Evolution of nonpeptide avb3 integrin antagonists for the treatment of osteoporosis

ORGN 490

Michael J. Breslin, michael_breslin@merck.com, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486
Antagonism of the RGD binding domain of the integrin vitronectin receptor, avb3, by potent, selective, small-molecule mimetics may result in an effective treatment for osteoporosis. The evolution of small molecule RGD peptidomimetics to a centrally-constrained zwitterionic antagonist suitable for clinical development will be described. The identification of potential sites of oxidative metabolism of our clinical candidate allowed subtle structural modifications to be incorporated providing a compound with an enhanced pharmacokinetic profile. Structure-activity relationships of the series will be described as well as the synthesis of the modified clinical candidate.
 

Technical Achievements in Organic Chemistry Awards
9:30 AM-12:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Ballroom C, Oral

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005