1H-Pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes: a unique structural class of dopamine D4 selective ligands.
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.
Thurkauf
Andrew
A
Neurogen Corporation, Branford, CT 06405, USA.
Chen
Xi
X
Zhang
Suoming
S
Gao
Yang
Y
Kieltyka
Andrzej
A
Wasley
Jan W F
JW
Brodbeck
Robbin
R
Greenlee
William
W
Ganguly
Ashit
A
Zhao
He
H
D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D008024:Ligands; D017448:Receptors, Dopamine D2; D013876:Thiophenes; D050638:Receptors, Dopamine D4