1.
Bioorg Med Chem Lett
; 23(15): 4370-3, 2013 Aug 01.
Article
in English
| MEDLINE
| ID: mdl-23777782
ABSTRACT
A series of potent α4ß1/α4ß7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn's disease.
Subject(s)
Integrin alpha4beta1/antagonists & inhibitors , Integrins/antagonists & inhibitors , Administration, Oral , Animals , Area Under Curve , Arthritis, Rheumatoid/chemically induced , Arthritis, Rheumatoid/drug therapy , Crohn Disease/drug therapy , Disease Models, Animal , Half-Life , Humans , Integrin alpha4beta1/metabolism , Integrins/metabolism , Jurkat Cells , Microsomes, Liver/metabolism , Rats
2.
Bioorg Med Chem Lett
; 21(6): 1741-3, 2011 Mar 15.
Article
in English
| MEDLINE
| ID: mdl-21316228
ABSTRACT
A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model.