Diamine containing VLA-4 antagonists

被引：13

作者：

Astles, PC ^{[1
]}

Harris, NV ^{[1
]}

Morley, AD ^{[1
]}

机构：

[1] Aventis Pharma Ltd, Dagenham Res Ctr, Dagenham RM10 7XS, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2001年 / 9卷 / 08期

关键词：

D O I：

10.1016/S0968-0896(01)00132-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Design and synthesis of a library as potential VLA-4 antagonists has been accomplished, based around a proposed pharmacophoric model. Compounds possessing submicromolar potency were identified and structure-activity relationships were seen across the library. Further derivatisation produced compounds with IC50'S < 10 nmol for inhibiting the VLA-4 mediated binding of fibronectin to RAMOS cells, providing an ideal starting point for a lead optimisation Programme. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：2195 / 2202

页数：8

共 20 条

[1] Blockade of late-phase airway responses and airway hyperresponsiveness in allergic sheep with a small-molecule peptide inhibitor of VLA-4 [J].

Abraham, WM ;

Ahmed, A ;

Sielczak, MW ;

Narita, M ;

Arrhenius, T ;

Elices, MJ .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 156 (03) :696-703

[2] ALPHA(4)-INTEGRINS MEDIATE ANTIGEN-INDUCED LATE BRONCHIAL RESPONSES AND PROLONGED AIRWAY HYPERRESPONSIVENESS IN SHEEP [J].

ABRAHAM, WM ;

SIELCZAK, MW ;

AHMED, A ;

CORTES, A ;

LAUREDO, IT ;

KIM, J ;

PEPINSKY, B ;

BENJAMIN, CD ;

LEONE, DR ;

LOBB, RR ;

WELLER, PF .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) :776-787

[3]

ADAMS SP, Patent No. 9622966

[4] Discovery and evaluation of potent, tyrosine-based α4β1 integrin antagonists [J].

Archibald, SC ;

Head, JC ;

Gozzard, N ;

Howat, DW ;

Parton, TAH ;

Porter, JR ;

Robinson, MK ;

Shock, A ;

Warrellow, GJ ;

Abraham, WM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (09) :997-999

[5]

ARRHENIUS TS, Patent No. 9606108

[6]

ASTLES PC, Patent No. 9923063

[7]

BUCCIARELLI M, J CHEM SOC P1, P3041

[8]

BUNIN BA, 1998, COMBINATORIAL INDEX, P82

[9] 1-HYDROXY-7-AZABENZOTRIAZOLE - AN EFFICIENT PEPTIDE COUPLING ADDITIVE [J].

CARPINO, LA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (10) :4397-4398

[10]

DUTTA AS, Patent No. 9702289

← 1 2 →