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Bioorg Med Chem Lett ; 18(7): 2509-12, 2008 Apr 01.
Article in English | MEDLINE | ID: mdl-18331794

ABSTRACT

A novel series of barbituric acid derivatives were identified as selective inhibitors of alpha4beta7 MAdCAM (mucosal addressin cell adhesion molecule-1) interactions via a high throughput screening exercise. These inhibitors were optimized to submicromolar potencies in whole cell adhesion assays, retaining their selectivity over alpha4beta1 VCAM.


Subject(s)
Barbiturates/pharmacology , Cell Adhesion/drug effects , Integrins/antagonists & inhibitors , Mucoproteins/antagonists & inhibitors , Animals , Barbiturates/chemical synthesis , Binding Sites , Cell Adhesion/physiology , Cell Adhesion Molecules , Immunoglobulins/metabolism , Integrin alpha4beta1/metabolism , Integrins/metabolism , Mice , Models, Chemical , Mucoproteins/metabolism , Structure-Activity Relationship , Vascular Cell Adhesion Molecule-1/metabolism
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