HK1150450A - Nucleoside phosphoramidate prodrugs - Google Patents

Description

Nucleoside phosphoramidate prodrugs

This application was filed as PCT international patent application on 25.3.2008, with the applicant designated in all countries except the united states being the american company Pharmasset, inc, and the applicant designated in the united states only being the american citizen Michael Joseph Sofia, the american citizen Jinfa Du, the people of the people's republic of china Peiyuan Wang, and the american citizen dhapalan nagathnam; this application claims priority from U.S. provisional application No. 60/909,315 filed on 30/3/2007, U.S. provisional application No. 60/982,309 filed on 24/10/2007, and U.S. non-provisional application No. 12/053,015 filed on 21/3/2008. The contents of each of the above applications are hereby incorporated by reference in their entirety.

Technical Field

The present invention relates to nucleoside phosphoramidates and their use as agents for the treatment of viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV ns5B polymerase, inhibitors of HCV replication, and for the treatment of hepatitis c infection in mammals. The present invention provides novel compounds and the use of these compounds, either alone or in combination with other antiviral agents for the treatment of HCV infection.

Background

Hepatitis C Virus (HCV) infection is a serious health problem that leads to chronic liver diseases such as cirrhosis and hepatocellular carcinoma in a large number of infected individuals, estimated to be 2-15% of the world population. According to the american centers for disease control, four hundred and fifty thousand people are infected in the united states alone. According to the world health organization, there are over 2 million infected individuals worldwide, with at least 3 to 4 million people infected per year. Once infected, approximately 20% of people clear the virus, but the rest of the people may carry HCV for the rest of their lives. From 10% to 20% of chronically infected individuals eventually develop liver-destructive cirrhosis or cancer. The viral disease is transmitted parenterally through contaminated blood and blood products, contaminated needles; or by sexual propagation; and vertical transmission from infected or carrier mothers to their offspring. Current treatments for HCV infection are limited to recombinant interferon alpha immunotherapy alone or in combination with the nucleoside analog ribavirin, which has limited clinical benefit. Furthermore, there is no complete vaccine against HCV. Thus, there is an urgent need for improved therapeutic agents that are effective in combating chronic HCV infection.

HCV virions are enveloped positive-strand RNA viruses with a single oligonucleotide genomic sequence of about 9600 bases encoding a polyprotein of about 3,010 amino acids. The protein products of the HCV gene consist of the structural proteins C, E1 and E2, and the non-structural proteins NS2, NS3, NS4A and NS4B, and NS5A and NS 5B. The Nonstructural (NS) proteins are thought to provide a catalytic structure for viral replication. NS3 protease releases NS5B, NS5B being an RNA-dependent RNA polymerase from a polyprotein chain. HCV NS5B polymerase is required for the synthesis of double-stranded RNA from single-stranded viral RNA used as a template in the HCV replication cycle. Thus, 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, and therefore constitutes an attractive approach to the development of HCV-specific antiviral therapies.

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

Flaviviridae (Flaviviridae) viruses

Viruses of the flaviviridae family include at least three distinct genera: pestiviruses (pestiviruses), which cause disease in cattle and pigs; flaviviruses (flavivruses), which are the major causes of diseases such as dengue and yellow fever; and hepaciviruses (hepaciviruses), the only member of which is HCV. The flavivirus genus comprises more than 68 members, grouped based on serological relatedness (Calisher et al, J.Gen.Virol (J.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). Flaviviruses of global interest in relation to human disease 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-.

Pestiviruses include Bovine Viral Diarrhea Virus (BVDV), classical swine fever virus (CSFV, also known as hog cholera virus) and sheep Borderline Disease Virus (BDV) (Moennig, V., et al. adv. Vir. Res.1992, 41, 53-98). Pestivirus infection of domestic livestock (cattle, pigs and sheep) causes significant economic losses worldwide. BVDV causes mucosal disease in cattle and is of significant economic importance to animal husbandry (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 pestiviruses have not been characterized as widely as animal pestiviruses. However, serological examination indicates considerable pestivirus exposure in humans.

Pestiviruses and hepaciviruses are closely related groups of viruses within the flaviviridae family. Other closely related viruses in this family include GB virus A, GB virus a-like pathogen, GB virus B, and GB virus C (also known as hepatitis G virus, HGV). The hepatitis C virus group (hepatitis C virus; HCV) consists of a large number of closely related but genotypically distinguishable viruses that infect humans. There are at least 6 HCV genotypes and more than 50 subtypes. Due to the similarity between pestiviruses and hepaciviruses and the weak ability of hepaciviruses to grow efficiently in cell culture, Bovine Viral Diarrhea Virus (BVDV) is often used as a surrogate for studying HCV virus.

Pestiviruses have a very similar genetic makeup to hepatitis c virus. These positive-stranded RNA viruses have a large Open Reading Frame (ORF) that encodes all the viral proteins required for viral replication. These proteins can be expressed as polyproteins that are co-translated and post-translationally processed by cellular and virally encoded proteases to obtain mature viral proteins. The viral proteins responsible for the replication of the viral genomic RNA are located within the proximity of the carboxy terminus. Two thirds of the ORF is called the Nonstructural (NS) protein. Pestiviruses are very similar in genetic composition and polyprotein processing to the nonstructural protein portion of the ORF of hepatitis c virus. In the case of pestiviruses and hepaciviruses, the mature Nonstructural (NS) protein consists of p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B in sequential order from the amino terminus of the nonstructural protein coding region to the carboxy terminus of the ORF.

The NS proteins of pestiviruses and hepaciviruses share sequence domains that are characterized by specific protein functions. For example, the NS3 proteins of both groups of viruses have amino Acid sequence motifs that are characterized by serine proteases and helicases (Gorbalenya et al, Nature, 1988, 333, 22; Bazan and Fletterick Virology, 1989, 171, 637-42 639; Gorbalenya et al, Nucleic Acid Res. (Nucleic acids research), 1989, 17, 3889-3897). Similarly, the NS5B protein of pestiviruses and hepaciviruses has motifs characterized by RNA-directed RNA polymerase (Koonin, E.V. and Dolja, V.V., Crir. Rev. biochem. molec. biol.1993, 28, 375- "430).

The actual role and function of the NS proteins of pestiviruses and hepaciviruses in the viral life cycle are completely similar. In both cases, the NS3 serine protease is responsible for all proteolytic processing of its polyprotein precursors 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. (J.Virol.) 1993, 67, 32-2843; Grauiko28et al, Proc.Natl.Acad. Sci.USA (Proc.Natl.Acad. Sci. USA) 1993, 90, 10583-10587; Hijikata et al, J.Virol. (J.Virol.) 1993, 67, 65 465; Tojj.467. Virol et al, 40267, 1993, 67, 7. Virol., J.7-7). In both cases, the NS4A protein was used as a cofactor for the NS3 serine protease (Bartenschlager et al, J.Virol., 1994, 68, 5045-5055; Faillea et al, J.Virol., 1994, 68, 3753-3760; Xu et al, J.Virol., 1997, (Virol.) 71: 5312-5322). The NS3 proteins of both viruses also function as helicases (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 (J.Virol) 1995, 69, 1720-1726). Finally, the NS5B protein of pestiviruses and hepaciviruses has the predicted RNA-directed RNA polymerase activity (Behrens et al, EMBO, 1996, 15, 12-22; Lechmann et al, J.Virol (J. Virol.), 1997, 71, 8416-.

Currently, there are limited treatment options for individuals infected with hepatitis c virus. The treatment option that has been approved today is the use of recombinant interferon alpha alone or in combination with the nucleoside analog ribavirin as an immunotherapy. This therapy is limited by its clinical efficacy, and only 50% of treated patients respond to the therapy. Thus, there is a significant need for more effective and novel therapies to address the unmet medical need caused by HCV infection.

A number of potential molecular targets for drug development of direct acting antiviral agents as anti-HCV therapeutics have been identified, including but not limited to NS2-NS3 autoprotease, N3 protease, N3 helicase, and NS5B polymerase. RNA-dependent RNA polymerases are absolutely necessary for single-stranded sense RNA genome replication, and this enzyme has attracted significant interest in pharmaceutical chemists.

Inhibitors of HCV NS5B have been reviewed as potential therapies for HCV infection in the following: tan, s. -l., et al, Nature rev. drug discov. (review for natural drug development), 2002, 1, 867-; walker, m.p., et al, exp.opin.investigational Drugs, 2003, 12, 1269-; ni, Z-J, et al, Current Opinion in Drug Discovery and Development (Current view of Drug Development and Development), 2004, 7, 446-; beaulieu, P.L., et al, Current Opinion in investigational Drugs, 2004, 5, 838-; wu, J, et al, Current Drug Targets-Infectious Disorders (Current Drug target-Infectious disease), 2003, 3, 207-; griffith, R.C., et al, Annual Reports in Medicinal Chemistry, 2004, 39, 223-; carrol, s., et al, Infectious Disorders-drug targets, 2006, 6, 17-29. The possibility of 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 potent nucleosides as inhibitors of HCV NS 5B.

Nucleoside inhibitors of NS5B polymerase can be used as non-natural substrates that lead to chain termination or as competitive inhibitors that compete with nucleotides for binding to the polymerase. To function as a chain terminator, the nucleoside analog must be taken up by the cell and converted in vivo to a triphosphate to compete for the polymerase nucleotide binding site. This conversion to the triphosphate is typically mediated by cellular kinases, which impose additional structural requirements on potential nucleoside polymerase inhibitors. Unfortunately, this limits the direct evaluation of nucleosides as inhibitors of HCV replication to cell-based assays capable of in situ phosphorylation.

In some cases, the biological activity of a nucleoside is hindered by its poor substrate properties for one or more kinases, which are required to convert the nucleoside to the active triphosphate form. Formation of monophosphate esters by nucleoside kinases is generally considered to be the rate-limiting step of the triphosphorylation event. To avoid the need for an initial phosphorylation step in the metabolism of nucleosides to active triphosphate analogs, stable phosphate prodrug preparations have been reported. Nucleoside phosphoramidate prodrugs have been shown to be precursors to active nucleoside triphosphates and to inhibit viral replication when administered to whole virus-infected cells (McGuigan, C. et al, J.Med.Chem. (J.Med.Chem., 1996, 39, 1748-1753; Valette, G. et al, J.Med.Chem., 1996, 39, 1981-1990; Balzarii, J. et al, Proc.National Acad Sci USA (Proc. Natl. Acad. Sci. USA), 1996, 93, 7295-7299; Siddiqui, A.Q. et al, J.Med.Chem., 1999, 42, 4122-4128; Eisenberg, E.J. et al, Nucleic Acids, Nucleotides and Nucleic Acids (Nucleotides, Nucleotides and Nucleic Acids), 2001, 20, 1-heenta. 1098; Lethroughput. J. 898, J. Acad. et al, J. Acad. A. 1098, J. C. Acad. C. 1981); US 2006/0241064 and WO 2007/095269.

Also limiting the utility of nucleosides as viable therapeutic agents are their physicochemical and pharmacokinetic properties with time differences. These poor properties can limit the intestinal absorption of the agent and limit uptake into the target tissue or cells. To improve their properties, prodrugs of nucleosides are used. Nucleoside phosphoramidate preparations have been demonstrated to improve systemic uptake of nucleosides, and further, the phosphoramidate portion of these "prokaryotic nucleotides" is masked by neutral lipophilic groups to obtain appropriate partition coefficients 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. Enzyme-mediated hydrolysis of the phosphate moiety produces nucleoside monophosphates in which the rate-limiting initial phosphorylation is not required.

Summary of The Invention

The present invention relates to novel phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which phosphoramidate prodrugs are compounds represented by the following structure, its stereoisomers, salts (acid or base addition salts), hydrates, solvates, or crystalline forms thereof:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c _1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl radicalOr C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3b；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C _1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl: (CH₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C _2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I),NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

Wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C ₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

Definition of

The terms "a" or "an" entity, as used herein, refer to one or more of the entities, e.g., a compound refers to one or more compounds or at least one compound. Likewise, the terms "a" (or "an"), "one or more," and "at least one" are used interchangeably herein.

The term "as defined above" refers to the initial definition provided in the summary of the invention.

The term "optional" or "optionally" as used herein means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "optional bond" means that the bond may or may not be present, and the description includes single, double, or triple bonds.

The term "independently" as used herein means that the variables can apply in either case without regard to the presence or absence of variables having the same or different definitions within the same compound. Thus, in a compound where R occurs twice and is defined as "independently carbon or nitrogen," two R's can be carbon, two R's can be nitrogen, or one R is carbon and the other is nitrogen.

The term "alkenyl" refers to an unsubstituted hydrocarbon chain radical having 2 to 10 carbon atoms with one or two olefinic double bonds, preferably with one olefinic double bond. The term "C_2-NAlkenyl "refers to alkenyl groups comprising 2 to N carbon atoms, where N is an integer having the following value: 3. 4, 5, 6, 7, 8, 9 or 10. The term "C_2-10Alkenyl "means an alkenyl group comprising 2 to 10 carbon atoms. The term "C_2-4Alkenyl "means an alkenyl group comprising 2 to 4 carbon atoms. Examples include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl (allyl), or 2-butenyl (crotyl).

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 alkyl groups containing 1 to 30 carbon atoms,A straight or branched chain saturated monovalent hydrocarbon residue. The term "C_1-MAlkyl "refers to an alkyl group comprising 1 to M carbon atoms, wherein M is an integer having the following value: 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 "C_1-4Alkyl "refers to an alkyl group containing 1 to 4 carbon atoms. The term "lower alkyl" refers to a straight or branched chain hydrocarbon residue comprising 1 to 6 carbon atoms. "C" as used herein _1-20Alkyl "refers to an alkyl group comprising 1 to 20 carbon atoms. "C" as used herein_1-10Alkyl "refers to an alkyl group including 1 to 10 carbons. 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 (ar) alkyl or (heteroaryl) alkyl refer to alkyl groups, respectively, optionally substituted with aryl or heteroaryl groups.

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

The term "cycloalkylalkyl" refers to an otherwise 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 by cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term "cycloheteroalkyl" refers to an unsubstituted or substituted heterocyclic ring, wherein the heterocyclic ring contains from 2 to 9 carbon atoms, preferably from 2 to 7 carbon atoms, more preferably from 2 to 5 carbon atoms. Examples of cycloheteroalkyl groups include, but are not limited to, aziridin-2-yl, N-C_1-3-alkyl-aziridin-2-yl, azetidinyl, N-C_1-3Alkyl-azetidin-m '-yl, pyrrolidin-m' -yl, N-C_1-3-alkyl-pyrrolidin-m '-yl, piperidin-m' -yl and N-C_1-3-alkyl-piperidin-m '-yl, wherein m' is 2, 3 or 4 depending on the cycloheteroalkyl. N-C_1-3Specific examples of-alkyl-cycloheteroalkyl groups include, but are not limited to, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-2-yl, N-methyl-piperidin-3-yl, and N-methyl-piperidin-4-yl. At R⁴In the case of (a), the point of attachment between a cycloheteroalkyl ring carbon and oxygen occurs at either m'.

The term "heterocycle" refers to an unsubstituted or substituted heterocycle containing carbon, hydrogen, and at least one of N, O and S, wherein C and N can be trivalent or tetravalent, i.e., sp²-or sp³Hybridization. Examples of heterocycles include, but are not limited to, aziridine, azetidine, pyrrolidine, piperidine, imidazole, oxazole, piperazine and the like. In the case of piperazine, such as with NR' ₂R of (A) to (B)¹⁰Related, the corresponding para-nitrogen atom on the piperazinyl group is substituted with a lower alkyl group represented by the following structure:

preferably, the nitrogen para to the piperazinyl group is substituted with a methyl group.

The term "halogenated alkyl" (or "haloalkyl") refers to a straight or branched chain alkyl group that includes at least one of F, Cl, Br, and I. The term "C_1-MHaloalkyl "refers to an alkyl group comprising 1 to M carbon atoms, the alkyl group comprising at least one of F, Cl, Br, and I, wherein M is an integer having the following value: 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. "C_1-3Haloalkyl "refers to haloalkyl comprising 1 to 3 carbons and at least one of F, Cl, Br, and I. The term "halogenated lower alkyl" (or "lower haloalkyl") Refers to haloalkyl groups comprising 1 to 6 carbon atoms and at least one of F, Cl, Br and I. Examples thereof 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-pentafluoroethyl.

The term "alkynyl" refers to a straight or branched hydrocarbon chain radical having 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms, and having one triple bond. The term "C_2-NAlkynyl "refers to alkynyl groups comprising 2 to N carbon atoms, where N is an integer having the following value: 3. 4, 5, 6, 7, 8, 9 or 10. The term "C C_2-4Alkynyl "refers to alkynyl groups comprising 2 to 4 carbon atoms. The term "C_2-10Alkynyl "refers to alkynyl groups including 2 to 10 carbons. 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 straight or branched hydrocarbon chain radical having from 2 to 10 carbon atoms, preferably from 2 to 5 carbon atoms, and having one triple bond and at least one of F, Cl, Br and I.

The term "cycloalkyl" refers to a saturated carbocyclic ring comprising 3 to 8 carbon atoms, i.e. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. The term "C" as used herein_3-7Cycloalkyl "refers to cycloalkyl groups including 3 to 7 carbons in the carbocyclic ring.

The term "alkoxy" refers to an-O-alkyl or an-O-cycloalkyl group, wherein alkyl and cycloalkyl are as defined above. Examples of-O-alkyl groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy. As used herein, "lower alkoxy" refers to a group having a structure such as Alkoxy of a "lower alkyl" group as previously defined. "C_1-10Alkoxy "means an-O-alkyl group wherein alkyl 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 an-O-alkyl group, wherein the alkyl group includes at least one of F, Cl, Br, and I.

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

The term "amino acid" includes naturally occurring and synthetic alpha, beta, gamma or delta amino acids, and includes, but is not limited to, the amino acids found in proteins, i.e., 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 in the L configuration. Alternatively, the amino acid may be a derivative of: alanyl, valyl, leucyl, isoleucyl, prolyl, phenylalanyl, tryptophanyl, methionyl, glycyl, seryl, threonyl, cysteinyl, tyrosyl, asparaginyl, glutaminyl, aspartyl, glutamyl, lysyl, arginyl, histidinyl, beta-alanyl, beta-valyl, beta-leucyl, beta-isoleucyl, beta-prolyl, beta-phenylalanyl, beta-tryptophanyl, beta-methionyl, beta-glycyl, beta-seryl, beta-threonyl, beta-cysteinyl, beta-tyrosyl, beta-asparaginyl, beta-glutaminyl, beta-aspartyl, beta-tyryl, beta-aspartyl, beta-alanyl, beta-glutaminyl, beta-aspartyl, prolyl, beta-alanyl, beta-, Beta-glutamyl, beta-lysyl, beta-arginyl, or beta-histidyl. When the term amino acid is used, it is believed that various esters of the following amino acids in the D and L configurations are specifically and independently disclosed: alpha, beta, gamma or delta 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 the N, N-unsubstituted, N-monosubstituted, and N, N-disubstituted derivatives of naturally occurring and synthetic alpha, beta, gamma, or delta aminoacyl groups, wherein the aminoacyl group is derived from an amino acid. The amino-nitrogen may be substituted or unsubstituted. When the amino-nitrogen is substituted, the nitrogen is mono-or di-substituted, wherein the substituent bonded to the amino-nitrogen is lower alkyl or alkaryl. In the case where it is used for Y, the expression "O (aminoacyl)" is used. It is understood that the C3' carbon of ribose is bonded to the oxygen "O" and then to the carbonyl carbon of the aminoacyl.

The term "alkylamino" or "arylamino" refers to an amino group having one or two alkyl or aryl substituents, respectively.

The term "protected" as used herein, unless otherwise specified, refers to a group that is added to an oxygen, nitrogen, or phosphorus atom to prevent further reaction thereof or for other purposes. Various 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, SO₂Alkyl, SO₂Aryl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and 1, 3- (1, 1, 3, 3-tetraisopropyldisiloxanylidene) groups.

The term "aryl" as used herein, unless otherwise specified, refers to a substituted or unsubstituted phenyl (Ph), diphenyl or naphthyl, the term aryl preferably referring to a substituted or unsubstituted phenyl. The aryl group may be substituted with one or more moieties selected from: hydroxyl, F, Cl, Br, I, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphoric acid, phosphate and phosphonate; it may be unprotected or protected as needed, as known to those skilled in the art, e.g., as taught by t.w.greene and p.g.m.wuts, "Protective Groups in organic synthesis," 3 rd edition, John Wiley & Sons, 1999.

The term "alkaryl" or "alkylaryl" refers to an alkyl group with an aryl substituent such as benzyl. The term "aralkyl" or "arylalkyl" refers to an aryl group with an alkyl substituent.

The term "di (lower alkyl) amino-lower alkyl" refers to a lower alkyl group substituted with an amino group which is itself substituted with two lower alkyl groups. Examples include, but are not limited to (CH)₃)₂NCH₂、(CH₃)₂NCH₂CH₂、(CH₃)₂NCH₂CH₂CH₂And the like. The above examples show lower alkyl groups substituted at the terminal carbon atom with an N, N-dimethyl-amino substituent. These are intended as examples only and are not intended to limit the meaning of the term "di (lower alkyl) amino-lower alkyl" such that the meaning of the term is the same as the examples. It is contemplated that the lower alkyl chain may be substituted with N, N-di (lower alkyl) -amino at any point along the chain, such as CH ₃CH (N- (lower alkyl)₂)CH₂CH₂。

The term "halogen" as used herein 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 the carbonyl carbon and a heteroatom selected from O, N and S. When the heteroatom is N, the N is substituted with a lower alkyl group. The non-carbonyl moiety is selected from: straight, branched, and cyclic alkyl groups, including but not limited to straight, branched, or cyclic C_1-20Alkyl radical, C_1-10Alkyl or lower alkyl; alkoxyalkyl groups including methoxymethyl; aralkyl groups including benzyl; aryloxyalkyl such as phenoxymethyl; or aryl radicals, including optionallyPhenyl substituted with: halogen (F, Cl, Br, I), hydroxy, C₁To C₄Alkyl or C₁To C₄Alkoxy, sulfonate esters such as alkyl or aralkyl sulfonyl including methanesulfonyl, mono, di or triphosphate, trityl or monomethoxytrityl, substituted benzyl, trialkylsilyl (e.g. dimethyl t-butylsilyl) or diphenylmethylsilyl. When at least one aryl group is present in the non-carbonyl moiety, the aryl group preferably comprises a phenyl group.

The term "lower acyl" refers to acyl groups wherein the non-carbonyl moiety is lower alkyl.

The term "purine" or "pyrimidine" base includes, but is not limited to, adenine, N⁶-alkylpurine, N⁶Acylpurines (in which the acyl group is C (O) (alkyl, aryl, alkylaryl or arylalkyl), N⁶-benzylpurine, N⁶-halopurine, N⁶-vinyl purine, N⁶-acetylenic purines, N⁶-acylpurine, N⁶Hydroxyalkyl purine, N⁶-alkylaminopurine (allcylaminopurine), N⁶Thioalkylpurines (thioalkylpurines), N²-alkylpurine, N²-alkyl-6-thiopurine, thymine, cytosine, 5-fluorocytosine, 5-methylcytosine, 6-azapyrimidines including 6-azacytosine, 2-and/or 4-mercaptopyrimidine (mercaptopyrmidine), uracil, 5-halouracils including 5-fluorouracil, C⁵Alkyl pyrimidines, C⁵-benzylpyrimidine, C⁵Halogen pyrimidine, C⁵-vinyl pyrimidine, C⁵Acetylenic pyrimidines, C⁵Acyl pyrimidine, C⁵-hydroxyalkyl purine, C⁵Acylamidopyrimidines, C⁵-cyanopyrimidine, C⁵Iodine pyrimidine, C⁶-iodo (lodo) -pyrimidine, C⁵-Br-vinyl pyrimidine C⁶-Br-vinyl pyrimidine C⁵-nitropyrimidine, C⁵-amino-pyrimidine, N²-alkylpurine, N²-alkyl-6-thiopurine, 5-azacytosine riboside, 5-azauracil, triazolopyridinyl, imidazopyridinyl, pyrrolopyrimidinyl and pyridinyl Oxazolopyrimidinyl. Purine bases include, but are not limited to, guanine, adenine, hypoxanthine, 2, 6-diaminopurine, and 6-chloropurine. The functional oxy and nitrogen groups on the base may be protected as needed or desired. Suitable protecting groups are well known to those skilled in the art and include trimethylsilyl, dimethylhexylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl, trityl, alkyl, and acyl groups such as acetyl and propionyl, methanesulfonyl and p-toluenesulfonyl.

The terms "tautomerism" and "tautomer" have their accepted, clear meanings.

The term "P" means that the phosphorus atom is chiral and has the corresponding Cahn-Ingold-Prelog designation "R" or "S" which have their accepted clear meaning. The compound of formula I is expected to be racemic due to the chirality of the phosphorus. Applicants contemplate the use of racemates and/or resolved enantiomers. In some cases, no asterisk is shown near the phosphorus atom of the phosphoramidate. In these cases, it is understood that the phosphorus atom is chiral, and one of ordinary skill would understand this to be so unless substituents bonded to the phosphorus preclude the possibility that the phosphorus is chiral, such as P (O) Cl ₃。

Detailed Description

One aspect of the present invention pertains to compounds represented by formula I, and salts, hydrates, solvates, crystalline forms, and the like thereof:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at leastA substitution is as follows: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3b；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH) ₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a structure comprising adjacent N and C atomsWherein 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, optionallyC substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH) ₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl radical)、SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C) _2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, C₂-C₆Optionally substituted alkynyl, C₂-C₆Optionally substituted lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C) _1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

As understood from the structure represented by formula I above, there are countless 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 having several aspects based on the identity of the purine or pyrimidine base being modified. This is not intended to be an explicit or implicit acknowledgement that the three embodiments are separate or distinct and should not be so interpreted. Rather, it is intended to convey information so that the full scope of the invention can be understood. Furthermore, the following embodiments and aspects thereof are not intended to limit the full scope of the invention as recited by the structures of formula I.

A first embodiment of the present invention is directed to compounds represented by formula I-1:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' independently areHydrogen or alkyl including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3b；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH) ₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) -amino, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, ethyleneRadical, O- (lower alkyl), hydroxy-lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R ⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, Cl, Br, I, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Which isThe alkyl, alkynyl, alkenyl and vinyl groups are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO ₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R⁷、R⁸、R⁹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂Lower alkyl, lower alkyl of halo (F, Cl, Br, I), C₂-C₆Lower alkenyl, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A first aspect of the first embodiment relates to compounds represented by formula I-1

Wherein

(a)R¹Is hydrogen, n-alkyl or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_1-6Alkoxy, F,Cl, Br, I, nitro, cyano, C_1-6A haloalkyl group;

(b)R²is hydrogen or CH₃；

(c)R^3aAnd R^3bIndependently is (i) R^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-3-yl, -CH ₂CH₂SCH₃、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 lower cycloalkyl; or (viii) R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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) or CH₂SH，R^3bIs H;

(d)R⁴is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, CN, CH₃Vinyl, OCH₃、OCH₂CH₃、CH₂OH、CH₂(halo) such as CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃；

(f)R⁶Is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, Cl, Br, I, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl, vinyl, N₃、CN、Cl、Br、F、I、O(C_1-6Acyl group), O (C)_1-4Alkyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-4Haloalkyl, O (aminoacyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C) _1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂Or N (C)_1-4Acyl radical)₂；

(i)R⁷、R⁸、R⁹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂Lower alkyl, lower alkyl of halo (F, Cl, Br, I), C₂-C₆Lower alkenyl, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A second aspect of the first embodiment relates to compounds represented by formula I-1

Wherein

(a) R¹Is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituents of the substituted phenyl are at least one of: c_1-3Alkyl radical, C_1-3Alkoxy, F, Cl, Br, I, nitro, cyano, and C_1-3A haloalkyl group;

(b)R²is hydrogen or CH₃；

(c)R^3aAnd R^3bIndependently is (i) R^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is ³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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) or CH₂SH，R^3bIs H;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, di (lower alkyl) amino-lower alkyl or aminoacyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂(halo) such as CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃；

(f)R⁶Is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH₃)、N(CH₃)₂、N(C(O)CH₃)₂Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂(ii) a And

(j)R⁹selected from the following: OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂OC (O) (C1-20 alkyl), including but not limited to OC (O) (CH)₂)_sCH₃(ii) a NHC (O) (C1-20 alkyl), including but not limited to NHC (O) (CH) ₂)_sCH₃(ii) a And N (C (O) (CH)₂)_sCH₃)₂Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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 third aspect of the first embodiment relates to a compound represented by formula I-1

Wherein

(a)R¹Is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituents of the substituted phenyl are at least one of: CH (CH)₃、OCH₃F, Cl, Br, I, nitro, cyano and CH_3-qX_qWherein X is F, Cl, Br or I, and q is 1-3;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, or R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, di (lower alkyl) amino-lower alkyl or aminoacyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂(halo) such as CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N ₃；

(f)R⁶Is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH₃)、N(CH₃)₂、N(C(O)CH₃)₂Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆An alkynyl group; and

(j)R⁹selected from the following: OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂OC (O) (C1-20 alkyl), including but not limited to OC (O) (CH)₂)_sCH₃(ii) a NHC (O) (C1-20 alkyl), including but not limited to NHC (O) (CH)₂)_sCH₃(ii) a And N (C (O) (CH)₂)_sCH₃)₂Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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 fourth aspect of the first embodiment relates to compounds represented by formula I-2

Wherein

(a)R¹Is 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 (CH)₃、OCH₃F, Cl, Br, I, nitro, cyano and CH_3-qX_qWherein X is F, Cl, Br or I, and q is 1-3;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, or R ^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H;

(d)R⁴is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl orSubstituted heteroaryl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃；

(f)R⁶Is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH₃)、N(CH₃)₂、N(C(O)CH₃)₂Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆An alkynyl group; and

(j)R⁹selected from the following: OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂OC (O) (C1-20 alkyl), including but not limited to OC (O) (CH)₂)_sCH₃；NHC(O)(C1-20 alkyl) including but not limited to nhc (o) (CH)₂)_sCH₃(ii) a And N (C (O) (CH)₂)_sCH₃Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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 fifth aspect of the first embodiment relates to compounds represented by formula I-2

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, di (lower alkyl) amino-lower alkyl or aminoacyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen, including F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆An alkynyl group; and

(j)R⁹selected from the following: OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、OC(O)(C_1-20Alkyl), including but not limited to OC (O) (CH)₂)_sCH₃；NHC(O)(C_1-20Alkyl) including but not limited to NHC (O) (CH)₂)_sCH₃(ii) a And N (C (O) (CH) ₂)_sCH₃)₂Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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 sixth aspect of the first embodiment relates to a compound represented by formula I-2

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, OMe, CN, CH₂F. F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃F, Cl, Br, I or N₃；

(h) Y is H, OH, CH₃F, Cl, Br, I or N₃、OCH₃、OC(O)CH₃Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Br, SCH₃、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂(ii) a And

(j)R⁹is selected fromThe following were used: OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、OC(O)(C_1-20Alkyl), including but not limited to OC (O) (CH) ₂)_sCH₃；NHC(O)(C_1-20Alkyl) including but not limited to NHC (O) (CH)₂)_sCH₃(ii) a And N (C (O) (CH)₂)_sCH₃)₂Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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 seventh aspect of the first embodiment relates to a compound represented by formula I-2

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃F or N₃；

(h) Y is OH, OCH₃、OC(O)CH₃Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Br, SCH₃、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂(ii) a And

(j)R⁹selected from the following: OH, OCH₃、NH₂、NHCH₃、N(CH₃)₂、OC(O)(C_1-20Alkyl), including but not limited to OC (O) (CH)₂)_sCH₃；NHC(O)(C_1-20Alkyl) including but not limited to NHC (O) (CH) ₂)_sCH₃(ii) a And N (C (O) (CH)₂)_sCH₃)₂Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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.

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

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu、2-Butyl, isobutyl, or isobutyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃F or N₃；

(h) Y is OH, OCH₃、OC(O)CH₃Or O (aminoacyl);

(i)R⁷and R⁸Independently H, F, Br, SCH₃、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂；

(j)R⁹Selected from the following: OH, OCH₃、NH₂、NHCH₃、N(CH₃)₂、OC(O)(C_1-20Alkyl), including but not limited to OC (O) (CH)₂)_sCH₃；NHC(O)(C_1-20Alkyl) including but not limited to NHC (O) (CH)₂)_sCH₃(ii) a And N (C (O) (CH)₂)_sCH₃)₂Including but not limited to N (C (O)) (CH)₂)_sCH₃)₂Wherein 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 compounds of formula I wherein the base is of the structure shown above as formula b, wherein R is¹、R²、R^3a、R^3b、R⁴、R⁵、R⁶、X、Y、R⁷And R⁸As defined in the summary of the invention section above.

A first aspect of the second embodiment relates to compounds represented by formula I-3

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r ^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R ⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, Cl, Br, I, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂Or N (C)_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO ₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂Or N (C)_1-4Acyl radical)₂；

(i)R⁷And R⁸Independently H, F, Cl, Br, I, OH, OR ', SH, SR'),NH₂、NHR′、NR′₂Lower alkyl, lower alkyl of halo (F, Cl, Br, I), C₂-C₆Lower alkenyl, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A second aspect of the second embodiment relates to compounds represented by formula I-3

Wherein

(a)R¹Is hydrogen, n-alkyl or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6A haloalkyl group;

(b)R²is hydrogen or CH₃；

(c)R^3aAnd R^3bIndependently is (i) R^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-3-yl, -CH ₂CH₂SCH₃、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 lower cycloalkyl; or (viii) R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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) or CH₂SH，R^3bIs H;

(d)R⁴is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, CN, CH₃Vinyl, OCH₃、OCH₂CH₃、CH₂OH、CH₂(halo) such as CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen, including F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe,Halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl, vinyl, N₃、CN、Cl、Br、F、I、O(C_1-6Acyl group), O (C)_1-4Alkyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C) _1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R⁷And R⁸Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂Lower alkyl, halo (F, Cl, Br, I) lower alkyl, C₂-C₆Lower alkenyl of, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A third aspect of the second embodiment relates to a compound represented by formula I-3,

wherein

(a)R¹Is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituents of the substituted phenyl are at least one of: c_1-3Alkyl radical, C_1-3Alkoxy, F, Cl, Br, I, nitro, cyano and C_1-3A haloalkyl group;

(b)R²is hydrogen, CH₃，R^3aOr R^3bAnd R²Together are (CH)₂)₃So as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3bAs defined herein;

(c)R^3aand R^3bIndependently is (i) R^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is ³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂(halo) such as CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen, including F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃Halogen, NH₂Or N₃

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH₃)、N(CH₃)₂、N(C(O)CH₃)₂；

(i)R⁷And R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂。

A fourth aspect of the second embodiment relates to compounds represented by formula I-3

Wherein

(a)R¹Is hydrogen, n-alkyl or substituted or unsubstituted phenyl, wherein the substituents of the substituted phenyl are at least one of: CH (CH) ₃、OCH₃F, Cl, Br, I, nitro, cyano and CH_3-qX_qWherein X is F, Cl, Br or I, and q is 1-3;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, or R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂(halo) such as CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen, including F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH₃)、N(CH₃)₂、N(C(O)CH₃)₂；

(i)R⁷And R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I, q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A fifth aspect of the second embodiment relates to compounds represented by formula I-4

Wherein

(a)R¹Is 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 (CH) ₃、OCH₃F, Cl, Br, I, nitro, cyano and CH_3-qX_qWherein X is F, Cl, Br or I, and q is 1-3;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, or R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen, including F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH₃)、N(CH₃)₂、N(C(O)CH₃)₂；

(i)R⁷And R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A sixth aspect of the second embodiment relates to a compound represented by formula I-4

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²Is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen, including F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R⁷And R⁸Independently H, F, Cl, Br, I, OH, OCH₃、SH、SCH₃、NH₂、NHCH₃、N(CH₃)₂、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂H、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂Wherein R' is C_1-20Alkyl radical, C_1-20Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl.

A seventh aspect of the second embodiment relates to compounds represented by formula I-4

Wherein

(a) R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, OMe, CN, CH₂F. F, Cl, Br or I;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃OCH3 or OC (O) CH₃；

(i)R⁷And R⁸Independently H, F, Br, SCH₃、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl、CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂；

An eighth aspect of the second embodiment relates to a compound represented by formula I-4

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R⁷And R⁸Independently H, F, Br, SCH₃、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂。

A ninth aspect of the second embodiment relates to a compound represented by formula I-4

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²Is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃F or N₃；

(h) Y is OH, OCH₃Or OC (O) CH₃；

(i)R⁷And R⁸Independently H, F, Br, SCH₃、CH₃、CH_3-qX_qWherein X is F, Cl, Br or I and q is 1 to 3, vinyl, CO₂CH₃、CONH₂、CONHCH₃Or CON (CH)₃)₂。

A third embodiment of the invention relates to compounds of formula I wherein the base is of the structure shown above in formula c, wherein R is¹、R²、R^3a、R^3b、R⁴、R⁵、R⁶、X、Y、Z、R¹⁰、R¹¹And R¹²As defined in the summary of the invention section above; provided that R is¹¹Is not H.

A first aspect of the third embodiment relates to compounds represented by formula I-5

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C _1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bFrom H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R ^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C) _2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C ₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Low gradeC of alkyl, halo (F, Cl, Br, I)₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A second aspect of the third embodiment relates to compounds represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl-yl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH ₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A third aspect of the third embodiment relates to a compound represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₂F. F, Cl, Br or I, with the proviso that X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A fourth aspect of the third embodiment relates to compounds represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-pyrrolidin-3-yl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A fifth aspect of the third embodiment relates to compounds represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenylP-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In the case where each R' includes at least one group linked to form a group including at least two carbon atomsC atom of the heterocycle of the son; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A sixth aspect of the third embodiment relates to a compound represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-ylN-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR' ₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A seventh aspect of the third embodiment relates to a compound represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₂F. F, Cl, Br or I, with the proviso that X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR' ₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

An eighth aspect of the third embodiment relates to a compound represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A ninth aspect of the third embodiment relates to a compound represented by formula I-5

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl or N-methyl-pyrrolidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH ₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A tenth aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitroAnd cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH) ₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R ⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, Cl, Br, I, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC(O)O(C_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C1-4 acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O) ₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R¹⁰And R¹¹Independently is H, F, Br, I, OH,OR′、NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

An eleventh aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms;and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A twelfth aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, CN, CH₂F. F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A thirteenth aspect of the third embodiment relates to compounds represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A fourteenth aspect of the third embodiment relates to the compounds represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R' with the proviso that when R¹⁰R is OH¹¹Is other than NH₂；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A fifteenth aspect of the third embodiment is directed to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R ¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkaneA group; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen _1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C) _2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂ R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A sixteenth aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH ₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A seventeenth aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₂F. F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR ¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHC O₂R′。

An eighteenth aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is NH₂And R is¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In the state ofWherein each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A nineteenth aspect of the third embodiment relates to a compound represented by formula I-6

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is NH₂And R is¹¹Independently H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′；

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²Is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

A fourth embodiment of the invention relates to compounds of formula I wherein the base is of the structure shown above as formula c, wherein R is¹¹Is H, R²、R^3a、R^3b、R⁴、R⁵、R⁶X and Y are defined in the summary section above.

A first aspect of the fourth embodiment relates to a compound represented by formula I-7

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r ^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising adjacent N and C atoms, wherein C is 1 to 6, d is 0 to 2, and e is 0 to3, f is 2 to 5, n is 2 to 4, and wherein R³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH) ₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl)、OS(O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C) _1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R¹⁰Is H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

A second aspect of the fourth embodiment relates to a compound represented by formula I-7

Wherein

(a)R¹Is hydrogen, methyl,Ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen (including F, Cl, Br or I), with the proviso that when X is OH, R ⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃Halogen, NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

A third aspect of the third embodiment relates to a compound represented by formula I-7

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, CN, CH₂F. F, Cl, Br or I, with the proviso that X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

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

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰And R¹¹Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

A fifth aspect of the fourth embodiment relates to a compound represented by formula I-7

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkanesOr di (lower alkyl) amino-lower alkyl;

(e)R⁵Is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′。

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

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C _1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising adjacent N and C atoms, wherein C is 1 to 6, d is 0 to 2, and e is 0 to3, f is 2 to 5, n is 2 to 4, and wherein R³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C _3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C) _1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

A seventh aspect of the fourth embodiment relates to the compounds represented by formula I-8

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃Halogen, NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH ₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

An eighth aspect of the fourth embodiment relates to a compound represented by formula I-8

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₂F. F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂ R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

A ninth aspect of the fourth embodiment relates to a compound represented by formula I-8

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lowerA lower alkyl group;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR′、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) C ≡ CH₂Or (iii) -NO₂。

A tenth aspect of the fourth embodiment relates to the compounds represented by formula I-8

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃；

(i)R¹⁰Is H, F, Br, I, OH, OR', NH₂、NHR、NR′₂、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R 'is lower alkyl, lower cycloalkyl or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

(j) Z is N or CR¹²(ii) a And

R¹²is H, halogen (including F, Cl, Br, I), OR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; provided that R is¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

A fifth embodiment of the invention relates to compounds of formula I wherein the base is of the structure shown above in formula d, wherein R is¹、R²、R^3a、R^3b、R⁴、R⁵、R⁶X and Y are defined in the summary section above.

A first aspect of the fifth embodiment relates to compounds represented by formula I-9

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen or CH₃；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C _1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy or halogen^1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, di (lower alkyl) amino-lower alkyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵Is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C) _1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂。

A second aspect of the fifth embodiment relates to compounds represented by formula I-9

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridine-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R ⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃Halogen, NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃。

A third aspect of the fifth embodiment relates to a compound represented by formula I-9

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3--yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₂F. F, Cl, Br or I, with the proviso that X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂、N₃、OCH₃Or OC (O) CH₃。

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

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃。

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

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH ₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃。

A sixth aspect of the fifth embodiment relates to compounds represented by formula I-10

Wherein

(a)R¹Is 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 (CH)₃、OCH₃F, Cl, Br, I, nitro, cyano and CH_3-qX_qWherein X is F, Cl, Br or I, and q is 1-3;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or R^3aIs CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F、N₃、CH₂CN、CH₂N₃、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃；

(h) Y is OH, H, CH₃Vinyl group, N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃、NH₂、NHCH₃NH (vinyl), NH (acetyl), NH (C (O) CH ₃)、N(CH₃)₂、N(C(O)CH₃)₂。

A seventh aspect of the fifth embodiment relates to a compound represented by formula I-10

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₃、OCH₃、CH₂OH、CH₂F. Halogen including F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OCH₃、Cl、Br、I、NH₂Or N₃(ii) a And

(h) y is OH, H, CH₃Vinyl group, NH₂、N₃、CN、Cl、Br、F、I、OC(O)CH₃、OCH₃。

An eighth aspect of the fifth embodiment relates to a compound represented by formula I-10

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen or CH₃；

(c)R^3aIs H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴Is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, CN, CH₂F. F, Cl, Br or I, with the proviso that when X is OH, R⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, F, OCH₃、F、Cl、Br、I、NH₂Or N₃；

(h) Y is H, OH, CH₃、F、Cl、Br、I、NH₂Or N₃、OCH₃Or OC (O) CH₃。

A ninth aspect of the fifth embodiment relates to a compound represented by formula I-10

Wherein

(a)R¹Is hydrogen, methyl, ethyl, n-propyl, isopropyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH ⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃。

A tenth aspect of the fifth embodiment relates to compounds represented by formula I-10

Wherein

(a)R¹Is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

(b)R²is hydrogen;

(c)R^3ais H and R^3bIs H, CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph or lower cycloalkyl;

(d)R⁴is hydrogen, CH₃、Et、ⁱPr、ⁿPr、ⁿBu, 2-butyl,^tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl or di (lower alkyl) amino-lower alkyl;

(e)R⁵is H, with the proviso that R is when X is OH⁶Is CH₃Or CH₂F，R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃Or F;

(g) x is H, OH, OCH₃、F、NH₂Or N₃；

(h) Y is OH, NH₂、OCH₃Or OC (O) CH₃。

The following table includes numerical identifiers associated with various substituent identifiers that should be viewed in light of the attached structure. These structures are contemplated for different aspects of the disclosed embodiments and are not intended to limit the structures represented by formula IAll ranges subsumed within the compounds indicated. However, it is also contemplated that any of the exemplary nucleobases can be associated with a designated R ¹、R²、R^3a、R^3b、R⁴、R⁵、R⁶Any of the contemplated substances in the specific combinations of X and Y is used in combination. In each given table, the inclusion of substituent R is depicted^3aAnd R^3bThe phosphoramidate substituent of (a) is not referred to in stereochemistry (see: structures I-1, I-3, I-5, I-7 and I-9 above). Compounds enumerated below are contemplated to include R^3aConvex toward the viewer and R^3bCompounds that protrude away from the viewer (see structures I-2, I-4, I-6, I-8, and I-10). In addition, it is contemplated that the compounds listed below also include R^3aConvex away from the viewer and R^3bCompounds that are convex towards the viewer. However, without intending to be limiting, it is contemplated that the preferred compound is R^3aConvex toward the viewer and R^3bThose that protrude away from the viewer so as to assume the (S) configuration of the natural L amino acid. Furthermore, the inventors have recognized that the phosphorus atom of the phosphoramidate moiety is another source of chirality. Although the following structure does not specifically depict the chirality of the phosphorus, the inventors have recognized that stereochemical configurations are possible such that in an interlaced (OR zigzag) linear structure, the oxygen-substituents project toward the viewer and the OR is¹The substituents project away from the viewer and vice versa, i.e., the Cahn-Ingold-Prelog stereochemistry of phosphorus is R or S. Thus, the following structure includes all possible stereochemical configurations that are reasonable for phosphorus.

Table II-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II to 17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II to 36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table II-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables II-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table III-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-18.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Tables III-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables III-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-1.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table IV-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-12.

*R²And R^3bBy (CH)₂)₃Is connected toTogether to form a five-membered ring.

Table IV-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IV-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables IV-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table V-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-43.

10

*R²And R^3bBy (CH)₂)₃Are connected together to formForming a five-membered ring.

Tables VI to 44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VI-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI to 49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VI-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 20.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Tables VII to 21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 36.

*R²And R^3bBy (CH)₂)₃Is connected toTogether to form a five-membered ring.

Tables VII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII to 49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-3.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table VIII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VIII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE VIII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table VIII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VIII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VIII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VIII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables VIII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-2.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table IX-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-12.

*R²And R^3bPer (CH)₂)₃Joined together to form a five-membered ring.

Table IX-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table IX-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-39.

*R²And R^3bBy (CH)₂)₃Is connected toTo form a five-membered ring.

Table X-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-43.

10

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table X-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XI-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XI-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-21.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Tables XII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-4.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XIII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-23.

*R²And R^3bBy (CH)₂)₃Are connected together toForming a five-membered ring.

Table XIII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-36.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XIV-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIV-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XV-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-5.

*R²And R^3bBy (CH)₂)₃Are connected together to formA five-membered ring.

Table XVI-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XVI-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-20.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

TABLE XVI-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVI-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XVI-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XVI-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVI-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-3.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

TABLE XVII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-9.

*R²And R^3bBy (CH)₂)₃Are connected togetherTo form a five-membered ring.

TABLE XVII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-2.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XVIII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XVIII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XVIII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XVIII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XIX-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-16.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XIX-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XIX-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-37.

*R²And R^3bBy (CH)₂)₃Is connected toTogether to form a five-membered ring.

Table XIX-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-49.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XIX-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XX-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XX-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-33.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XXI-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-43.

10*R²And R^3b

By (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXI-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-32.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-43.

10

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-48.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-10.

*R²And R^3bBy (CH)₂)₃Is connected toTogether to form a five-membered ring.

Table XXIII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-43.

10

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXIII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXIII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-21.

*R²And R^3bBy (CH)₂)₃Are connected together toForming a five-membered ring.

Table XXIV-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-43.

Table XXIV-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIV-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-2.

*R²And R^3bBy (CH)₂)₃Is connected toTo form a five-membered ring.

Table XXV-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-28.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XXV-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXV-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXV-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-11.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-27.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XXVI-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-43.

Joined together to form a five-membered ring.

Table XXVI-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVI to 49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVI-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-22.

*R²And R^3bBy (CH)₂)₃Are connected togetherTo form a five-membered ring.

Table XXVIII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXVIII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXVIII-49.

*R²And R^3bBy (a)CH₂)₃Joined together to form a five-membered ring.

Table XXVIII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-2.

*R²And R^3bBy (CH)₂)₃Is connected toTo form a five-membered ring.

Table XXIX-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-38.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXIX-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-2.

*R²And R^3bBy (CH)₂)₃Is connected toTo form a five-membered ring.

TABLE XXX-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-4.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

TABLE XXX-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-22.

D

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring。

Table XXX-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-37.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XXX-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXX-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Tables XXX-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXX-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-2.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-18.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-36.

*R²And R ^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-43.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXI-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

TABLE XXXI-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-1.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-2.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XXXII-3.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-4.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-5.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-6.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-7.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-8.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-9.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-10.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-11.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-12.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-13.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-14.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-15.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-16.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-17.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-18.

*R²And R^3bBy (CH) ₂)₃Joined together to form a five-membered ring.

Table XXXII-19.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-20.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-21.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-22.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-23.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-24.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-25.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-26.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-27.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-28.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-29.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-30.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-31.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-32.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-33.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-34.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-35.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-36.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-37.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-38.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-39.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-40.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-41.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-42.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-43.

Watch (A)

XXXII-44.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-45.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-46.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-47.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-48.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-49.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Table XXXII-50.

*R²And R^3bBy (CH)₂)₃Joined together to form a five-membered ring.

Dosage, administration and use

A sixth embodiment of the invention relates to a composition for use in the treatment of 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, which compound is intended to include salts (acid or base addition salts), hydrates, solvates and crystalline forms thereof, which may be obtained.

It is contemplated that the formulation (formulation) of the sixth embodiment may comprise a compound comprised in any of the first, second, third, fourth and fifth embodiments or any of those specifically recited in the above table or exemplified herein, alone or in combination with another compound of the invention.

The compounds of the present invention may be formulated with carriers into a variety of oral dosage forms. Oral administration may be in the form of tablets, coated tablets, hard and soft gelatin capsules, solutions, emulsions, syrups or suspensions. The compounds of the present invention are effective when administered by suppository administration as well as other routes of administration. The most convenient mode of administration is usually oral, using a convenient daily dosage regimen, which may be adjusted according to the severity of the disease and the patient's response to the antiviral drug.

The compounds of the present invention and their pharmaceutically acceptable salts may be incorporated in the form of pharmaceutical compositions and unit dosages, together with one or more conventional excipients, carriers or diluents. The pharmaceutical compositions and unit dosage forms can comprise conventional ingredients in conventional proportions, with or without other active compounds, and the unit dosage form can contain any suitable effective amount of the active ingredient commensurate with the intended daily dosage range to be employed. The pharmaceutical composition can be in the form of a solid such as a tablet or a filled capsule, a semi-solid, a powder, a sustained release formulation or a liquid such as a suspension, an emulsion or a filled capsule for oral use; or in the form of suppositories for rectal or vaginal administration. Typical formulations contain from about 5% to about 95% active compound (w/w). The term "formulation" or "dosage form" is intended to include both solid and liquid formulations of the active compound, and it will be understood by those skilled in the art that the active ingredient may be present in different formulations depending on the desired dosage and pharmacokinetic parameters.

The term "excipient" as used herein refers to a compound used to prepare a pharmaceutical composition, which is generally safe, non-toxic, biologically or otherwise desirable, and includes excipients that are acceptable for veterinary use as well as for human pharmaceutical use. The compounds of the invention may be administered alone, but will generally be administered in admixture with one or more suitable pharmaceutical excipients, diluents or carriers selected with regard to the intended route of administration and standard pharmaceutical practice.

The "pharmaceutically acceptable salt" form of the active ingredient may also initially impart desirable pharmacokinetic properties not present in the non-salt form of the active ingredient, and may even positively affect the pharmacodynamics of the active ingredient with respect to its therapeutic activity in vivo. The phrase "pharmaceutically acceptable salt" of a compound, as used herein, refers to a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and mixtures thereof,Sulfuric acid, nitric acid, phosphoric acid, and the like; 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, dodecylsulfuric acid, gluconic acid, glutamic acid, salicylic acid, muconic acid, and the like; or (2) a base addition salt formed with a conjugate base of any of the inorganic acids listed above, wherein the conjugate base comprises a base selected from Na ⁺、K⁺、Mg²⁺、Ca²⁺And NH_gR′″_4-g ⁺Wherein R' ″ is C_1-3Alkyl, g is a number selected from 0, 1, 2, 3 or 4. It is to be understood that all references to pharmaceutically acceptable salts include the solvate addition forms (solvates) or crystalline forms (polymorphs) as defined herein of the same acid addition salt.

Solid form preparations include powders, tablets, pills, capsules, suppositories, and dispersible granules. A solid carrier may be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material. In powders, the carrier is usually a finely divided solid which is in admixture with the finely divided active component. In tablets, the active ingredient is usually mixed with a carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired. Suitable carriers include, but are not limited to, magnesium carbonate, magnesium stearate, talc, sucrose, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. Formulations in solid form may contain, in addition to the active ingredient, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

Liquid preparations also suitable for oral administration include liquid preparations including emulsions, syrups, elixirs and aqueous suspensions. These include solid form preparations which are intended to be converted, shortly before use, to liquid form preparations. Emulsions may be prepared in solution, for example in aqueous propylene glycol solution, or may contain emulsifying agents such as lecithin, sorbitan monooleate, or acacia. Aqueous suspensions may be prepared by dispersing the finely divided active component in water with viscous material such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.

The compounds of the present invention may be formulated for administration as suppositories. A low melting wax such as a mixture of fatty acid glycerides or cocoa butter is first melted and the active component is then dispersed homogeneously, for example by stirring. The molten homogeneous mixture is then poured into a suitably sized mold, allowed to cool and solidify.

The compounds of the invention may be formulated for vaginal administration. Pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

Suitable formulations are those which, together with pharmaceutical carriers, diluents and excipients, are described in "remington: pharmaceutical Science and Practice "(Remington: The Science and Practice of Pharmacy)1995, edited by E.W. Martin, Mack publishing company, 19 th edition, Easton, Pa, which is hereby incorporated by reference. The compounds of the invention may also be encapsulated in liposomes, such as those disclosed in U.S. patent nos. 6,180,134, 5,192,549, 5,376,380, 6,060,080, 6,132,763, each of which is incorporated by reference. Experienced formulators, within the teachings of this specification, may modify the formulation to provide a large number of formulations for a particular route of administration without rendering the compositions of the present invention unstable or compromising their therapeutic activity.

For example, modification of the compounds of the present invention to render them more soluble in water or other carriers is readily accomplished by minor modifications (e.g., salt formulations), which are well within the ordinary skill in the art. It is also well within the ordinary skill in the art to modify the route of administration and dosage regimen of a particular compound to take advantage of the pharmacokinetics of the compounds of the present invention to produce the greatest beneficial effect in a patient.

A seventh embodiment of the invention relates to the use of a compound of formula I for the preparation of a medicament for the treatment of any condition caused by infection with any one of the following viral agents: 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 "drug" refers to a substance used in a method of treating and/or preventing a subject in need thereof, wherein the substance includes, but is not limited to, compositions, formulations, dosage forms, and the like, comprising a compound of formula I. It is contemplated that the compound of the seventh embodiment for use of the compound represented by formula I in the manufacture of a medicament for the treatment of any of the antiviral conditions disclosed herein can be a compound encompassed by any of the first, second, third, fourth, fifth embodiments, or any of those specifically recited in the above table or exemplified herein, alone or in combination with another compound of the invention. Medicaments include, but are not limited to, any of the compositions contemplated by the sixth embodiment of the present invention.

An eighth embodiment of the present invention relates to a method of treating and/or preventing a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula I.

A first aspect of an eighth embodiment relates to a method of treating and/or preventing a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least two or more different compounds falling within the scope of the compound of formula I.

A second aspect of the eighth embodiment relates to a method of treating and/or preventing a subject in need thereof, the method comprising administering to the subject alternately or simultaneously therapeutically effective at least two compounds falling within the scope of the compound of formula I.

By subject in need thereof is meant a subject having any of the conditions 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 and japanese encephalitis virus, flavivirus or pestivirus or hepatitis c virus, or a viral agent causing symptoms equivalent or equivalent to those caused by any of the viruses listed above.

The term "subject" refers to a mammal, including but not limited to cattle, pigs, sheep, chickens, turkeys, buffalo, camels (llama), ostriches, dogs, cats, and humans, preferably the subject is a human. It is envisaged that the method of the sixth embodiment of treating a subject thereof may be a compound encompassed by any of the first, second and third embodiments, or any of those compounds specifically recited in the above table, alone or in combination with another compound of the invention.

The term "therapeutically effective amount" as used herein refers to the amount required to reduce the symptoms of a disease in an individual. In each particular case, the dosage should be adjusted to the individual requirements. The dosage may vary within wide limits depending on a number of factors, such as the severity of the disease to be treated, the age and general health of the patient, the other drugs being treated for the patient, the route and form of administration, and the preferences and experience of the relevant medical practitioner. For oral administration, suitable daily dosages per day in monotherapy and/or in combination therapy are between about 0.1g and about 10g, including all values such as between 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, and the like. Preferred daily dosages are between about 0.5 g/day to about 7.5 g/day, more preferably 1.5 g/day to about 6.0 g/day. Generally, treatment is initiated with a large initial "loading dose" to rapidly reduce or eliminate the virus, and then the dose is reduced to a level sufficient to prevent recurrence of the infection. One of ordinary skill in the treatment of the diseases described herein will be able to determine, without undue experimentation and depending on the individual's knowledge, experience, and disclosure of the application, a therapeutically effective amount of a compound of the present invention for a given disease and patient.

The efficacy of treatment can be determined according to the following assay: 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-glutamyltranspeptidase, etc.), the synthesis of bilirubin, cholesterol, and bile acid; hepatic metabolic functions, including but not limited to carbohydrate metabolism, amino acid and ammonia metabolism. Alternatively, the effect of treatment can be monitored by measuring HCV-RNA. The results of these assays allow optimization of the dose.

A third aspect of the eighth embodiment relates to a method of treating and/or preventing a subject in need thereof, 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 administrations are simultaneous or alternating. It is to be understood that the time between alternating administrations can range between 1-24 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 WO 2008010921, WO 2008010921, EP 1881001, WO2007015824, WO 2007014925, WO 2007014926, WO 2007014921, WO2007014920, WO 2007014922, US 2005267018, WO 2005095403, WO2005037214, WO 2004094452, US 2003187018, WO 200364456, WO2005028502, and WO 2003006490); HCV NS5B inhibitors (see US 2007275947, US 20072759300, WO 2007095269, WO 2007092000, WO 2007076034, WO 200702602, US 2005-oz 98125, WO 2006093801, US 2006166964, WO 2006065590, WO 2006065335, US 2006040927, US 2006040890, WO2006020082, WO 2006012078, WO 2005123087, US 2005154056, US2004229840, WO 2004065367, WO 2004003138, WO 2004002977, WO2004002944, WO 2004002940, WO 2004000858, WO 2003105770, WO2003010141, WO 2002057425, WO 2002057287, WO 2005021568, WO2004041201, US 20060293306, US 20060194749, US 20060241064, US 4167866, WO 2007088148, WO 2007039142, WO 2005103045, WO2007039145, WO 2004096210 and WO 2003037895); HCV NS4 inhibitors (see WO 2007070556 and WO 2005067900); HCV NS5a inhibitors (see US2006276511, WO 2006120252, WO 2006120251, WO 2006100310, WO 2006035061); toll-like receptor agonists (see WO 2007093901); and other inhibitors (see WO 2004035571, WO 2004014852, WO 2004014313, WO2004009020, WO 2003101993, WO 2000006529).

A fourth aspect of the eighth embodiment relates to a method of treating a subject in need thereof, the method comprising administering to the subject alternately or simultaneously a therapeutically effective compound of formula I and another antiviral agent. It is to be understood that the time between alternating administrations can range between 1-24 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.

A fifth aspect of the eighth embodiment relates to a method of treating and/or preventing a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least one compound represented by formula I and a therapeutically effective amount of another antiviral agent, wherein the administration is simultaneous or alternating. It is to be understood that the time between alternating administrations can range between 1-24 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.

A sixth aspect of the eighth embodiment relates to a method of treating a subject in need thereof, the method comprising administering to the subject alternately or simultaneously therapeutically effective at least one compound represented by formula I and another antiviral agent. It is to be understood that the time between alternating administrations can range between 1-24 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.

It is contemplated that another antiviral agent includes, but is not limited to, interferon alpha, interferon beta, pegylated interferon alpha, ribavirin, levovirin, viramidine, another nucleoside HCV polymerase inhibitor, an HCV non-nucleoside polymerase inhibitor, an HCV protease inhibitor, an HCV helicase inhibitor, or an HCV fusion inhibitor. The activity of the active compounds, or derivatives or salts thereof, may be increased over the parent compound when administered in combination with another antiviral agent. When the treatment is a combination treatment, such administration may be simultaneous or sequential with respect to the administration of the nucleoside derivative. Thus, "simultaneously administering" as used herein includes administering the agents simultaneously 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 substantially simultaneous administration of two or more dosage forms of a single active agent.

It will be understood that reference herein to treatment extends to both prophylaxis and treatment of the conditions present. Furthermore, the term "treatment" of HCV infection as used herein also includes the treatment or prevention of a disease or disorder associated with or mediated by HCV infection or clinical symptoms thereof.

Preparation method

A ninth embodiment of the present invention relates to a process for the preparation of a compound of formula I, which comprises reacting a suitably substituted phosphorochloridate compound 4 with a nucleoside analogue 5.

Wherein the substituent R¹、R²、R^3a、R^3b、R⁴、R⁵、X、Y、R⁶And the base group has the meaning as disclosed in the detailed description of the invention, X' is a leaving group, such as Cl, Br, I, tosylate, mesylate, trifluoroacetate, triflate, pentafluorobenzene oxide, p-NO₂Phenoxy compounds, or other customary leaving groups as disclosed in March (March) fourth edition "Advanced Organic Chemistry". Leaving groups and methods that can be used to influence the formation of phosphoramidate nucleoside conjugates are found in US 20060142238 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 a preferred solvent. The reaction is generally initiated at a temperature in the range of-78 ℃ to 40 ℃, with a preferred reaction temperature being between 0 ℃ and room temperature. The nucleoside is first stirred with a base (5 to 12 equivalents) such as N-methylimidazole, collidine, pyridine, 2, 6-lutidine, 2, 6- ^tBu-pyridine, etc.; tertiary amine bases such as triethylamine, diisopropylethylamine, and the like; or alkyl grignard reagents such as tbugcl, tbuggbr, MeMgCl, MeMgBr, and the like. Phosphorus oxychloride (3-10 equivalents) was dissolved in the reaction solvent and added to the mixture of nucleoside and base. The reaction is then allowed to stir at a temperature between room temperature and 40 ℃ for a period of time ranging from 30min to 24hr, preferably at room temperature and for a period of 24 hr. The solvent was removed from the reaction mixture and the product was purified by silica gel chromatography.

A tenth embodiment of the invention relates to the product obtained by a process comprising reacting a suitably substituted phosphorus chloride compound 4 with a nucleoside analogue 5

Wherein the substituent R¹、R²、R^3a、R^3b、R⁴、R⁵、X、Y、R⁶X', and base 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, with tetrahydrofuran being a preferred solvent, or other suitable solvent. The reaction is generally initiated at a temperature in the range of-78 ℃ to 40 ℃, with a preferred reaction temperature being between 0 ℃ and room temperature. The nucleoside is first stirred with a base (5 to 12 equivalents) such as N-methylimidazole, tertiary amine base or tert-butylmagnesium chloride. Phosphorus oxychloride (3-10 equivalents (or a suitable "phosphorus- (leaving group) -compound")) is dissolved in the reaction solvent and added to the mixture of nucleoside and base. The reaction is then allowed to stir at a temperature between room temperature and 40 ℃ for a period of time ranging from 30min to 24hr, preferably at room temperature and for a period of 24 hr. The solvent was removed from the reaction mixture and the product was purified by silica gel chromatography.

Compounds and formulations

The phosphoramidate compounds of the present invention can be prepared by condensing nucleoside analogs 5 with appropriately substituted phosphorus chloride compounds 4 (scheme 1). Nucleoside analogs are prepared by conventional procedures disclosed in any of U.S. published application nos. 2005/0009737, 2006/0199783, 2006/0122146 and 2007/0197463, the entire contents of each of which are incorporated by reference.

The 1H-NMR values disclosed are recorded on a Varian AS-400 instrument. Mass spectral data were acquired using either the Micromass-Quattromic API or the Waters Acity.

Thus, by way of example only, a suitably substituted phenol may be reacted with phosphorus oxychloride (1) to give aryloxyphosphoryl dichloride 2 (see example 1), which is subsequently treated with an acid addition salt of an alpha-amino acid ester in the presence of TEA to give aryloxyphosphoryl chloride 4. This arylalkoxy-amino acid phosphoramidate is reacted with a nucleoside analogue to give the product I (for the procedure see, e.g., C.McGuigan et al, antibacterial Res.199217: 311-321; D.Curley et al, antibacterial Res.199014: 345-356; McGuigan et al, antibacterial Chem.Chemother 19901 (2): 107-113).

Scheme 1

The preparation of nucleoside phosphoramidates requires the reaction of an appropriately substituted phosphorus chloride with a nucleoside containing a free 5' -hydroxy moiety. In the case where only one hydroxyl group is present, the preparation of phosphoramidates generally proceeds smoothly when the phosphorus chloride is reacted with the desired nucleoside. In the case of nucleosides containing more than one free hydroxyl group, it may be necessary to prepare appropriately protected nucleosides. Silyl, acetonide or other alcohol protecting groups known in the art may ensure protection of the sugar moiety. For protection of nucleobases, protection of the free amino group requires an amidine protection strategy.

The condensation of phosphorus chloride can be performed on an unprotected nucleoside. Since the 5 '-OH group of nucleosides is much less hindered than the 3' -OH group, selective phosphorylation of amino groups is possible under carefully controlled conditions. Following condensation to form a protected phosphoramidate nucleoside, deprotection to obtain a free phosphoramidate nucleoside can be performed using standard protocols of nucleic acid chemistry. In most cases, the desired product can be easily isolated from the starting material using silica gel column chromatography. A schematic of the synthesis is summarized in scheme 1.

A further understanding of the disclosed embodiments will be obtained by consideration of the following examples, which are intended to be illustrative only and do not limit the disclosed invention.

Example 1

General procedure for the preparation of Phosphoryldichloride

The appropriate phenol R is reacted with¹A solution of-OH (1 eq) and triethylamine (1 eq) in anhydrous ether was added dropwise to a stirred solution of phosphoryl trichloride 1(1 eq) under nitrogen at 0 ℃ over a period of 3 hours. The temperature was then raised to room temperature and the reaction was stirred overnight. The triethylamine salt was quickly removed using suction filtration and the filtrate was concentrated to dryness in vacuo to give 2 as an oil which was used without further purification.

Example 2

General procedure for the preparation of phosphorus oxychloride

A solution of triethylamine (2 equivalents) in dry dichloromethane was added dropwise over a period of 30 to 120 minutes to a solution of aryloxy-phosphorus dichloride 2(1 equivalent) and the appropriate amino ester 3(1 equivalent) in dry dichloromethane at-78 ℃ with vigorous stirring. The reaction temperature was then allowed to rise to room temperature and stirred overnight. The solvent was removed. The residue was washed with diethyl ether and filtered, and the filtrate was dried under reduced pressure to give 4.

Example 3

General procedure for nucleoside phosphoramidate derivatives

A solution of the appropriate phosphoryl chloride 4(6.5 equivalents) in anhydrous Tetrahydrofuran (THF) was added to a mixture of nucleoside 5(1 equivalent) and N-methylimidazole (8 equivalents) in anhydrous THF at room temperature with vigorous stirring, and the reaction mixture was stirred overnight. The solvent is removed in vacuo and the crude product is purified by column chromatography and/or preparative thin layer chromatography to give I.

Example 4

Preparation of 2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine

2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (1.0g, 1 equivalent) (Clark, J. et al, J.Med. chem., 2005, 48, 5504-. The resulting slurry was dissolved in 20ml of anhydrous pyridine under nitrogen and cooled to 0 ℃ with stirring. The brown solution was treated dropwise over 10min using benzoyl chloride (1.63g, 3 equivalents). The ice bath was removed and stirring was continued for 1.5h, whereby Thin Layer Chromatography (TLC) showed no starting material remaining. The mixture was quenched by addition of water (0.5ml) and concentrated to dryness. The residue was dissolved in 50mL Dichloromethane (DCM) and saturated NaHCO ₃Aqueous solution and H₂And O washing. The organic phase is passed through NaSO₄Drying, filtering, concentrating to dryness to obtain N⁴3 ', 5 ' -Tribenzoyl-2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (2.0g, yield: 91%).

Will N⁴3 ', 5 ' -Tribenzoyl-2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (2.0g, 1 equivalent) was refluxed overnight in 80% aqueous AcOH. After cooling and standing at room temperature (15 ℃), 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 the other product, which was washed with water to give a white solid. The two white solids were combined to give 1.50g of 3 ', 5 ' -dibenzoyl-2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (yield: 91%).

A saturated solution of ammonia in MeOH (20mL) was added to a solution of 3 ', 5 ' -dibenzoyl-2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (1.5g, 1 eq) in MeOH (10 mL). The reaction mixture was stirred at 0 ℃ for 30min and then slowly warmed to room temperature. After the reaction mixture was stirred for another 18 hours, the reaction mixture was evaporated under reduced pressure to give a residue, which was purified by column chromatography to obtain pure compound 2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (500mg, yield: 60%).

Example 5

Preparation of 2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-alanyl phosphate)

Phenylmethoxyalaninyl (alaninyl) phosphoryl chloride (1g, 6.5 equivalents) dissolved in 3mL THF is added to a mixture of 2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (0.15g, 1 equivalent) and N-methylimidazole (0.3g, 8 equivalents) in 3mL THF at room temperature with vigorous stirring, and the reaction is stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Removal of acetonitrile and water under reduced pressure gave the desired product (50.1mg, 15.6%).¹H NMR(DMSO-d₆)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-valyl phosphate)

Phenylmethoxy-valyl phosphoryl chloride (0.6g, 3.6 equivalents) dissolved in 3mL THF is added to a mixture of 2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (0.15g, 1 equivalent) and N-methylimidazole (0.44g, 9 equivalents) in 3mL THF at room temperature with vigorous stirring, and the reaction is stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Removal of acetonitrile and water under reduced pressure gave the desired product (60mg, 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)，4.23-4.43(m，2H)，5.56(t，J＝16.0Hz，1H)，5.85-5.92(m，1H)，6.01-6.07(m，1H)，7.16-7.21(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-bromophenyl-methoxy-valyl phosphate)

4-bromophenylmethoxy-valylphosphoryl chloride (1g, 3.4 equivalents) dissolved in 3mL of THF was added to a mixture of 2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (0.2g, 1 equivalent) and N-methylimidazole (0.35g, 6 equivalents) in 3mL of THF at room temperature with vigorous stirring, and the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Acetonitrile and water were removed under reduced pressure to give the desired product (120mg, 26%).¹H NMR(DMSO-d₆)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-bromophenyl-methoxy-alanyl phosphate)

4-bromophenyl methoxy-alanyl phosphoryl chloride (0.6g, 5 equivalents) dissolved in 3mL of THF was added to a mixture of 2 ' -deoxy-2 ' -fluoro-2 ' -C-methyluridine (0.15g, 1 equivalent) and N-methylimidazole (0.3g, 7.8 equivalents) in 3mL of THF at room temperature with vigorous stirring, and the reaction was stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Acetonitrile and water were removed under reduced pressure to give the desired product (40mg, 12%); ¹H NMR(DMSO-d₆)δ1.20-1.26(m，6H)，3.57(d，J＝2.8Hz，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＝10.2Hz，2H)，7.52-7.57(m，3H)，11.52(s，1H)；MS，m/e 580(M+1)⁺。

Example 9

N⁴Preparation of (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine

2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (500mg, 1.9mmol) is stirred with a solution of dimethylformamide dimethyl acetal in DMF (10 mL). The resulting mixture was stirred at room temperature overnight. After removal of the solvent, the crude product was used in the next step without further purification.

Example 10

Preparation of 2 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-alanyl phosphate)

Phenylmethoxyalaninyl phosphoryl chloride (0.6g, 6 equivalents) dissolved in 3mL THF is added to N at room temperature with vigorous stirring⁴A mixture of- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (0.15g, 1 eq) and N-methylimidazole (0.3g, 7.8 eq) in 3mL THF was then the reaction stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Removal of acetonitrile and water under reduced pressure gave the desired product (62mg, 20.6%).¹H NMR(DMSO-d₆)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-bromophenyl methoxy-valyl phosphate)

4-bromophenylmethoxy-valylphosphoryl chloride (1.0g, 3.4 equivalents) dissolved in 3mL of THF was added to N at room temperature with vigorous stirring⁴A mixture of- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (0.2g, 1 eq) and N-methylimidazole (0.35g, 6 eq) in 3mL THF was then the reaction stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Removal of acetonitrile and water under reduced pressure gave the desired product as a white solid (59mg, 13%);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)，5.70-5.72(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' - (phenyl methoxy-valyl phosphate)

Phenylmethoxy-valyl phosphoryl chloride (0.6g, 6 equivalents) dissolved in 3mL THF is added to N at room temperature with vigorous stirring⁴A mixture of- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine (0.15g, 1 eq) and N-methylimidazole (0.3g, 7.8 eq) in 3mL THF was then the reaction stirred overnight. The solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol and purified on a preparative HPLC YMC 25X30X2mm column by eluting the mobile phase with a water/acetonitrile gradient. Acetonitrile and water were removed under reduced pressure to give the desired product as a white solid (86mg, 42) .9％)。¹H NMR(DMSO-d₆)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)⁺。

Examples

Examples Nos. 13-54 and 56-66 were prepared using procedures similar to those described for examples 5-8. Example number, compound identification and NMR/MS details are shown below:

*R²and R^3bAre jointly L-preserved fruitAmino acid obtained- (CH)₂)₃-

Purification step by preparative HPLC:

the crude product was dissolved in methanol. The injection volume of these solutions was 5 mL.

The preparative HPLC system included 2 sets of Gilson 306 pumps, Gilson 156 UV/Vis detector, Gilson 215 injector & fraction collector, and Unipoint control software. Ymc 25X 30X 2mm columns were used. The mobile phases were HPLC grade water (a) and HPLC grade acetonitrile (B). Fractions were collected into 100 x 15mm glass tubes.

The HPLC gradients are shown in table 1. After selection of the gradient, the acetonitrile solution was injected into the HPLC system and fractions were collected according to the UV peak. After separation, each glass tube was subjected to MS test to collect the desired compound. Fractions with the target MS were combined in an accurately weighed flask. Most of the acetonitrile was removed under reduced pressure and the remaining solution was freeze-dried to give the desired compound.

Table 1:

preparation of example 66

Illustration of the drawings

Preparation of Compound (b)

Mixing LiAl (OBu-t)₃A1M solution of H in THF (2.69mL, 2.69mmol) was added dropwise to a solution of compound a (1g, 2.69mmol) in dry THF (30mL) at-20 ℃. The reaction mixture was stirred at the same temperature for 2-3 h. EtOAc (100mL) was added followed by saturated NH ₄Cl solution (10mL), the reaction mixture was slowly warmed 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 0.8g of crude compound b as a clear oil, which was used directly in the next reaction.

Preparation of Compound (d)

DEAD (1.8mL) was added to compound b (0.8g, 2.1mmol), compound c (0.45g, 2.5mmol) and Ph under a nitrogen atmosphere₃P (0.56g, 2.1mmol) in dry THF (20 mL). The reaction mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure. The residue was separated by preparative layer chromatography (hexane: EtOAc ═ 3: 1) to give crude compound d (0.8 g). The crude compound d was used in the next step without further purification.

Preparation of Compound (e)

Compound d (0.8g, 1.57mmol) was dissolved in THF (2mL) and ammonia saturated THF (5mL) was added to the solution. The reaction mixture was heated to 90 ℃ overnight. After 18 hours, the solution was cooled to room temperature by ice water, then the solvent was removed under reduced pressure, and the residue was purified by column to give compound e (0.75g) which was used in the next step.

Preparation of Compound (f)

Compound e (0.5g, 1.01mmol) was dissolved in methanol (2mL) and then ammonia saturated methanol (5mL) was added to the solution. The reaction mixture was stirred at room temperature overnight. After 18 h, the solvent was removed under reduced pressure and the residue was purified by column to give crude compound f (0.15g) for the next step.

Preparation of Compound (i)

A solution of triethylamine (1.07g, 10.6mmol) in dry dichloromethane (15mL) was added dropwise over a period of 2 hours to a solution of compound g (1.16g, 5.3mmol) and compound h (1.31g, 5.3mmol) in dichloromethane (10mL) at-78 deg.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, 20mL of anhydrous ether was added, the precipitated salt was filtered and the precipitate was washed with ether. The combined organic phases were concentrated to give compound i as a colourless oil (1.0 g).

Preparation of Compound 66

0.4g NMI was added to a stirred solution of compound j (0.1g, 0.35mmol) in 10mL anhydrous THF until the solution became clear, a solution of compound i (0.8g, 2.89mmol) in 10mL THF was added dropwise and stirred at room temperature overnight. The purity of the compound was confirmed by LCMS and identified. The solvent was evaporated and purified by preparative HPLC to give 66(25mg, yield: 13.6%).¹H NMR(DMSO-d₆)δ 1.08(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)，5.85-5.92(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 following identified examples, nos. 67-74, were prepared using procedures similar to those disclosed above for example 66.

Examples No. 75-80 were prepared using procedures analogous to those disclosed above for example 66.

Example 81

Due to the chirality at the phosphorus, certain exemplified compounds are obtained as mixtures of diastereomers. The diastereomers were separated on a Chiralpak-AS-H (2X25cm) column under Supercritical Fluid Chromatography (SFC) conditions using 20% methanol in carbon dioxide AS solvent. The absolute stereochemistry of the diastereomer P-chiral center is not determined. However, chromatographic resolution of these two diastereomers provides an isomer characterized by a fast elution and a slow elution. Some examples are shown below.

Compound (I)	EC90(uM)
		Example 15 (mixture of diastereomers)	0.86
Example 15 fast moving isomers	1.35
		Example 15 Slow moving isomer	0.26
Example 39 (diastereomer mixture)	0.47
		Compound (I)	EC90(uM)
Example 39 fast moving isomers	0.78

Example 39 Slow moving isomer	0.02
		Example 49 (diastereomer mixture)	0.126
Example 49 fast moving isomers	0.03
		Example 49 Slow moving isomer	5.78

Example 82

HCV replicon assay Huh7 cells (clone A cells; Apath, LLC, St.Louis, Mo.) containing HCV replicon RNA were maintained in exponential growth in Darbeck (Dulbecco's) modified Eagle's medium (high glucose) containing 10% fetal bovine serum, 4mM L-glutamine and 1mM sodium pyruvate, 1 × non-essential amino acids and G418(1,000 μ G/ml). The antiviral assay was performed in the same medium without G418. Cells were seeded in 96-well plates at 1,500 cells/well and test compounds were added immediately after seeding. The incubation time was 4 days. At the end of the incubation step, total cellular RNA was isolated (RNeasy 96 kit; Qiagen). Replicon RNA and internal control controls were amplified in a one-step multiplex RT-PCR protocol recommended by the manufacturer (TaqMan rRNA control reagents; Applied Biosystems). HCV primers and probes were designed using Primer expression software (Primer Express 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 show the antiviral effect of the compounds, the mean RT-PCR cycle threshold for the no drug control was subtracted by the RT-PCR cycle threshold (Δ Ct) for the test compound_HCV). Delta Ct 3.3 corresponds to a 1-log 10 reduction in replicon RNA levels (equivalent to an effective concentration of 90% [ EC ]₉₀]). Cytotoxicity of test compounds can also be determined by calculating the Δ Ct_rRNAA value. Then substituting the specific parameter of delta Ct into (delta Ct)_HCV-ΔCt_rRNA) Wherein HCV RNA levels are normalized to rRNA levels and corrected relative to no drug controls.

¹(4-BrPh): 4-bromo-phenyl.

60/909,315 filed 3/30/2007, 60/982,309 filed 10/24/2007, and 12/053,015 filed 3/21/2008 are hereby incorporated by reference in their entirety to supplement the present disclosure and/or correct any errors as needed. Further, the patent documents and non-patent documents disclosed herein are incorporated by reference. In the event that the incorporated patent and non-patent documents contain a term that conflicts with the term disclosed in either provisional application or the present application text, the meaning of the term contained in the present application text and in both provisional applications shall govern, provided that the overall meaning of the incorporated subject matter is not lost.

Claims (12)

1. A compound represented by formula I, a stereoisomer, salt, hydrate, solvate, or crystalline form thereof:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthaleneOptionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a composite comprising adjacent N and C atoms and R¹、R^3aAnd R^3bCyclic ring C (O) CR^3aR^3bNHR¹Wherein n is 2 to 4;

(c)R^3aand R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r ^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising adjacent N and C atomsWherein 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' independently is hydrogen or C_1-6Alkyl radical, and R³"is-O R' or-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, optionally substituted by lower alkyl, alkoxy,Di (lower alkyl) -amino or halogen substituted C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R ⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl), OC (O) O (C)_1-4Alkyl), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl radical)、OS(O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl), C (O) O (C)_1-4Alkyl), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO ₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²Is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

2. A compound, its stereoisomer, salt, hydrate, solvate, or crystalline form thereof, selected from the group consisting of:

52 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

62 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-valyl 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-butyric acid methyl ester;

72 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl 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-butyric acid methyl ester);

82 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-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 } -propionic acid methyl ester);

9 N⁴- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine;

102 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

112 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (4-bromophenyl methoxy-valyl phosphate (2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl phosphate ((S) -2- { (4-bromo-phenoxy) - [ (2R, the ratio of 3R to 4R, 5R) -5- (2-oxo-3-amino-pyrimidin-1-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phosphorylamino } -3-methyl-butyric acid methyl ester);

122 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-valyl 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-butyric acid 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 } -propionic acid ethyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid benzyl 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 } -acetic acid methyl ester;

16(S) -2- { (2, 4-dichloro-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 } -propionic acid methyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid methyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl 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 ] -propionic acid methyl ester;

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 } -propionic acid methyl ester;

23(S) -2- { (3, 4-dichloro-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 } -propionic acid methyl ester;

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 } -propionic acid sec-butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

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 ] -propionic acid ethyl ester;

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 ] -propionic acid phenylmethyl 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 } -propionic acid benzyl ester;

32(S) -2- { (2, 4-dichloro-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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

35(S) -2- { (3, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid benzyl 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 } -propionic acid pentyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid ethyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl ester;

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 } -butyric acid methyl ester;

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-benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid 3-methyl-butyl ester;

48(S) -2- { (2, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid cyclohexyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid cyclohexyl ester;

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 ] -propionic acid cyclohexyl ester;

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 } -butyric acid cyclohexyl ester;

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 ] -butyric acid cyclohexyl ester;

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 } -butyric acid isopropyl ester;

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 } -propionic acid cyclopropylmethyl ester;

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 } -butyric acid cyclopentyl ester;

66(S) -2- { [ (2R, 3R, 4R, 5R) -5- (6-amino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

67(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-hydroxy-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

68(S) -2- { (R) - [ (2R, 3R, 4R, 5R) -5- (2, 6-diamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

69(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclopentylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

70(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-azetidin-1-yl-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

71(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-diethylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

72(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-propylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

73(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclobutylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

74(S) -2- ({ (2R, 3R, 4R, 5R) -5- [ 2-amino-6- (4-methyl-piperazin-1-yl) -purin-9-yl ] -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy } -phenoxy-phosphorylamino) -propionic acid methyl ester;

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-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

77(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (cyclopentylamino) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propionate;

78(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (aziridin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

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) propanoate; and

80(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (azetidin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate.

3. A composition for the treatment and/or prevention of any of the viral agents disclosed herein, said composition comprising a pharmaceutically acceptable medium selected from excipients, carriers, diluents and equivalent media, and a compound represented by formula I, a stereoisomer, salt, hydrate, solvate or crystalline form thereof:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C _1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a composite comprising adjacent N and C atoms and R¹、R^3aAnd R^3bCyclic ring C (O) CR^3aR^3bNHR¹Wherein n is 2 to 4;

(c)R^3aand R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R ³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen,including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl), OC (O) O (C)_1-4Alkyl), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C) _2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl), C (O) O (C)_1-4Alkyl), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C ₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R ¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

4. A composition for the treatment and/or prevention of any of the viral agents disclosed herein, said composition comprising a pharmaceutically acceptable medium selected from excipients, carriers, diluents and equivalent media, and a compound selected from the group consisting of:

52 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

62 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-valyl 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-butyric acid methyl ester;

72 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl 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-butyric acid methyl ester);

82 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-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 } -propionic acid methyl ester);

9 N⁴- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine;

102 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

112 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (4-bromophenyl methoxy-valyl phosphate (2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl phosphate ((S) -2- { (4-bromo-phenoxy) - [ (2R, the ratio of 3R to 4R, 5R) -5- (2-oxo-3-amino-pyrimidin-1-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phosphorylamino } -3-methyl-butyric acid methyl ester);

122 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-valyl 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-butyric acid 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 } -propionic acid ethyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid benzyl 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 } -acetic acid methyl ester;

16(S) -2- { (2, 4-dichloro-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 } -propionic acid methyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid methyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl 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 ] -propionic acid methyl ester;

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 } -propionic acid methyl ester;

23(S) -2- { (3, 4-dichloro-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 } -propionic acid methyl ester;

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 } -propionic acid sec-butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

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 ] -propionic acid ethyl ester;

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 ] -propionic acid phenylmethyl 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 } -propionic acid benzyl ester;

32(S) -2- { (2, 4-dichloro-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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

35(S) -2- { (3, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid benzyl 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 } -propionic acid pentyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid ethyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl ester;

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 } -butyric acid methyl ester;

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-benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid 3-methyl-butyl ester;

48(S) -2- { (2, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid cyclohexyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid cyclohexyl ester;

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 ] -propionic acid cyclohexyl ester;

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 } -butyric acid cyclohexyl ester;

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 ] -butyric acid cyclohexyl ester;

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 } -butyric acid isopropyl ester;

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 } -propionic acid cyclopropylmethyl ester;

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 } -butyric acid cyclopentyl ester;

66(S) -2- { [ (2R, 3R, 4R, 5R) -5- (6-amino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

67(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-hydroxy-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

68(S) -2- { (R) - [ (2R, 3R, 4R, 5R) -5- (2, 6-diamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

69(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclopentylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

70(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-azetidin-1-yl-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

71(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-diethylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

72(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-propylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

73(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclobutylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

74(S) -2- ({ (2R, 3R, 4R, 5R) -5- [ 2-amino-6- (4-methyl-piperazin-1-yl) -purin-9-yl ] -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy } -phenoxy-phosphorylamino) -propionic acid methyl ester;

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-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

77(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (cyclopentylamino) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propionate;

78(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (aziridin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

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) propanoate; and

80(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (azetidin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate.

5. Use of a compound of formula I for the manufacture of a medicament for the treatment of any condition 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:

wherein the compound, its stereoisomer, salt, hydrate, solvate, or crystalline form thereof is represented by formula I:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R ^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a composite comprising adjacent N and C atoms and R¹、R^3aAnd R^3bCyclic ring C (O) CR^3aR^3bNHR¹Wherein n is 2 to 4;

(c)R^3aand R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C _1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl), OC (O) O (C)_1-4Alkyl), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO ₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl), C (O) O (C)_1-4Alkyl), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I) ₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR′₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO ₂。

6. Use of a compound selected from the group consisting of:

52 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

62 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-valyl 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-butyric acid methyl ester;

72 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl 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-butyric acid methyl ester);

82 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-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 } -propionic acid methyl ester);

9 N⁴- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine;

102 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

112 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (4-bromophenyl methoxy-valyl phosphate (2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl phosphate ((S) -2- { (4-bromo-phenoxy) - [ (2R, the ratio of 3R to 4R, 5R) -5- (2-oxo-3-amino-pyrimidin-1-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phosphorylamino } -3-methyl-butyric acid methyl ester);

122 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-valyl 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-butyric acid 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 } -propionic acid ethyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid benzyl 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 } -acetic acid methyl ester;

16(S) -2- { (2, 4-dichloro-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 } -propionic acid methyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid methyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl 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 ] -propionic acid methyl ester;

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 } -propionic acid methyl ester;

23(S) -2- { (3, 4-dichloro-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 } -propionic acid methyl ester;

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 } -propionic acid sec-butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

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 ] -propionic acid ethyl ester;

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 ] -propionic acid phenylmethyl 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 } -propionic acid benzyl ester;

32(S) -2- { (2, 4-dichloro-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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

35(S) -2- { (3, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid benzyl 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 } -propionic acid pentyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid ethyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl ester;

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 } -butyric acid methyl ester;

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-benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid 3-methyl-butyl ester;

48(S) -2- { (2, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid cyclohexyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid cyclohexyl ester;

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 ] -propionic acid cyclohexyl ester;

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 } -butyric acid cyclohexyl ester;

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 ] -butyric acid cyclohexyl ester;

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 } -butyric acid isopropyl ester;

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 } -propionic acid cyclopropylmethyl ester;

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 } -butyric acid cyclopentyl ester;

66(S) -2- { [ (2R, 3R, 4R, 5R) -5- (6-amino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

67(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-hydroxy-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

68(S) -2- { (R) - [ (2R, 3R, 4R, 5R) -5- (2, 6-diamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

69(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclopentylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

70(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-azetidin-1-yl-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

71(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-diethylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

72(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-propylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

73(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclobutylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

74(S) -2- ({ (2R, 3R, 4R, 5R) -5- [ 2-amino-6- (4-methyl-piperazin-1-yl) -purin-9-yl ] -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy } -phenoxy-phosphorylamino) -propionic acid methyl ester;

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-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

77(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (cyclopentylamino) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propionate;

78(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (aziridin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

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) propanoate; and

80(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (azetidin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate.

7. A method of treating a subject in need thereof, comprising:

administering to the subject a therapeutically effective amount of a compound of formula I;

wherein the compound or a stereoisomer, salt, hydrate, solvate, or crystalline form thereof is represented by formula I:

wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3b；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C _1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally substitutedIs selected from hydroxyl and C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen _1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl), OC (O) O (C)_1-4Alkyl), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C) _1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C _1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂。

8. A method of treating a subject in need thereof, comprising:

administering a therapeutically effective amount of a compound, its stereoisomer, salt, hydrate, solvate, or crystalline form thereof, selected from the group consisting of:

52 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

62 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-valyl 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-butyric acid methyl ester;

72 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl 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-butyric acid methyl ester);

82 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-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 } -propionic acid methyl ester);

9 N⁴- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine;

102 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

112 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (4-bromophenyl methoxy-valyl phosphate (2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl phosphate ((S) -2- { (4-bromo-phenoxy) - [ (2R, the ratio of 3R to 4R, 5R) -5- (2-oxo-3-amino-pyrimidin-1-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phosphorylamino } -3-methyl-butyric acid methyl ester);

122 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-valyl 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-butyric acid 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 } -propionic acid ethyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid benzyl 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 } -acetic acid methyl ester;

16(S) -2- { (2, 4-dichloro-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 } -propionic acid methyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid methyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl 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 ] -propionic acid methyl ester;

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 } -propionic acid methyl ester;

23(S) -2- { (3, 4-dichloro-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 } -propionic acid methyl ester;

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 } -propionic acid sec-butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

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 ] -propionic acid ethyl ester;

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 ] -propionic acid phenylmethyl 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 } -propionic acid benzyl ester;

32(S) -2- { (2, 4-dichloro-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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

35(S) -2- { (3, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid benzyl 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 } -propionic acid pentyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid ethyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl ester;

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 } -butyric acid methyl ester;

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-benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid 3-methyl-butyl ester;

48(S) -2- { (2, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid cyclohexyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid cyclohexyl ester;

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 ] -propionic acid cyclohexyl ester;

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 } -butyric acid cyclohexyl ester;

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 ] -butyric acid cyclohexyl ester;

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 } -butyric acid isopropyl ester;

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 } -propionic acid cyclopropylmethyl ester;

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 } -butyric acid cyclopentyl ester;

66(S) -2- { [ (2R, 3R, 4R, 5R) -5- (6-amino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

67(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-hydroxy-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

68(S) -2- { (R) - [ (2R, 3R, 4R, 5R) -5- (2, 6-diamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

69(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclopentylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

70(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-azetidin-1-yl-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

71(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-diethylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

72(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-propylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

73(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclobutylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

74(S) -2- ({ (2R, 3R, 4R, 5R) -5- [ 2-amino-6- (4-methyl-piperazin-1-yl) -purin-9-yl ] -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy } -phenoxy-phosphorylamino) -propionic acid methyl ester;

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-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

77(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (cyclopentylamino) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propionate;

78(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (aziridin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

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) propanoate; and

80(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (azetidin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate.

9. A process for preparing a compound of formula I, its stereoisomers, salts, hydrates, solvates or crystalline forms thereof:

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy radical,F. Cl, Br, I, nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3b；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r ^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroAlkyl, aminoacyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl, or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R ⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-0Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl) and (C),NH(C_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl group), C (O) O (C)_1-4Alkyl group), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO ₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I)₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²Is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH₂Or (iii) -NO₂；

The method comprises the following steps:

reacting a substituted phosphorus chloride compound 4 with a nucleoside analog 5

10. A process for preparing a compound, its stereoisomer, salt, hydrate, solvate or crystalline form thereof, selected from the group consisting of:

52 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

62 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-valyl 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-butyric acid methyl ester;

72 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl 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-butyric acid methyl ester);

82 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-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 } -propionic acid methyl ester);

9 N⁴- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine;

102 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

112 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (4-bromophenyl methoxy-valyl phosphate (2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl phosphate ((S) -2- { (4-bromo-phenoxy) - [ (2R, the ratio of 3R to 4R, 5R) -5- (2-oxo-3-amino-pyrimidin-1-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phosphorylamino } -3-methyl-butyric acid methyl ester);

122 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-valyl 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-butyric acid 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 } -propionic acid ethyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid benzyl 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 } -acetic acid methyl ester;

16(S) -2- { (2, 4-dichloro-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 } -propionic acid methyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid methyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl 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 ] -propionic acid methyl ester;

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 } -propionic acid methyl ester;

23(S) -2- { (3, 4-dichloro-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 } -propionic acid methyl ester;

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 } -propionic acid sec-butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

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 ] -propionic acid ethyl ester;

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 ] -propionic acid phenylmethyl 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 } -propionic acid benzyl ester;

32(S) -2- { (2, 4-dichloro-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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

35(S) -2- { (3, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid benzyl 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 } -propionic acid pentyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid ethyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl ester;

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 } -butyric acid methyl ester;

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-benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid 3-methyl-butyl ester;

48(S) -2- { (2, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid cyclohexyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid cyclohexyl ester;

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 ] -propionic acid cyclohexyl ester;

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 } -butyric acid cyclohexyl ester;

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 ] -butyric acid cyclohexyl ester;

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 } -butyric acid isopropyl ester;

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 } -propionic acid cyclopropylmethyl ester;

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 } -butyric acid cyclopentyl ester;

66(S) -2- { [ (2R, 3R, 4R, 5R) -5- (6-amino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

67(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-hydroxy-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

68(S) -2- { (R) - [ (2R, 3R, 4R, 5R) -5- (2, 6-diamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

69(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclopentylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

70(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-azetidin-1-yl-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

71(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-diethylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

72(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-propylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

73(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclobutylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

74(S) -2- ({ (2R, 3R, 4R, 5R) -5- [ 2-amino-6- (4-methyl-piperazin-1-yl) -purin-9-yl ] -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy } -phenoxy-phosphorylamino) -propionic acid methyl ester;

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-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

77(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (cyclopentylamino) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propionate;

78(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (aziridin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

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) propanoate; and

80(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (azetidin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

the method comprises the following steps:

reacting a substituted phosphorus chloride compound 4 with a nucleoside analog 5

11. A product, its stereoisomers, salts, hydrates, solvates or crystalline forms thereof, prepared by a process comprising:

reacting a substituted phosphorus chloride compound 4 with a nucleoside analog 5

Wherein

(a)R¹Is hydrogen, n-alkyl, branched alkyl, cycloalkyl, or aryl, including but not limited to phenyl or naphthyl, wherein phenyl or naphthyl is optionally substituted with at least one of: c_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, F, Cl, Br,I. Nitro, cyano, C_1-6Haloalkyl, -N (R)¹′)₂、C_1-6Amido, -NHSO₂C_1-6Alkyl, -SO₂N(R¹′)₂、COR¹"and-SO₂C_1-6An alkyl group; (R)¹' is independently hydrogen or alkyl, including but not limited to C_1-20Alkyl radical, C _1-10Alkyl or C_1-6Alkyl radical, R¹"is-OR' OR-N (R)¹′)₂)；

(b)R²Is hydrogen, C_1-10Alkyl radical, R^3aOr R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring C (O) CR comprising adjacent N and C atoms^3aR^3bNHR¹Wherein n is 2 to 4, R¹、R^3aAnd R^3b；

(c)R^3aAnd R^3b(i) Independently selected from hydrogen, C_1-10Alkyl, cycloalkyl, - (CH)₂)_c(NR³′)₂、C_1-6Hydroxyalkyl, -CH₂SH、-(CH₂)₂S(O)_dMe、-(CH₂)₃NHC(＝NH)NH₂- (1H-indol-3-yl) methyl, (1H-imidazol-4-yl) methyl, - (CH)₂)_eCOR³", aryl, and aryl C_1-3Alkyl, said aryl being optionally selected from hydroxy, C_1-10Alkyl radical, C_1-6Alkoxy, halogen, nitro and cyano; (ii) r^3aAnd R^3bAre all C_1-6An alkyl group; (iii) r^3aAnd R^3bTogether are (CH)₂)_fSo as to form a spiro ring; (iv) r^3aIs hydrogen, and R^3bAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous N and C atoms; (v) r^3bIs hydrogen, and R^3aAnd R²Together are (CH)₂)_nSo as to form a cyclic ring comprising contiguous 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 R is³' independently is hydrogen or C_1-6Alkyl radical, and R³"is-OR' OR-N (R)³′)₂)；(vi)R^3aIs H and R^3bIs H, CH₃、CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl; or (viii) R^3aIs CH₃、-CH₂CH₃、CH(CH₃)₂、CH₂CH(CH₃)₂、CH(CH₃)CH₂CH₃、CH₂Ph、CH₂-indol-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 lower cycloalkyl, R^3bIs H, wherein R³' is independently hydrogen or alkyl, including but not limited to C _1-20Alkyl radical, C_1-10Alkyl or C_1-6Alkyl radical, R³"is-OR' OR-N (R)³′)₂)；

(d)R⁴Is hydrogen, C_1-10Alkyl, C optionally substituted by lower alkyl, alkoxy, di (lower alkyl) -amino or halogen_1-10Alkyl radical, C_1-10Haloalkyl, C_3-10Cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, aminoAcyl, aryl such as phenyl, heteroaryl such as pyridyl, substituted aryl or substituted heteroaryl;

(e)R⁵is H, lower alkyl, CN, vinyl, O- (lower alkyl), hydroxy lower alkyl, i.e. - (CH)₂)_pOH, wherein p is 1-6, including hydroxymethyl (CH)₂OH)、CH₂F、N₃、CH₂CN、CH₂NH₂、CH₂NHCH₃、CH₂N(CH₃)₂Alkyne (optionally substituted) or halogen, including F, Cl, Br or I, with the proviso that when X is OH, the base is cytosine and R⁶Is H, R⁵Is not N₃And when X is OH, R⁶Is CH₃Or CH₂F and B are purine bases, R⁵Is not H;

(f)R⁶is H, CH₃、CH₂F、CHF₂、CF₃F or CN;

(g) x is H, OH, F, OMe, halogen, NH₂Or N₃；

(h) Y is OH, H, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, vinyl, N₃、CN、Cl、Br、F、I、NO₂、OC(O)O(C_1-4Alkyl group), OC (O) O (C)_1-4Alkyl group), OC (O) O (C)_2-4Alkynyl), OC (O) O (C)_2-4Alkenyl), OC_1-10Haloalkyl, O (aminoacyl), O (C)_1-10Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C) _2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-18Acyl radical)₂Wherein alkyl, alkynyl, alkenyl, and vinyl are optionally substituted with: n is a radical of₃CN, 1-3 halogens (Cl, Br, F, I), NO₂、C(O)O(C_1-4Alkyl), C (O) O (C)_1-4Alkyl), C (O) O (C)_2-4Alkynyl), C (O) O (C)_2-4Alkenyl), O (C)_1-4Acyl group), O (C)_1-4Alkyl), O (C)_2-4Alkenyl), S (C)_1-4Acyl group), S (C)_1-4Alkyl), S (C)_2-4Alkynyl), S (C)_2-4Alkenyl), SO (C)_1-4Acyl group), SO (C)_1-4Alkyl), SO (C)_2-4Alkynyl), SO (C)_2-4Alkenyl), SO₂(C_1-4Acyl), SO₂(C_1-4Alkyl), SO₂(C_2-4Alkynyl), SO₂(C_2-4Alkenyl), OS (O)₂(C_1-4Acyl group), OS (O)₂(C_1-4Alkyl), OS (O)₂(C_2-4Alkenyl), NH₂、NH(C_1-4Alkyl), NH (C)_2-4Alkenyl), NH (C)_2-4Alkynyl), NH (C)_1-4Acyl group), N (C)_1-4Alkyl radical)₂、N(C_1-4Acyl radical)₂；

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

wherein

Z is N or CR¹²；

R⁷、R⁸、R⁹、R¹⁰And R¹¹Independently H, F, Cl, Br, I, OH, OR ', SH, SR', NH₂、NHR′、NR′₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl such as C.ident.CH, C halogenated (F, Cl, Br, I) ₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R′，

Wherein R' is optionally substituted alkyl including, but not limited to, optionally substituted C_1-20Alkyl, optionally substituted C_1-10Alkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted C₂-C₆Alkynyl, optionally substituted C₂-C₆Lower alkenyl, or optionally substituted acyl including, but not limited to, C (O) alkyl, C (O) (C)_1-20Alkyl group), C (O) (C)_1-10Alkyl) or C (O) (lower alkyl), or alternatively, at NR'₂In which case each R' includes at least one C atom that is linked to form a heterocyclic ring including at least two carbon atoms; and

R¹²is H, halogen (including F, Cl, Br, I), OH, OR ', SH, SR', NH₂、NHR′、NR′₂、NO₂、C₁-C₆Lower alkyl, halo (F, Cl, Br, I) C₁-C₆Lower alkyl, C₂-C₆Lower alkenyl, halo (F, Cl, Br, I) C₂-C₆Lower alkenyl, C₂-C₆Lower alkynyl, halo (F, Cl, Br, I) C₂-C₆Lower alkynyl, C₁-C₆C of lower alkoxy, halo (F, Cl, Br, I)₁-C₆Lower alkoxy, CO₂H、CO₂R′、CONH₂、CONHR′、CONR′₂、CH＝CHCO₂H or CH ═ CHCO₂R'; with the proviso that when the base consists of R¹¹When structure c represents hydrogen, R¹²Is not: (i) -C ≡ C-H, (ii) -C ═ CH ₂Or (iii) -NO₂；

And

wherein X' is a leaving group, such as Cl.

12. A product, its stereoisomers, salts, hydrates, solvates or crystalline forms thereof, prepared by a process comprising:

reacting a substituted phosphorus chloride compound 4 with a nucleoside analog 5

Wherein the product comprises a compound selected from the group consisting of its stereoisomers, salts, hydrates, solvates or crystalline forms thereof

52 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

62 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (phenyl methoxy-valyl 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-butyric acid methyl ester;

72 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl 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-butyric acid methyl ester);

82 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-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 } -propionic acid methyl ester);

9 N⁴- (N, N-dimethylcarbamimidoyl) -2 ' -deoxy-2 ' -fluoro-2 ' -C-methylcytidine;

102 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-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 } -propionic acid methyl ester);

112 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (4-bromophenyl methoxy-valyl phosphate (2 '-deoxy-2' -fluoro-2 '-C-methyluridine 5' - (4-bromophenyl methoxy-valyl phosphate ((S) -2- { (4-bromo-phenoxy) - [ (2R, the ratio of 3R to 4R, 5R) -5- (2-oxo-3-amino-pyrimidin-1-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phosphorylamino } -3-methyl-butyric acid methyl ester);

122 '-deoxy-2' -fluoro-2 '-C-methylcytidine 5' - (phenyl methoxy-valyl 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-butyric acid 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 } -propionic acid ethyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid benzyl 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 } -acetic acid methyl ester;

16(S) -2- { (2, 4-dichloro-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 } -propionic acid methyl ester;

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 ] - (naphthalen-1-yloxy) -phosphorylamino ] -propionic acid methyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl 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 ] -propionic acid methyl ester;

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 } -propionic acid methyl ester;

23(S) -2- { (3, 4-dichloro-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 } -propionic acid methyl ester;

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 } -propionic acid sec-butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

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 ] -propionic acid ethyl ester;

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 ] -propionic acid phenylmethyl 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 } -propionic acid benzyl ester;

32(S) -2- { (2, 4-dichloro-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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid butyl ester;

35(S) -2- { (3, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid benzyl 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 } -propionic acid pentyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid ethyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid benzyl ester;

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 } -butyric acid methyl ester;

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-benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid 3-methyl-butyl ester;

48(S) -2- { (2, 4-dichloro-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 } -propionic acid ethyl ester;

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 } -propionic acid cyclohexyl ester;

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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 } -propionic acid benzyl 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 } -propionic acid butyl ester;

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 } -propionic acid isopropyl ester;

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 ] -propionic acid cyclohexyl ester;

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 ] -propionic acid cyclohexyl ester;

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 } -butyric acid cyclohexyl ester;

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 ] -butyric acid cyclohexyl ester;

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 } -butyric acid isopropyl ester;

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 } -propionic acid cyclopropylmethyl ester;

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 } -butyric acid cyclopentyl ester;

66(S) -2- { [ (2R, 3R, 4R, 5R) -5- (6-amino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

67(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-hydroxy-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

68(S) -2- { (R) - [ (2R, 3R, 4R, 5R) -5- (2, 6-diamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

69(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclopentylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

70(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-azetidin-1-yl-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

71(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-diethylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

72(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-propylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

73(S) -2- { [ (2R, 3R, 4R, 5R) -5- (2-amino-6-cyclobutylamino-purin-9-yl) -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy ] -phenoxy-phosphorylamino } -propionic acid methyl ester;

74(S) -2- ({ (2R, 3R, 4R, 5R) -5- [ 2-amino-6- (4-methyl-piperazin-1-yl) -purin-9-yl ] -4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy } -phenoxy-phosphorylamino) -propionic acid methyl ester;

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-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

77(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (cyclopentylamino) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propionate;

78(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (aziridin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

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) propanoate; and

80(2S) -methyl 2- (((((2R, 3R, 4R, 5R) -5- (6- (azetidin-1-yl) -9H-purin-9-yl) -4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphorylamino) propanoate;

wherein the base' is as exemplified for each of compounds 5-74; and

wherein X' is a leaving group such as Cl.