1-10 alkyl, _C1-6 alkoxy, halogen, nitro and cyano; (ii) ^R3a and ^R3b are both _C1-6 alkyl; (iii) ^R3a and ^R3b together are ( _CH2 ) _f to form a spirocycle; (iv) R (v) ^R3b is hydrogen, while ^R3b and ^R2 together form ( _CH2 ) _n to form a cyclic ring including adjacent N and C atoms; where c is ¹ to 6, d is 0 to 2, e is 0 to 3, f is 2 to ₅ , n is 2 to ⁴ , and where ^R3 ' is independently hydrogen or ^C1-6 alkyl, and _R3 ^" is -OR' or –N( ^R3 ') ₂ ); (vi) ^R3a is H and ^R3b is H, CH3, _{CH2CH3 ,} CH( _CH3 ) _{2 , CH2CH} (CH3) ₂ , CH( _CH3 ) _CH2CH3 , _CH2Ph , _{CH2 -} indole- ₃ -yl, _{-CH 2} CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH , CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl , CH ₂ OH , CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph ), CH ₂ SH or lower cycloalkyl; or (viii)R ^3a is CH ₃ , -CH ₂ CH ₃ , CH(CH ₃ ) ₂ , CH ₂ CH(CH ₃ ) ₂ , CH(CH ₃ )CH ₂ CH ₃ , CH ₂ Ph , CH ₂ -indole-3-yl , -CH ₂ CH ₂ SCH ₃ , CH ₂ CO ₂ H , CH ₂ C(O)NH ₂ , CH ₂ CH ₂ COOH, CH ₂ CH ₂ C(O)NH ₂ , CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , -CH ₂ CH ₂ CH ₂ NHC(NH)NH ₂ , CH ₂ -imidazol-4-yl, CH ₂ OH, CH(OH)CH ₃ , CH ₂ ((4'-OH)-Ph), CH ₂ SH or lower cycloalkyl, R ^3b is H, wherein R ³ ' is independently hydrogen or alkyl, including but not limited to C _1-20 alkyl, C _1-10 alkyl or C _1-6 alkyl, R ^3" is –OR' or -N(R ³ ') ₂ ); (d) ^R4 is hydrogen, _C1-10 alkyl, C1-10 alkyl, _C1-10 alkyl, _C1-10 haloalkyl, _C3-10 cycloalkyl, cycloalkylalkyl, cyclohexaalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl; (e) ^R5 is H, a lower alkyl group, CN, vinyl, O-(lower alkyl group), hydroxy-lower alkyl group, i.e. -( _CH2 ) _pOH , where p is 1-6, including hydroxymethyl ( _CH2OH ), _CH2F , _N3 , _CH2CN , _CH2NH2 , _CH2NHCH3 , _CH2N ( _{CH3 ) 2 ,} alkynes (optionally substituted), or halogens including F, Cl, Br, or I, provided that when X is OH, the base is cytosine and ^R6 is H, and ^R5 is not _N3 , and when X is OH, ^R6 is _CH3 or _CH2F and B is a purine base, and ^R5 is not H; (f) ^R6 is H, _CH3 , _CH2F , _CHF2 , _CF3 , F or CN; (g)X is H, OH, F, OMe, halogen, _NH2 or _N3 ; (h)Y represents OH, H, _C1-4 alkyl, _C2-4 alkenyl, _C2-4 ynyl, vinyl, _N3 , CN, Cl, Br, F, I, _NO2 , OC(O)O ( _C1-4 alkyl), OC(O)O ( _C1-4 alkyl), OC(O)O ( _C2-4 ynyl), OC(O)O ( _C2-4 alkenyl), _OC1-10 haloalkyl, O (aminoacyl), O ( _C1-10 acyl), O ( _C1-4 alkyl), O ( _C2-4 alkenyl), S ( _C1-4 acyl), S ( _C1-4 alkyl), S ( _C2-4 ynyl), S ( _{C2-4 alkenyl), SO (C1-4 acyl} ), SO ( _{C1-4 alkyl), SO (C2-4 ynyl} ), SO ( _C2-4 alkenyl), _SO2 ( _C1-4 acyl), _SO2 (C _1-4 alkyl), SO ₂ (C _2-4 alkynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH (C _1-4 alkyl), NH (C _2-4 alkenyl), NH (C 2-4 alkynyl), NH (C _1-4 acyl), N (C _1-4 alkyl) ₂ , N (C _1-18 acyl) ₂ , wherein the alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: N ₃ , CN, 1-3 halogens (Cl, Br, F, I), NO ₂ , C(O)O (C _1-4 alkyl), C(O)O (C _1-4 alkyl), C(O)O (C _2-4 alkynyl), C(O)O (C _2-4 alkynyl), C(O)O (C 1-4 alkyl), _2-4 alkenyl), O(C _1-4 acyl), O(C _1-4 alkyl), O(C _2-4 alkenyl), S(C _1-4 acyl), S(C _1-4 alkyl), S(C _2-4 ynyl), S(C _2-4 alkenyl), SO(C _1-4 acyl), SO(C _1-4 alkyl), SO(C _2-4 ynyl), SO(C _2-4 alkenyl), SO ₂ (C _1-4 acyl), SO ₂ (C _1-4 alkyl), SO ₂ (C _2-4 ynyl), SO ₂ (C _2-4 alkenyl), OS(O) ₂ (C _1-4 acyl), OS(O) ₂ (C _1-4 alkyl), OS(O) ₂ (C _2-4 alkenyl), NH ₂ , NH(C _1-4 alkyl), NH(C _2-4 alkenyl), NH(C _2-4 ynyl), NH(C _1-4 acyl), N(C _1-4 alkyl) ₂ , N(C _1-4 acyl) ₂ ; The bases are naturally occurring or modified purine or pyrimidine bases, represented by the following structures: in Z is N or CR ¹² ; ^R7 , ^R8 , ^R9 , ^R10 , and ^R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _C1 - _C6 lower alkyl, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkyl, _C2 - _C6 lower alkenyl, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkenyl, _C2 - _C6 lower alkynyl such as C≡CH, halogenated (F, Cl, Br, I) _C2 - _C6 lower alkynyl, _C1 - _C6 lower alkoxy, halogenated (F, Cl, Br, I) _C1 - _C6 lower alkoxy, _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH＝ _CHCO2 H or CH=CHCO ₂ R', Wherein R' is an optionally substituted alkyl group, including but not limited to optionally substituted _C1-20 alkyl, optionally substituted _C1-10 alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted _C2 - _C6 ynyl, optionally substituted _C2 - _C6 lower alkenyl, or optionally substituted acyl, wherein the optionally substituted acyl group includes but is not limited to C(O) alkyl, C(O)( _C1-20 alkyl), C(O)( _C1-10 alkyl), or C(O)(lower alkyl), or optionally, in the case of NR' ₂ , each R' includes at least one C atom attached to form a heterocycle comprising at least two carbon atoms; and ^R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', _NH2 , NHR', _NR'2 , _NO2 , _C1 -C6 lower alkyl, _C1 - _C6 lower alkyl (F, Cl, Br, I), _C2 - _{C6 lower} alkenyl, _C2 - _C6 lower alkenyl (F, Cl, Br, I), _C2 - _C6 lower alkynyl (F, Cl, Br, I), _C1 - _C6 lower alkoxy, _{C1 - C6} lower alkoxy (F, Cl, Br, I ₎ , _CO2H , _CO2R ', _CONH2 , CONHR', _CONR'2 , CH= _CHCO2H or CH= _CHCO2R '; the condition is that when the base is R When ¹¹ is represented by the structure c of hydrogen, R ¹² is not: (i)–C≡C–H, (ii)–C＝CH ₂ or (iii)–NO ₂ ; as well as Where X' is a leaving group, such as Cl. 12. A product, its stereoisomer, its salt, hydrate, solvate, or crystalline form, prepared by a method comprising: The substituted phosphorus chloride compound 4 is reacted with nucleoside analog 5. The product includes compounds selected from the following, their stereoisomers, their salts, hydrates, solvates, or crystalline forms. 5 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-alanyl phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 6 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 7 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 8 2'-Deoxy-2'-Fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-alanyl phosphate (((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate); 9 N ⁴ -(N,N-dimethylformamidinyl)-2'-deoxy-2'-fluoro-2'-C-methylcytidine; 10 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-alanyl phosphate (((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate); 11 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(4-bromophenylmethoxy-valine phosphate (2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-(4-bromophenylmethoxy-valine phosphate ((S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-3-methyl-butyrate methyl ester); 12 2'-Deoxy-2'-Fluoro-2'-C-methylcytidine 5'-(phenylmethoxy-valine phosphate ((S)-2-{[(2R,3R,4R,5R)-5-(2-oxo-3-amino-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-3-methyl-butyrate methyl ester; 13(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-ethyl propionate; 14(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-benzoic acid ester; 15{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl acetate; 16(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 17(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalene-1-yloxy)-phosphorylamino]-methyl propionate; 18(S)-1-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyrrolidine-2-carboxylic acid methyl ester; 19(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 20(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 21(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-methyl propionate; 22(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 23(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-methyl propionate; 24(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-sec-butyl propionate; 25(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 26(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-butyl propionate; 27(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-ethyl propionate; 28(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-isopropyl propionate; 29(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-benzoic acid ester; 30(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-isopropyl propionate; 31(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-benzoyl propionate; 32(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 33(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-isopropyl propionate; 34(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-butyl propionate; 35(S)-2-{(3,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 36(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 37(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-benzoic acid ester; 38(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-pentyl propionate; 39(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 40(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 41(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 42(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-butyl propionate; 43(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylamino}-benzoyl propionate; 44(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl butyrate; 45(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 4-fluoro-benzoyl ester; 46(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 47(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl-butyl propionate; 48(S)-2-{(2,4-dichlorophenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-ethyl propionate; 49(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl propionate; 50(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-butyl propionate; 51(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl propionate; 52(R)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-benzoic acid ester; 53(S)-2-{(2-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyl propionate; 54(S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl propionate; 55(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl propionate; 56(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosphorylamino]-cyclohexyl propionate; 57(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-isopropyl butyrate; 58(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclohexyl butyrate; 59(S)-2-[[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phosphorylamino]-cyclohexyl butyrate; 60(S)-2-{(4-chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-isopropyl butyrate; 61(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2-difluoro-ethyl ester; 62(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; 63(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; 64(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopropyl methyl propionate; 65(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-cyclopentyl butyrate; 66(S)-2-{[(2R,3R,4R,5R)-5-(6-amino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 67(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-hydroxy-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 68(S)-2-{(R)-[(2R,3R,4R,5R)-5-(2,6-diamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 69(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclopentylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 70(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-acetidin-1-yl-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 71(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-diethylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 72(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-propylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 73(S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-cyclobutylamino-purine-9-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-methyl propionate; 74(S)-2-({(2R,3R,4R,5R)-5-[2-amino-6-(4-methyl-piperazin-1-yl)-purine-9-yl]-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy}-phenoxy-phosphorylamino)-methyl propionate; 75(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(propylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 76(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclobutylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 77(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(cyclopentylamino)-9H-purine-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 78(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acrididin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; 79(2S)-methyl 2-((((2R,3R,4R,5R)-4-fluoro-3-hydroxy-4-methyl-5-(6-(piperidin-1-yl)-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; and 80(2S)-methyl 2-((((2R,3R,4R,5R)-5-(6-(acetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propionate; The bases ' are as listed in each of compounds 5-74; and Where X' is a leaving group such as Cl.