Rigid analogues of buspirone and gepirone, 5-HT1A receptors partial agonists
Drug Institute, 30/34 Chełmska Str., 00-725 Warsaw, Poland.Il Farmaco 12/2002; 57(11):917-23. DOI: 10.1016/S0014-827X(02)01279-X
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.
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- "Cl N N O OH Antihistamine Niaprazine  N N N H O F N Antihistamine Cetrizine  N N O OH O Cl Antihistamine Trimetazidine  O O O N NH Antianginal Ranolazine  N N O H N O OH O Antianginal Buspirone  N N N O O N N Antidepressant Amoxapine  N O Cl N N H Antidepressant Befuraline  N N O O Antidepressant Gepirone  N N N O O Antidepressant (continued on next page) M. Shaquiquzzaman et al. / European Journal of Medicinal Chemistry 102 (2015) 487e529 491 Table 1 (continued ) Drug Structure Pharmacological class Ipsapirone  N N N N N S O O O Antidepressant Flesinoxan  F O HN N N O O HO Antidepressant Nefazodone  Cl N N N N N O O Antidepressant Vilazodone  N NH N N O O H 2 N Antidepressant Tandospirone  N N H H O O N N Antidepressant Trazodone  N N N N N O Cl Antidepressant Sildenafil  N N H 3 C S O O O N H N N N O CH 3 CH 3 Erectile dysfunction Vardenafil  N N H 3 C S O O O CH 3 N N HN N O CH 3 Cl "
ABSTRACT: Piperazine is one of the most sought heterocyclics for the development of new drug candidates. This ring can be traced in a number of well established, commercially available drugs. Wide array of pharmacological activities exhibited by piperazine derivatives have made them indispensable anchors for the development of novel therapeutic agents. The review herein highlights the therapeutic significance of piperazine derivatives. Various therapeutically active piperazine derivatives developed by several chemists are reported here. Copyright © 2015 Elsevier Masson SAS. All rights reserved.European Journal of Medicinal Chemistry 07/2015; 102:487-529. DOI:10.1016/j.ejmech.2015.07.026 · 3.45 Impact Factor
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ABSTRACT: Novel, flexible arylpiperazine gepirone analogs (1a-3a) with a mixed 5-HT1A/5-HT2A receptor profile, low D2 receptor affinity, and agonistic (2a) or partial agonistic (1a, 3a) activity toward 5-HT1A receptor sites were synthesized. Their conformationally restricted counterparts (1b-3b) were selective 5-HT1A ligands (over 5-HT2A and D2 receptors), which turned out to be agonists (2b, 3b), or partial agonist (1b) of 5-HT1A receptors.Bioorganic & Medicinal Chemistry 03/2005; 13(4):1195-200. DOI:10.1016/j.bmc.2004.11.019 · 2.79 Impact Factor
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