RU2009105196A

RU2009105196A - ANTIVIRAL COMPOUNDS (OPTIONS), PHARMACEUTICAL COMPOSITION BASED ON THEM, CALLED COMPOUNDS FOR THE PRODUCTION OF A MEDICINE, A METHOD FOR TREATING OR PREVENTING VIRAL INFECTIONS FROM THEM

Info

Publication number: RU2009105196A
Application number: RU2009105196/04A
Authority: RU
Inventors: Януш БОТЯНСКИ (HU); Януш БОТЯНСКИ; Рональд Конрад ГРИФФИТ (US); Рональд Конрад Гриффит; Сон Мин ПХАМ (US); Сон Мин ПХАМ; Кристофер Дон РОБЕРТС (US); Кристофер Дон Робертс; Фрвнц Ульрих ШМИЦ (DE); Фрвнц Ульрих ШМИЦ
Original assignee: СмитКлайн Бичэм Конэрейшн (US); СмитКлайн Бичэм Конэрейшн
Priority date: 2006-07-14
Filing date: 2007-07-12
Publication date: 2010-08-27
Also published as: WO2008008907A2; WO2008008912A1; CN101490058A; AU2007272441A1; MX2009000513A; TW200813070A; JP2009543807A; AU2007272441A2; EP2044083A1; KR20090033881A; BRPI0714346A2; AR062258A1; CA2657651A1; PE20080427A1; WO2008008907A3

Abstract

1. Противовирусные соединения, охватываемые общей структурной формулой (I) ! ! где Y выбран из группы, состоящей из арила, гетероарила, замещенного арила и замещенного гетероарила; ! НЕТ выбран из группы, состоящей из шестичленного ариленового цикла, шестичленного гетероариленового цикла, содержащего один, два или три гетероатома, выбранных из N, О или S, и бициклического цикла формулы ! или ! при этом НЕТ необязательно замещен группой (Х)t; ! Х выбран из группы, состоящей из алкила, замещенного алкила, алкокси, замещенного алкокси, амино, замещенного амино, галогена, гидрокси и нитро; ! t представляет собой целое число 0, 1 или 2; ! W1, W4 и W5 независимо друг от друга представляют собой N или СН; ! W3 представляет собой N, СН или при необязательном наличии в бициклическом цикле по меньшей мере одного атома азота, окисленного до N-оксида, W3 представляет собой связь; и ! каждая пунктирная линия представляет собой простую или двойную связь между двумя соседними атомами, при условии, что если одна из пунктирных линий представляет собой простую связь, то каждый из соседних атомов замещен одним или двумя атомами водорода в соответствии с их валентностью; ! один из D или Е представляет собой C-Ra, а другой из D или Е представляет собой S; ! Ra и R независимо друг от друга выбраны из группы, состоящей из водорода, алкила и замещенного алкила; ! Q выбран из группы, состоящей из циклоалкила, замещенного циклоалкила, циклоалкенила, замещенного циклоалкенила, гетероцикла, замещенного гетероцикла, арила, замещенного арила, гетероарила и замещенного гетероарила; ! Z выбран из группы, состоящей из карбокси, эстерифицированного карбокси, -C(X4)NR8R9, -C(X3)NR21S 1. Antiviral compounds covered by the general structural formula (I)! ! where Y is selected from the group consisting of aryl, heteroaryl, substituted aryl and substituted heteroaryl; ! NO is selected from the group consisting of a six-membered arylene ring, a six-membered heteroarylene ring containing one, two or three heteroatoms selected from N, O or S, and a bicyclic ring of the formula! or ! wherein NO is optionally substituted with group (X) t; ! X is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, halogen, hydroxy and nitro; ! t is an integer of 0, 1 or 2; ! W1, W4 and W5 independently of one another are N or CH; ! W3 represents N, CH or, if the bicyclic ring optionally contains at least one nitrogen atom oxidized to N-oxide, W3 represents a bond; and! each dashed line represents a simple or double bond between two adjacent atoms, provided that if one of the dashed lines is a simple bond, then each of the neighboring atoms is replaced by one or two hydrogen atoms in accordance with their valency; ! one of D or E is C-Ra, and the other of D or E is S; ! Ra and R are independently selected from the group consisting of hydrogen, alkyl and substituted alkyl; ! Q is selected from the group consisting of cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heterocycle, substituted heterocycle, aryl, substituted aryl, heteroaryl and substituted heteroaryl; ! Z is selected from the group consisting of carboxy, esterified carboxy, -C (X4) NR8R9, -C (X3) NR21S

Claims

1. Antiviral compounds covered by the General structural formula (I)

where Y is selected from the group consisting of aryl, heteroaryl, substituted aryl and substituted heteroaryl;

NO is selected from the group consisting of a six-membered arylene ring, a six-membered heteroarylene ring containing one, two or three heteroatoms selected from N, O or S, and a bicyclic ring of the formula

or

wherein NO is optionally substituted with group (X) _t ;

X is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, halogen, hydroxy and nitro;

t is an integer of 0, 1 or 2;

W ¹ , W ⁴ and W ⁵ independently from each other represent N or CH;

W ³ represents N, CH or, if the bicyclic ring optionally contains at least one nitrogen atom oxidized to N-oxide, W ³ represents a bond; and

each dashed line represents a simple or double bond between two adjacent atoms, provided that if one of the dashed lines is a simple bond, then each of the neighboring atoms is replaced by one or two hydrogen atoms in accordance with their valency;

one of D or E is CR ^a and the other of D or E is S;

R ^a and R are independently selected from the group consisting of hydrogen, alkyl and substituted alkyl;

Q is selected from the group consisting of cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heterocycle, substituted heterocycle, aryl, substituted aryl, heteroaryl and substituted heteroaryl;

Z is selected from the group consisting of carboxy, esterified carboxy, -C (X ⁴ ) NR ⁸ R ⁹ , -C (X ³ ) NR ²¹ S (O) ₂ R ⁴ , -C (X ² ) N (R ³ ) CR ² R ^{2 '} C (= O) R ¹ , -C (X ² ) -N (R ³ ) CR ²⁵ R ²⁶ R ²⁷ and carboxylic acid isostere, which does not match any of the above;

X ² represents = O, = S or = NR ¹¹ ;

X ³ represents = O, = NR ²⁴ or = S;

X ⁴ represents = O, = NH or = N-alkyl;

R ¹ represents —OR ⁷ or —NR ⁸ R ⁹ ;

R ² and R ^{2 ′ are} independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocycle and substituted heterocycle, or

R ² and R ^{2 '} together with the carbon atom to which they are attached form a cycloalkyl, substituted cycloalkyl, heterocycle or substituted heterocycle, or

one of R ² or R ^{2 ′} is hydrogen, alkyl or substituted alkyl, and the other, together with the carbon atom to which it is attached, and either together with R ⁷ and the oxygen atom to which it is attached, or together with R ⁸ and the nitrogen atom to which it is attached forms a heterocyclic or substituted heterocyclic group;

R ^{3 is} selected from the group consisting of hydrogen and alkyl, or if R ² and R ^{2 '} do not form a ring together, and if R ² or R ^2' and R ⁷ or R ^{8 are} not connected to form a heterocyclic or substituted heterocyclic group, then R ³ , together with the nitrogen atom to which it is attached, forms together with one of R ² and R ^{2 ′ a} heterocyclic or substituted heterocyclic group;

R ^{4 is} selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, and NR ²² R ²³ ;

R ^{7 is} selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle and substituted heterocycle;

R ⁸ and R ^{9 are} independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle and substituted heterocycle, or

R ⁸ and R ⁹ together with the nitrogen atom to which they are attached form a heterocyclic, substituted heterocyclic, heteroaryl or substituted heteroaryl ring group;

R ¹¹ represents hydrogen or alkyl;

R ²¹ , R ²² and R ²³ independently of one another are hydrogen, alkyl, substituted alkyl, cycloalkyl or substituted cycloalkyl, or

R ²¹ and R ²² or R ²² and R ²³ together with the atoms to which they are attached form an optionally substituted heterocyclic group;

R ²⁴ represents hydrogen, alkyl or substituted alkyl;

R ²⁵ , R ²⁶ and R ^{27 are} independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl, or

R ²⁵ and R ²⁶ together with the carbon atom to which they are attached form a cycloalkyl, substituted cycloalkyl, heterocyclic or substituted heterocyclic group; and

their pharmaceutically acceptable salts and tautomers.

2. The compounds according to claim 1, in which Y is selected from the group consisting of substituted biphenyl, substituted phenyl, substituted six-membered heteroaryl ring, optionally fused to the phenyl ring and containing one, two or three heteroatoms independently selected from the group consisting of N , O or S, wherein N or S heteroatoms are optionally oxidized, and the substituted five-membered heteroaryl ring is optionally fused to the phenyl ring and contains one, two or three heteroatoms independently selected from N, O or S, wherein N heteroatoms or S is optionally oxidized.

3. The compounds according to claim 2, in which Y is selected from the group consisting of 4'-chloro-4-methoxybiphen-2-yl, bifen-2-yl, bifen-4-yl, 4-amino-4'-chlorobiphen -2-yl, 4'-aminomethyl-4-methoxybiphen-2-yl, 4-carbamoyl-4'-methoxybifen-2-yl, 4-carbamoyl-4'-fluorobiphen-2-yl, 4-carbamoyl-4 ' -methoxybiphen-2-yl, 4-carbamoyl-4'-nitrobiphen-2-yl, 4- (carbamoylmethylcarbamoyl) bifen-2-yl, 4- (carbamoylmethylcarbamoyl) -4'-chlorobiphen-2-yl, 4-carboxy- 4'-chlorobiphen-2-yl, 3-carboxy-4'-methoxybiphen-2-yl, 4-carboxy-4'-methoxybiphen-2-yl, 4'-carboxy-4- (pyrrolidin-1-ylcarbonyl) bifen -2-yl, 4-carboxymethoxybifen-2-yl, 4-car boxymethoxy-4'-chlorobiphen-2-yl, 4'-chlorobiphen-2-yl, 4'-chloro-4-chlorobiphen-2-yl, 4'-chloro-4- (dimethylaminoethylcarbamoyl) bifen-2-yl, 4 '-chloro-4- (2-ethoxyethoxy) bifen-2-yl, 3'-chloro-4'-fluoro-4-methoxybifen-2-yl, 4'-chloro-4-fluorobiphen-2-yl, 4' -chloro-4-hydroxybiphen-2-yl, 3'-chloro-4-methoxybiphen-2-yl, 4'-chloro-4-methylcarbamoylbifen-2-yl, 4'-chloro-4- (2-methoxyethoxy) biphene -2-yl, 4'-chloro-4-nitrobiphen-2-yl, 4'-chloro-4- (2-oxo-2-pyrrolidin-1-yl-ethoxy) bifen-2-yl, 4'-chloro-4 - (pyrrolidin-1-ylcarbonyl) bifen-2-yl, 4'-chloro-4- (3-pyrrolidin-1-ylpropoxy) bifen-2-yl, 4'-cyano-4-methoxybiphen-2-yl, 3 ', 4'-dichloro-4-methoxy phen-2-yl, 4,4'-dimethoxybifen-2-yl, 3 ', 4'-dimethoxy-4- (pyrrolidin-1-ylcarbonyl) bifen-2-yl, 4'-dimethylamino-4-methoxybiphen-2 -yl, 4- (2-dimethylaminoethylcarbamoyl) bifen-2-yl, 4'-ethoxy-4-methoxybiphen-2-yl, 4'-fluoro-4-methoxybiphen-2-yl, 4-hydroxybiphen-2-yl, 4-methoxybiphen-2-yl, 4-methoxy-4'-hydroxybiphen-2-yl, 4- (2-methoxyethoxy) biphen-2-yl, 4-methoxy-4'-methylbiphen-2-yl, 4-methoxy -3'-nitrobiphen-2-yl, 4-methoxy-4'-nitrobiphen-2-yl, 4-methylcarbamoylbifen-2-yl, 3'-methyl-4-methoxybiphen-2-yl, 4'-nitro-4 - (pyrrolidin-1-ylcarbonyl) biphen-2-yl, 4- (2-oxo-2-pyrrolidin-1-yl-ethoxy) biphen-2-yl, 4- (3- pyrrolidin-1-ylpropoxy) bifen-2-yl and 4'-trifluoromethyl-4-methoxybifen-2-yl.

4. The compounds of claim 2, wherein said substituted phenyl is substituted with one, two, or three substituents independently selected from the group consisting of halogen, heteroaryl, hydroxy, nitro, cyano, alkyl, substituted alkyl, alkenyl, alkoxy, substituted alkoxy, acyl, acylamino, aminoacyl, amino, substituted amino, carboxy and esterified carboxy.

5. The compounds according to claim 2, in which Y is selected from the group consisting of substituted quinolyl, substituted benzofuryl, substituted thiazolyl, substituted furyl, substituted thienyl, substituted pyridinyl, substituted pyrazinyl, substituted oxazolyl, substituted isoxazolyl, substituted pyrrolyl, substituted imidazolyl, substituted pyrrolidinyl, substituted pyrazolyl, substituted isothiazolyl, substituted 1,2,3-oxadiazolyl, substituted 1,2,3-triazolyl, substituted 1,3,4-thiadiazolyl, substituted pyrimidinyl, substituted 1,3,5-triazinyl, substituted indolisinyl, substituted indolyl, substituted isoindolyl, substituted indazolyl, substituted benzothienyl, substituted benzothiazolyl, substituted purinyl, substituted quinolysinyl, substituted quinolinyl, substituted isoquinolinyl, substituted substituted phthalazinyl-yl-ynyl-ynyl-yenyl-substituted, substituted pteridinyl.

6. The compounds according to claim 5, in which Y is substituted by one, two or three substituents independently selected from the group consisting of alkyl, haloalkyl, halogen, hydroxy, nitro, cyano, alkoxy, substituted alkoxy, acyl, acylamino, aminoacyl, amino, substituted amino, carboxy and esterified carboxy.

7. The compounds of claim 6, wherein Y is 2,4-dimethylthiazol-5-yl.

8. The compounds of claim 1, wherein Q is cycloalkyl or cycloalkenyl.

9. The compound of claim 8, in which Q represents cyclohexyl or cyclohexenyl.

10. The compounds of claim 1, wherein Z is carboxy, esterified carboxy, carboxylic acid isoster, -C (O) NR ⁸ R ⁹ or -C (O) NHS (O) ₂ R ⁴ , R ⁸ and R ⁹ have the meanings indicated in claim 1, a R ⁴ represents alkyl or aryl.

11. The compounds of claim 10, wherein Z is carboxy, methoxycarbonyl, ethoxy carbonyl, 6- (β-D-glucopyranosiduronide) ether, 1H-tetrazol-5-yl, 5-oxo-4,5-dihydro-1 2,4-oxadiazol-3-yl, N-2-cyanoethylamide, N-2- (1H-tetrazol-5-yl) ethylamide, methylsulfonylaminocarbonyl, trifluoromethylsulfonylaminocarbonyl or phenylsulfonylaminocarbonyl.

12. The compounds of claim 11, wherein Z is carboxy.

13. The compounds according to claim 1, in which D represents CH, and E represents S.

14. Compounds according to claim 1, in which R is a substituted alkyl selected from the group consisting of aminoalkyl, substituted aminoalkyl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, -CH ₂ COOH and -CH ₂ CONR ¹² R ¹³ ;

R ¹² and R ^{13 are} independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, - (CH ₂ ) _0-3 R ¹⁶ , and —NR ¹⁷ R ¹⁸ , or

R ¹² and R ^{13 are} both not hydrogen atoms and, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocycle;

R ¹⁶ represents aryl, heteroaryl or heterocycle; and

R ¹⁷ and R ¹⁸ independently mean hydrogen or alkyl, or R ¹⁷ and R ¹⁸ together with the nitrogen atom to which they are attached form a heterocycle containing from four to seven atoms in the ring.

15. The compounds of claim 1, wherein R is —CH ₂ CONR ¹² R ¹³ and at least one of R ¹² or R ¹³ is alkyl, substituted alkyl, or heteroaryl.

16. The compound of claim 15, wherein at least one of R ¹² or R ¹³ is methyl, carboxymethyl, 2-hydroxyethyl, 2-morpholin-4-yl-ethyl or tetrazol-5-yl.

17. The compounds of claim 14, wherein R is —CH ₂ CONR ¹² R ¹³ , and R ¹² and R ^13, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocycle.

18. The compounds of claim 17, wherein R ¹² and R ^13, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted morpholino, substituted or unsubstituted piperidinyl, or substituted or unsubstituted pyrrolidinyl.

19. The compounds of claim 18, wherein the substituted or unsubstituted morpholino, piperidinyl or pyrrolidinyl is selected from the group consisting of morpholino, 4-pyrrolidin-1-ylpiperidinyl, piperidinyl, 4-hydroxypiperidinyl, 4-carboxypiperidinyl, 4-dimethylaminopiperidinyl diethylaminopiperidinyl, 2-methylpyrrolidinyl, 4-morpholin-4-ylpiperidinyl, 3,5-dimethylmorpholin-4-yl, 4-methylpiperidinyl.

20. The compound of claim 14, wherein R is selected from the group consisting of N, N-dimethylaminocarbonylmethyl, [N- (4-hydroxy-1,1-dioxidotetrahydro-3-thienyl) amino] carbonylmethyl, (cyclopropylmethylamino) carbonylmethyl, (prop-2-yn-1-ylamino) carbonylmethyl, (2- (morpholino) et-1-ylamino) carbonylmethyl, (phenylsulfonylamino) carbonylmethyl, [N-benzylamino] carbonylmethyl, (N- (4-methylsulfonylbenzyl) amino) carbonylmethyl , (tryptophanyl) carbonylmethyl, (tyrosine) carbonylmethyl, (N- (1-carboxyprop-1-ylamino) carbonylmethyl, (N- (2-carboxyethyl-1-yl) amino) carbonylmethyl, (N- (4-carboxyben il) amino) carbonylmethyl, N- [3- (N '- (4- (acrylic acid) phenyl) carboxamido) pyrrolidin-3-yl] aminocarbonylmethyl, N- [4- (N' - (4- (acrylic acid) phenyl) carboxamido) piperidin-4-yl] aminocarbonylmethyl, [2- (N, N-dimethylamino) eth-1-ylamino] carbonylmethyl [(1- (5-methyl-4H-1,2,4-triazol-3- il) ethyl) amino] carbonylmethyl, (1-methyl-1- [N- (1-methyl-2-carboxy-1H-indol-5-yl) aminocarbonyl] et-1-ylaminocarbonylmethyl, [N- (1-methylpyrrolidine -3-yl-ethyl) amino] carbonylmethyl, (1-methyl-1- [N- (4- (acrylic acid) phenyl) aminocarbonyl] et-1-ylaminocarbonylmethyl, (1-methyl-1- [N- (4- ( 2-carboxyfuran-5-yl) phenyl) amine carbonyl] eth-1-ylaminocarbonylmethyl, (1-methyl-1- [N- (4- (4-carboxythiazol-2-yl) phenyl) aminocarbonyl] et-1-ylaminocarbonylmethyl, (2- (4-methylpiperazin-1- il) eth-1-ylamino) carbonylmethyl, [(1-methylpyrrolidin-3-yl) methylamino] carbonylmethyl, [N- (1-methylpiperidin-3-ylmethyl) amino] carbonylmethyl, (1-piperidin-1-ylcyclopentyl) methylamino ] carbonylmethyl, (1- (acetyl) pyrrolidin-2-ylmethyl) amino) carbonylmethyl, [(2- (N, N-dimethylamino) carbonyl) methylamino] carbonylmethyl, [N- (1,1-dioxidotetrahydro-3-thienyl) methylamino] carbonylmethyl, (N-methyl-N-cyclohexylamino) carbonylmethyl, (N-meth l-N-carboxymethylamino) carbonylmethyl, [N-methyl-N-benzylamino] carbonylmethyl, (N-methyl-N- (N ', N'-dimethylaminoacetyl) amino) carbonylmethyl, [N-methyl-N-phenylamino] carbonylmethyl, (N-methyl-N-isopropylamino) carbonylmethyl, (N-methyl-N- (N'-methylpiperidin-4-yl) amino) carbonylmethyl, [N-methyl-N- (1-methylpiperidin-4-yl) amino] carbonylmethyl, [N-methyl-N- (1-methylpiperidin-4-ylmethyl) amino] carbonylmethyl, [N-methyl-N- (1-methylpiperidin-3-ylmethyl) amino] carbonylmethyl, [N-methyl-N- ( 1-methylpyrazin-2-ylmethyl) amino] carbonylmethyl, [N-methyl-N- (5-methyl-1H-imidazol-2-ylmethyl) amino] carbonylmethyl, (N-methyl-N- [2- (hydroxy) eth-1-yl] amino) carbonylmethyl, (N-methyl-N- [2- (N ', N'-dimethylamino) et-1-yl] amino) carbonylmethyl, (N-methyl-N- [2- (N ', N'-diethylamino) et-1-yl] amino) carbonylmethyl, (N-methyl-N- [2- (pyridin-2-yl) et 1-yl] amino) carbonylmethyl, (N-methyl-N- [2- (pyridin-4-yl) et-1-yl] amino) carbonylmethyl, [N-methyl-N- (1- (1,3- thiazol-2-yl) ethyl) amino] carbonylmethyl (N-methyl-N- [3- (N ', N'-dimethylamino) prop-1-yl] amino) carbonylmethyl, (N-methyl-N- (1- carboxy-2-methylprop-1-yl) amino) carbonylmethyl, (N-ethyl-N-propylamino) carbonylmethyl, (N-ethyl-N- [2- (methoxy) eth-1-yl] amino) carbonylmethyl, (N ethyl N- [2- (N ', N'-diethylamino) et-1-i l] amino) carbonylmethyl, [7-methyl-2,7-diazaspiro [4.4] non-2-yl] carbonylmethyl, (5-methyl-2,5-diazabicyclo [2.2.1] heptyl-2-yl) carbonylmethyl, (4-methyl-1,4-diazepan-1-yl) carbonylmethyl, (piperidinyl) carbonylmethyl, (4-carboxypiperidinyl) carbonylmethyl, (3-carboxypiperidinyl) carbonylmethyl, (4-hydroxypiperidinyl) carbonylmethyl (4- (2-hydroxyethyl- 1-yl) piperidin-1-yl) carbonylmethyl, [4- (N, N-dimethylamino) piperidin-1-yl] carbonylmethyl, (3- (N, N-dimethylamino) methylpiperidin-1-yl) carbonylmethyl, (2 - (2- (N, N-dimethylamino) eth-1-yl) piperidin-1-yl) carbonylmethyl, [4- (4-methyl-4H-1,2,4-triazol-3-yl) Iperidin-1-yl] carbonylmethyl, (4-pyrrolidinylpiperidinyl) carbonylmethyl, (3-pyrrolidinylpiperidinyl) carbonylmethyl, [4- (N, N-diethylamino) piperidin-1-yl] carbonylmethyl, (4- (azetidin-1-yl) piperidin-1-yl) carbonylmethyl, (4- (piperidin-1-yl) piperidin-1-yl) carbonylmethyl, (hexahydropyrrolo [1,2-a] pyrazin-2 (1H) -yl) carbonylmethyl, [(2- (N, N-dimethylamino) methyl) morpholino] carbonylmethyl, (3,5-dimethylmorpholino) carbonylmethyl, (thiomorpholino) carbonylmethyl, morpholinocarbonylmethyl, (pyrrolidinyl) carbonylmethyl, (2-carboxypyrrolidin-1-yl) carbonylmethyl, and (2- ( ) -4-guide hydroxypyrrolidin-1-yl) carbonylmethyl, (2-carboxamide pyrrolidin-1-yl) carbonylmethyl, (2- (N, N-dimethylaminocarbonyl) pyrrolidin-1-yl) carbonylmethyl, (3- (N ', N'-dimethylamino) pyrrolidine -1-yl) carbonylmethyl, (3- (N ', N'-diethylamino) pyrrolidin-1-yl) carbonylmethyl, (3- (pyridin-3-yl) pyrrolidin-1-yl) carbonylmethyl, (2-pyridin- 4-ylpyrrolidin-1-yl) carbonylmethyl, piperazin-1-ylcarbonylmethyl, (4-methylpiperazinyl) carbonylmethyl, (4- (carboxymethyl) piperazin-1-yl) carbonylmethyl, (4- (2-hydroxyeth-1-yl) piperazine -1-yl) carbonylmethyl, (4- (isopropyl) piperazin-1-yl) carbonyl methyl, (4- (2-metho diethyl-1-yl) piperazin-1-yl) carbonylmethyl, (4- (ethyl) piperazin-1-yl) carbonylmethyl, (4- (N ', N'-dimethylaminoacetyl) piperazin-1-yl) carbonylmethyl and (4 - (6-methoxypyridin-2-yl) piperazin-1-yl) carbonylmethyl.

21. The compounds according to claim 1, in which t has a value of 0.

22. The compounds of claim 1, wherein t is 1 and X is amino, nitro, methyl or halogen.

23. Compounds according to any one of claims 1 to 22, in which NO is 1,4-phenylene, optionally substituted with group (X) _t , where X and t are as defined in claim 1.

24. The compounds of claim 23, wherein t is 0.

25. Compounds according to any one of claims 1 to 22, in which NO represents a group

optionally substituted with group (X) _t , where X, t, W ¹ , W ³ , W ⁴ and W ⁵ are as defined in claim 1.

26. The compounds of claim 25, wherein W ¹ is nitrogen.

27. The compounds of claim 26, wherein NO is selected from the group consisting of

and

where X and t are defined in claim 1.

28. Antiviral compounds covered by the General structural formula (Ia)

where Y is selected from the group consisting of substituted aryl and substituted heteroaryl;

X is independently selected from the group consisting of amino, nitro, alkyl, haloalkyl and halogen;

t is an integer of 0, 1 or 2;

Q is selected from the group consisting of cyclohexyl and cyclopentyl;

R ¹² and R ^{13 are} independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, - (CH ₂ ) _0-3 R ¹⁶ and —NR ¹⁷ R ¹⁸ , or R ¹² and R ¹³ , if both of them are not hydrogen atoms, then together with the nitrogen atom to which they are attached, they form an optionally substituted heterocycle;

R ¹⁶ represents aryl, heteroaryl or heterocycle;

R ¹⁷ and R ¹⁸ independently from each other mean hydrogen or alkyl, or R ¹⁷ and R ¹⁸ together with the nitrogen atom to which they are attached form a heterocycle containing from four to seven atoms in the cycle;

one A or B is CR ^a and the other A or B is S;

R ^{a is} selected from the group consisting of hydrogen, alkyl and substituted alkyl;

Z is selected from the group consisting of carboxy, esterified carboxy and carboxylic acid isoster; and

their pharmaceutically acceptable salts or tautomers.

29. The compounds of claim 28, wherein Y is selected from the group consisting of substituted biphenyl, substituted phenyl, substituted six-membered heteroaryl ring, optionally fused to the phenyl ring, and containing one, two, or three heteroatoms independently selected from N, O, or S moreover, N or S heteroatoms are optionally oxidized, and the substituted five-membered heteroaryl ring is optionally fused to the phenyl ring and contains one, two or three heteroatoms independently selected from N, O or S, wherein N or S heteroatoms are optionally oxidized.

30. The compound according to clause 29, in which Y is selected from the group consisting of 4'-chloro-4-methoxybiphen-2-yl, bifen-2-yl, bifen-4-yl, 4-amino-4'-chlorobiphen -2-yl, 4'-aminomethyl-4-methoxybiphen-2-yl, 4-carbamoyl-4'-methoxybifen-2-yl, 4-carbamoyl-4'-fluorobiphen-2-yl, 4-carbamoyl-4 ' -methoxybiphen-2-yl, 4-carbamoyl-4'-nitrobiphen-2-yl, 4- (carbamoylmethylcarbamoyl) bifen-2-yl, 4- (carbamoylmethylcarbamoyl) -4'-chlorobiphen-2-yl, 4-carboxy- 4'-chlorobiphen-2-yl, 3-carboxy-4'-methoxybiphen-2-yl, 4-carboxy-4'-methoxybiphen-2-yl, 4'-carboxy-4- (pyrrolidin-1-ylcarbonyl) bifen -2-yl, 4-carboxymethoxybifen-2-yl, 4-ka Rboxymethoxy-4'-chlorobiphen-2-yl, 4'-chlorobiphen-2-yl, 4'-chloro-4-chlorobiphen-2-yl, 4'-chloro-4- (dimethylaminoethylcarbamoyl) bifen-2-yl, 4 '-chloro-4- (2-ethoxyethoxy) bifen-2-yl, 3'-chloro-4'-fluoro-4-methoxybifen-2-yl, 4'-chloro-4-fluorobiphen-2-yl, 4' -chloro-4-hydroxybiphen-2-yl, 3'-chloro-4-methoxybiphen-2-yl, 4'-chloro-4-methylcarbamoylbifen-2-yl, 4'-chloro-4- (2-methoxyethoxy) biphene -2-yl, 4'-chloro-4-nitrobiphen-2-yl, 4'-chloro-4- (2-oxo-2-pyrrolidin-1-yl-ethoxy) bifen-2-yl, 4'-chloro-4 - (pyrrolidin-1-ylcarbonyl) bifen-2-yl, 4'-chloro-4- (3-pyrrolidin-1-ylpropoxy) bifen-2-yl, 4'-cyano-4-methoxybiphen-2-yl, 3 ', 4'-dichloro-4-methoxyb ifen-2-yl, 4,4'-dimethoxybifen-2-yl, 3 ', 4'-dimethoxy-4- (pyrrolidin-1-ylcarbonyl) bifen-2-yl, 4'-dimethylamino-4-methoxybiphen-2 -yl, 4- (2-dimethylaminoethylcarbamoyl) bifen-2-yl, 4'-ethoxy-4-methoxybiphen-2-yl, 4'-fluoro-4-methoxybiphen-2-yl, 4-hydroxybiphen-2-yl, 4-methoxybiphen-2-yl, 4-methoxy-4'-hydroxybifen-2-yl, 4- (2-methoxyethoxy) biphen-2-yl, 4-methoxy-4'-methylbiphen-2-yl, 4-methoxy -3'-nitrobiphen-2-yl, 4-methoxy-4'-nitrobiphen-2-yl, 4-methylcarbamoylbifen-2-yl, 3'-methyl-4-methoxybiphen-2-yl, 4'-nitro-4 - (pyrrolidin-1-ylcarbonyl) biphen-2-yl, 4- (2-oxo-2-pyrrolidin-1-yl-ethoxy) biphen-2-yl, 4- (3-pyrrolidin-1-ylpropoxy) bifen-2-yl and 4'-trifluoromethyl-4-methoxybiphen-2-yl.

31. The compounds of clause 29, wherein said substituted phenyl is substituted with one, two, or three substituents independently selected from the group consisting of halogen, heteroaryl, hydroxy, nitro, cyano, alkyl, substituted alkyl, alkenyl, alkoxy, substituted alkoxy, acyl, acylamino, aminoacyl, amino, substituted amino, carboxy and esterified carboxy.

32. The compounds of clause 29, wherein Y is selected from the group consisting of substituted quinolyl, substituted benzofuryl, substituted thiazolyl, substituted furyl, substituted thienyl, substituted pyridinyl, substituted pyrazinyl, substituted oxazolyl, substituted isoxazolyl, substituted pyrrolyl, substituted imidazolyl, substituted pyrrolidinyl, substituted pyrazolyl, substituted isothiazolyl, substituted 1,2,3-oxadiazolyl, substituted 1,2,3-triazolyl, substituted 1,3,4-thiadiazolyl, substituted pyrimidinyl, substituted 1,3,5-triazinyl , substituted indolisinyl, substituted indolyl, substituted isoindolyl, substituted indazolyl, substituted benzothienyl, substituted benzothiazolyl, substituted purinyl, substituted quinolisinyl, substituted quinolinyl, substituted isoquinolinyl, substituted substituted phthalazininyl-ynyl-ynyl, ynyl, substituted substituted pteridinyl.

33. The compounds of claim 32, wherein Y is substituted with one, two, or three substituents independently selected from the group consisting of alkyl, haloalkyl, halogen, hydroxy, nitro, cyano, alkoxy, substituted alkoxy, acyl, acylamino, aminoacyl, amino, substituted amino, carboxy and esterified carboxy.

34. The compounds of claim 33, wherein Y is 2,4-dimethylthiazol-5-yl.

35. The compounds of claim 28, wherein Q is cyclohexyl or cyclohexenyl.

36. The compounds of claim 35, wherein Z is methoxycarbonyl, ethoxycarbonyl, 6- (β-D-glucopyranosiduronide) ether, 1H-tetrazol-5-yl, 5-oxo-4,5-dihydro-1,2, 4-oxadiazol-3-yl, N-2-cyanoethylamide, N-2- (1H-tetrazol-5-yl) ethylamide, methylsulfonylaminocarbonyl, trifluoromethylsulfonylaminocarbonyl or phenylsulfonylaminocarbonyl.

37. The compounds of claim 36, wherein Z is carboxy.

38. The compounds of claim 28, wherein at least one of R ¹² or R ¹³ is alkyl, substituted alkyl, or heteroaryl.

39. The compounds of claim 38, wherein at least one of R ¹² or R ¹³ is methyl, carboxymethyl, 2-hydroxymethyl, 2-morpholin-4-yl-ethyl or tetrazol-5-yl.

40. The compounds of claim 28, wherein R ¹² and R ^13, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocycle.

41. The compounds of claim 40, wherein R ¹² and R ^13, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted morpholino, substituted or unsubstituted piperidinyl, or substituted or unsubstituted pyrrolidinyl.

42. The compounds of claim 41, wherein the substituted or unsubstituted morpholino, piperidinyl or pyrrolidinyl is selected from the group consisting of morpholino, 4-pyrrolidin-1-ylpiperidinyl, piperidinyl, 4-hydroxypiperidinyl, 4-carboxypiperidinyl, 4-dimethylaminoperidinyl diethylaminopiperidinyl, 2-methylpyrrolidinyl, 4-morpholin-4-ylpiperidinyl, 3,5-dimethylmorpholin-4-yl and 4-methylpiperidinyl.

43. The compounds of claim 28, wherein R ¹² and R ^13, together with the nitrogen atom to which they are attached, form a group selected from the group consisting of N, N-dimethylamino, N- (4-hydroxy-1,1 -dioxotetrahydro-3-thienyl) amino, cyclopropylmethylmino, prop-2-yn-1-ylamino, 2- (morpholino) et-1-ylamino, phenylsulfonylamino, N-benzylamino, N- (4-methylsulfonylbenzyl) amino, tryptophanyl, tyrosine , N- (1-carboxyprop-1-ylamino, N- (2-carboxyeth-1-yl) amino, N- (4-carboxybenzyl) amino, N- [3- (N '(4- (acrylic acid) phenyl ) carboxamido) pyrrolidin-3-yl] amino, N- [4- (N '- (4- (acrylic acid) phenyl) carboxy o) piperidin-4-yl] amino, 2- (N, N-dimethylamino) et-1-ylamino, (1- (5-methyl-4H-1,2,4-triazol-3-yl) ethyl) amino , 1-methyl-1- [N- (1-methyl-2-carboxy-1H-indol-5-yl) aminocarbonyl] et-1-ylamino, N- (1-methylpyrrolidin-3-yl-ethyl) amino, 1- methyl-1- [N- (4- (acrylic acid) phenyl) aminocarbonyl] et-1-ylamino, 1-methyl-1- [N- (4- (2-carboxyfuran-5-yl) phenyl) aminocarbonyl] et -1-ylamino, 1-methyl-1- [N- (4- (4-carboxythiazol-2-yl) phenyl) aminocarbonyl] et-1-ylamino, 2- (4-methylpiperazin-1-yl) et-1 -amylamino, (1-methylpyrrolidin-3-yl) methylamino, N- (1-methylpiperidin-3-ylmethyl) amino, (1-piperidin-1-ylcyclopentyl) methylamino, 1- (acetyl) pyrro idin-2-ylmethyl) amino, (2- (N, N-dimethylamino) carbonyl) methylamino, N- (1,1-dioxidotetrahydro-3-thienyl) methylamino, N-methyl-N-cyclohexylamino, N-methyl-N -carboxymethylamino, N-methyl-N-benzylamino, N-methyl-N- (N ', N'-dimethylaminoacetyl) amino, N-methyl-N-phenylamino, N-methyl-N-isopropylamino, N-methyl-N- (N'-methylpiperidin-4-yl) amino, N-methyl-N- (1-methylpiperidin-4-yl) amino, N-methyl-N- (1-methylpiperidin-4-ylmethyl) amino, N-methyl- N- (1-methylpiperidin-3-ylmethyl) amino, N-methyl-N- (1-methylpyrazin-2-ylmethyl) amino, N-methyl-N- (5-methyl-1H-imidazol-2-ylmethyl) amino , N-methyl-N- [2- (hydroxy) eth-1-yl] amino, N-methyl-N- [2- (N ', N' -dimethylamino) et-1-yl] amino, N-methyl-N- [2- (N ', N'-diethylamino) et-1-yl] amino, N-methyl-N- [2- (pyridin-2 -yl) eth-1-yl] amino, N-methyl-N- [2- (pyridin-4-yl) eth-1-yl] amino, N-methyl-N- (1- (1,3-thiazole -2-yl) ethyl) amino, N-methyl-N- [3- (N ', N'-dimethylamino) prop-1-yl] amino, N-methyl-N- (1-carboxy-2-methylprop- 1-yl) amino, N-ethyl-N-propylamino, N-ethyl-N- [2- (methoxy) eth-1-yl] amino, N-ethyl-N- [2- (N ', N'- diethylamino) et-1-yl] amino, 7-methyl-2,7-diazaspiro [4.4] non-2-yl, 5-methyl-2,5-diazabicyclo [2.2.1] hept-2-yl, 4- methyl-1,4-diazepan-1-yl, piperidinyl, 4-carboxypiperidinyl, 3-carboxypiperidinyl, 4-hydroxypiperidinyl, 4- (2-hydroxyeth-1-yl) piperidine -1-yl, 4- (N, N-dimethylamino) piperidin-1-yl, 3- (N, N-dimethylamino) methylpiperidin-1-yl, 2- (2- (N, N-dimethylamino) et-1 -yl) piperidin-1-yl, 4- (4-methyl-4H-1,2,4-triazol-3-yl) piperidin-1-yl, 4-pyrrolidinyl-piperidinyl, 3-pyrrolidinyl-piperidinyl, 4- (N, N -diethylamino) piperidin-1-yl, 4- (azetidin-1-yl) piperidin-1-yl, 4- (piperidin-1-yl) piperidin-1-yl, hexahydropyrrolo [1,2-a] pyrazin-2 (1H) -yl, (2- (N, N-dimethylamino) methyl) morpholino, 3,5-dimethylmorpholino, thiomorpholino, morpholino, pyrrolidinyl, 2-carboxypyrrolidin-1-yl, 2- (carboxy) -4-hydroxypyrrolidin- 1-yl, 2-carboxamide-pyrrolidin-1-yl, 2- (N, N-dim ethylaminocarbonyl) pyrrolidin-1-yl, 3- (N ', N'-dimethylamino) pyrrolidin-1-yl, 3- (N', N'-diethylamino) pyrrolidin-1-yl, 3- (pyridin-3-yl ) pyrrolidin-1-yl, 2-pyridin-4-ylpyrrolidin-1-yl, piperazin-1-yl, 4-methylpiperazinyl, 4- (carboxymethyl) piperazin-1-yl, 4- (2-hydroxyeth-1-yl ) piperazin-1-yl, 4- (isopropyl) piperazin-1-yl, 4- (2-methoxyeth-1-yl) piperazin-1-yl, 4- (ethyl) piperazin-1-yl, 4- (N ', N'-dimethylaminoacetyl) piperazin-1-yl and 4- (6-methoxypyridin-2-yl) piperazin-1-yl.

44. The compounds of claim 28, wherein t is 0.

45. The compounds of claim 28, wherein t is 1 and X is amino, nitro, methyl or halogen.

46. The compounds of claim 28, wherein D is CH and E is S.

47. Antiviral compounds selected from the group consisting of the compounds listed in table 1, and their tautomers, pharmaceutically acceptable salts or partial salts.

48. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an antiviral compound according to any one of claims 1, 28 or 47.

49. The use of the antiviral compound according to any one of claims 1, 28 or 47 for the manufacture of a medicament for the treatment or prophylaxis of a viral infection in a mammal, mediated at least in part by a virus of the Flaviviridae family.

50. A method of treating or preventing a viral infection in a mammal, at least partially mediated by a virus of the Flaviviridae family, comprising administering to said mammal a composition according to claim 48.

51. The method of claim 50, wherein the viral infection is mediated by hepatitis C.

52. The method according to item 50, including the additional use of a therapeutically effective amount of at least one agent against hepatitis C virus (HCV).

53. The method according to paragraph 52, in which as the mentioned agent against hepatitis C virus, protease inhibitors of HCV, HCV polymerase, HCV helicase, HCV NS4B protein, penetration of HCV into host cells, assembly of HCV, exit of HCV virus from infectious cells, protein are used HCV NS5A or Inosine 5'-Monophosphate Dehydrogenase.