Organic phosphorus compounds. 5. (4-Benzothiazol-2-ylbenzyl)amidophosphonate as potent calcium antagonistic vasodilators.
Structural modifications of the calcium antagonist fostedil (KB-944) and their coronary vasodilator activity are described. Amidophosphonates 4a-m, lactam amidophosphonates 7a-1, and diamide dilactam 10 were prepared, and their coronary vasodilator activity was assessed in dogs. Many compounds exhibited coronary vasodilator activity superior to that of fostedil. Among them, the 2-oxopyrrolidine derivative 7a was the most effective compound. Its action as a coronary vasodilator was 3 and 2 times more potent than that of fostedil and diltiazem hydrochloride, respectively.
Yoshino
K
K
Pharmaceuticals Research Center, Kanebo Ltd., Osaka, Japan.
Goto
K
K
Yoshiizumi
K
K
Morita
T
T
Tsukamoto
G
G
D000818:Animals; D052160:Benzothiazoles; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D006168:Guinea Pigs; D008297:Male; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology*
D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D009943:Organophosphorus Compounds; D011759:Pyrrolidines; D013844:Thiazoles; D014665:Vasodilator Agents; C065057:ethyl (4-benzothiazol-2-ylbenzyl)(2-oxopyrrolidino)phosphinate; C035950:fosfedil