Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route

Julian Blagg; Charlotte M N Allerton; David V J Batchelor; Andrew D Baxter; Denise J Burring; Christopher L Carr; Andrew S Cook; Carly L Nichols; Joanne Phipps; Vivienne G Sanderson; Hugh Verrier; Stephen Wong

doi:10.1016/j.bmcl.2007.10.059

Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6691-6. doi: 10.1016/j.bmcl.2007.10.059. Epub 2007 Oct 22.

Authors

Julian Blagg¹, Charlotte M N Allerton, David V J Batchelor, Andrew D Baxter, Denise J Burring, Christopher L Carr, Andrew S Cook, Carly L Nichols, Joanne Phipps, Vivienne G Sanderson, Hugh Verrier, Stephen Wong

Affiliation

¹ Pfizer Global Research & Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.

PMID: 17976986
DOI: 10.1016/j.bmcl.2007.10.059

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.

MeSH terms

Administration, Intranasal
Animals
Crystallography, X-Ray
Dogs
Dopamine Agonists / administration & dosage*
Dopamine Agonists / chemical synthesis*
Dopamine Agonists / chemistry
Dopamine Agonists / pharmacokinetics
Drug Design*
Humans
Models, Molecular
Molecular Structure
Rats
Receptors, Dopamine D3 / agonists*
Receptors, Dopamine D3 / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Dopamine Agonists
Receptors, Dopamine D3