title: Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route.
abstract: This paper reports the synthesis and biological activity of a novel series of aryl-morpholine dopamine receptor agonists. Several compounds show high levels of functional selectivity for the D3 over the D2 dopamine receptor. Compound 26 has >1000-fold functional selectivity and has been successfully progressed in vivo using an intranasal delivery route.
authors.affiliation: Pfizer Global Research & Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Blagg
authors.forename: Charlotte M N
authors.initials: CM
authors.lastname: Allerton
authors.forename: David V J
authors.initials: DV
authors.lastname: Batchelor
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Baxter
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Burring
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Carr
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Cook
authors.forename: Carly L
authors.initials: CL
authors.lastname: Nichols
authors.forename: Joanne
authors.initials: J
authors.lastname: Phipps
authors.forename: Vivienne G
authors.initials: VG
authors.lastname: Sanderson
authors.forename: Hugh
authors.initials: H
authors.lastname: Verrier
authors.forename: Stephen
authors.initials: S
authors.lastname: Wong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018360:Crystallography, X-Ray; D004285:Dogs; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3