Hydrazides of clozapine: a new class of D1 dopamine receptor subtype selective antagonists

T K Sasikumar; D A Burnett; H Zhang; A Smith-Torhan; A Fawzi; J E Lachowicz

doi:10.1016/j.bmcl.2006.06.022

Hydrazides of clozapine: a new class of D1 dopamine receptor subtype selective antagonists

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4543-7. doi: 10.1016/j.bmcl.2006.06.022. Epub 2006 Jun 30.

Authors

T K Sasikumar¹, D A Burnett, H Zhang, A Smith-Torhan, A Fawzi, J E Lachowicz

Affiliation

¹ Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. thavalakulamgar.sasikumar@spcorp.com

PMID: 16809034
DOI: 10.1016/j.bmcl.2006.06.022

Abstract

Acylated and aroylated hydrazinoclozapines are highly potent dopamine D(1) antagonists that show remarkable selectivity over other dopamine receptors. The most potent compound in this series is the 2,6-dimethoxybenzhydrazide 33 with a D(1)K(i) of 1.6 nM and 212-fold selectivity over D(2) receptor.

MeSH terms

Clozapine / chemical synthesis
Clozapine / chemistry*
Clozapine / classification
Clozapine / pharmacology*
Dopamine Antagonists / chemical synthesis*
Dopamine Antagonists / chemistry
Dopamine Antagonists / classification
Dopamine Antagonists / pharmacology*
Dopamine D2 Receptor Antagonists
Hydrazines / chemistry*
Molecular Structure
Receptors, Dopamine D1 / antagonists & inhibitors*
Receptors, Dopamine D1 / metabolism
Receptors, Dopamine D2 / metabolism
Structure-Activity Relationship

Substances

Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Hydrazines
Receptors, Dopamine D1
Receptors, Dopamine D2
hydrazine
Clozapine