Design, synthesis and in vivo anticonvulsant screening in mice of novel phenylacetamides.
A set of seven novel N-substituted 2-anilinophenylacetamides were designed by pharmacophore generation and using flexible alignment module of MOE software. The novel molecules were synthesized and screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Test compounds were found to be potent in MES test. Compounds 12 and 14 were found to be more potent with ED(50) values 24.0 and 8.0 mg kg(-1), respectively, and their activity was comparable to standard drugs (Phenytoin, Carbamazepine). Test compounds did not show significant activity in ScPTZ test. Compounds 12 and 14 also exhibited higher protective indices (20.3 and 87.5, respectively) when assessed for neurotoxicity by rotarod test as compared to the standards.
Shindikar
A V
AV
The Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai 400098, Maharashtra, India. anandshindikar@yahoo.com
Khan
F
F
Viswanathan
C L
CL
D000577:Amides / Q000737:chemistry; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D000577:Amides; D000927:Anticonvulsants; D010648:Phenylacetates; C025136:phenylacetic acid