Synthesis and biological activity of 4-methyl-3,5-dioxane derivatives as thromboxane A2 receptor antagonists.
The synthesis and biological activity of novel 4-methyl-3,5-dioxane analogues are described. All compounds were produced through modification of the substituent formally corresponding to the omega-octenol side chain of thromboxane A2 (TXA2), in reference to the structure of SQ29548. Several compounds were found to be potent TXA2 receptor antagonists. Compound 8b was the most effective inhibitor of 9,11-epoxymethano PGH2 (U-46619)-induced human platelet aggregation (IC50 = 7.4 nM).
Marusawa
H
H
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Setoi
H
H
Kuroda
A
A
Sawada
A
A
Seki
J
J
Motoyama
Y
Y
Tanaka
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000502:physiology; D004146:Dioxanes / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013928:Thromboxane A2 / Q000737:chemistry
C403513:7-(2-(2-aza-2-(((phenylamino)thioxomethyl)amino)vinyl)-4-methyl-3,5-dioxanyl)hept-5-enoic acid; D004146:Dioxanes; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D013890:Thiourea