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US 2004/0023958 A1Published application
Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same
AssigneeAgouron Pharmaceuticals, Inc.
InventorsAllen J. Borchardt, Peter Scott Dragovich, Javier Gonzalez, Tanya Michelle Jewell, Hui Li, Maria Angelica Linton, John Howard Tatlock, Ru Zhou, Thomas Jay Prins, Melwyn A. Abreo
Life of this patent
Estimating the term…
Abstract
Compounds of formula I are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus. 1
Claims15
A method of inhibiting HCV polymerase activity comprising contacting an HCV polymerase with an effective amount of a compound represented by formula (I) or a salt, solvate, prodrug, or metabolite thereof:
- 498
- wherein:
- r is 0, 1, 2, 3, 4 or 5;
- R1 is hydrogen, or an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O ;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H—;
- —NHC(SO)H;
- —NHC(S)H—;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- phenyl;
- cycloalkane;
- —O—;
- —OH;
- and CH3;
- R2 is an isopropyl, cyclopentyl, or cyclohexyl group, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups;
- R3 is hydrogen;
- halogen;
- ═S;
- —SH;
- —S—(CH2)z-heteroaryl where z is an integer from 0 to 4;
- —S—(CH2)z-heterocycloalkyl where z is an integer from 0 to 4;
- —S—(CH2)z-aryl where z is an integer from 0 to 4;
- —(CH2)z-aryl where z is an integer from 0 to 4;
- —O-aryl;
- —C(O)H;
- —C(O)-alkyl;
- amino;
- or a halogen, unsubstituted or substituted with an aryl group, halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- phenyl;
- cycloalkane;
- —O—;
- —OH;
- and CH3;
- R4 is ═O or —OR5;
- X—W is C—CH when R4 is ═O, and X—W is C═C when R4 is —OR5;
- or R3 and R4 taken together with X and W form a cycloalkyl, heteroaryl, cycloalkyl, or heterocycloalkyl group unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2—;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- aryl;
- cycloalkyl;
- —OR5;
- haloalkyl;
- and alkyl;
- and
- R5 is an alkyl or H.
494 more elements
A method of inhibiting HCV polymerase activity comprising contacting an HCV polymerase with an effective amount of a compound represented by formula (I) or a salt thereof:
- 516
- wherein:
- r is 0, 1, 2, 3, 4 or 5;
- R1 is hydrogen, or an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2, —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- phenyl;
- cycloalkane;
- —O—;
- —OH;
- and CH3;
- R2 is an isopropyl, cyclopentyl, or cyclohexyl group, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups;
- R3 is hydrogen;
- halogen;
- ═S;
- —SH;
- —S—(CH2)z—heteroaryl where z is an integer from 0 to 4;
- —S—(CH2)z-heterocycloalkyl where z is an integer from 0 to 4;
- —S—(CH2)z-aryl where z is an integer from 0 to 4;
- —(CH2)z-aryl where z is an integer from 0 to 4;
- —O-aryl;
- —C(O)H;
- —C(O)-alkyl;
- amino;
- or a halogen, unsubstituted or substituted with an aryl group, halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H—;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- phenyl;
- cycloalkane;
- —O—;
- —OH;
- and CH3;
- R4 is ═O or —OR5;
- X—W is C—CH when R4 is ═O, and X—W is C═C when R4 is —OR5;
- or R3 and R4 taken together with X and W form a cycloalkyl, heteroaryl, cycloalkyl, or heterocycloalkyl group unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H,;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(O)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl, heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- aryl;
- cycloalkyl;
- —OR5;
- haloalkyl;
- and alkyl;
- and
- R5 is an alkyl or H.
492 more elements
A method of treating a condition that is mediated by HCV polymerase in a patient, comprising administering to said patient an effective amount of compound represented by formula (I) or a salt, solvate, prodrug, or metabolite thereof:
- 517
- wherein:
- r is 0, 1, 2, 3, 4 or 5;
- R1 is hydrogen, or an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H—;
- —NHC(SO)H;
- —NHC(S)H—;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from i to 4;
- —NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H—;
- —NHC(SO)H—;
- —NHC(S)H—;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- phenyl;
- cycloalkane;
- —O—;
- —OH;
- and CH3;
- R2 is an isopropyl, cyclopentyl, or cyclohexyl group, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups;
- R3 is hydrogen;
- halogen;
- ═S;
- —SH;
- —S—(CH2)z—heteroaryl where z is an integer from 0 to 4;
- —S—(CH2)z-heterocycloalkyl where z is an integer from 0 to 4;
- —S—(CH2)z-aryl where z is an integer from 0 to 4;
- —(CH2)z-aryl where z is an integer from 0 to 4;
- —O-aryl;
- —C(O)H;
- —C(O)-alkyl;
- amino;
- or a halogen, unsubstituted or substituted with an aryl group, halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;I—C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H—;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- phenyl;
- cycloalkane;
- —O—;
- —OH;
- and CH3;
- R4 is ═O or —OR5;
- X—W is C—CH when R4 is ═O, and X—W is C═C when R4 is —OR5;
- or R3 and R4 taken together with X and W form a cycloalkyl, heteroaryl, cycloalkyl, or heterocycloalkyl group unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- isopropyl;
- t-butyl;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —OCH3, —OCH2—;
- —OCH2CH3;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —CH2CH(O)OCH3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(NH)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —SO2CH3;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)OH;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- ═O;
- ═S;
- —CN;
- —NO2;
- alkane, branched or unbranched;
- alkyl;
- heteroalkyl;
- alkenyl;
- alkynyl;
- aryl;
- cycloalkyl;
- heterocycloalkyl;
- heteroaryl;
- alkoxy;
- —(CH2)zCN where z is an integer from 1 to 4;
- ═NH;
- —NHOH;
- —OH;
- —C(O)H;
- —OC(O)H;
- —C(O)OH;
- —C(O)OC(CH3)n, where n is an integer from 1 to 3;
- —OC(O)OH;
- —OC(O)OC(O)H;
- —OOH;
- —C(N H)NH2;
- —NHC(NH)NH2;
- —C(S)NH2;
- —NHC(S)NH2;
- —NHC(O)NH2;
- —S(O2)H;
- —S(O)H;
- —NH2;
- —C(O)NH2;
- —OC(O)NH2;
- —NHC(O)H;
- —NHC(O)OH;
- —C(O)NHC(O)H;
- —OS(O2)H;
- —OS(O)H;
- —OSH;
- —SC(O)H;
- —SCH2CH3;
- —S(O)C(O)OH;
- —SO2C(O)OH;
- —NHSH;
- —NHS(O)H;
- —NHSO2H;
- —C(O)SH;
- —C(O)S(O)H;
- —C(O)S(O2)H;
- —C(S)H;
- —C(SO)OH;
- —C(SO2)OH;
- —NHC(S)H;
- —OC(S)H;
- —OC(S)OH;
- —OC(SO2)H;
- —S(O2)NH2;
- —S(O)NH2;
- —SNH2;
- —NHCS(O2)H;
- —NHC(SO)H;
- —NHC(S)H;
- and —SH groups, unsubstituted or substituted with one or more substituents selected from the group consisting of halogens;
- aryl;
- cycloalkyl;
- —OR5;
- haloalkyl;
- and alkyl;
- and
- R5 is an alkyl or H.
493 more elements
Dependencies are inferred from the claim text.