Organic phosphorus compounds. 1. 4-(Benzothiazol-2-yl)benzylphosphonate as potent calcium antagonistic vasodilator.
A series of 4-(benzothiazol-2-yl)benzylphosphonic acid dialkyl ester derivatives were synthesized and evaluated for coronary vasodilatory activity by Langendorff's method in the isolated guinea pig heart. Many of the phosphonic acid dialkyl esters exhibited vasodilatory activity and calcium antagonism comparable with those of diltiazem hydrochloride, whereas phosphonic acid 1b and its nonphosphonated precursor 7a were inactive. These results indicate the necessity of the diethoxyphosphinyl moiety for vasodilatory activity. Substitution of the benzothiazole ring with a variety of substituents did not significantly enhance the activity of the unsubstituted compound. Compound 10b (KB-944) was chosen for detailed pharmacological evaluation.
K
K
Yoshino
T
T
Kohno
T
T
Uno
T
T
Morita
G
G
Tsukamoto
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006168:Guinea Pigs; D008297:Male; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis*
D002121:Calcium Channel Blockers; D009943:Organophosphorus Compounds; D014665:Vasodilator Agents