Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl-methyl]-3-thiophenecarboxylic acid (BMS-587101)--a small molecule antagonist of leukocyte function associated antigen-1.
J Med Chem
; 49(24): 6946-9, 2006 Nov 30.
Article
in En
| MEDLINE
| ID: mdl-17125246
ABSTRACT
LFA-1 (leukocyte function-associated antigen-1), is a member of the beta2-integrin family and is expressed on all leukocytes. This letter describes the discovery and preliminary SAR of spirocyclic hydantoin based LFA-1 antagonists that culminated in the identification of analog 8 as a clinical candidate. We also report the first example of the efficacy of a small molecule LFA-1 antagonist in combination with CTLA-4Ig in an animal model of transplant rejection.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spiro Compounds
/
Thiophenes
/
Lymphocyte Function-Associated Antigen-1
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2006
Type:
Article
Affiliation country:
France