Removal of the 20-methyl group from 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) selectively eliminates bone calcium mobilization activity
作者:Rafal Barycki、Rafal R. Sicinski、Lori A. Plum、Pawel Grzywacz、Margaret Clagett-Dame、Hector F. DeLuca
DOI:10.1016/j.bmc.2009.09.047
日期:2009.11
convergent syntheses. The known phosphine oxide 10 was coupled by the Wittig–Horner process with the corresponding C,D-fragments (13–15), obtained by a multi-step procedure from commercial vitamin D2. The goal of our studies was to examine the influence of removal of the methyl groups located at carbons 13 and 20 on the biological potency of 2MD in the hope of finding analogs with improved therapeutic
(20 S )-1α,25-dihydroxy-2-methylene-19-norvitamin D 3 ( 6 , 2MD )的 18-nor ( 7 )、21-nor ( 8 ) 和 18,21-dinor ( 9 ) 类似物由收敛合成制备。已知的氧化膦10与相应的C,d-片段(偶联通过维蒂希-霍纳过程13 - 15,从商业维生素d通过多步骤方法获得)2。我们研究的目的是检查去除位于碳 13 和 20 上的甲基对 2MD 的生物效力的影响,希望找到具有改进治疗特性的类似物。 在 2-methylene-19- nor- (20 S )-1α,25-dihydroxyvitamin D 3 (2MD)中用氢取代 20-甲基不影响与大鼠维生素 D 受体的结合,对转录活性几乎没有影响, HL-60 分化。然而,骨骼中钙的动员在很大程度上被消除,而肠道钙转运仍然很强。奇怪的是,去除 C-13-甲基和