ICI 180080, a novel selective thromboxane receptor antagonist: synthesis and relative activity.
The preparation of a novel potent thromboxane receptor antagonist ICI 180080, 5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1,3-dioxan-cis-5-yl] heptenoic acid, is described together with its methyl ether and methyl ester. Thromboxane antagonist pA2 data against U 46619 is presented for rabbit thoracic aorta in-vitro (ICI 180080, pA2 = 7.5). The relative antagonist pA2 values obtained are discussed in terms of the chemical structure of the molecules. The potent activity of ICI 180080 is attributed to a specific orientation of the phenolic oxygen, due to an intramolecular hydrogen bond.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane
D004146:Dioxanes; D004147:Dioxins; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C050724:ICI 180080