公开(公告)号：WO0157022A2

公开(公告)日：2001-08-09

申请号：PCT/US0103911

申请日：2001-02-05

Applicant: VERTEX PHARMA ,  GREEN JEREMY ,  CAO JINGRONG ,  HALE MICHAEL ,  BAKER CHRISTOPHER ,  MALTAIS FRANCOIS ,  JANETKA JAMES ,  MULLICAN MICHAEL ,  BEMIS GUY ,  XIE XIAOLING ,  STRAUB JUDITH ,  TANG QING ,  MASHALL ROBERT

Inventor： GREEN JEREMY ,  CAO JINGRONG ,  HALE MICHAEL ,  BAKER CHRISTOPHER ,  MALTAIS FRANCOIS ,  JANETKA JAMES ,  MULLICAN MICHAEL ,  BEMIS GUY ,  XIE XIAOLING ,  STRAUB JUDITH ,  TANG QING ,  MASHALL ROBERT

IPC: A61B17/00 ,  A61F2/02 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/433 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/00 ,  A61L27/00 ,  A61P1/00 ,  A61P1/16 ,  A61P1/18 ,  A61P3/10 ,  A61P5/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P13/00 ,  A61P13/10 ,  A61P13/12 ,  A61P15/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P21/00 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  A61P31/12 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  A61P37/02 ,  A61P37/04 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D231/38 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04 ,  C07D403/00

CPC classification number: C07D401/14 ,  C07D231/38 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04

Abstract: Described herein are compounds that are useful as protein kinase inhibitors having the formula: (I) where R , Q, and T are described inthe specification. The compounds are useful for treating disease states in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, and cardiovascular disease.

Abstract translation: 本文描述了可用作具有下式的蛋白激酶抑制剂的化合物：其中R 1-4，Q和T在说明书中描述。 该化合物可用于治疗由蛋白激酶抑制剂，特别是诸如癌症，炎症性疾病，再狭窄和心血管疾病等疾病减轻的哺乳动物的疾病状态。

公开(公告)号：WO0102363A3

公开(公告)日：2001-07-05

申请号：PCT/US0018564

申请日：2000-07-06

Applicant: VERTEX PHARMA ,  LAUFFER DAVID ,  LEDFORD BRIAN ,  MULLICAN MICHAEL

Inventor： LAUFFER DAVID ,  LEDFORD BRIAN ,  MULLICAN MICHAEL

IPC: A61K31/4409 ,  A61K31/444 ,  A61K38/22 ,  A61P9/10 ,  A61P21/04 ,  A61P25/00 ,  A61P25/02 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P27/02 ,  C07D213/40 ,  A61K31/4465

CPC classification number: C07D213/40

Abstract: The present invention relates N-substituted glycine derivatives for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.

Abstract translation: 本发明涉及用于治疗或预防与神经疾病相关的神经元损伤的N-取代甘氨酸衍生物。 本发明还提供了包含本发明化合物的组合物和利用这些组合物治疗或预防神经元损伤的方法。

公开(公告)号：WO0158891A3

公开(公告)日：2002-04-25

申请号：PCT/US0104210

申请日：2001-02-09

Applicant: TOMLINSON RONALD ,  LAUFFER DAVID ,  MULLICAN MICHAEL ,  VERTEX PHARMA

Inventor： TOMLINSON RONALD ,  LAUFFER DAVID ,  MULLICAN MICHAEL

IPC: A61K31/40 ,  A61K31/4025 ,  A61K31/427 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4995 ,  A61K31/506 ,  A61K38/22 ,  A61K38/27 ,  A61P19/04 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P29/00 ,  C07D20060101 ,  C07D205/04 ,  C07D207/16 ,  C07D209/52 ,  C07D211/26 ,  C07D211/60 ,  C07D211/62 ,  C07D211/78 ,  C07D277/06 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/06 ,  C07D417/12 ,  C07D487/08

CPC classification number: C07D401/04 ,  C07D205/04 ,  C07D207/16 ,  C07D211/60 ,  C07D211/62 ,  C07D277/06 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D487/08

Abstract: The present invention relates to piperazine and piperidine derivatives of Formula (1), with Q, X, Y, A, B and P as defined herein, which are especially useful for treating or preventing neuronal damage, particularly damage associated with neurological diseases. These compounds are also useful for stimulating nerve growth. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage or for stimulating nerve growth.

公开(公告)号：WO0102358A3

公开(公告)日：2001-07-12

申请号：PCT/US0018418

申请日：2000-07-05

Applicant: VERTEX PHARMA ,  LAUFFER DAVID ,  MULLICAN MICHAEL ,  LEDFORD BRIAN

Inventor： LAUFFER DAVID ,  MULLICAN MICHAEL ,  LEDFORD BRIAN

IPC: C07D243/12 ,  A61K31/4015 ,  A61K31/45 ,  A61K31/4545 ,  A61K31/55 ,  A61K31/5513 ,  A61K38/27 ,  A61P19/08 ,  A61P21/04 ,  A61P25/00 ,  A61P25/02 ,  A61P25/16 ,  A61P25/28 ,  C07D207/26 ,  C07D207/273 ,  C07D211/76 ,  C07D223/12 ,  C07D223/16 ,  C07D243/14 ,  C07D243/24 ,  C07D401/06 ,  C07D401/14 ,  A61K31/554 ,  C07D211/72 ,  C07D413/14 ,  C07D417/14

CPC classification number: C07D207/273 ,  C07D211/76 ,  C07D223/16 ,  C07D243/24 ,  C07D401/14

Abstract: The present invention relates to cyclized amide derivatives of formula (I) for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.

Abstract translation: 本发明涉及用于治疗或预防与神经疾病相关的神经元损伤的式（I）的环化酰胺衍生物。 本发明还提供包含本发明化合物的组合物和利用这些组合物治疗或预防神经元损伤的方法。

公开(公告)号：EP1207882A4

公开(公告)日：2003-03-19

申请号：EP00952238

申请日：2000-07-27

Applicant: VERTEX PHARMA

Inventor： MULLICAN MICHAEL ,  LAUFFER DAVID ,  TUNG ROGER

IPC: C07D333/22 ,  A61K31/137 ,  A61K31/165 ,  A61K31/27 ,  A61K31/381 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/41 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4439 ,  A61K31/444 ,  A61K45/00 ,  A61P3/10 ,  A61P17/04 ,  A61P19/00 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P41/00 ,  A61P43/00 ,  C07C211/27 ,  C07C211/28 ,  C07C211/29 ,  C07C215/28 ,  C07C225/16 ,  C07C233/11 ,  C07C233/13 ,  C07C233/18 ,  C07C233/31 ,  C07C233/65 ,  C07C233/66 ,  C07C233/69 ,  C07C233/76 ,  C07C235/78 ,  C07C271/12 ,  C07C271/14 ,  C07C271/16 ,  C07C271/18 ,  C07C327/44 ,  C07D207/06 ,  C07D207/16 ,  C07D213/38 ,  C07D213/40 ,  C07D213/50 ,  C07D213/53 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D409/06 ,  A61K31/445 ,  A61K38/18

CPC classification number: C07D401/06 ,  C07D207/06 ,  C07D207/16 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04

公开(公告)号：CA2369504C

公开(公告)日：2009-01-06

申请号：CA2369504

申请日：2001-02-05

Applicant: VERTEX PHARMA

Inventor： BEMIS GUY ,  CAO JINGRONG ,  MULLICAN MICHAEL ,  XIE XIAOLING ,  GREEN JEREMY ,  STRAUB JUDITH ,  MASHALL ROBERT ,  JANETKA JAMES ,  MALTAIS FRANCOIS ,  BAKER CHRISTOPHER ,  HALE MICHAEL ,  TANG QING

IPC: A61B17/00 ,  C07D403/04 ,  A61F2/02 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/433 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/00 ,  A61L27/00 ,  A61L27/28 ,  A61L31/08 ,  A61P1/00 ,  A61P1/16 ,  A61P1/18 ,  A61P3/10 ,  A61P5/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P13/00 ,  A61P13/10 ,  A61P13/12 ,  A61P15/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P21/00 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  A61P31/12 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  A61P37/02 ,  A61P37/04 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D231/38 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: Described herein are compounds that are useful as protein kinase inhibitors having the formula: (I) where R1-4, Q, and T are described in the specification. Th e compounds are useful for treating disease states in mammals that are alleviated by a prote in kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, an d cardiovascular disease.

公开(公告)号：SG129998A1

公开(公告)日：2007-03-20

申请号：SG2002012623

申请日：1998-08-27

Applicant: VERTEX PHARMA

Inventor： MCCAFFREY PATRICIA ,  NOVAK PERRY M ,  MULLICAN MICHAEL

IPC: A61K31/4406 ,  A61K31/4427 ,  A61K31/4458 ,  A61K31/4545 ,  A61P25/04 ,  A61P25/16 ,  A61P25/28 ,  C07D211/60 ,  C07D213/40 ,  C07D401/12 ,  C07D401/14 ,  A61K31/16 ,  A61K31/445 ,  C07C233/01

公开(公告)号：BG64465B1

公开(公告)日：2005-03-31

申请号：BG10262498

申请日：1998-07-13

Applicant: VERTEX PHARMA

Inventor： BATCHELOR MARK ,  BEBBINGTON DAVID ,  BEMIS GUY ,  FRIDMAN WOLF ,  GILLESPIE ROGER ,  GOLEC JULIAN ,  GU YONG ,  LAUFFER DAVID ,  LIVINGSTON DAVID ,  MATHARU SAROOP ,  MULLICAN MICHAEL ,  MURCKO MARK ,  MURDOCH ROBERT ,  NYCE PHILIP ,  ROBIDOUX ANDREA ,  SU MICHAEL ,  WANNAMAKER M ,  WILSON KEITH ,  ZELLE ROBERT

IPC: C07D243/12 ,  A61K31/55 ,  A61K31/551 ,  A61K31/553 ,  A61K31/675 ,  A61K38/00 ,  A61K38/04 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61K38/55 ,  A61P13/12 ,  A61P19/08 ,  A61P19/10 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  A61P35/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07D243/10 ,  C07D243/14 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D487/04 ,  C07D491/048 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07D519/00 ,  C07F9/645 ,  C07F9/6561 ,  C07K5/02 ,  C07K5/023 ,  C07K5/06 ,  C07K5/078 ,  C07K5/097 ,  A61K38/08 ,  C07D243/00 ,  C07D237/00

Abstract: The present invention relates to novel classes of compounds, which are inhibitors of interleukin-1-beta converting enzyme (ICE), to a method for the preparation thereof, and to pharmaceutical compositions containing these compounds. The compounds and the pharmaceutical compositions according to the invention are suitable for the inhibition of ICE activity and can be used as agents against interleukin-1- (IL-1), apoptosis, inducing interferon gamma (IGIF) and interferon (IFN-gamma), including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases and degenerative diseases.

公开(公告)号：NZ516888A

公开(公告)日：2004-02-27

申请号：NZ51688800

申请日：2000-07-27

Applicant: VERTEX PHARMA

Inventor： MULLICAN MICHAEL ,  LAUFFER DAVID ,  TUNG ROGER

IPC: A61K31/137 ,  A61K31/165 ,  A61K31/27 ,  A61K31/381 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/41 ,  C07D333/22 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4439 ,  A61K31/444 ,  A61K45/00 ,  A61P3/10 ,  A61P17/04 ,  A61P19/00 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P41/00 ,  A61P43/00 ,  C07C211/27 ,  C07C211/28 ,  C07C211/29 ,  C07C215/28 ,  C07C225/16 ,  C07C233/11 ,  C07C233/13 ,  C07C233/18 ,  C07C233/31 ,  C07C233/65 ,  C07C233/66 ,  C07C233/69 ,  C07C233/76 ,  C07C235/78 ,  C07C271/12 ,  C07C271/14 ,  C07C271/16 ,  C07C271/18 ,  C07C327/44 ,  C07D207/06 ,  C07D207/16 ,  C07D213/38 ,  C07D213/40 ,  C07D213/50 ,  C07D213/53 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D409/06 ,  A61K31/445 ,  A61K38/18 ,  A61K31/44 ,  C07D211/06 ,  C07D211/32

Abstract: An acyclic or cyclic amine derivative or pharmaceutically acceptable salts thereof has the formula (I) wherein: X is -CH2CH2-, -CH=CH-, -C(OH)CH2-, -CH2C(OH)-, =C(F)CH2-, - C(F)=CH2-, -NHC(O)-, -P(O)(OH)CH2-, -CH2SO2-, -C(S)NR1-, - C(O)CH2CH(OH)-, -C(OH)CF2-, -C(O)CF2-, -CH(F)CH2-, - C(F)2CH2-, tetrazolyl or an epoxy group; A, B and R1 are independently E, optionally substituted alkyl, alkenyl or alkynyl, cycloalkyl or cycloalkenyl wherein 1 to 2 of the-CH2- groups in the alkyl, alkenyl, or alkynyl is optionally and independently replaced by -O-, - S(O)0-2-, =N-, -N= or -N(R3)- or B and R1 are independently hydrogen; E is an optionally substituted optionally saturated or aromatic monocyclic or bicyclic ring system, wherein each ring comprises 5 to 7 ring atoms independently selected from C, N, N(R3), O or S(O)0-2 and wherein no more than 4 ring atoms are selected from N, N(R3), O or S(O)0-2; J is H, methyl, ethyl or benzyl and K and K1 are independently optionally substituted alkyl, alkenyl or alkynyl, or cyclohexylmethyl, or J and K, taken together with the nitrogen and carbon atom to which they are respectively bound, form optionally substituted 5-7 membered heterocyclic ring, optionally containing up to 3 additional heteroatoms selected from N, N(R3), O, or S(O)0- 2; G, when present, is -S(O)-2-, -C(O)-, S(O)2-Y-, C(O)-Y-, - C(O)-C(O)-, or -C(O)-C(O)-Y-; Y is oxygen or N(R6); D is hydrogen or optionally substituted alkyl, alkenyl or alkynyl, cycloalkyl or cycloalkenyl optionally substituted with alkyl or alkenyl or alkynyl, alkyl-E, -alkenyl-E or alkynyl-E, or E; x is 0 or 1 and R3 and R6 are as defined in the specification; provided that when J is hydrogen or G is S(O)2, C(O)C(O), SO2-Y, C(O)-Y, or C(O)C(O)-Y and Y is O; then D is not hydrogen. The compounds are useful for stimulating neuronal regeneration or preventing neurodegeneration in a patient or in an ex vivo nerve cell.

公开(公告)号：HU0202332A2

公开(公告)日：2002-10-28

申请号：HU0202332

申请日：2001-02-05

Applicant: VERTEX PHARMA

Inventor： BAKER CHRISTOPHER ,  BEMIS GUY ,  CAO JINGRONG ,  GREEN JEREMY ,  HALE MICHAEL ,  JANETKA JAMES ,  MALTAIS FRANCOIS ,  MASHALL ROBERT ,  MULLICAN MICHAEL ,  STRAUB JUDITH ,  TANG QING ,  XIE XIAOLING

IPC: A61B17/00 ,  A61F2/02 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/433 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/00 ,  A61L27/00 ,  A61P1/00 ,  A61P1/16 ,  A61P1/18 ,  A61P3/10 ,  A61P5/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P13/00 ,  A61P13/10 ,  A61P13/12 ,  A61P15/00 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P21/00 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  A61P31/12 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  A61P37/02 ,  A61P37/04 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D231/38 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D471/04 ,  C07D403/00

Abstract: Described herein are compounds that are useful as protein kinase inhibitors having the formula: where R 1-4 , Q, and T are described in the specification. The compounds are useful for treating disease states in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, and cardiovascular disease.