Bioorganic and Medicinal Chemistry Letters p. 4285 - 4288 (2003)
Update date:2022-08-04
Topics:
Perkins, James J.
Duong
Fernandez-Metzler, Carmen
Hartman, George D.
Kimmel, Donald B.
Leu, Chih-Tai
Lynch, Joseph J.
Prueksaritanont, Thomayant
Rodan, Gideon A.
Rodan, Sevgi B.
Duggan, Mark E.
Meissner, Robert S.
Antagonists of the integrin receptor αvβ3 are expected to have utility in the treatment of osteoporosis through inhibition of bone resorption. A series of potent, chain-shortened, pyrrolidinone-containing αvβ3 receptor antagonists is described. Two sets of diasteromeric pairs of high-affinity antagonists demonstrated marked differences in log P values, which translated into differing dog pharmacokinetic properties. One member of this set was demonstrated to be effective in reducing bone resorption in rats.
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