公开(公告)号：JP2013253114A

公开(公告)日：2013-12-19

申请号：JP2013196681

申请日：2013-09-24

Applicant: VERTEX PHARMA

Inventor： LEDEBOER MARK W ,  WANNAMAKER MARION W ,  FARMER LUC J ,  WANG TIANSHENG ,  PIERCE ALBERT C ,  MARTINEZ-BOTELLA GABRIEL ,  BETHIEL RANDY S ,  BEMIS GUY W ,  WANG JIAN ,  SALITURO FRANCESCO G ,  ARNOST MICHAEL J ,  COME JON H ,  GREEN JEREMY ,  STEWART MICHELLE ,  MARHEFKA CRAIG

IPC: C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/55 ,  A61K31/551 ,  A61K45/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/06 ,  A61P15/06 ,  A61P15/10 ,  A61P17/06 ,  A61P17/14 ,  A61P19/00 ,  A61P19/10 ,  A61P21/00 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D519/00 ,  C12N9/99 ,  C12Q1/48

Abstract: PROBLEM TO BE SOLVED: To provide pyrrolopyridine compounds useful as inhibitors of protein kinase.SOLUTION: The present invention relates to compounds of formula (I) (wherein Q, Z, R, Rand Rare described in specification), useful as inhibitors of protein kinases, particularly of JAK family and ROCK family kinases. The invention also provides pharmaceutically acceptable compositions comprising the compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

公开(公告)号：WO0181330A3

公开(公告)日：2002-03-07

申请号：PCT/US0112769

申请日：2001-04-19

Applicant: VERTEX PHARMA ,  WANNAMAKER MARION W ,  FORSTER CORNELIA

Inventor： WANNAMAKER MARION W ,  FORSTER CORNELIA

IPC: C07D307/33 ,  C07D307/66 ,  C07F9/655 ,  C07D307/32 ,  C07F9/535

CPC classification number: C07D307/33 ,  C07D307/66 ,  C07F9/65515

Abstract: Disclosed herein is a method for making compounds that are useful as caspase inhibitor prodrugs of formula (I), wherein R is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R is preferably a P2-P4 moiety of a caspase inhibitor. Key intermediates include the azidolactones (III) and (VIII).

Abstract translation: 本文公开了一种制备可用作式（I）的半胱天冬酶抑制剂前药的化合物的方法，其中R 1是选自脂族基团，芳烷基，杂环基烷基或芳基的任选取代的基团，R 2 >优选为胱天蛋白酶抑制剂的P2-P4部分。 主要中间体包括叠氮内酯（III）和（VIII）。

公开(公告)号：WO2012083122A8

公开(公告)日：2013-12-05

申请号：PCT/US2011065389

申请日：2011-12-16

Applicant: VERTEX PHARMA ,  CHARIFSON PAUL S ,  CLARK MICHAEL P ,  BANDARAGE UPUL K ,  DENG HONGBO ,  DAVIES IOANA ,  DUFFY JOHN P ,  FARMER LUC J ,  GAO HUAI ,  GU WENXIN ,  KENNEDY JOSEPH M ,  LEDEBOER MARK W ,  LEDFORD BRIAN ,  MALTAIS FRANCOIS ,  PEROLA EMANUELE ,  WANNAMAKER MARION W ,  WANG TIANSHENG ,  SALITURO FRANCESCO G

Inventor： CHARIFSON PAUL S ,  CLARK MICHAEL P ,  BANDARAGE UPUL K ,  DENG HONGBO ,  DAVIES IOANA ,  DUFFY JOHN P ,  FARMER LUC J ,  GAO HUAI ,  GU WENXIN ,  KENNEDY JOSEPH M ,  LEDEBOER MARK W ,  LEDFORD BRIAN ,  MALTAIS FRANCOIS ,  PEROLA EMANUELE ,  WANNAMAKER MARION W ,  WANG TIANSHENG ,  SALITURO FRANCESCO G

IPC: C07D471/04 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/506 ,  A61K31/53

CPC classification number: C07D471/04

Abstract: Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A compound is represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

Abstract translation: 抑制生物样品或患者中流感病毒的复制，减少生物样品或患者中流感病毒的量以及治疗患者中的流感的方法包括向所述生物样品或患者施用有效量的 由结构式（I）表示的化合物或其药学上可接受的盐，其中结构式（I）的值如本文所述。 结构式（I）表示的化合物或其药学上可接受的盐，其中结构式（I）的值如本文所述。 药物组合物包含有效量的这样的化合物或其药学上可接受的盐和药学上可接受的载体，助剂或媒介物。

公开(公告)号：WO9947545A3

公开(公告)日：1999-11-25

申请号：PCT/US9905919

申请日：1999-03-19

Applicant: VERTEX PHARMA ,  WANNAMAKER MARION W ,  BEMIS GUY W ,  CHARIFSON PAUL S ,  LAUFFER DAVID J ,  MULLICAN MICHAEL D ,  MURCKO MARK A ,  WILSON KEITH P ,  JANETKA JAMES W ,  DAVIES ROBERT J ,  GRILLOT ANNE LAURE ,  SHI ZHAN ,  FORSTER CORNELIA J

Inventor： WANNAMAKER MARION W ,  BEMIS GUY W ,  CHARIFSON PAUL S ,  LAUFFER DAVID J ,  MULLICAN MICHAEL D ,  MURCKO MARK A ,  WILSON KEITH P ,  JANETKA JAMES W ,  DAVIES ROBERT J ,  GRILLOT ANNE-LAURE ,  SHI ZHAN ,  FORSTER CORNELIA J

IPC: C07D207/273 ,  A61K31/47 ,  A61K38/00 ,  A61K38/03 ,  A61K38/04 ,  A61P5/48 ,  A61P7/00 ,  A61P9/00 ,  A61P17/00 ,  A61P19/00 ,  A61P19/08 ,  A61P19/10 ,  A61P25/00 ,  A61P29/00 ,  A61P31/04 ,  A61P35/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07D401/12 ,  C07K5/02 ,  C07K5/023

CPC classification number: C07K5/0202 ,  A61K38/00 ,  C07D401/12

Abstract: The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1 beta converting enzyme ("ICE") inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1- ("IL-1"), apoptosis-, interferon- gamma inducing factor- (IGIF), or interferon- gamma - ("IFN- gamma ") mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN- gamma production and methods for treating interleukin-1, apoptosis-, and interferon- gamma - mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

Abstract translation: 本发明涉及新型的化合物，它们是半胱天冬酶抑制剂，特别是白细胞介素-1β转化酶（“ICE”）抑制剂。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适用于抑制半胱天冬酶活性，因此可以有利地用作抗白细胞介素-1（“IL-1”），细胞凋亡 - ，干扰素-γ诱导因子 - （IGIF） ，或干扰素-γ-（“IFN-γ”）介导的疾病，包括炎性疾病，自身免疫性疾病，破坏性骨病，增殖性疾病，感染性疾病和退行性疾病。 本发明还涉及抑制半胱天冬酶活性并降低IGIF产生和IFN-γ产生的方法以及使用本发明的化合物和组合物治疗白细胞介素-1，细胞凋亡和干扰素-γ介导的疾病的方法。 本发明还涉及制备本发明化合物的方法。

公开(公告)号：WO9824804A3

公开(公告)日：1998-09-03

申请号：PCT/US9722355

申请日：1997-12-05

Applicant: VERTEX PHARMA ,  GOLEC JULIAN M C ,  LAUFFER DAVID J ,  LIVINGSTON DAVID J ,  MULLICAN MICHAEL D ,  NYCE PHILIP L ,  ROBIDOUX ANDREA L C ,  WANNAMAKER MARION W

Inventor： GOLEC JULIAN M C ,  LAUFFER DAVID J ,  LIVINGSTON DAVID J ,  MULLICAN MICHAEL D ,  NYCE PHILIP L ,  ROBIDOUX ANDREA L C ,  WANNAMAKER MARION W

IPC: A61K38/00 ,  A61P19/08 ,  A61P25/28 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07K5/02 ,  C07K5/078

CPC classification number: C07K5/06139 ,  A61K38/00 ,  C07K5/0202

Abstract: The present invention relates to novel classes of compounds which are inhibitors of interleukin-1beta converting enzyme ("ICE"). This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1-("IL-1"), apoptosis-, interferon-gamma inducing factor-(IGIF), or interferon-gamma-("IFN-gamma") mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting ICE activity and decreasing IGIF production and IFN-gamma production and methods for treating interleukin-1, apoptosis- and interferon-gamma-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

公开(公告)号：ES2548869T3

公开(公告)日：2015-10-21

申请号：ES10177537

申请日：2001-05-18

Applicant: VERTEX PHARMA

Inventor： WANNAMAKER MARION W ,  DAVIES ROBERT J

IPC: A61K38/00 ,  C07D405/12 ,  A61K31/4025 ,  A61P1/02 ,  A61P1/04 ,  A61P1/16 ,  A61P1/18 ,  A61P3/04 ,  A61P3/10 ,  A61P5/14 ,  A61P7/04 ,  A61P7/06 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P17/06 ,  A61P17/14 ,  A61P19/00 ,  A61P19/02 ,  A61P19/10 ,  A61P21/04 ,  A61P25/00 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  A61P31/10 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P35/02 ,  A61P35/04 ,  A61P37/02 ,  A61P37/06 ,  A61P43/00 ,  C07D207/12 ,  C07D477/02 ,  C07D477/20 ,  C07K5/02 ,  C07K5/06

Abstract: Un compuesto de fórmula I-B:**Fórmula** o una sal farmacéuticamente aceptable del mismo.

公开(公告)号：AU2011343647A1

公开(公告)日：2013-05-02

申请号：AU2011343647

申请日：2011-12-16

Applicant: VERTEX PHARMA

Inventor： CHARIFSON PAUL S ,  CLARK MICHAEL P ,  BANDARAGE UPUL K ,  DENG HONGBO ,  DAVIES IOANA ,  DUFFY JOHN P ,  FARMER LUC J ,  GAO HUAI ,  GU WENXIN ,  KENNEDY JOSEPH M ,  LEDEBOER MARK W ,  LEDFORD BRIAN ,  MALTAIS FRANCOIS ,  PEROLA EMANUELE ,  WANNAMAKER MARION W ,  WANG TIANSHENG ,  SALITURO FRANCESCO G

IPC: C07D471/04 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/506 ,  A61K31/53

Abstract: Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A compound is represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

公开(公告)号：UA96113C2

公开(公告)日：2011-10-10

申请号：UA20041210341

申请日：2004-12-15

Applicant: VERTEX PHARMA

Inventor： WANNAMAKER MARION W ,  BEMIS GUY W ,  CHARIFSON PAUL S ,  LAUFFER DAVID J ,  MULLICAN MICHAEL D ,  MURCKO MARK A ,  WILSON KEITH P ,  JANETKA JAMES W ,  DAVIES ROBERT J ,  GRILLOT ANNE-LAURE ,  SHI ZHAN ,  FORESTER CORNELIA J

IPC: C07D207/273 ,  A61K31/47 ,  A61K38/00 ,  A61K38/03 ,  A61K38/04 ,  A61P5/48 ,  A61P7/00 ,  A61P9/00 ,  A61P17/00 ,  A61P19/00 ,  A61P19/08 ,  A61P19/10 ,  A61P25/00 ,  A61P29/00 ,  A61P31/04 ,  A61P35/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07D401/12 ,  C07K5/02 ,  C07K5/023

Abstract: Этоизобретениекасаетсяновыхклассовсоединений, которыепредставляютсобойингибиторыкаспаз, вчастностиингибиторыинтерлейкин-1-преобразующегофермента (ICE).Этоизобретениекасаетсятакжефармацевтическихкомпозиций, которыесодержатэтисоединения.Соединенияи фармацевтическиекомпозицииэтогоизобретения, вчастности, хорошоприменимыдляторможенияактивностикаспазыи, итак, могутбытьуспешнопримененыкакагенты, направленыпротивзаболеваний, опосредованныхинтерлейкином-1 (IL-1), апоптозом, фактором, индуцирующиминтерферон-(IGIF), илиинтерфероном-(IFN-), включаявоспалительныезаболевания, аутоиммунныезаболевания, деструктивныезаболеваниякостей, н

公开(公告)号：NZ564065A

公开(公告)日：2011-03-31

申请号：NZ56406506

申请日：2006-05-22

Applicant: VERTEX PHARMA

Inventor： LEDEBOER MARK W ,  WANNAMAKER MARION W ,  FARMER LUC J ,  WANG TIANSHENG ,  PIERCE ALBERT C ,  MARTINEZ-BOTELLA GABRIEL ,  BETHIEL RANDY S ,  BEMIS GUY W ,  WANG JIAN ,  SALITURO FRANCESCO G ,  ARNOST MICHAEL J ,  COME JON H ,  GREEN JEREMY ,  STEWART MICHELLE ,  MARHEFKA CRAIG

IPC: C07D471/04 ,  A61K31/437 ,  A61P35/00 ,  C07D487/04

Abstract: The disclosure relates to compounds of formula (I), wherein Q, Z, R1, R2 , and R3 are as defined in the specification useful as inhibitors of protein kinases, particularly of JAK family and ROCK family kinases. The disclosure also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders, such as atherosclerosis, hypertension, erectile dysfunction (ED), reperfusion/ischemia, stroke, cerebral vasospasm, coronary vasospasm, cardiac hypertrophy, glaucoma, asthma, transplant rejection and the like.

公开(公告)号：AU2010224367A1

公开(公告)日：2010-10-14

申请号：AU2010224367

申请日：2010-09-22

Applicant: VERTEX PHARMA

Inventor： WANNAMAKER MARION W ,  BEMIS GUY W ,  CHARIFSON PAUL S ,  LAUFFER DAVID J ,  MULLICAN MICHAEL D ,  MURCKO MARK A ,  WILSON KEITH P ,  JANETKA JAMES W ,  DAVIES ROBERT J ,  GRILLOT ANNE-LAURE ,  SHI ZHAN ,  FORSTER CORNELIA J

IPC: C07K5/023 ,  A61K31/47 ,  A61K38/03 ,  A61K38/04 ,  C07D401/12