Rigid analogues of buspirone and gepirone, 5-HT1A receptors partial agonists.
Rigid analogues of buspirone and gepirone, 5-HT1A receptors partial agonists, were obtained. The compounds exhibited very low affinity to the receptors. Their structural features resembled to a large extent the arrangement of the respective structural elements found in the solid state of buspirone and in the theoretical structure of NAN-190 (5-HT1A postsynaptic antagonist) rigid analogue exhibiting high affinity to the receptor. The obtained results would thus suggest that the bioactive conformation of buspirone might not be the extended one. That would additionally suggest that either both groups of compounds could occupy different areas at the receptor binding sites (or bind to different receptor states) or the constrained structure of 2 does not represent well 5-HT1A receptor binding site requirements.
Chilmonczyk
Zdzisław
Z
Drug Institute, 30/34 Chełmska Str., 00-725 Warsaw, Poland. chilmon@il.waw.pl
Krajewski
Krzysztof J
KJ
Cybulski
Jacek
J
D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002065:Buspirone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D011743:Pyrimidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C039979:gepirone; D002065:Buspirone