title: 4-N-linked-heterocyclic piperidine derivatives with high affinity and selectivity for human dopamine D4 receptors.
abstract: The syntheses of a number of different N-linked heterocyclic pyrazole replacements based on the structure 1 are described (compounds 3-12) as hD4 ligands. After further optimisation the best compound identified was 13 which has high affinity for hD4 (5.2 nM) and >300-fold selectivity for hD4 receptors over hD2 and hD3 receptors.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK. Kevin_Moore@Merck.com
authors.forename: K W
authors.initials: KW
authors.lastname: Moore
authors.forename: K
authors.initials: K
authors.lastname: Bonner
authors.forename: E A
authors.initials: EA
authors.lastname: Jones
authors.forename: F
authors.initials: F
authors.lastname: Emms
authors.forename: P D
authors.initials: PD
authors.lastname: Leeson
authors.forename: R
authors.initials: R
authors.lastname: Marwood
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: Rowley
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: R W
authors.initials: RW
authors.lastname: Carling
mesh_terms: D000818:Animals; D016466:CHO Cells; D003024:Clozapine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006224:Cricetinae; D006801:Humans; D007700:Kinetics; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C493599:DRD4 protein, human; D010880:Piperidines; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D050638:Receptors, Dopamine D4; C032727:piperidine; D003024:Clozapine