Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: Transition state inhibitors

被引：25

作者：

Bachand, B

Tarazi, M

St-Denis, Y

Edmunds, JJ

Winocour, PD

Leblond, L

Siddiqui, MA

机构：

[1] BioChem Pharma Inc, Laval, PQ H7V 4A7, Canada

[2] Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(00)00636-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P-1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：287 / 290

页数：4

共 7 条

[1] SYNTHESIS OF OPTICALLY PURE ANALOGS OF D-ARGININE METHYL-ESTER WITH ANTIARRHYTHMIC ACTIVITY
BANFI, A
BENEDINI, F
SALA, A
RUSSO, G
[J]. SYNTHETIC COMMUNICATIONS, 1990, 20 (10) : 1531 - 1542
[2] BRADY SF, 1996, PEPTIDES CHEM STRUCT, P331
[3] BCH-2763, a novel potent parenteral thrombin inhibitor, is an effective antithrombotic agent in rodent models of arterial and venous thrombosis - Comparisons with heparin, r-hirudin, hirulog, inogatran and argatroban
Finkle, CD
St Pierre, A
Leblond, L
Deschenes, I
DiMaio, J
Winocour, PD
[J]. THROMBOSIS AND HAEMOSTASIS, 1998, 79 (02) : 431 - 438
[4] Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor
Lyle, TA
Chen, ZG
Appleby, SD
Freidinger, RM
Gardell, SJ
Lewis, SD
Li, Y
Lyle, EA
Lynch, JJ
Mulichak, AM
Ng, AS
NaylorOlsen, AM
Sanders, WM
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (01) : 67 - 72
[5] Potent and selective bicyclic lactam inhibitors of thrombin: Part 2: P1 modifications
Plummer, JS
Berryman, KA
Cai, C
Cody, WL
DiMaio, J
Doherty, AM
Edmunds, JJ
He, JX
Holland, DR
Levesque, S
Kent, DR
Narasimhan, LS
Rubin, JR
Rapundalo, ST
Siddiqui, MA
Susser, AJ
St-Denis, Y
Winocour, PD
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (23) : 3409 - 3414
[6] Potent bicyclic lactam inhibitors of thrombin:: Part I:: P3 modifications
St-Denis, Y
Augelli-Szafran, CE
Bachand, B
Berryman, KA
DiMaio, J
Doherty, AM
Edmunds, JJ
Leblond, L
Lévesque, S
Narasimhan, LS
Penvose-Yi, JR
Rubin, JR
Tarazi, M
Winocour, PD
Siddiqui, MA
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (22) : 3193 - 3198
[7] VEBER DF, 1994, Patent No. 9425051

← 1 →