Design, synthesis, and discovery of 5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives: a novel series of mixed dopamine D2/D4 receptor antagonist

He Zhao; Xiaoyan Zhang; Kevin Hodgetts; Andrew Thurkauf; Jack Hammer; Jayaraman Chandrasekhar; Andrzej Kieltyka; Robbin Brodbeck; Stanislaw Rachwal; Renee Primus; Charles Manly

doi:10.1016/s0960-894x(02)01056-9

Design, synthesis, and discovery of 5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives: a novel series of mixed dopamine D2/D4 receptor antagonist

Bioorg Med Chem Lett. 2003 Feb 24;13(4):701-4. doi: 10.1016/s0960-894x(02)01056-9.

Authors

He Zhao¹, Xiaoyan Zhang, Kevin Hodgetts, Andrew Thurkauf, Jack Hammer, Jayaraman Chandrasekhar, Andrzej Kieltyka, Robbin Brodbeck, Stanislaw Rachwal, Renee Primus, Charles Manly

Affiliation

¹ Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405, USA. [email protected]

PMID: 12639562
DOI: 10.1016/s0960-894x(02)01056-9

Abstract

5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives were designed, synthesized, and identified as a new series of mixed dopamine D(2)/D(4) receptor antagonists. This series featured a rigid tricyclic ring system as an important pharmacophore core structure for high binding affinity. Molecular modeling studies are also described.

MeSH terms

Dopamine D2 Receptor Antagonists*
Drug Design
Drug Evaluation, Preclinical
Humans
Indoles / chemical synthesis*
Indoles / pharmacology*
Models, Molecular
Monte Carlo Method
Protein Binding
Radioligand Assay
Receptors, Dopamine D4
Structure-Activity Relationship

Substances

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