Combinatorial synthesis and biological evaluation of isoxazole-based libraries as antithrombotic agents

被引：52

作者：

Batra, S ^{[1
]}

Srinivasan, T

Rastogi, SK

Kundu, B

Patra, A

Bhaduri, AP

Dixit, M

机构：

[1] Cent Drug Res Inst, Div Med Chem, Lucknow 226001, Uttar Pradesh, India

[2] Cent Drug Res Inst, Div Pharmacol, Lucknow 226001, Uttar Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(02)00333-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 3-substituted phenyl-5-isoxazolecarboxaldehydes have been identified as activated aldehydes for the generation of isoxazole-based combinatorial libraries on solid phase through automation. Three highly functionalized isoxazole-based libraries comprising of 32, 96 and 45 compounds each have been synthesized in parallel format using Baylis Hillman reaction, Michael addition, reductive amination and alkylation reactions. With an objective of lead generation all the three libraries were evaluated for their antithrombin activity in vivo. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1905 / 1908

页数：4

共 24 条

[1]

BARALDI PG, 1987, SYNTHESIS-STUTTGART, P857

[2] A novel isoxazole-based scaffold for combinatorial chemistry [J].

Batra, S ;

Rastogi, SK ;

Kundu, B ;

Patra, A ;

Bhaduri, AP .

TETRAHEDRON LETTERS, 2000, 41 (31) :5971-5974

[3] Solid-phase synthesis of 3-hydroxymethyl isoxazoles via resin bound nitrile oxides [J].

Cereda, E ;

Ezhaya, A ;

Quai, M ;

Barbaglia, W .

TETRAHEDRON LETTERS, 2001, 42 (30) :4951-4953

[4]

CHIARINO D, 1986, FARMACO, V41, P440

[5]

DEJNA E, 1979, THROMB RES, V15, P191

[6] ENANTIOMERIC EFFECTS OF HOMOLOGS OF DISOXARIL ON THE INHIBITORY ACTIVITY AGAINST HUMAN RHINOVIRUS-14 [J].

DIANA, GD ;

OTTO, MJ ;

TREASURYWALA, AM ;

MCKINLAY, MA ;

OGLESBY, RC ;

MALISKI, EG ;

ROSSMANN, MG ;

SMITH, TJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (03) :540-544

[7] NOVEL ISOXAZOLES WHICH INTERACT WITH BRAIN CHOLINERGIC CHANNEL RECEPTORS HAVE INTRINSIC COGNITIVE ENHANCING AND ANXIOLYTIC ACTIVITIES [J].

GARVEY, DS ;

WASICAK, JT ;

DECKER, MW ;

BRIONI, JD ;

BUCKLEY, MJ ;

SULLIVAN, JP ;

CARRERA, GM ;

HOLLADAY, MW ;

ARNERIC, SP ;

WILLIAMS, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (08) :1055-1059

[8]

GARVEY DS, 1995, Patent No. 5409946

[9] DABCO-CATALYZED COUPLING OF ALDEHYDES WITH ACTIVATED DOUBLE-BONDS .1. PREPARATION OF 2-(1-HYDROXYALKYL)ACRYLIC ESTERS - SIMPLE 3-STEP SYNTHESIS OF MIKANECIC ACID [J].

HOFFMANN, HMR ;

RABE, J .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1983, 22 (10) :795-796

[10] Solid-phase synthesis of isoxazoles and isoxazolines: En route to a new class of ionophores [J].

Kantorowski, EJ ;

Kurth, MJ .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (20) :6797-6803

← 1 2 3 →