(5Z)-7-(2,2-Dimethyl-4-phenyl-1,3-dioxan-cis-5-yl)heptenoi c acid: a specific thromboxane A2 receptor antagonist.
(5Z)-7-(2,2-Dimethyl-4-phenyl-1,3-dioxan-cis-5-yl)heptenoic acid (2) was found to be a specific, competitive thromboxane A2 receptor antagonist that acts at platelet, vascular, and pulmonary receptors. No antagonism was detected at receptors for prostacyclin, SRSA, norepinephrine, and serotonin. The synthesis of a series of analogues is described; activity at the thromboxane receptor was observed in cis-substituted compounds but not in their trans counterparts. Compound 2 inhibited the bronchoconstriction induced by a stable thromboxane mimetic in the anesthetized guinea pig.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004146:Dioxanes / Q000138:chemical synthesis* / Q000494:pharmacology; D004147:Dioxins / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000378:metabolism; D017482:Receptors, Thromboxane; D013329:Structure-Activity Relationship; D013931:Thromboxanes / Q000378:metabolism*
D004146:Dioxanes; D004147:Dioxins; D007202:Indicators and Reagents; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C050942:7-(2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl)heptenoic acid