Dehydrophenylalanine derivatives as VLA-4 integrin antagonists
摘要:
We describe a series of dehydrophenylalanine derivatives where the Z isomers are potent VLA-4 antagonists but are subject to rapid biliary clearance and the E isomers have poor activity but have a slower rate of clearance. These configurationally constrained molecules have led to the design of a novel class of benzodiazepine VLA-4 antagonists. (C) 2003 Elsevier Science Ltd. All rights reserved.
Access to 1H-indazoles, 1H-benzoindazoles and 1H-azaindazoles from (het)aryl azides: a one-pot Staudinger-aza-Wittig reaction leading to N–N bond formation?
Benzodiazapine derivatives of formula (1) are described:
wherein
Ar1 is an aromatic or heteroaromatic group;
L1 is a linker atom or group;
Ar2 is an optionally substituted aromatic or heteroaromatic group;
R5 is a carboxylic acid (—CO2H) or a derivative thereof;
The compounds are able to inhibit the binding of alpha 4 integrins to their ligands and are of use in the prophylaxis and treatment of immune in inflammatory disorders.
1,3-BENZODIAZEPINES WITH INTEGRIN INHIBITORY ACTIVITY FOR USE IN THE TREATMENT OF INFLAMMATORY DISORDERS
申请人:CELLTECH THERAPEUTICS LIMITED
公开号:EP1117658A1
公开(公告)日:2001-07-25
US6274577B1
申请人:——
公开号:US6274577B1
公开(公告)日:2001-08-14
[EN] 1,3-BENZODIAZEPINES WITH INTEGRIN INHIBITORY ACTIVITY FOR USE IN THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] 1,3-BENZODIAZEPINES POSSEDANT UNE ACTIVITE INHIBANT L'INTEGRINE UTILES POUR TRAITER DES TROUBLES INFLAMMATOIRES
申请人:CELLTECH THERAPEUTICS LTD
公开号:WO2000018760A1
公开(公告)日:2000-04-06
1,3-Benzodiazapine derivatives of formula (1) are described wherein Ar1 is an aromatic or heteroaromatic group; L1 is a linker atom or group; Ar2 is an optionally substituted aromatic or heteroaromatic group; R5 is a carboxylic acid (-CO¿2?H) or a derivative thereof. The compounds are able to inhibit the binding of alpha 4 integrins to their ligands and are of use in the prophylaxis and treatment of immune in inflammatory disorders.
Access to 1<i>H</i>-indazoles, 1<i>H</i>-benzoindazoles and 1<i>H</i>-azaindazoles from (het)aryl azides: a one-pot Staudinger-aza-Wittig reaction leading to N–N bond formation?