Synthesis and biological evaluation of nonpeptide integrin antagonists containing spirocyclic scaffolds

Joanne M Smallheer; Carolyn A Weigelt; Francis J Woerner; Jennifer S Wells; Wayne F Daneker; Shaker A Mousa; Ruth R Wexler; Prabhakar K Jadhav

doi:10.1016/j.bmcl.2003.10.057

Synthesis and biological evaluation of nonpeptide integrin antagonists containing spirocyclic scaffolds

Bioorg Med Chem Lett. 2004 Jan 19;14(2):383-7. doi: 10.1016/j.bmcl.2003.10.057.

Authors

Joanne M Smallheer¹, Carolyn A Weigelt, Francis J Woerner, Jennifer S Wells, Wayne F Daneker, Shaker A Mousa, Ruth R Wexler, Prabhakar K Jadhav

Affiliation

¹ Bristol-Myers Squibb Company, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.

PMID: 14698164
DOI: 10.1016/j.bmcl.2003.10.057

Abstract

Analogues of isoxazoline alpha(v)beta(3) antagonist 1 designed to further restrict the four carbon alkyl tether were prepared by incorporating two spirocyclic scaffolds, 1-oxa-2-azaspiro[4,5]dec-2-ene and 1-oxa-2,7-diazaspiro[4,4]non-2-ene. Additional optimization provided potent antagonists of both alpha(v)beta(3) and alpha(5)beta(1) which are selective over GPIIb/IIIa.

MeSH terms

Binding Sites / physiology
Drug Evaluation, Preclinical / methods
Humans
Imidazoles / chemical synthesis*
Imidazoles / metabolism
Integrins / antagonists & inhibitors*
Integrins / metabolism
Stereoisomerism

Substances

Imidazoles
Integrins