Design, synthesis and structure-activity relationship of a series of arginine aldehyde factor Xa inhibitors. Part 1: Structures based on the (D)-Arg-Gly-Arg tripeptide sequence

被引：23

作者：

Marlowe, CK ^{[1
]}

Sinha, U ^{[1
]}

Gunn, AC ^{[1
]}

Scarborough, RM ^{[1
]}

机构：

[1] COR Therapeut Inc, S San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 01期

关键词：

D O I：

10.1016/S0960-894X(99)00582-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of arginine aldehyde inhibitors was designed as transition state (TS) analogues based on the known factor Xa specific substrate Cbz-D-Arg-Gly-Arg-pNA. BnSO2-(D)Arg-Gly-Arg-H (20) was found to be the most potent and selective inhibitor of factor Xa and prothrombinase activity in this series. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：13 / 16

页数：4

共 19 条

[1]

BAJUSZ S, 1978, INT J PEPT PROT RES, V12, P217

[2]

BARTLETT PA, 1983, BIOCHEMISTRY-US, V22, P1085

[3] X-ray structure of active site-inhibited clotting factor Xa - Implications for drug design and substrate recognition [J].

Brandstetter, H ;

Kuhne, A ;

Bode, W ;

Huber, R ;

vonderSaal, W ;

Wirthensohn, K ;

Engh, RA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (47) :29988-29992

[4]

BRUNCK TK, Patent No. 13693

[5]

CLAESON G, 1994, BLOOD COAGUL FIBRIN, V5, P411

[6] Thrombin and factor Xa inhibition [J].

Edmunds, JJ ;

Rapundalo, ST ;

Siddiqui, MA .

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 31, 1996, 31 :51-60

[7]

GASTAVSSON SI, Patent No. 4797472

[8] Highly selective mechanism-based thrombin inhibitors: Structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes [J].

Krishnan, R ;

Zhang, E ;

Hakansson, K ;

Arni, RK ;

Tulinsky, A ;

Lim-Wilby, MSL ;

Levy, OE ;

Semple, JE ;

Brunck, TK .

BIOCHEMISTRY, 1998, 37 (35) :12094-12103

[9] PROPOSED CATION-PI MEDIATED BINDING BY FACTOR XA - A NOVEL ENZYMATIC MECHANISM FOR MOLECULAR RECOGNITION [J].

LIN, ZL ;

JOHNSON, ME .

FEBS LETTERS, 1995, 370 (1-2) :1-5

[10] AUTOMATED SYNTHESIS OF PEPTIDE C-TERMINAL ALDEHYDES [J].

MURPHY, AM ;

DAGNINO, R ;

VALLAR, PL ;

TRIPPE, AJ ;

SHERMAN, SL ;

LUMPKIN, RH ;

TAMURA, SY ;

WEBB, TR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (08) :3156-3157

← 1 2 →