title: Optimization of 1H-tetrazole-1-alkanenitriles as potent orally bioavailable growth hormone secretagogues.
abstract: 1H-tetrazole-1-alkanenitrile SR-9g exhibits a >10-fold in vivo potency enhancement over the lead nitrile 1 and has acceptable oral bioavailability in rats and dogs. An enantiospecific synthesis of 1H-tetrazole-1-alkanenitrile nitriles 9 has been developed.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. andres.hernandez@bms.com
authors.forename: Andrés S
authors.initials: AS
authors.lastname: Hernández
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swartz
authors.forename: Dorothy
authors.initials: D
authors.lastname: Slusarchyk
authors.forename: Mujing
authors.initials: M
authors.lastname: Yan
authors.forename: R Krishna
authors.initials: RK
authors.lastname: Seethala
authors.forename: Paul
authors.initials: P
authors.lastname: Sleph
authors.forename: Gary
authors.initials: G
authors.lastname: Grover
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickinson
authors.forename: Leah
authors.initials: L
authors.lastname: Giupponi
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Harper
authors.forename: W Griffith
authors.initials: WG
authors.lastname: Humphreys
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Longhi
authors.forename: Neil
authors.initials: N
authors.lastname: Flynn
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Murphy
authors.forename: David A
authors.initials: DA
authors.lastname: Gordon
authors.forename: Scott A
authors.initials: SA
authors.lastname: Biller
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tino
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D013006:Growth Hormone / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D010902:Pituitary Gland; D051381:Rats; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D009570:Nitriles; D013777:Tetrazoles; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System