Synthesis and pharmacological evaluation of aminopyrimidine series of 5-HT1A partial agonists.

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Dounay AB, Barta NS, Bikker JA, Borosky SA, Campbell BM, Crawford T, Denny L, Evans LM, Gray DL, Lee P, Lenoir EA, Xu W

Synthesis and pharmacological evaluation of aminopyrimidine series of 5-HT1A partial agonists.

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1159-63. doi: 10.1016/j.bmcl.2008.12.087. Epub 2008 Dec 25.

PubMed ID

19147349 [ View in PubMed

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Abstract

Aminopyrimidine 2 (4-(1-(2-(1H-indol-3-yl)ethyl)piperidin-3-yl)-N-cyclopropylpyrimidin-2-amine) emerged from a high throughput screen as a novel 5-HT(1A) agonist. This compound showed moderate potency for 5-HT(1A) in binding and functional assays, as well as moderate metabolic stability. Implementation of a strategy for improving metabolic stability by lowering the lipophilicity (cLogD) led to identification of methyl ether 31 (4-(1-(2-(1H-indol-3-yl)ethyl)piperidin-3-yl)-N-(2-methoxyethyl)pyrimidin-2-amine ) as a substantially improved compound within the series.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Buspirone	5-hydroxytryptamine receptor 1A	Ki (nM)	15	N/A	N/A	Details
Buspirone	5-hydroxytryptamine receptor 1A	EC 50 (nM)	41	N/A	N/A	Details