Ligand-based design, synthesis, and pharmacological evaluation of 3-Methoxyquinoxalin-2-carboxamides as structurally novel serotonin type-3 receptor antagonists.
Employing a ligand-based approach, 3-methoxyquinoxalin-2-carboxamides were designed as serotonin type-3 (5-HT(3) ) receptor antagonists and synthesized from the starting material o-phenylenediamine in a sequence of reactions. The structures of the synthesized compounds were confirmed by spectral data. These carboxamides were investigated for their 5-HT(3)  receptor antagonisms in longitudinal muscle myenteric plexus preparations from guinea-pig ileum against a standard 5-HT(3)  agonist, 2-methy-5-HT, and their antagonism activities are expressed as pA(2)  values. Compounds 6a (pA(2) : 7.2), 6e (pA(2) : 7.0), 6f (pA(2) : 7.5), 6g (pA(2) : 7.5), 6n (pA(2) : 7.0), and 6o (pA(2) : 7.2) exhibited antagonism greater than that of the standard 5-HT(3)  antagonist, ondansetron (pA(2) : 6.9).
Faculty Division-III (FD-III), Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan, India.
Radhakrishnan
R
Mahesh
Thangaraj
T
Devadoss
Arghya Kusum
AK
Dhar
Sudali Muthu
SM
Venkatesh
Sourabh
S
Mundra
Dilip Kumar
DK
Pandey
Shvetank
S
Bhatt
Ankur Kumar
AK
Jindal
D000818:Animals; D015195:Drug Design; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D008024:Ligands; D011810:Quinoxalines; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists