公开(公告)号：US5434248A

公开(公告)日：1995-07-18

申请号：US70483

申请日：1993-06-02

申请人： Kevin T. Chapman ,  Herb G. Bull ,  Malcolm MacCoss ,  Nancy A. Thornberry ,  Jeffrey R. Weidner ,  Adnan M. Mjalli

发明人： Kevin T. Chapman ,  Herb G. Bull ,  Malcolm MacCoss ,  Nancy A. Thornberry ,  Jeffrey R. Weidner ,  Adnan M. Mjalli

IPC分类号： A61K38/55 ,  A61P11/00 ,  A61P29/00 ,  C07C233/47 ,  C07C233/51 ,  C07C237/22 ,  C07K5/02 ,  C07K5/06 ,  C07K5/08 ,  A61K38/00 ,  C07K5/00 ,  C07K7/00 ,  C07K17/00

CPC分类号： C07K5/0202 ,  C07C233/47 ,  C07C233/51

摘要： Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1.beta. converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia. ##STR1##

公开(公告)号：US06348570B1

公开(公告)日：2002-02-19

申请号：US07808994

申请日：1991-12-17

申请人： Kevin T. Chapman ,  Malcolm Maccoss ,  Richard A. Mumford ,  Nancy A. Thornberry ,  Jeffrey R. Weidner ,  William K. Hagmann

发明人： Kevin T. Chapman ,  Malcolm Maccoss ,  Richard A. Mumford ,  Nancy A. Thornberry ,  Jeffrey R. Weidner ,  William K. Hagmann

IPC分类号： A61K3804

CPC分类号： C07K5/1016 ,  C07K14/545

摘要： Disclosed are novel chromophore containing compounds of Formula I and their use in determining interleukin-1&bgr; convertase (ICE) activity. ICE has been implicated in inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes.

摘要翻译： 公开了含有式I化合物的新颖发色团及其在测定白细胞介素-1β转化酶（ICE）活性中的用途。 ICE已经涉及肺和气道的炎性或免疫性疾病; 中枢神经系统和周围膜; 眼睛和耳朵 关节，骨骼和结缔组织; 包括心包的心血管系统; 胃肠道和泌尿生殖系统; 皮肤和粘膜。

公开(公告)号：US5278061A

公开(公告)日：1994-01-11

申请号：US746685

申请日：1991-08-16

申请人： Herb G. Bull ,  Kevin T. Chapman

发明人： Herb G. Bull ,  Kevin T. Chapman

IPC分类号： B01J20/32 ,  C07K5/02 ,  C12N9/64 ,  C12N9/48 ,  A23J1/00

CPC分类号： B01J20/286 ,  B01D15/3804 ,  B01J20/3212 ,  B01J20/3251 ,  B01J20/3253 ,  B01J20/3255 ,  C07K5/0202 ,  C12N9/6475 ,  Y10S435/814 ,  Y10S435/815

摘要： Affinity chromatography matrices are disclosed which are useful in purifying interleukin-1.beta. converting enzyme (ICE) from crude or partially purified cell lysate preparations. The chromatographic matrices comprise a specific ICE inhibitor of Formula I which is attached to an affinity column support by means of a bifunctional spacer. ##STR1##

摘要翻译： 公开了亲和层析基质，其可用于从粗制或部分纯化的细胞裂解物制剂纯化白细胞介素-1（β）转化酶（ICE）。 色谱基质包括通过双功能间隔物连接到亲和柱支持体上的特定的式I的ICE抑制剂。 （*化学结构*）I

公开(公告)号：US06500844B1

公开(公告)日：2002-12-31

申请号：US09590487

申请日：2000-06-08

申请人： Paul E. Finke ,  Kevin T. Chapman ,  Malcolm Maccoss ,  Sander G. Mills ,  Bryan Oates

发明人： Paul E. Finke ,  Kevin T. Chapman ,  Malcolm Maccoss ,  Sander G. Mills ,  Bryan Oates

IPC分类号： A61K31445

CPC分类号： C07D401/08 ,  C07D211/58 ,  C07D413/08

摘要： The present invention is directed to compounds of the formula I: (wherein R1, R2, R3, R7, R8, X, Y, Z, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

摘要翻译： 本发明涉及可用作趋化因子受体活性调节剂的式I化合物（其中R1，R2，R3，R7，R8，X，Y，Z，x和y如本文所定义）。 特别地，这些化合物可用作趋化因子受体CCR-5和/或CCR-3的调节剂。

公开(公告)号：US06399619B1

公开(公告)日：2002-06-04

申请号：US09542898

申请日：2000-04-04

申请人： Scott Berk ,  Charles G. Caldwell ,  Kevin T. Chapman ,  Jeffrey Hale ,  Christopher Lynch ,  Malcolm MacCoss ,  Sander G. Mills ,  Christopher Willoughby

发明人： Scott Berk ,  Charles G. Caldwell ,  Kevin T. Chapman ,  Jeffrey Hale ,  Christopher Lynch ,  Malcolm MacCoss ,  Sander G. Mills ,  Christopher Willoughby

IPC分类号： A61K31495

CPC分类号： C07D401/06 ,  C07C259/06 ,  C07C2601/02 ,  C07C2601/04 ,  C07D401/14 ,  C07D405/14

摘要： The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

公开(公告)号：US06498161B1

公开(公告)日：2002-12-24

申请号：US09543019

申请日：2000-04-04

申请人： Charles G. Caldwell ,  Kevin T. Chapman ,  Jeffrey Hale ,  Dooseop Kim ,  Christopher Lynch ,  Malcolm MacCoss ,  Sander G. Mills ,  Christopher Willoughby ,  Scott Berk ,  Ronald M. Kim

发明人： Charles G. Caldwell ,  Kevin T. Chapman ,  Jeffrey Hale ,  Dooseop Kim ,  Christopher Lynch ,  Malcolm MacCoss ,  Sander G. Mills ,  Christopher Willoughby ,  Scott Berk ,  Ronald M. Kim

IPC分类号： A61K31165

CPC分类号： C07D401/14 ,  C07D401/06 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D491/10 ,  C07F9/59 ,  C07F9/65583

摘要： The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

摘要翻译： 本发明涉及可用作趋化因子受体活性的调节剂的式I的吡咯烷化合物（其中R 1，R 2，R 3，R 4，R 5，R 6和n如本文所定义）。 特别地，这些化合物可用作趋化因子受体CCR-5和/或CCR-3的调节剂。

公开(公告)号：US06265434B1

公开(公告)日：2001-07-24

申请号：US09543024

申请日：2000-04-04

申请人： Charles Caldwell ,  Kevin T. Chapman ,  Jeffrey Hale ,  Dooseop Kim ,  Christopher Lynch ,  Malcolm MacCoss ,  Sander G. Mills ,  Keith Rosauer ,  Christopher Willoughby ,  Scott Berk

发明人： Charles Caldwell ,  Kevin T. Chapman ,  Jeffrey Hale ,  Dooseop Kim ,  Christopher Lynch ,  Malcolm MacCoss ,  Sander G. Mills ,  Keith Rosauer ,  Christopher Willoughby ,  Scott Berk

IPC分类号： A61K3140

CPC分类号： C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04

摘要： The present invention is directed to pyrrolidine compounds of the formula 1: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

摘要翻译： 本发明涉及可用作趋化因子受体活性调节剂的式1的吡咯烷化合物（其中R 1，R 2，R 3，R 4，R 5，R 6和n如本文所定义）。 特别地，这些化合物可用作趋化因子受体CCR-5和/或CCR-3的调节剂。

公开(公告)号：US06593346B2

公开(公告)日：2003-07-15

申请号：US10075163

申请日：2002-02-14

申请人： Paul E. Finke ,  Kerry A. Hilfiker ,  Malcolm MacCoss ,  Kevin T. Chapman ,  Jennifer L. Loebach ,  Sander G. Mills ,  Ravi N. Guthikonda ,  Shrenik K. Shah ,  Dooseop Kim ,  Dong-Ming Shen ,  Bryan Oates

发明人： Paul E. Finke ,  Kerry A. Hilfiker ,  Malcolm MacCoss ,  Kevin T. Chapman ,  Jennifer L. Loebach ,  Sander G. Mills ,  Ravi N. Guthikonda ,  Shrenik K. Shah ,  Dooseop Kim ,  Dong-Ming Shen ,  Bryan Oates

IPC分类号： A61K31445

CPC分类号： C07D401/04 ,  C07D211/14 ,  C07D211/18 ,  C07D211/20 ,  C07D211/24 ,  C07D211/34 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/06 ,  C07D417/04 ,  C07D471/04 ,  Y02P20/582

摘要： The present invention is directed to compounds of the formula I: (wherein R1, R3, R4, R5, R6, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

公开(公告)号：US5430128A

公开(公告)日：1995-07-04

申请号：US342991

申请日：1994-11-21

申请人： Kevin T. Chapman ,  Malcolm MacCoss ,  Adnan Mjalli

发明人： Kevin T. Chapman ,  Malcolm MacCoss ,  Adnan Mjalli

IPC分类号： A61K38/00 ,  C07K5/02 ,  C07K5/06 ,  C07K5/08 ,  C07K5/00 ,  C07K7/00 ,  C07K17/00

CPC分类号： C07K5/0202 ,  A61K38/00

摘要： Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1.beta. converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia. ##STR1##

摘要翻译： 发现式I的新型肽基衍生物是白细胞介素-1β转换酶（ICE）的有效抑制剂。 式I化合物可用于治疗肺和气道炎性或免疫性疾病; 中枢神经系统和周围膜; 眼睛和耳朵 关节，骨骼和结缔组织; 包括心包的心血管系统; 胃肠道和泌尿生殖系统; 皮肤和粘膜。 式I化合物也可用于治疗感染（例如，革兰氏阴性休克）的并发症和其中IL1作为自分泌生长因子或作为恶病质介质的肿瘤。

公开(公告)号：US06472410B1

公开(公告)日：2002-10-29

申请号：US09590318

申请日：2000-06-08

申请人： Paul E. Finke ,  Kevin T. Chapman ,  Malcolm Maccoss ,  Sander G. Mills ,  Jennifer L. Loebach ,  Bryan Oates

发明人： Paul E. Finke ,  Kevin T. Chapman ,  Malcolm Maccoss ,  Sander G. Mills ,  Jennifer L. Loebach ,  Bryan Oates

IPC分类号： A61K314468

CPC分类号： C07D401/08 ,  C07D211/58 ,  Y02P20/582

摘要： The present invention is directed to compounds of the formula I: (wherein R1, R3, R4, R5, R6, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.