Benzylamine-based selective and orally bioavailable inhibitors of thrombin

被引：29

作者：

Lee, K ^{[1
]}

Jung, WH ^{[1
]}

Park, CW ^{[1
]}

Hong, CY ^{[1
]}

Kim, IC ^{[1
]}

Kim, S ^{[1
]}

Oh, YS ^{[1
]}

Kwon, OH ^{[1
]}

Lee, SH ^{[1
]}

Park, HD ^{[1
]}

Kim, SW ^{[1
]}

Lee, YH ^{[1
]}

Yoo, YJ ^{[1
]}

机构：

[1] LG Chem Ltd Res Pk, Biotech Res Inst, Taejon 305380, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 18期

关键词：

D O I：

10.1016/S0960-894X(98)00456-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of p-aminomethylphenylalanine derivatives were investigated as novel thrombin inhibitors. This study led to potent inhibitors of thrombin (Ki up to 3.3 nM) that are trypsin-selective, highly orally bioavailable in rats, and highly permeable across Caco-2 cells. The P1 benzylamine binding mode in the thrombin active site was identified by X-ray crystallographic analysis. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：2563 / 2568

页数：6

共 24 条

[11] Solid phase synthesis of benzylamine-derived sulfonamide library
Kim, SW
Hong, CY
Lee, K
Lee, EJ
Koh, JS
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (07) : 735 - 738
[12] CHALLENGES IN THE DEVELOPMENT OF ORALLY BIOAVAILABLE THROMBIN ACTIVE-SITE INHIBITORS
KIMBALL, SD
[J]. BLOOD COAGULATION & FIBRINOLYSIS, 1995, 6 (06) : 511 - 519
[13] Structural modification of an orally active thrombin inhibitor, LB30057: Replacement of the D-pocket-binding naphthyl moiety
Lee, K
Hwang, SY
Hong, S
Hong, CY
Lee, CS
Shin, Y
Kim, S
Yun, M
Yoo, YJ
Kang, M
Oh, YS
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1998, 6 (06) : 869 - 876
[14] LEE K, 1997, J KOR MED CHEM, V6, P127
[15] LEE K, 1997, 214 ACS NAT M LAS VA
[16] Design of novel, potent, noncovalent inhibitors of thrombin with nonbasic P-1 substructures: Rapid structure-activity studies by solid-phase synthesis
Lumma, WC
Witherup, KM
Tucker, TJ
Brady, SF
Sisko, JT
Naylor-Olsen, AM
Lewis, SD
Lucas, BJ
Vacca, JP
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (07) : 1011 - 1013
[17] MILLET J, 1992, THROMB HAEMOSTASIS, V67, P176
[18] ARGATROBAN ANALOGS - SYNTHESIS, THROMBIN INHIBITORY ACTIVITY AND CELL-PERMEABILITY OF AMINOHETEROCYCLIC GUANIDINE SURROGATES
MISRA, RN
KELLY, YF
BROWN, BR
ROBERTS, DGM
CHONG, SH
SEILER, SM
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (18) : 2165 - 2170
[19] Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor
Oh, YS
Yun, M
Hwang, SY
Hong, S
Shin, Y
Lee, K
Yoon, KH
Yoo, YJ
Kim, DS
Lee, SH
Lee, YH
Park, HD
Lee, CH
Lee, SK
Kim, S
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (06) : 631 - 634
[20] OH YS, 1996, Patent No. 739886

← 1 2 3 →