N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D(2) and serotonin 5-HT(1A) receptor dual ligands.
A small series of N-propylnoraporphin-11-O-yl carboxylic esters with variant ester lengths were synthesized and their binding potencies at dopamine receptors (D(1), D(2)) and serotonin receptors (5-HT(1A), 5-HT(2A)) were evaluated. Monoesters 3a-f showed binding potency of 100 nM or less for the D(2) receptor, and potency of 10-30 nM for the 5-HT(1A) receptor. Butyryl ester 3d was found to be the best compound possessing the highest potency for both receptors, with K(i) values of 55 and 12 nM for D(2) and 5-HT(1A) receptors, respectively. There is no correlation between the binding potency and the length of the monoesters, but the diesters 9 and 10 were inactive for the D(2) receptor. The dual binding profile of these monoesters for the D(2) and 5-HT(1A) receptors may be useful for the treatment of neuropsychiatric disorders.
Liu
Zhili
Z
Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Chen
Xuetao
X
Sun
Peihua
P
Yu
Leiping
L
Zhen
Xuechu
X
Zhang
Ao
A
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001060:Aporphines / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D001060:Aporphines; D018492:Dopamine Antagonists; D004952:Esters; D008024:Ligands; D017448:Receptors, Dopamine D2; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A