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  2. Structure-activity relationship studies of CNS agents, Part 25. 4,6-di(heteroaryl)-2-(N-methylpiperazino)pyrimidines as new, potent 5-HT2A receptor ligands: a verification of the topographic model

Structure-activity relationship studies of CNS agents, Part 25. 4,6-di(heteroaryl)-2-(N-methylpiperazino)pyrimidines as new, potent 5-HT2A receptor ligands: a verification of the topographic model

  • Arch Pharm (Weinheim). 1995 Sep;328(9):659-66. doi: 10.1002/ardp.19953280906.
M J Mokrosz 1 L Strekowski W X Kozak B Duszyńska A J Bojarski A Kłodzinska A Czarny M T Cegła A Dereń-Wesoøek E Chojnacka-Wójcik
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Abstract

A series of new 4,6-di(heteroaryl)pyrimidines containing an N-methylpiperazino group (6-13) or an ethylenediamine chain (15-20) in position 2 were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. It was shown that the substituent effects on the 5-HT2A affinity are additive and could be described quantitatively. In a behavioral model it was also demonstrated that 6-11 are 5-HT2A receptor antagonists. The molecular modelling results suggested that the distances between the basic nitrogen atom and the two aromatic centers (d1 = 5.2-8.4 A, d2 = 5.7-8.5 A, and d3 = 4.6-7.3 A) define the molecular topography of the 5-HT2A receptor antagonists under study.

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