Pharmacophore Based Synthesis of 3-Chloroquinoxaline-2-carboxamides as Serotonin3 (5-HT3) Receptor Antagonist

Abstract

A series of 3-chloroquinoxaline-2-carboxamides were designed and prepared by the condensation of 3-chloro-2-quinoxaloylchloride with appropriate Mannich bases of the p-aminophenol in the microwave environment. The synthesized compounds were evaluated for serotonin 3 (5-HT 3 ) receptor antagonistic activities in longitudinal muscle-myenteric plexus (LMMP) preparation from guinea pig ileum against the 5-HT 3 agonist, 2-methyl-5-HT. Compound 3g exhibited comparable 5-HT 3 antagonistic activity (pA 2 6.4) to that of standard antagonist Ondansetron (pA 2 6.9), while the other compounds exhibited mild to moderate 5-HT 3 antagonistic activities.

Pyrazolo[4′,3′:5,6]pyrano[2,3‐b]quinoxalin‐4(1H)‐one: Synthesis and characterization of a novel tetracyclic ring system

“…Unfortunately, methylquinoxaline 5 was not oxidized to the corresponding acid 8, which has been reported recently by Mahesh et al [9] using Na 2 CrO 7 / H 2 SO 4 as the oxidation reagent. Even switching to aqueous KMnO 4 did not yield the desired acid.…”

Design, Synthesis and Evaluation of Antidepressant Activity of Novel 2‐Methoxy 1, 8 Naphthyridine 3‐Carboxamides as 5‐HT3 Receptor Antagonists

“…The contractions were recorded using a T‐305 Force transducer coupled to a Student's physiograph (Bio Devices, Ambala, India). 5‐HT 3 receptor antagonism was expressed in the form of p A 2 values, which was determined according to literature methods . The p A 2 values of the test compounds were compared with the standard 5‐HT 3 receptor antagonist ondansetron (Natco Pharma, Hyderabad, India).…”

Quinoxalin-2-carboxamides: synthesis and pharmacological evaluation as serotonin type-3 (5-HT3) receptor antagonists

“…Although nausea and vomiting seems like harmless sideeffects, inadequately controlled emesis can result in serious dehydration, loss of sodium and other electrolytes, nutritional depletion and loss of appetite, weight loss, oesophageal tears, deterioration of patient's physical, and mental status (anxiety and depression) which prompt them into non-adherence to the life saving anticancer treatment [5][6] . The recent incorporation of supportive treatment, that is 5-HT 3 antagonists substantially increase the patience compliance of anticancer treatment 3 by decreasing their side-effects (nausea and vomiting), but this 5-HT 3 receptor antagonists are ineffective in 10-30% of patients [7][8] and they possess chiral centres, which increases the synthetic cost of these drugs 9 and further only a very few selective 5-HT 3 antagonist are available 10 . With this information one may conclude the need of newer 5-HT 3 antagonists.…”

“…Several new chemical entities for 5-HT 3 receptor antagonists have been reported thus [10][11][12][13] based on the Hibert et al pharmacophore model 14 , which consists of an aromatic ring, a linking carbonyl group and a basic nitrogen centre at specific distances ( Figure 1). In our previous studies 10,13 , we evaluated various 3-substituted quinoxalin-2-carboxamides (consists of mannich base as linking unit for piperazine moiety and quinoxaline nucleus) as 5-HT 3 receptor antagonists, unfortunately none of the compound showed antagonism greater than or equal to 5-HT 3 receptor antagonist, ondansetron ( Figure 2). So in the present study to develop new 5-HT 3 receptor antagonists without chiral centre, our attempts were concentrated on developing quinoxlin-2-carboxamides with devoid of mannich base and no substituent at third position of quinoxaline nucleus as potential 5-HT 3 receptor antagonists.…”