# US 7,012,066 B2 · Peptides as NS3-serine protease inhibitors of hepatitis C virus > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,012,066 B2 - Document ID: US7012066B2 - Status: Granted - Kind: B2 - Application number: 09/908,955 - Filed: 2001-07-19 - Published: 2003-11-20 - Granted: 2006-03-14 - Earliest claimed: 2000-07-21 - Assignees: Schering Corporation; Dendreon Corporation - Inventors: Anil K. Saksena; Viyyoor Moopil Girijavallabhan; Raymond G. Lovey; Edwin Jao; Frank Bennett; Jinping L. Mc Cormick; Haiyan Wang; Russell E. Pike; Stephane L. Bogen; Tin-Yau Chan; Yi-Tsung Liu; Zhaoning Zhu; F. George Njoroge; Ashok Arasappan; Tejal Parekh; Ashit K. Ganguly; Kevin X. Chen; Srikanth Venkatraman; Henry A. Vaccaro; Patrick A. Pinto; Bama Santhanam; Scott Jeffrey Kemp; Odile Esther Levy; Marguerita Lim-Wilby; Susan Y. Tamura; Wanli Wu; Siska Hendrata; Yuhua Huang - Web page: https://patentgrep.com/patent/US7012066B2 ## CPC - C07K 5/0202: {containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids} - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/12: Antivirals - A61P 31/14: for RNA viruses - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 5/0812: {and aromatic or cycloaliphatic} - C07K 5/0827: {containing heteroatoms different from O, S, or N} - C07K 7/02: Linear peptides containing at least one abnormal peptide link - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease. ## Claims ### Claim 1 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from the compounds of structures listed below: ### Claim 2 (depends on 1) A pharmaceutical composition for treating disorders associated with hepatitis C virus (HCV), said composition comprising therapeutically effective amount of one or more compounds in claim 1 and a pharmaceutically acceptable carrier. ### Claim 3 (depends on 2) The pharmaceutical composition of claim 2, additionally containing an antiviral agent. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, further containing an interferon or pegylated-interferon alpha conjugate. ### Claim 5 (depends on 4) The pharmaceutical composition of claim 4, wherein said antiviral agent is ribavirin and said interferon is α-interferon. ### Claim 6 (depends on 1) A method of treatment of a hepatitis C virus associated disorder, comprising administering an effective amount of one or more compounds of claim 1. ### Claim 7 (depends on 1) A method of modulating the activity of hepatitis C virus (HCV) protease, comprising contacting HCV protease with one or more compounds of claim 1. ### Claim 8 (depends on 1) A method of treating, or ameliorating one or more symptoms of hepatitis C, comprising administering an effective amount of one or more compounds of claim 1. ### Claim 9 (depends on 7) The method of claim 7, wherein the HCV protease is the NS3/NS4a protease. ### Claim 10 (depends on 9) The method of claim 9, wherein the compound or compounds inhibit HCV NS3/NS4a protease. ### Claim 11 (depends on 1) A method of modulating the processing of hepatitis C virus (HCV) polypeptide, comprising contacting a composition containing the HCV polypeptide under conditions in which the polypeptide is processed with one or more compounds of claim 1. ### Claim 12 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 13 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 14 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being compound of structure shown below: ### Claim 15 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 16 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 17 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 18 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 19 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 20 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 21 A compound exhibiting hepatitis C virus (HCV) protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: ### Claim 22 A pharmaceutical composition comprising as an active ingredient a compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being compound of structure shown below: ### Claim 23 (depends on 22) The pharmaceutical composition of claim 22, additionally containing an antiviral agent. ### Claim 24 (depends on 23) The pharmaceutical composition of claim 23, further containing an interferon or pegylated-interferon alpha conjugate. ### Claim 25 (depends on 24) The pharmaceutical composition of claim 24, wherein said antiviral agent is ribavirin and said interferon is α-interferon. ### Claim 26 (depends on 12) A compound of claim 12, which has the formula shown below: ### Claim 27 (depends on 12) A compound of claim 12, which has the formula shown below: ### Claim 28 (depends on 13) A compound of claim 13, which has the formula shown below: ### Claim 29 (depends on 13) A compound of claim 13, which has the formula shown below: ### Claim 30 (depends on 14) A compound of claim 14, which has the formula shown below: ### Claim 31 (depends on 14) A compound of claim 14, which has the formula shown below: ### Claim 32 (depends on 15) A compound of claim 15, which has the formula shown below: ### Claim 33 (depends on 15) A compound of claim 15, which has the formula shown below: ### Claim 34 (depends on 16) A compound of claim 16, which has the formula shown below: ### Claim 35 (depends on 16) A compound of claim 16, which has the formula shown below: ### Claim 36 (depends on 17) A compound of claim 17, which has the formula shown below: ### Claim 37 (depends on 17) A compound of claim 17, which has the formula shown below: ### Claim 38 (depends on 18) A compound of claim 18, which has the formula shown below: ### Claim 39 (depends on 18) A compound of claim 18, which has the formula shown below: ### Claim 40 (depends on 19) A compound of claim 19, which has the formula shown below: ### Claim 41 (depends on 19) A compound of claim 19, which has the formula shown below: ### Claim 42 (depends on 20) A compound of claim 20, which has the formula shown below: ### Claim 43 (depends on 20) A compound of claim 20, which has the formula shown below: ### Claim 44 (depends on 21) A compound of claim 21, which has the formula shown below: ### Claim 45 (depends on 21) A compound of claim 21, which has the formula shown below: ### Claim 46 (depends on 22) The pharmaceutical composition of claim 22, wherein said compound is selected from the following: ### Claim 47 (depends on 46) The pharmaceutical composition of claim 46, additionally containing an antiviral agent. ### Claim 48 (depends on 47) The pharmaceutical composition of claim 47, additionally containing an interferon or pegylated-interferon alpha conjugate. ### Claim 49 (depends on 48) The pharmaceutical composition of claim 48, wherein said antiviral agent is ribavirin and said interferon is alpha-interferon. ### Claim 50 A method of treating disorders associated with the HCV, said method comprising administering to a patient in need of such treatment, a pharmaceutical composition which comprises therapeutically effective amounts of a compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from the following: ### Claim 51 (depends on 50) The method of claim 50, wherein said compound is selected from the following: ### Claim 52 (depends on 1) A method of treating disorders associated with the hepatitis C virus (HCV), said method comprising administering to a patient in need of such treatment, a compound of claim 1 and an interferon. ### Claim 53 (depends on 52) The method of claim 52, wherein said interferon is alpha-interferon or pegylated interferon. ### Claim 54 (depends on 53) The method of claim 53, wherein said administration is oral or subcutaneous. ### Claim 55 (depends on 1) A method of treating disorders associated with the hepatitis C virus (HCV), comprising administering to a patient in need of such treatment, a compound of claim 1 and an interferon. ### Claim 56 (depends on 55) The method of claim 55, wherein said interferon is alpha-interferon or pegylated interferon. ### Claim 57 (depends on 56) The method of claim 56, wherein said administration is oral or subcutaneous. ### Claim 58 (depends on 22) A method of treating disorders associated with the hepatitis C virus (HCV), comprising administering to a patient in need of such treatment the pharmaceutical composition of claim 22 and an interferon. ### Claim 59 (depends on 58) The method of claim 58, wherein said interferon is alpha-interferon or pegylated interferon. ### Claim 60 (depends on 59) The method of claim 59, wherein said administration is oral or subcutaneous. ### Claim 61 (depends on 52) The method of claim 52 wherein said treatment further comprising administering an antiviral agent. ### Claim 62 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45) A method of treating disorders associated with the hepatitis C virus (HCV), comprising administering to a patient in need of such treatment a compound of any one of claims 26-45 and an interferon. ### Claim 63 (depends on 46) A method of treating disorders associated with the hepatitis C virus (HCV), comprising administering to a patient in need of such treatment the pharmaceutical composition of claim 46 and an interferon. ### Claim 64 (depends on 51) The method of claim 51, further comprising administering an interferon.