Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT6 and Dopamine D2 Receptor Ligands

被引：19

作者：

Krogsgaard-Larsen, Niels ^{[1
]}

Jensen, Anders A. ^{[1
]}

Schroder, Tenna J. ^{[2
]}

Christoffersen, Claus. T. ^{[2
]}

Kehler, Jan ^{[2
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark

[2] H Lundbeck & Co AS, Dept Med Chem, DK-2500 Valby, Denmark

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 13期

关键词：

MONOAMINERGIC RECEPTOR; COGNITIVE IMPAIRMENT; ANTIPARKINSON AGENTS; DIFFERENTIAL ACTIONS; MULTIPLE CLASSES; ANTAGONISTS; BINDING; AGONIST; RAT; ARIPIPRAZOLE;

D O I：

10.1021/jm5003759

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D-2 and serotonin S-HT6 receptor subtype, respectively. While the S-HT6 ligands were antagonists, the D-2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson's disease, and cognitive deficits.

引用

页码：5823 / 5828

页数：6

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