公开(公告)号：WO2005007681A2

公开(公告)日：2005-01-27

申请号：PCT/US2004023054

申请日：2004-07-16

Applicant: VERTEX PHARMA ,  BRITT SHAWN D ,  COTTRELL KEVIN M ,  PERNI ROBERT B ,  PITLIK JANOS

Inventor： BRITT SHAWN D ,  COTTRELL KEVIN M ,  PERNI ROBERT B ,  PITLIK JANOS

IPC: A61P31/12 ,  C07K7/06 ,  C07K5/10 ,  A61K38/04

CPC classification number: C07K7/06

Abstract: The present invention relates to compounds of formula I or formula Ia or pharmaceutically acceptable salts thereof, that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are useful as antiviral agents. The invention further relates to pharmaceutically acceptable compositions comprising said compounds either for ex vivo use or for administration to a patient suffering from HCV infection and processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by15 administering a pharmaceutical composition comprising a compound of this invention.

Abstract translation: 本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒NS3-NS4A蛋白酶活性的式I或式Ia化合物或其药学上可接受的盐。 因此，它们通过干扰丙型肝炎病毒的生命周期起作用，并且作为抗病毒剂是有用的。 本发明还涉及包含用于离体使用或用于给予HCV感染的患者的所述化合物的药学上可接受的组合物和用于制备所述化合物的方法。 本发明还涉及通过施用包含本发明化合物的药物组合物来治疗患者HCV感染的方法。

公开(公告)号：WO2008106058A2

公开(公告)日：2008-09-04

申请号：PCT/US2008002395

申请日：2008-02-20

Applicant: VERTEX PHARMA ,  FARMER LUC ,  BETHIEL RANDY SCOTT ,  JACOBS DYLAN ,  PERNI ROBERT B ,  MAXWELL JOHN ,  COTTRELL KEVIN ,  HALAS SUMMER

Inventor： FARMER LUC ,  BETHIEL RANDY SCOTT ,  JACOBS DYLAN ,  PERNI ROBERT B ,  MAXWELL JOHN ,  COTTRELL KEVIN ,  HALAS SUMMER

CPC classification number: C07D487/10 ,  C07D498/10

Abstract: The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.

Abstract translation: 本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒NS3-NS4A蛋白酶活性的化合物。 因此，它们通过干扰丙型肝炎病毒的生命周期起作用，也可用作抗病毒剂。 本发明还涉及包含这些化合物的组合物，用于离体使用或给予患有HCV感染的患者。 本发明还涉及通过施用包含本发明化合物的组合物来治疗患者HCV感染的方法。

公开(公告)号：WO2005043118A3

公开(公告)日：2010-09-02

申请号：PCT/US2004035751

申请日：2004-10-27

Applicant: VERTEX PHARMA ,  PERNI ROBERT B ,  GATES CYNTHIA ,  THOMSON JOHN A

Inventor： PERNI ROBERT B ,  GATES CYNTHIA ,  THOMSON JOHN A

IPC: A61K38/21 ,  A61K38/55 ,  C12Q1/18 ,  G01N20060101

CPC classification number: A61K38/553 ,  A61K38/212 ,  A61K38/215 ,  A61K38/217 ,  C12Q1/18 ,  G01N2333/18 ,  A61K2300/00

Abstract: The application discloses a method for selecting Hepatitis C (HCV) inhibitors that form long-lived, tight complexes (EI complex) with their targets (eg NS3/4a protease). It also discloses the compound VX-950 which has such properties and its medical use for treating HCV infection and eliminating HCV contamination. The use of cellular viral replication assays for selecting viral inhibitors are equally claimed.

Abstract translation: 该申请公开了一种选择丙型肝炎（HCV）抑制剂与其靶标（例如NS3 / 4a蛋白酶）形成长寿命，紧密复合物（EI复合物）的方法。 它还公开了具有这些性质的化合物VX-950及其用于治疗HCV感染和消除HCV污染的医疗用途。 同样要求使用细胞病毒复制测定法来选择病毒抑制剂。

公开(公告)号：WO2005077969A3

公开(公告)日：2005-12-01

申请号：PCT/US2005003381

申请日：2005-02-04

Applicant: VERTEX PHARMA ,  COTTRELL KEVIN M ,  COURT JOHN J ,  DEININGER DAVID D ,  FARMER LUC J ,  PITLIK JANOS ,  PERNI ROBERT B

Inventor： COTTRELL KEVIN M ,  COURT JOHN J ,  DEININGER DAVID D ,  FARMER LUC J ,  PITLIK JANOS ,  PERNI ROBERT B

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/05 ,  C07K5/02 ,  C07K5/04 ,  C07K7/02 ,  C07K14/18 ,  A61K38/07 ,  A61K38/08

CPC classification number: C07K5/10 ,  A61K38/00 ,  A61K38/07 ,  A61K45/06 ,  C07K5/0202 ,  C07K7/02 ,  C07K14/005 ,  C12N2770/24222

Abstract: The present invention relates to compounds of formula (I), or a pharmaceutically acceptable salt or mixtures thereof that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection and to processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

Abstract translation: 本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒NS3-NS4A蛋白酶活性的式（I）化合物或其药学上可接受的盐或其混合物。 因此，它们通过干扰丙型肝炎病毒的生命周期起作用，也可用作抗病毒剂。 本发明还涉及包含用于离体使用或用于给予HCV感染患者的这些化合物的组合物和制备该化合物的方法。 本发明还涉及通过施用包含本发明化合物的组合物来治疗患者HCV感染的方法。 本发明还涉及制备这些化合物的方法。

公开(公告)号：WO2007016589A2

公开(公告)日：2007-02-08

申请号：PCT/US2006029988

申请日：2006-08-01

Applicant: VERTEX PHARMA ,  LYONS STEVE ,  PERNI ROBERT B

Inventor： LYONS STEVE ,  PERNI ROBERT B

CPC classification number: C07K7/06 ,  A01N37/46 ,  A61K31/497 ,  A61K38/00 ,  A61K38/005 ,  A61K38/08 ,  A61K45/06 ,  C07D403/12 ,  C07K5/06139 ,  C07K5/1024 ,  C12N9/99

Abstract: This invention relates to compounds of formula (I): or a pharmaceutically acceptable salt or mixtures thereof wherein C* represents a diastereomeric carbon comprising a mixture of R andS isomers wherein the R isomer is greater than 50% of the mixture.

Abstract translation: 本发明涉及式（I）化合物或其药学上可接受的盐或其混合物，其中C *表示包含R和S异构体的混合物的非对映异构体，其中R异构体大于混合物的50％。

公开(公告)号：WO2005042020A3

公开(公告)日：2005-06-23

申请号：PCT/US2004035549

申请日：2004-10-27

Applicant: VERTEX PHARMA ,  TUNG ROGER D ,  CHANDORKAR GURUDATT ,  PERNI ROBERT B

Inventor： TUNG ROGER D ,  CHANDORKAR GURUDATT ,  PERNI ROBERT B

IPC: A61K31/7056 ,  A61K38/21 ,  A61K45/00 ,  A61K45/06

CPC classification number: A61K45/06 ,  A61K31/496 ,  A61K31/7056 ,  A61K38/21 ,  A61K38/2292 ,  A61K2300/00

Abstract: The present invention relates to co-administering a Hepatitis C virus NS3/4A protease inhibitor and a cytochrome P450 monooxygenase inhibitor. The combination acts by interfering with the life cycle of the hepatitis C virus and is therefore useful as an antiviral therapy. As such, the combination may be used for treating or preventing Hepatitis C infections in patients. The invention also relates to compositions comprising the combination of inhibitors. The invention also relates to kits and pharmaceutical packs comprising a Hepatitis C virus NS3/4A protease inhibitor and a cytochrome P450 monooxygenase inhibitor. The invention also relates to processes for preparing these compositions, combinations, kits, and packs.

Abstract translation: 本发明涉及共同给予丙型肝炎病毒NS3 / 4A蛋白酶抑制剂和细胞色素P450单加氧酶抑制剂。 该组合通过干扰丙型肝炎病毒的生命周期起作用，因此可用作抗病毒疗法。 如此，该组合可用于治疗或预防患者的丙型肝炎感染。 本发明还涉及包含抑制剂组合的组合物。 本发明还涉及包含丙型肝炎病毒NS3 / 4A蛋白酶抑制剂和细胞色素P450单加氧酶抑制剂的试剂盒和药物包装。 本发明还涉及制备这些组合物，组合物，试剂盒和包装的方法。

公开(公告)号：WO2007109080A3

公开(公告)日：2007-11-15

申请号：PCT/US2007006493

申请日：2007-03-14

Applicant: VERTEX PHARMA ,  PERNI ROBERT B ,  CHEN MINZHANG ,  JUNG YOUNG CHUN ,  FORSLUND RAYMOND E ,  TANOURY GERALD J ,  BENNANI YOUSSEF ,  ZLOKARNIK GREGOR ,  MALTAIS FRANCOIS

Inventor： PERNI ROBERT B ,  CHEN MINZHANG ,  JUNG YOUNG CHUN ,  FORSLUND RAYMOND E ,  TANOURY GERALD J ,  BENNANI YOUSSEF ,  ZLOKARNIK GREGOR ,  MALTAIS FRANCOIS

IPC: C07C231/20 ,  A61K31/403 ,  A61K31/422 ,  A61K31/498 ,  A61P31/12 ,  C07C237/04 ,  C07D209/52 ,  C07D403/12 ,  C07D403/14 ,  C07D498/10

CPC classification number: C07C231/20 ,  C07B2200/05 ,  C07B2200/07 ,  C07C237/04 ,  C07C2601/02 ,  C07D209/52 ,  C07D301/14 ,  C07D303/48 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D498/10 ,  C07K5/0202 ,  C07K7/02

Abstract: A deuterated a-ketoamido steric specific compound of the formula (I), wherein D denotes a deuterium atom on a steric specific carbon atom.

Abstract translation: 式（I）的氘代α-酮酰胺基空间特异性化合物，其中D表示空间特异性碳原子上的氘原子。

公开(公告)号：WO2005035525A3

公开(公告)日：2005-10-20

申请号：PCT/US2004029093

申请日：2004-09-07

Applicant: VERTEX PHARMA ,  PERNI ROBERT B ,  COURT JOHN J ,  BRITT SHAWN D ,  PITLIK JANOS ,  VAN DRIE JOHN H

Inventor： PERNI ROBERT B ,  COURT JOHN J ,  BRITT SHAWN D ,  PITLIK JANOS ,  VAN DRIE JOHN H

IPC: A61K31/4178 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/517 ,  A61K38/00 ,  A61K38/05 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07K5/02 ,  C07K5/06 ,  C07K5/10 ,  C07K7/02 ,  A61P31/14

CPC classification number: C07K5/1016 ,  A01N43/60 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/517 ,  A61K38/00 ,  A61K45/06 ,  C04B35/632 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07K5/0202 ,  C07K5/0207 ,  C07K5/1027 ,  C07K7/02 ,  A61K2300/00

Abstract: The present invention relates to compounds of formula I-A and I-B that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

Abstract translation: 本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒NS3-NS4A蛋白酶活性的式I-A和I-B化合物。 因此，它们通过干扰丙型肝炎病毒的生命周期起作用，并且也可用作抗病毒剂。 本发明还涉及包含这些化合物的组合物，用于离体使用或用于给予HCV感染患者。 本发明还涉及通过施用包含本发明化合物的组合物来治疗患者HCV感染的方法。 本发明还涉及制备这些化合物的方法。

公开(公告)号：AU2006275413B2

公开(公告)日：2012-07-19

申请号：AU2006275413

申请日：2006-08-01

Applicant: VERTEX PHARMA

Inventor： LYONS STEVE ,  PERNI ROBERT B

IPC: C07D403/12 ,  A61K31/501 ,  A61P31/12

Abstract: This invention relates to compounds of formula (I): or a pharmaceutically acceptable salt or mixtures thereof wherein C* represents a diastereomeric carbon comprising a mixture of and isomers wherein the isomer is greater than 50% of the mixture.

公开(公告)号：CA2481369C

公开(公告)日：2012-07-10

申请号：CA2481369

申请日：2003-04-11

Applicant: VERTEX PHARMA

Inventor： PITLIK JANOS ,  COTTRELL KEVIN M ,  FARMER LUC J ,  PERNI ROBERT B ,  COURTNEY LAWRENCE F ,  VAN DRIE JOHN H ,  MURCKO MARK A

IPC: C07D403/12 ,  C12N9/99 ,  A61K31/404 ,  A61K38/00 ,  A61K38/04 ,  A61P1/16 ,  A61P31/12 ,  A61P31/14 ,  A61P37/02 ,  A61P43/00 ,  C07D209/42 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D417/12 ,  C07D471/04 ,  C07F5/02 ,  C07K5/04 ,  C07K5/06 ,  C07K5/08 ,  C07K5/10 ,  C07K7/02

Abstract: The present invention relates to compounds of formula IA (see formula IA) as defined herein, that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.