title: Design and synthesis of tricyclic tetrahydroquinolines as a new series of nonsteroidal selective androgen receptor modulators (SARMs).
abstract: Some tricyclic tetrahydroquinolines (THQs) were found to have the potential of a new series of nonsteroidal selective androgen receptor modulators (SARMs). Compound 5b was first designed and synthesized under our hypothesis based on a four-point pharmacophoric requirement of the 3-carbonyl, 18-methyl, 17-hydroxyl, and 13-quaternary carbon groups of dihydrotestosterone (DHT). It was revealed that this compound exhibits not only a strong androgen receptor (AR) agonistic activity (EC(50)=9.2 nM) but also the highest selectivity in binding affinity to AR among the steroid hormone receptors. Furthermore, this compound showed a weak virilizing effect with retention of the desired anabolic effect as compared with DHT in vivo.
authors.affiliation: Central Research Laboratories, Kaken Pharmaceutical Co., Ltd, Yamashina, Kyoto, Japan. nagata_naoya@kaken.co.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Nagata
authors.forename: Motonori
authors.initials: M
authors.lastname: Miyakawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Amano
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Furuya
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Inoguchi
mesh_terms: D015195:Drug Design; D008958:Models, Molecular; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000187:drug effects*
chemical_list: D011804:Quinolines; D011944:Receptors, Androgen; C542964:1,2,3,4-tetrahydroquinoline