N-(1-Benzylpyrrolidin-3-yl)arylbenzamides as potent and selective human dopamine D4 antagonists

Ian Egle; Nancy Barriault; Michel Bordeleau; Jillian Drage; Laurence Dube; Jack Peragine; Lucy Mazzocco; Jalaj Arora; Keith Jarvie; Ashok Tehim

doi:10.1016/j.bmcl.2004.07.045

N-(1-Benzylpyrrolidin-3-yl)arylbenzamides as potent and selective human dopamine D4 antagonists

Bioorg Med Chem Lett. 2004 Oct 4;14(19):4847-50. doi: 10.1016/j.bmcl.2004.07.045.

Authors

Ian Egle¹, Nancy Barriault, Michel Bordeleau, Jillian Drage, Laurence Dube, Jack Peragine, Lucy Mazzocco, Jalaj Arora, Keith Jarvie, Ashok Tehim

Affiliation

¹ NPS Pharmaceuticals Inc., 6850 Goreway Dr., Mississauga, Ontario L4V 1V7, Canada. iegle@npsp.com

PMID: 15341937
DOI: 10.1016/j.bmcl.2004.07.045

Abstract

A series of N-(1-benzylpyrrolidin-3-yl)arylbenzamides 8 has been prepared, and their structure-activity relationships studied. Potent ligands selective for human D(4) (hD(4)) over hD(2) and alpha(1) have been identified. One example was determined to be an antagonist in a cAMP assay, with an IC(50) of 1500 nM.

MeSH terms

Benzamides / chemical synthesis*
Benzamides / pharmacology
Dopamine Antagonists / chemical synthesis*
Dopamine Antagonists / pharmacology
Dopamine D2 Receptor Antagonists*
Humans
Receptors, Dopamine D4
Structure-Activity Relationship

Substances

Benzamides
DRD4 protein, human
Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Receptors, Dopamine D4