A novel class of sodium/calcium exchanger inhibitors: design, synthesis, and structure-activity relationships of 4-phenyl-3-(piperidin-4-yl)-3,4-dihydro-2(1H)-quinazolinone derivatives.
Design, synthesis, and structure-activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives as sodium/calcium (Na+/Ca2+) exchanger inhibitors are described. In these studies, optimization of the substituents at the 3-position of this series of compounds was carried out and dramatic effects of the substituent on the activities were observed. Based on these SAR studies, a highly potent inhibitor of the Na+/Ca2+ exchanger, which showed single-digit-nanomolar activity, was discovered.
Hasegawa
Hirohiko
H
Research Division, Sumitomo Pharmaceuticals Co. Ltd, 1-98, Kasugadenaka 3-Chome, Konohana-ku, Osaka 554-0022, Japan. hhasegaw@sumitomopharm.co.jp
Muraoka
Masami
M
Matsui
Kazuki
K
Kojima
Atsuyuki
A
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010880:Piperidines; D011799:Quinazolines; D019831:Sodium-Calcium Exchanger