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
- 1 January 1995
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 328 (9) , 659-666
- https://doi.org/10.1002/ardp.19953280906
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 Å, d2 = 5.7−8.5 Å, and d3 = 4.6−7.3 Å) define the molecular topography of the 5‐HT2A receptor antagonists under study.Keywords
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