Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model

W H Miller; W E Bondinell; R D Cousins; K F Erhard; D R Jakas; R M Keenan; T W Ku; K A Newlander; S T Ross; R C Haltiwanger; J Bradbeer; F H Drake; M Gowen; S J Hoffman; S M Hwang; I E James; M W Lark; B Lechowska; D J Rieman; G B Stroup; J A Vasko-Moser; D L Zembryki; L M Azzarano; P C Adams; W F Huffman

doi:10.1016/s0960-894x(99)00283-8

Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model

Bioorg Med Chem Lett. 1999 Jul 5;9(13):1807-12. doi: 10.1016/s0960-894x(99)00283-8.

Authors

Affiliation

¹ Research & Development Division, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426-0989, USA.

PMID: 10406646
DOI: 10.1016/s0960-894x(99)00283-8

Abstract

A new series of potent nonpeptide vitronectin receptor antagonists, based on a novel carbocyclic Gly-Asp mimetic, has been discovered. A representative of this series, SB 265123 (4), has 100% oral bioavailability in rats, and is orally active in vivo in the ovariectomized rat model of osteoporosis.

MeSH terms

Acetates / chemical synthesis*
Acetates / pharmacokinetics*
Administration, Oral
Aminopyridines / chemical synthesis*
Aminopyridines / pharmacokinetics*
Animals
Benzodiazepinones / chemical synthesis
Benzodiazepinones / pharmacokinetics
Biological Availability
Disease Models, Animal
Kinetics
Osteoporosis / drug therapy*
Rats
Receptors, Vitronectin / antagonists & inhibitors*
Time Factors

Substances

Acetates
Aminopyridines
Benzodiazepinones
Receptors, Vitronectin
SB 223245
SB 265123