Pharmaceutical Research Division, Takeda Pharmaceutical Co. Ltd, Yodogawa-ku, Osaka, Japan.
Bioorg Med Chem. 2011 Sep 1;19(17):5175-82. doi: 10.1016/j.bmc.2011.07.014. Epub 2011 Jul 19.
A series of novel 3-benzhydryl-4-piperidone derivatives were identified as potent tachykinin neurokinin-1 (NK(1)) receptor antagonists. An efficient and versatile synthesis of this series was achieved with a coupling reaction of 1-benzylpiperidones with benzhydryl bromides or benzhydrols in the presence of trifluoromethanesulfonate and a condensation reaction of piperidones with benzyl alcohols using ethyl o-phenylenephosphate. The 3-benzhydryl-4-piperidone skeleton, which has a 1,1-diphenylmethane moiety that is a known privileged substructure targeting G-protein coupled receptors, can be used for chemical library synthesis because of chemical accessibility and diversity.
一系列新型 3-苯并基-4-哌啶酮衍生物被鉴定为强效速激肽神经激肽-1（NK(1)）受体拮抗剂。通过在三氟甲磺酸存在下将 1-苄基哌啶酮与苯并基溴或苯并基醇进行偶联反应，以及使用邻苯二酚乙基磷酸酯将哌啶酮与苄醇进行缩合反应，实现了该系列的高效和多功能合成。3-苯并基-4-哌啶酮骨架具有 1,1-二苯甲烷部分，这是一种已知的针对 G 蛋白偶联受体的特权亚结构，可以用于化学文库合成，因为其具有化学可及性和多样性。
