Piperidine-containing beta-arylpropionic acids as potent antagonists of alphavbeta3/alphavbeta5 integrins

  • Bioorg Med Chem Lett. 2004 Oct 18;14(20):5227-32. doi: 10.1016/j.bmcl.2004.06.061.
Bart L De Corte  1 ,  William A Kinney ,  Li Liu ,  Shyamali Ghosh ,  Livia Brunner ,  William J Hoekstra ,  Rosemary J Santulli ,  Robert W Tuman ,  Judith Baker ,  Candace Burns ,  Jef C Proost ,  Brett A Tounge ,  Bruce P Damiano ,  Bruce E Maryanoff ,  Dana L Johnson ,  Robert A Galemmo Jr
Affiliations
  • 1. Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477-0776, USA. [email protected]
PMID: 15380233 DOI: 10.1016/j.bmcl.2004.06.061
Abstract

The synthesis and SAR of a new class of piperidine-based alphavbeta3/alphavbeta5 Integrin antagonists is described. Replacement of an amide bond in a prototype isonipecotamide by a C-C isostere, and adjustment of the spacer length between the carboxylic acid and basic moieties, led to low nanomolar antagonists of alphavbeta3 and/or alphavbeta5 integrins with excellent selectivity versus Alpha(IIb)beta3.

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