title: Synthesis and biological activity of 1-phenylsulfonyl-4-phenylsulfonylaminopyrrolidine derivatives as thromboxane a(2) receptor antagonists.
abstract: The synthesis and biological activity of novel 1-phenylsulfonyl-4- phenylsulfonylaminopyrrolidine analogues are described. All compounds were produced through modification of the substituent formally corresponding to the 1,3-dioxane ring system and the omega-octenol side chain of thromboxane A(2) (TXA(2)), in reference to the structure of Daltroban. Several compounds were found to be potent TXA(2) receptor antagonists. Compound 51a was the most effective inhibitor of 9,11-epoxymethano PGH(2) (U-46619)-induced rat aortic strip contraction (IC(50)=0.48 nM).
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd. 5-2-3 Tokodai, Tsukuba-shi, 300--2698, Ibaraki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Marusawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Setoi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sawada
authors.forename: Akio
authors.initials: A
authors.lastname: Kuroda
authors.forename: Jiro
authors.initials: J
authors.lastname: Seki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Motoyama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta; D004195:Disease Models, Animal; D004285:Dogs; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000188:drug therapy / Q000517:prevention & control; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors
chemical_list: D011759:Pyrrolidines; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid