dc.contributor.author |
Mahesh, R. |
|
dc.date.accessioned |
2023-11-20T06:43:09Z |
|
dc.date.available |
2023-11-20T06:43:09Z |
|
dc.date.issued |
2010-11 |
|
dc.identifier.uri |
https://www.sciencedirect.com/science/article/abs/pii/S0960894X10012643 |
|
dc.identifier.uri |
http://dspace.bits-pilani.ac.in:8080/xmlui/handle/123456789/13175 |
|
dc.description.abstract |
A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds’ structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT3 receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT, which was expressed in the form of pA2 value. All the synthesized compounds showed antagonism towards 5-HT3 receptor; based on this result, a structure–activity relationship was derived, which reveals that the aromatic residue in 5-HT3 receptor antagonists may have hydrophobic interaction with 5-HT3 receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA2 values exhibited good anti-depressant-like activity as compared to the vehicle-treated group. |
en_US |
dc.language.iso |
en |
en_US |
dc.publisher |
Elsevier |
en_US |
dc.subject |
Pharmacy |
en_US |
dc.subject |
EDC·HCl |
en_US |
dc.subject |
Hydroxybenzotriazole (HOBt) |
en_US |
dc.subject |
Ethylcarbodiimide hydrochloride (EDC·HCl) |
en_US |
dc.title |
Design, synthesis and structure–activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression |
en_US |
dc.type |
Article |
en_US |