Structure‐Activity Relationship Studies of CNS Agents, Part 25: 4,6‐Di(heteroaryl)‐2‐( N ‐methylpiperazino)pyrimidines as New, Potent 5‐HT 2A Receptor Ligands: A Verification of the Topographic Model

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‐HT 1A and 5‐HT 2A receptor affinities were determined. It was shown that the substituent effects on the 5‐HT 2A affinity...

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Veröffentlicht in:Archiv der Pharmazie (Weinheim) 1995-01, Vol.328 (9), p.659-666
Hauptverfasser: Mokrosz, Maria J., Strekowski, Lucjan, Kozak, Wei Xing, Duszyńska, Beata, Bojarski, Andrzej J., Kłodzinska, Aleksandra, Czarny, Agnieszka, Cegła, Marek T., Dereń‐Wesołek, Anna, Chojnacka‐Wójcik, Ewa, Dove, Stefan, Mokrosz, Jerzy L.
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Sprache:eng
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Zusammenfassung: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‐HT 1A and 5‐HT 2A receptor affinities were determined. It was shown that the substituent effects on the 5‐HT 2A affinity are additive and could be described quantitatively. In a behavioral model it was also demonstrated that 6 – 11 are 5‐HT 2A receptor antagonists. The molecular modelling results suggested that the distances between the basic nitrogen atom and the two aromatic centers ( d 1 = 5.2−8.4 Å, d 2 = 5.7−8.5 Å, and d 3 = 4.6−7.3 Å) define the molecular topography of the 5‐HT 2A receptor antagonists under study.
ISSN:0365-6233
1521-4184
DOI:10.1002/ardp.19953280906