In an effort to improve physical properties by introducing polar functionality into the bicyclic pyrimidine gamma-secretase modulator (GSM) clinical candidate BMS-932481, we prepared several oxidative products of BMS-932481. Among the analogs that were prepared, the C-5 alcohol 3 was identified as the predominant metabolite of BMS-932481 found in rat and human liver microsomes. Alcohol 3 was determined to be chemically unstable, leading to the hypothesis that 3 may lead to the production of reactive species both in vitro and in vivo.

中文翻译：

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γ-分泌酶调节剂BMS-932481的功能化衍生物的合成及其主要代谢物的鉴定。

为了通过将极性官能团引入双环嘧啶γ-分泌酶调节剂（GSM）临床候选药物BMS-932481中来改善物理性质，我们制备了BMS-932481的几种氧化产物。在制备的类似物中，C-5醇3被确定为在大鼠和人肝微粒体中发现的BMS-932481的主要代谢产物。醇3被确定为化学性质不稳定的，从而导致的假设3可导致产生两个反应性物种的体外和体内。