Non-peptide alpha v beta 3 antagonists. Part 7: 3-Substituted tetrahydro-naphthyridine derivatives.
A series of 3-substituted tetrahydro-[1,8]naphthyridine containing alpha(v)beta(3) antagonists was prepared. A comparison of their in vitro IC(50) values to the electron properties of the 3-substituents revealed a good linear Hammett correlation (rho=-1.96, R(2)=0.959). Electron-withdrawing groups at the 3-position of the tetrahydro-[1,8]naphthyridine decreased potency while electron-donating groups enhanced potency.
Wang
Jiabing
J
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. jiabing_wnag@merck.com
Breslin
Michael J
MJ
Coleman
Paul J
PJ
Duggan
Mark E
ME
Hunt
Cecilia A
CA
Hutchinson
John H
JH
Leu
Chih-Tai
CT
Rodan
Sevgi B
SB
Rodan
Gideon A
GA
Duong
Le T
LT
Hartman
George D
GD
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D039302:Integrin alphaVbeta3; D009287:Naphthyridines