title: Design and synthesis of tetrazole-based growth hormone secretagogue: the SAR studies of the O-benzyl serine side chain.
abstract: The structure-activity relationship of the O-benzyl serine side chain was investigated based on the tetrazole-based growth hormone secretagogue BMS-317180 (2). The ortho position of the benzyl moiety was found to be favorable for introduction of substituents. A series of ortho-substituted compounds were synthesized with improved in-vitro and in-vivo activity. Among them, the biphenyl compound 2p shows twofold improvement in potency compared to its parent compound BMS-317180 (2).
authors.affiliation: Discovery Chemistry, Bristol Myers Squibb, Princeton, NJ 08543, USA. jun.li@bms.com
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Stephanie Y
authors.initials: SY
authors.lastname: Chen
authors.forename: Shiwei
authors.initials: S
authors.lastname: Tao
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.forename: James J
authors.initials: JJ
authors.lastname: Li
authors.forename: Steve
authors.initials: S
authors.lastname: Swartz
authors.forename: Christa
authors.initials: C
authors.lastname: Musial
authors.forename: Andres A
authors.initials: AA
authors.lastname: Hernandez
authors.forename: Neil
authors.initials: N
authors.lastname: Flynn
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Murphy
authors.forename: Blake
authors.initials: B
authors.lastname: Beehler
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Dickinson
authors.forename: Leah
authors.initials: L
authors.lastname: Giupponi
authors.forename: Gary
authors.initials: G
authors.lastname: Grover
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Seethala
authors.forename: Paul
authors.initials: P
authors.lastname: Sleph
authors.forename: Dorothy
authors.initials: D
authors.lastname: Slusarchyk
authors.forename: Mujing
authors.initials: M
authors.lastname: Yan
authors.forename: William G
authors.initials: WG
authors.lastname: Humphreys
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.forename: William R
authors.initials: WR
authors.lastname: Ewing
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
authors.forename: David
authors.initials: D
authors.lastname: Gordon
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tino
mesh_terms: D000818:Animals; D002219:Carbamates / Q000494:pharmacology; D015195:Drug Design; D013006:Growth Hormone / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D012694:Serine / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C526808:4-(hydroxybutyl)carbamic acid 2-(5-(1-(2-amino-2-methylpropionylamino)-2-benzyloxyethyl)tetrazol-1-yl)ethyl ester; D002219:Carbamates; D013777:Tetrazoles; D012694:Serine; C052987:O-benzoylserine; D013006:Growth Hormone