Structure-activity study of antihypertensive 1,4-dihydropyridine derivatives having nitrooxyalkyl moieties at the 3 and 5 positions.
1,4-Dihydropyridine derivatives having two nitrooxyalkyl moieties as esters at the 3 and 5 positions possess antihypertensive activity. To understand how substituents affect the biological activity, the quantitative structure-activity relationship (QSAR) of 27 compounds was analyzed using the Fuzzy adaptive least-squares (FALS 91) method. The QSAR models suggested that the hydrophobicity and electronic effect at the 4 position of the 1,4-dihydropyridine along with the special structures of the nitrooxyalkylester components are important for antihypertensive activity.
Kawashima
Y
Y
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Ogawa
T
T
Kato
M
M
Nakazato
A
A
Tsuchida
K
K
Hatayama
K
K
Hirono
S
S
Moriguchi
I
I
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002845:Chromatography; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D004095:Dihydropyridines; C038806:1,4-dihydropyridine