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Conformational Flexibility of Serotonin 1A Receptor Ligands from Crystallographic Data. Updated Model of the Receptor Pharmacophore
Author(s) -
Chilmonczyk Zdzislaw,
SzelejewskaWozniakowska Agnieszka,
Cybulski Jacek,
Cybulski Marcin,
Koziol Anna E.,
Gdaniec Maria
Publication year - 1997
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.19973300507
Subject(s) - pharmacophore , buspirone , chemistry , receptor , stereochemistry , ligand (biochemistry) , 5 ht receptor , 5 ht1a receptor , g protein coupled receptor , serotonin , biochemistry
Preparation and affinity to 5‐HT 1A and 5‐HT 2A receptors of new buspirone analogues 7–17 are reported. The compounds possess high to low affinity to 5‐HT 1A and moderate to low to 5‐HT 2A receptors. The crystal structures have been determined for compounds 11, 12, 13 , and 14 . For low affinity ligand ( 15 ) of 5‐HT 1A receptor conformational analysis was performed and compared with similar analyses performed for know high (buspirone 1 ) and very high (WY‐48, 723 2 ) affinity ligands of the receptor. Structure‐activity relationship is discussed for the affinity to 5‐HT 1A receptor. A three‐point pharmacophore explaining interactions of buspirone‐like molecules with the receptor binding site is proposed.