Orally available and efficacious α4β1/α4β7 integrin inhibitors

Ying-zi Xu; Jenifer L Smith; Christopher M Semko; Kassandra I Rossiter; Juri Y Fukuda; Michael S Dappen; David A Quincy; Andrei W Konradi; Wenxian Mao; Brent Welch; Mark L Dreyer; Bhushan Samant; Hongbin Zhang; Judevin Lugar; Zhenmei Liao; Carrol Henschel; Eric Petersen; Christopher Vandevert; Mark Shoemaker; Nancy Wehner; Linda Mutter; George Shopp; Michael Krimm; Linda Chen; Brian Wipke; Lilibeth Dofiles; Ian Gallager; John-Michael Sauer; Elizabeth K Messersmith; Michael A Pleiss; Frederique Bard; Ted A Yednock

doi:10.1016/j.bmcl.2013.05.076

Orally available and efficacious α4β1/α4β7 integrin inhibitors

Bioorg Med Chem Lett. 2013 Aug 1;23(15):4370-3. doi: 10.1016/j.bmcl.2013.05.076. Epub 2013 May 31.

Affiliation

¹ Elan Pharmaceuticals, 180 Oyster Point Blvd., South San Francisco, CA 94080, United States.

PMID: 23777782
DOI: 10.1016/j.bmcl.2013.05.076

Abstract

A series of potent α4β1/α4β7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn's disease.

MeSH terms

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 / antagonists & inhibitors*
Integrin alpha4beta1 / metabolism
Integrins / antagonists & inhibitors*
Integrins / metabolism
Jurkat Cells
Microsomes, Liver / metabolism
Rats

Substances

Integrin alpha4beta1
Integrins
integrin alpha4beta7