Broughton B J, Caton M P, Coffee E C, Hambling D J, Palfreyman M N, Withnall M T, Wooldridge K R
Prostaglandins. 1980 Apr;19(4):559-75. doi: 10.1016/s0090-6980(80)80006-2.
Some omega-chain phenyl- and 16-phenoxy- analogues of (+/-)-11-deoxyprostaglandin F1 alpha have been synthesized and evaluated for anti-fertility activity in the hamster. 11-Deoxy-16-phenoxy-17,18,19,20-tetranor-PGF1 alpha was the most active member of the series with an ED50 equal to that of PGF2 alpha. 11-Deoxy-17-phenyl-18,19,20-trinor-PGF1 alpha, which was one third as active as PGF2 alpha, was more potent than the corresponding 16- and 18-phenyl compounds. Aryl ring substitution was found to lower activity, except that with the 16-phenyl compound, p-bromo and m-trifluoromethyl substitution increased the potency. The antifertility activity of the phenoxy compounds, which were poor substrates for 15-hydroxyprostaglandin dehydrogenase, was shown to correlate well with the binding affinity for the bovine corpus luteum PGF2 alpha receptor. Some quantitative structure-activity data supporting this finding are presented.
已合成了一些（±）-11-脱氧前列腺素F1α的ω-链苯基和16-苯氧基类似物，并在仓鼠中评估了其抗生育活性。11-脱氧-16-苯氧基-17,18,19,20-四去甲-PGF1α是该系列中活性最高的成员，其半数有效剂量（ED50）与PGF2α相当。活性仅为PGF2α三分之一的11-脱氧-17-苯基-18,19,20-三去甲-PGF1α比相应的16-和18-苯基化合物更有效。发现芳环取代会降低活性，但16-苯基化合物的对溴和间三氟甲基取代会提高效力。苯氧基化合物作为15-羟基前列腺素脱氢酶的不良底物，其抗生育活性与对牛黄体PGF2α受体的结合亲和力密切相关。本文给出了支持这一发现的一些定量构效关系数据。
