(Aryloxy)alkylamines as selective human dopamine D-4 receptor antagonists: Potential antipsychotic agents

被引：15

作者：

Unangst, PC ^{[1
]}

Capiris, T ^{[1
]}

Connor, DT ^{[1
]}

Doubleday, R ^{[1
]}

Heffner, TG ^{[1
]}

MacKenzie, RG ^{[1
]}

Miller, SR ^{[1
]}

Pugsley, TA ^{[1
]}

Wise, LD ^{[1
]}

机构：

[1] PARKE DAVIS PHARMACEUT RES,DEPT THERAPEUT,ANN ARBOR,MI 48105

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1997年 / 40卷 / 25期

关键词：

D O I：

10.1021/jm970422s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery of a series of novel (aryloxy)alkyamines with selective affinity for the dopamine D-4 receptor is described, Target compounds were tested. for binding to cloned human dopamine D-2, D-3, and D-4 receptor subtypes expressed in Chinese hamster ovary (CHO) K-l cells. A number of compounds demonstrated subnanomolar K-i values for binding to the D-4 receptor, with several 100-fold selectivities toward the D-2 and D-3 receptors. Several compounds with combined D-3/D-4 receptor binding selectivity were also identified, A limited structure-activity relationship study of this chemical series is discussed. In a mitogenesis functional assay, the effect of the test compounds on cellular uptake of [H-3]thymidine in D-4-transfected CHO 10001 cells was measured and compared to the response of the full dopamine agonist quinpirole. The activity of the compounds varied from full antagonist to weak partial agonist activity(intrinsic activity of 0-19% in comparison to quinpirole).

引用

页码：4026 / 4029

页数：4

共 22 条

[21] Chromeno[3,4-c]pyridin-5-ones: Selective human dopamine D-4 receptor antagonists as potential antipsychotic agents
Unangst, PC
Capiris, T
Connor, DT
Heffner, TG
MacKenzie, RG
Miller, SR
Pugsley, TA
Wise, LD
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (17) : 2688 - 2693
[22] CLONING OF THE GENE FOR A HUMAN DOPAMINE D4-RECEPTOR WITH HIGH-AFFINITY FOR THE ANTIPSYCHOTIC CLOZAPINE
VANTOL, HHM
BUNZOW, JR
GUAN, HC
SUNAHARA, RK
SEEMAN, P
NIZNIK, HB
CIVELLI, O
[J]. NATURE, 1991, 350 (6319) : 610 - 614

← 1 2 3 →