Comparative QSAR studies of two series of 1,4-dihydropyridines as slow calcium channel blockers.
Quantitative structure activity analysis was applied to two series of dihydropyridine (DHP) calcium channel blocking agents. One series of compounds was composed of DHPs substituted in the 4-position with an ortho or meta nitro substituted phenyl ring. The second group consisted of DHPs substituted at the 4-position with a novel thieno [3,2-c] pyridine ring. Both series consisted of compounds with unsymmetrical ester substitutions on the dihydropyridine ring. The antihypertensive activity of the compounds were determined in a spontaneously hypertensive rat model. Regression analysis indicated the antihypertensive activity of an i.v. dose correlated with the calculated octanol/water coefficent (clogP). Regression analysis did not find correlation with the in vitro potency and the clogP values.
Wikel
J H
JH
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Bemis
K G
KG
Kurz
K
K
Denney
M L
ML
Main
B W
BW
Moore
R A
RA
Smith
T
T
Shingleton
L
L
Holland
D R
DR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012044:Regression Analysis; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines