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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
Author(s) -
Mokrosz Maria J.,
Strekowski Lucjan,
Kozak Wei Xing,
Duszyńska Beata,
Bojarski Andrzej J.,
Kłodzinska Aleksandra,
Czarny Agnieszka,
Cegła Marek T.,
DereńWesołek Anna,
ChojnackaWójcik Ewa,
Dove Stefan,
Mokrosz Jerzy L.
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953280906
Subject(s) - substituent , chemistry , ethylenediamine , stereochemistry , affinities , molecular model , receptor , 5 ht receptor , nitrogen atom , 5 ht3 receptor , serotonin , ring (chemistry) , biochemistry , organic chemistry
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.