title: Nonpeptide cholecystokinin-2 receptor agonists.
abstract: In the course of structural explorations around a series of potent CCK2 receptor antagonists, it was noted that simple N-methylation of the indolic N-H in the parent molecule gave rise to behavior in vivo that was consistent with the compound acting as an agonist. Exploration in vitro confirmed this property, and it was shown that the agonist action could be blocked by the reference CCK2 receptor antagonist, L-365,260. Further examples of this type of modification were explored, and a common theme with regard to agonist behavior was uncovered. Some molecular modeling is also presented in an attempt to throw light on the nature of the ligand receptor interactions that may be giving rise to the differing properties of these, apparently, structurally similar molecules.
authors: James Black Foundation, 68 Half Moon Lane, London SE24 9JE, UK. barret.kalindjian@kcl.ac.uk
authors: S B
authors: SB
authors: Kalindjian
authors: D J
authors: DJ
authors: Dunstone
authors: C M
authors: CM
authors: Low
authors: M J
authors: MJ
authors: Pether
authors: S P
authors: SP
authors: Roberts
authors: M J
authors: MJ
authors: Tozer
authors: G F
authors: GF
authors: Watt
authors: N P
authors: NP
authors: Shankley
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D010418:Pentagastrin / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D013270:Stomach / Q000187:drug effects
chemical_list: D001570:Benzodiazepinones; D007211:Indoles; D008024:Ligands; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D010418:Pentagastrin; D000218:Adamantane