Novel bicyclic lactam inhibitors of thrombin:: Highly potent and selective inhibitors

被引：18
|
作者：
St-Denis, Y
Lévesque, S
Bachand, B
Edmunds, JJ
Leblond, L
Préville, P
Tarazi, M
Winocour, PD
Siddiqui, MA
机构：
[1] Shire BioChem, Laval, PQ H7V 4A7, Canada
[2] Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 08期
关键词：
D O I：
10.1016/S0960-894X(02)00131-2
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The potency and selectivity of a previous series of low molecular weight thrombin inhibitors were improved through modifications of the P1 and P3 residues. Introduction of diphenyl substituted sulfonamides in the P3 moiety led to highly efficacious compounds. By correctly selecting the combination of P1 and P3 residues, high levels of potency, selectivity and in vivo efficacy were obtained. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
下载
收藏
页码：1181 / 1184
页数：4
相关论文
共 50 条
  • [11] In vitro and in vivo properties of bicyclic lactam inhibitors: A novel class of low molecular weight peptidomimetic thrombin inhibitors
    Leblond, L
    Grouix, B
    Boudreau, C
    Yang, Q
    Siddiqui, MA
    Winocour, PD
    THROMBOSIS RESEARCH, 2000, 100 (03) : 195 - 209
  • [12] Preparation of bicyclic pyrazoloheterocycles as highly potent, selective inhibitors of coagulation Factor Xa
    Li, Yun-Long
    Fevig, John M.
    Han, Qi
    Luettgen, Joseph M.
    Knabb, Robert M.
    Wexler, Ruth R.
    Lam, Patrick Y. S.
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 231
  • [13] Bicyclic pyridones as potent, efficacious and orally bioavailable thrombin inhibitors
    Coburn, CA
    Rush, DM
    Williams, PD
    Homnick, C
    Lyle, EA
    Lewis, SD
    Lucas, BJ
    Di Muzio-Mower, JM
    Juliano, M
    Krueger, JA
    Vastag, K
    Chen, IW
    Vacca, JP
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (10) : 1069 - 1072
  • [14] HIGHLY SELECTIVE TRIPEPTIDE THROMBIN INHIBITORS
    SHUMAN, RT
    ROTHENBERGER, RB
    CAMPBELL, CS
    SMITH, GF
    GIFFORDMOORE, DS
    GESELLCHEN, PD
    JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (03) : 314 - 319
  • [15] Discovery of novel N-acylpyrazoles as potent and selective thrombin inhibitors
    Short, Kevin M.
    Estiarte, M. Angels
    Pham, Son M.
    Williams, David C.
    Igoudin, Lev
    Dash, Subhadra
    Sandoval, Nichole
    Datta, Anirban
    Pozzi, Nicola
    Di Cera, Enrico
    Kita, David B.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, 246
  • [16] Novel bicyclic lactam inhibitors of thrombin:: Potency and selectivity optimization through P1 residues
    Lévesque, S
    St-Denis, Y
    Bachand, B
    Préveille, P
    Leblond, L
    Winocour, PD
    Edmunds, JJ
    Rubin, JR
    Siddiqui, MA
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (24) : 3161 - 3164
  • [17] Design and synthesis of potent and selective macrocyclic thrombin inhibitors
    Nantermet, PG
    Barrow, JC
    Newton, CL
    Pellicore, JM
    Young, MB
    Lewis, SD
    Lucas, BJ
    Krueger, JA
    McMasters, DR
    Yan, YW
    Kuo, LC
    Vacca, JP
    Selnick, HG
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (16) : 2781 - 2784
  • [18] The discovery of potent and selective peptidomimetic inhibitors of thrombin.
    Cody, WL
    Berryman, KA
    Cai, C
    Doherty, AM
    Edmunds, JJ
    He, JX
    Holland, DR
    Narasimhan, L
    Plummer, JS
    Rapundalo, ST
    Susser, A
    VanHuis, CA
    Siddiqui, MA
    St-Denis, Y
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1999, 217 : U1178 - U1178
  • [19] Identification of novel potent bicyclic peptide deformylase inhibitors
    Molteni, V
    He, XH
    Nabakka, J
    Yang, KY
    Kreusch, A
    Gordon, P
    Bursulaya, B
    Warner, I
    Shin, T
    Biorac, T
    Ryder, NS
    Goldberg, R
    Doughty, J
    He, Y
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (06) : 1477 - 1481
  • [20] Novel, potent non-covalent thrombin inhibitors incorporating P3-lactam scaffolds
    Ho, JZ
    Gibson, TS
    Semple, JE
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (05) : 743 - 748
12345