6-Alkoxyisoindolin-1-one based dopamine D2 partial agonists as potential antipsychotics

David A Favor; James J Powers; Andrew D White; Lawrence W Fitzgerald; Vincent Groppi; Kevin A Serpa

doi:10.1016/j.bmcl.2010.08.023

6-Alkoxyisoindolin-1-one based dopamine D2 partial agonists as potential antipsychotics

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5666-9. doi: 10.1016/j.bmcl.2010.08.023. Epub 2010 Aug 8.

Authors

David A Favor¹, James J Powers, Andrew D White, Lawrence W Fitzgerald, Vincent Groppi, Kevin A Serpa

Affiliation

¹ Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, United States. dafavor@gmail.com

PMID: 20801650
DOI: 10.1016/j.bmcl.2010.08.023

Abstract

A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological profile are presented as potential antipsychotics. The in vitro pharmacological profile includes D(2) partial agonism (30-55%), 5-HT(1A) partial agonism (60-90%), and 5-HT(2A) antagonism. Selected compounds in this series displayed good in vivo activity and potency.

MeSH terms

Animals
Antipsychotic Agents / chemical synthesis
Antipsychotic Agents / chemistry*
Antipsychotic Agents / pharmacology
Cell Line
Humans
Isoindoles / chemical synthesis
Isoindoles / chemistry*
Isoindoles / pharmacology
Mice
Rats
Receptors, Dopamine D2 / agonists*
Receptors, Dopamine D2 / metabolism
Serotonin 5-HT1 Receptor Agonists / chemical synthesis
Serotonin 5-HT1 Receptor Agonists / chemistry
Serotonin 5-HT1 Receptor Agonists / pharmacology
Serotonin 5-HT2 Receptor Agonists / chemical synthesis
Serotonin 5-HT2 Receptor Agonists / chemistry
Serotonin 5-HT2 Receptor Agonists / pharmacology
Serotonin Plasma Membrane Transport Proteins / chemistry
Serotonin Plasma Membrane Transport Proteins / metabolism
Structure-Activity Relationship

Substances

Antipsychotic Agents
Isoindol-1-one
Isoindoles
Receptors, Dopamine D2
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT2 Receptor Agonists
Serotonin Plasma Membrane Transport Proteins