4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones: synthesis, chromatographic resolution and pharmacological activity.
In this study, a series of 4-aryl-6,6-dimethyl-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-diones were synthesized by condensing urea with 4,4-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were characterized by spectroscopic methods. The racemic compounds were resolved into the enantiomers by HPLC on amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD). The compounds were tested in vitro for their calcium antagonistic activities. BaCl2-induced contractions of rat ileum were inhibited dose-dependently. Compounds 3 and 5 exerted weak calcium antagonistic activity on smooth muscles compared with the standard, nicardipine.
Saraç
S
S
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Yarim
M
M
Ertan
M
M
Kiliç
F S
FS
Erol
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D007202:Indicators and Reagents; D011799:Quinazolines; D004121:Dimethyl Sulfoxide