Potent and selective bicyclic lactam inhibitors of thrombin: Part 2: P1 modifications

被引：24

作者：

Plummer, JS ^{[1
]}

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

机构：

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

[2] BioChem Therapeut Inc, Laval, PQ H7V 4A7, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 23期

关键词：

D O I：

10.1016/S0960-894X(98)00613-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the pi site. The introduction of arginine mimetics at the pi site led to potent and selective thrombin inhibitors. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：3409 / 3414

页数：6

共 18 条

[1] BERRYMAN KA, 1997, Patent No. 9748687
[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] New routes to conformationally restricted peptide building blocks: A convenient preparation of bicyclic piperazinone derivatives
Fobian, YM
dAvignon, DA
Moeller, KD
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (03) : 315 - 318
[5] FRANCIS CW, 1994, HEMOSTASIS THROMBOSI, P1076
[6] GELDMACHER V, 1997, ANAL TOXICOL CLIN FO, P609
[7] DIRECT THROMBIN INHIBITORS IN CARDIOVASCULAR MEDICINE
LEFKOVITS, J
TOPOL, EJ
[J]. CIRCULATION, 1994, 90 (03) : 1522 - 1536
[8] Potent and selective thrombin inhibitors incorporating the constrained arginine mimic L-3-piperidyl(N-guanidino)alanine at P-1
Levy, OE
Semple, JE
Lim, ML
Reiner, J
Rote, WE
Dempsey, E
Richard, BM
Zhang, E
Tulinsky, A
Ripka, WC
Nutt, RF
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (23) : 4527 - 4530
[9] LOWE DGO, 1985, HEMOSTASIS THROMBOSI, pCH10
[10] Lyle T., 1993, PERSPECT DRUG DISCOV, V1, P453

← 1 2 →