Organic phosphorus compounds. 2. Synthesis and coronary vasodilator activity of (benzothiazolylbenzyl) phosphonate derivatives.
Structural modification and the coronary vasodilator activity of the calcium antagonist fostedil (KB-944) are described. Elimination of the bezothiazole ring or replacement of the benzothiazole ring of fostedil with other hetero rings leads to a decrease in vasodilator activity. Change of the distance from the aromatic ring to the phosphorus of fostedil causes a decrease in the activity. The present study indicates that the presence of an aromatic ring substituted thiazole ring and the presence of phosphonate at an appropriate distance from the thiazole ring are important for the coronary vasodilator action of fostedil.
Yoshino
K
K
Pharmaceuticals Research Center, Kanebo Ltd., Osaka, Japan.
Kohno
T
T
Morita
T
T
Tsukamoto
G
G
D000495:Allosteric Site; D000818:Animals; D052160:Benzothiazoles; D055598:Chemical Phenomena; D002621:Chemistry; D003326:Coronary Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D013844:Thiazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000138:chemical synthesis*
D052160:Benzothiazoles; D013844:Thiazoles; D014665:Vasodilator Agents; C035950:fosfedil