title: Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor.
abstract: Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the pyrazole. Both series supplied compounds with excellent affinity for the human D4 and good selectivity over other dopamine receptors. Excellent selectivity over calcium, sodium, and potassium ion channels was also achieved.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bourrain
authors.forename: I
authors.initials: I
authors.lastname: Collins
authors.forename: J G
authors.initials: JG
authors.lastname: Neduvelil
authors.forename: M
authors.initials: M
authors.lastname: Rowley
authors.forename: P D
authors.initials: PD
authors.lastname: Leeson
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: F
authors.initials: F
authors.lastname: Emms
authors.forename: R
authors.initials: R
authors.lastname: Marwood
authors.forename: K L
authors.initials: KL
authors.lastname: Chapman
authors.forename: A E
authors.initials: AE
authors.lastname: Fletcher
authors.forename: G A
authors.initials: GA
authors.lastname: Showell
mesh_terms: D014150:Antipsychotic Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship
chemical_list: C116516:3-(4-(4-methoxyphenyl)piperazin-1-ylmethyl)-1,4-dihydro-5-oxa-1,2-diazacyclopenta(a)naphthalene; D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D006571:Heterocyclic Compounds; D007473:Ion Channels; D010879:Piperazines; D011720:Pyrazoles; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4