title: Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists.
abstract: The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration.
authors.affiliation: AMRI, 26 Corporate Circle, Albany, NY 12212, USA. cheng.guo@amriglobal.com
authors.forename: Cheng
authors.initials: C
authors.lastname: Guo
authors.forename: Peter R
authors.initials: PR
authors.lastname: Guzzo
authors.forename: Mark
authors.initials: M
authors.lastname: Hadden
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Sargent
authors.forename: Larry
authors.initials: L
authors.lastname: Yet
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Kan
authors.forename: Oksana
authors.initials: O
authors.lastname: Palyha
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Kelly
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Guan
authors.forename: Kim
authors.initials: K
authors.lastname: Rosko
authors.forename: Karen
authors.initials: K
authors.lastname: Gagen
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Metzger
authors.forename: Jasminka
authors.initials: J
authors.lastname: Dragovic
authors.forename: Kathryn
authors.initials: K
authors.lastname: Lyons
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Nargund
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D057166:High-Throughput Screening Assays; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D018004:Receptors, Bombesin / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C550999:7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo(3,4-c)(2,7)-naphthyridin-1-ylamine; D019440:Anti-Obesity Agents; D009287:Naphthyridines; D011720:Pyrazoles; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3