title: The discovery of a series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles as highly brain penetrant, selective muscarinic M1 agonists.
abstract: A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M1 agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain penetration were identified. An exemplar of the series was shown to be pro-cognitive in the novel object recognition rat model of temporal induced memory deficit.
authors: GlaxoSmithKline, New Frontiers Science Park, 3rd Avenue, Harlow, Essex CM19 5AW, UK. dalejames.johnson@gmail.com
authors: Dale J
authors: DJ
authors: Johnson
authors: Ian T
authors: IT
authors: Forbes
authors: Steve P
authors: SP
authors: Watson
authors: Vincenzo
authors: V
authors: Garzya
authors: Graeme I
authors: GI
authors: Stevenson
authors: Graham R
authors: GR
authors: Walker
authors: Harminder S
authors: HS
authors: Mudhar
authors: Sean T
authors: ST
authors: Flynn
authors: Paul A
authors: PA
authors: Wyman
authors: Paul W
authors: PW
authors: Smith
authors: Graham S
authors: GS
authors: Murkitt
authors: Adam J
authors: AJ
authors: Lucas
authors: Claudette R
authors: CR
authors: Mookherjee
authors: Jeannette M
authors: JM
authors: Watson
authors: Jane E
authors: JE
authors: Gartlon
authors: Andrea M
authors: AM
authors: Bradford
authors: Fiona
authors: F
authors: Brown
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008569:Memory Disorders / Q000188:drug therapy*; D018721:Muscarinic Agonists / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018697:Nootropic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000078183:Oxindoles; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*
chemical_list: D001583:Benzoxazoles; D007211:Indoles; D018721:Muscarinic Agonists; D018697:Nootropic Agents; D000078183:Oxindoles; D043643:Receptor, Muscarinic M1; C022960:2-oxindole; C017057:benzoxazolone