title: 3-benzhydryl-4-piperidones as novel neurokinin-1 receptor antagonists and their efficient synthesis.
abstract: 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.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Co. Ltd, Yodogawa-ku, Osaka, Japan. Shirai_Junya@takeda.co.jp
authors.forename: Junya
authors.initials: J
authors.lastname: Shirai
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamaoka
authors.forename: Eikoh
authors.initials: E
authors.lastname: Imamiya
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Tarui
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikeura
mesh_terms: D002460:Cell Line; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D010881:Piperidones; D043562:Receptors, G-Protein-Coupled; D018040:Receptors, Neurokinin-1; D054852:Small Molecule Libraries