DESIGN OF NOVEL, NONPEPTIDIC THROMBIN INHIBITORS AND STRUCTURE OF A THROMBIN-INHIBITOR COMPLEX

被引：54

作者：

OBST, U

GRAMLICH, V

DIEDERICH, F

WEBER, L

BANNER, DW

机构：

[1] ETH ZENTRUM, ORGAN CHEM LAB, CH-8092 ZURICH, SWITZERLAND

[2] F HOFFMANN LA ROCHE & CIE AG, PRAKLIN FORSCH, DIV PHARMA, CH-4002 BASEL, SWITZERLAND

[3] ETH ZENTRUM, INST KRISTALLOG & PETROG, CH-8092 ZURICH, SWITZERLAND

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 1995年 / 34卷 / 16期

关键词：

AZOMETHINE YLIDES; CYCLOADDITIONS; DE NOVO DESIGN; ENZYME INHIBITORS; THROMBIN;

D O I：

10.1002/anie.199517391

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A strong inhibition of the serine protease thrombin, important in the blood coagulation process, was achieved through de novo designed inhibitors. The most active compound is shown. The X‐ray crystal structure of the thrombin–inhibitor complex showed the binding mode of these compounds and confirmed that only the enantiomer predicted by computer modeling was bound in the active site. (Figure Presented.) Copyright © 1995 by VCH Verlagsgesellschaft mbH, Germany

引用

页码：1739 / 1742

页数：4

共 22 条

[1] ENANTIOSELECTIVE COMPLEXATION OF CHIRAL DICARBOXYLIC-ACIDS IN CLEFTS OF FUNCTIONALIZED 9,9'-SPIROBIFLUORENES
ALCAZAR, V
DIEDERICH, F
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1992, 31 (11): : 1521 - 1523
[2] ALCAZAR V, 1992, ANGEW CHEM, V104, P1503
[3] BANNER DW, 1991, J BIOL CHEM, V266, P20085
[4] THE REFINED 1.9 A CRYSTAL-STRUCTURE OF HUMAN ALPHA-THROMBIN - INTERACTION WITH D-PHE-PRO-ARG CHLOROMETHYLKETONE AND SIGNIFICANCE OF THE TYR-PRO-PRO-TRP INSERTION SEGMENT
BODE, W
MAYR, I
BAUMANN, U
HUBER, R
STONE, SR
HOFSTEENGE, J
[J]. EMBO JOURNAL, 1989, 8 (11) : 3467 - 3475
[5] Diederich F, 1991, CYCLOPHANES
[6] DECARBOXYLATIVE TRANSAMINATION - MECHANISM AND APPLICATIONS TO THE SYNTHESIS OF HETEROCYCLIC-COMPOUNDS
GRIGG, R
THIANPATANAGUL, S
[J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1984, (03) : 180 - 181
[7] THE DECARBOXYLATIVE ROUTE TO AZOMETHINE YLIDES - STEREOCHEMISTRY OF 1,3-DIPOLE FORMATION
GRIGG, R
SURENDRAKUMAR, S
THIANPATANAGUL, S
VIPOND, D
[J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1987, (02) : 47 - 49
[8] DESIGN AND SYNTHESIS OF POTENT AND HIGHLY SELECTIVE THROMBIN INHIBITORS
HILPERT, K
ACKERMANN, J
BANNER, DW
GAST, A
GUBERNATOR, K
HADVARY, P
LABLER, L
MULLER, K
SCHMID, G
TSCHOPP, TB
VANDEWATERBEEMD, H
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (23) : 3889 - 3901
[9] DE-NOVO DESIGN AND SYNTHESIS OF SOMATOSTATIN NONPEPTIDE PEPTIDOMIMETICS UTILIZING BETA-D-GLUCOSE AS A NOVEL SCAFFOLDING
HIRSCHMANN, R
NICOLAOU, KC
PIETRANICO, S
LEAHY, EM
SALVINO, J
ARISON, B
CICHY, MA
SPOORS, PG
SHAKESPEARE, WC
SPRENGELER, PA
HAMLEY, P
SMITH, AB
REISINE, T
RAYNOR, K
MAECHLER, L
DONALDSON, C
VALE, W
FREIDINGER, RM
CASCIERI, MR
STRADER, CD
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (26) : 12550 - 12568
[10] KURINOV IV, 1994, STRUCT BIOL, V1, P735

← 1 2 3 →