Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route.
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.
Blagg
Julian
J
Pfizer Global Research & Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Allerton
Charlotte M N
CM
Batchelor
David V J
DV
Baxter
Andrew D
AD
Burring
Denise J
DJ
Carr
Christopher L
CL
Cook
Andrew S
AS
Nichols
Carly L
CL
Phipps
Joanne
J
Sanderson
Vivienne G
VG
Verrier
Hugh
H
Wong
Stephen
S
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
D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3