title: 3-[2-(N-phenylacetamide)]-1,5-benzodiazepines: orally active, binding selective CCK-A agonists.
abstract: A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.
authors.affiliation: Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA. willsontm@glaxo.com
authors.forename: T M
authors.initials: TM
authors.lastname: Willson
authors.forename: B R
authors.initials: BR
authors.lastname: Henke
authors.forename: T M
authors.initials: TM
authors.lastname: Momtahen
authors.forename: P L
authors.initials: PL
authors.lastname: Myers
authors.forename: E E
authors.initials: EE
authors.lastname: Sugg
authors.forename: R J
authors.initials: RJ
authors.lastname: Unwalla
authors.forename: D K
authors.initials: DK
authors.lastname: Croom
authors.forename: R W
authors.initials: RW
authors.lastname: Dougherty
authors.forename: M K
authors.initials: MK
authors.lastname: Grizzle
authors.forename: M F
authors.initials: MF
authors.lastname: Johnson
authors.forename: K L
authors.initials: KL
authors.lastname: Queen
authors.forename: T J
authors.initials: TJ
authors.lastname: Rimele
authors.forename: J D
authors.initials: JD
authors.lastname: Yingling
authors.forename: M K
authors.initials: MK
authors.lastname: James
mesh_terms: D000083:Acetanilides; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002766:Cholecystokinin / Q000819:agonists*; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D051379:Mice; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000378:metabolism
chemical_list: C100739:2-(2,4-dioxo-5-phenyl-3-methyl-3-((phenylcarbamoyl)methyl)-2,3,4,5-tetrahydrobenzo(b)(1,5)diazepin-1-yl)-N-isopropyl-N-phenylacetamide; D000083:Acetanilides; D001381:Azepines; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin