title: Anticonvulsant evaluation of clubbed indole-1,2,4-triazine derivatives: a synthetic approach.
abstract: A series of thirty indole C-3 substituted 5-amino-6-(5-substituted-2-phenyl-1H-indol-1-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-thione 5a-f, 6a-f, 7a-f, 8a-f and 9a-f were synthesized to explore prospective anticonvulsant agents. The derivative 1-(1-(5-amino-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-5-fluoro-2-phenyl-1H-indol-3-yl)ethanone (6b) had significant activity in maximal electroshock test with minimal duration of limb extension (5.40 ± 0.61 s) and quantitative median dose of 7 mg/kg. In subcutaneous pentylenetetrazole screen 1-(5-amino-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-5-fluoro-2-phenyl-1H-indole-3-sulfonamide (7b) increased the seizure latency to onset of clonus and was effective at a median dose of 35 mg/kg. An in vitro radioligand binding assay on sodium channel and γ-amino butyric acid estimation was also performed on active compounds to perceive the mechanistic procedure responsible for it action.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Ahuja
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. Electronic address: nadeems_03@rediffmail.com.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D015222:Sodium Channels / Q000378:metabolism; D014227:Triazines / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D015222:Sodium Channels; D014227:Triazines; C093444:1,2,4-triazine; D005680:gamma-Aminobutyric Acid
keywords: Anticonvulsant; GABA; Quantification; Sodium channel; Triazine