- Thromboxane A2 receptor antagonists. Synthesis and activities of phenylsulfonamido derivatives
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A number of phenylsulfonamido derivatives have been synthesized and tested for their ability to inhibit: a) thromboxane A2/prostaglandin H2 (TXA2/PGH2) mimetic (U46619)-induced guinea pig platelet aggregation; b) aortic ring contraction; and c) binding of a radioiodinated TXA2/PGH2 mimetic (I-BOP) to platelets.In platelets, Kd values ranged from 9 nM to > 50 μM. pKb values in aortic rings ranged from 7.63 to 3.66 and in platelets from 7.7 to A high degree of correlation was observed between the Kd and pKb values found in the 3 sytems.Antagonist activity at the TXA2/PGH2 receptor was sensitive to both the substitution pattern of the 2 aromatic rings and the presence of heteroatoms.For 2 of the derivatives (4 and 11) molecular mechanics calculations were performed which indicated subtle structural differences that may account for the > 300-fold difference in potency observed for these analogs at the platelet TXA2/PGH2 receptor. thromboxane A2 / antagonist / platelet / artery / receptor / phenylsulfonamido derivative
- Mais, DE,Mohamadi, F,Dube, GP,Kurtz, WL,Brune, KA,et al.
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p. 821 - 827
(2007/10/02)
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- Phenoxyalkylcarboxylic acid compounds and thrombocyte-aggregation inhibition
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Phenoxyalkylcarboxylic acid compounds of the formula STR1 wherein R is hydrogen or lower alkyl R1 is alkyl or aryl, aralkyl or aralkenyl radical, the aryl moiety of which can be substituted one or more times by halogen, hydroxyl, trifluoromethyl or lower alkyl, alkoxy or acyl R2 and R3 are individually selected from hydrogen or lower alkyl, and n is 0, 1, 2 or 3 and the physiologically acceptable salts, esters and amides thereof; are outstandingly effective in inhibiting thrombocyte aggregation.
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