Brown G R, Foubister A J, Hudson J A
ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
J Pharm Pharmacol. 1990 Jan;42(1):53-5. doi: 10.1111/j.2042-7158.1990.tb05349.x.
A study of the synthetic routes to the thromboxane receptor antagonist ICI 192605 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid is described which led to an improvement in overall synthetic yield from 20 to 55%. Invitro thromboxane receptor antagonist data are reported for the novel 1,3-dioxane synthetic intermediates. These data indicated that shortening of the side chain in an appropriately substituted 2,2-dimethyl-1,3-dioxane (e.g. ICI 180080) from a heptenoic acid, to a hexenoic acid, had little effect on thromboxane receptor antagonist potency (pA2 = 7.5 rabbit thoracic aorta for the heptenoic acid ICI 180080 and pA2 = 6.9 for the corresponding hexenoic acid. Human platelet aggregation pA2 values were 6.7 and 7.0, respectively).
描述了对血栓素受体拮抗剂 ICI 192605（4(Z)-6-(2-邻氯苯基-4-邻羟基苯基-1,3-二氧杂环己烷-顺式-5-基)己烯酸）合成路线的研究，该研究使总合成产率从 20%提高到了 55%。报告了新型 1,3-二氧杂环己烷合成中间体的体外血栓素受体拮抗剂数据。这些数据表明，在适当取代的 2,2-二甲基-1,3-二氧杂环己烷（例如 ICI 180080）中，侧链从庚烯酸缩短为己烯酸，对血栓素受体拮抗剂的效力影响不大（庚烯酸 ICI 180080 在兔胸主动脉中的 pA2 = 7.5，相应的己烯酸的 pA2 = 6.9。人血小板聚集的 pA2 值分别为 6.7 和 7.0）。
