1H-Pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes: a unique structural class of dopamine D4 selective ligands

Andrew Thurkauf; Xi Chen; Suoming Zhang; Yang Gao; Andrzej Kieltyka; Jan W F Wasley; Robbin Brodbeck; William Greenlee; Ashit Ganguly; He Zhao

doi:10.1016/s0960-894x(03)00587-0

1H-Pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes: a unique structural class of dopamine D4 selective ligands

Bioorg Med Chem Lett. 2003 Sep 1;13(17):2921-4. doi: 10.1016/s0960-894x(03)00587-0.

Authors

Andrew Thurkauf¹, Xi Chen, Suoming Zhang, Yang Gao, Andrzej Kieltyka, Jan W F Wasley, Robbin Brodbeck, William Greenlee, Ashit Ganguly, He Zhao

Affiliation

¹ Neurogen Corporation, Branford, CT 06405, USA.

PMID: 14611858
DOI: 10.1016/s0960-894x(03)00587-0

Abstract

A series of novel 1H-pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes was prepared and screened at selected dopamine receptor subtypes. Compound 4 (NGB 4420) displayed high affinity and selectivity (>100-fold) for the D(4) over D(2) and other CNS receptors. This compound was identified as a D(4) antagonist via its attenuation of dopamine agonist-induced GTPgamma(35)S binding at D(4) receptor.

MeSH terms

Dopamine Antagonists / metabolism
Dopamine Antagonists / pharmacology
Humans
Ligands
Protein Binding
Receptors, Dopamine D2 / metabolism*
Receptors, Dopamine D4
Structure-Activity Relationship
Thiophenes / chemistry
Thiophenes / metabolism*
Thiophenes / pharmacology

Substances

DRD4 protein, human
Dopamine Antagonists
Ligands
Receptors, Dopamine D2
Thiophenes
Receptors, Dopamine D4