title: 2-Arylindoles as gonadotropin releasing hormone (GnRH) antagonists: optimization of the tryptamine side chain.
abstract: A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, NJ Rahway 07065-0900, USA. young@merck.com
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Young
authors.forename: Song X
authors.initials: SX
authors.lastname: Huang
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Walsh
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: Yi Tien
authors.initials: YT
authors.lastname: Yang
authors.forename: Joel B
authors.initials: JB
authors.lastname: Yudkovitz
authors.forename: Jisong
authors.initials: J
authors.lastname: Cui
authors.forename: George R
authors.initials: GR
authors.lastname: Mount
authors.forename: Rena Ning
authors.initials: RN
authors.lastname: Ren
authors.forename: Tsuei Ju
authors.initials: TJ
authors.lastname: Wu
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Shen
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: An Hua
authors.initials: AH
authors.lastname: Mao
authors.forename: Josephine R
authors.initials: JR
authors.lastname: Carlin
authors.forename: Bindhu V
authors.initials: BV
authors.lastname: Karanam
authors.forename: Stella H
authors.initials: SH
authors.lastname: Vincent
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goulet
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D002064:Buserelin / Q000378:metabolism; D005300:Fertility Agents, Female / Q000037:antagonists & inhibitors*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000737:chemistry*
chemical_list: D005300:Fertility Agents, Female; D007211:Indoles; D007295:Inositol Phosphates; D011804:Quinolines; D014363:Tryptamines; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D002064:Buserelin