title: Synthesis of Am80 (tamibarotene) prodrug candidates, congeners and metabolites.
abstract: Compound 1 (IT-M-07000) was previously reported as a candidate prodrug of Am80 (Tamibarotene; used to treat acute promyelocytic leukemia), and shown to be efficiently metabolized to Am80 via β-oxidation. Here, we describe in detail the synthesis of 1, together with another tetradeuterated candidate prodrug, IT-YA-00616 (2), as well as two congeners, and several metabolic intermediates of 1 previously detected in mouse plasma.
authors.affiliation: Research Foundation Itsuu Laboratory, 2–28–10 Tamagawa, Setagaya-ku, Tokyo 158–0094, Japan. hmuratake@itsuu.or.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Muratake
authors.forename: Yohei
authors.initials: Y
authors.lastname: Amano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Toda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
mesh_terms: D001565:Benzoates / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000378:metabolism*
chemical_list: D001565:Benzoates; C548358:IT-M-07000; D010666:Phenylpropionates; D011355:Prodrugs; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; C061133:tamibarotene