Syntheses of monocyclic and bicyclic 2,4(1H,3H)-pyrimidinediones and their serotonin 2 antagonist activities.
New serotonine 2 (5-HT2) antagonists with a monocyclic or bicyclic 2,4(1H,3H)-pyrimidinedione have been prepared and their activities evaluated. In a series of monocyclic compounds, 1-substituted 5-phenyl-2,4(1H,3H)-pyrimidinedione 14 showed potent in vitro activity, and the corresponding 3-substituted 5-phenyl and 6-phenyl derivatives 3, 8 and 20a also showed moderate activity. In the bicyclic compounds, 3-substituted 5,6,7,8-tetrahydro-2,4(1H,3H)-quinazolinedione 33 exhibited the most potent activity among the compounds prepared in this paper. The in vivo antagonist activity of 33 was comparable to that of ketanserin, a typical peripheral 5-HT2 antagonist.
Watanabe
Y
Y
Daiichi Pharmaceutical Co., Ltd., Research Institute, Tokyo, Japan.
Usui
H
H
Shibano
T
T
Tanaka
T
T
Kanao
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D011744:Pyrimidinones; D012702:Serotonin Antagonists