Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole

• Published in: European journal of medicinal chemistry Vol. 45; no. 1; pp. 149 - 159
• Main Authors: Amnerkar, Nikhil D., Bhusari, Kishore P.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 2010; Elsevier
• Subjects: 3D-QSAR; Alanine Transaminase - blood; Alkenes - chemistry; Aminobenzothiazole; Animals; Anticonvulsant activity; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Anticonvulsants - toxicity; Anticonvulsants. Antiepileptics. Antiparkinson agents; Aspartate Aminotransferases - blood; Behavior, Animal - drug effects; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Benzothiazoles - pharmacology; Benzothiazoles - toxicity; Biological and medical sciences; Chemistry, Medicinal; Female; Life Sciences & Biomedicine; Liver - drug effects; Male; Medical sciences; Mice; Models, Molecular; Molecular Conformation; Neuropharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Prop-2-eneamide; Pyrazoles - chemistry; Pyrazoline; Quantitative Structure-Activity Relationship; Rats; Science & Technology; Software; Prop-2-eneamide; Anticonvulsant activity; 3D-QSAR; Aminobenzothiazole; Pyrazoline; PHASE; QSAR; SEMICARBAZONES; NEUROTOXICITY EVALUATION; ANTIEPILEPTIC DRUGS; ALKALOIDS; Rodentia; Prediction; Anticonvulsant; Benzothiazole derivatives; Modeling; Vertebrata; Three dimensional model; Mammalia; Structure activity relation; Mouse; Animal; Chlorine Organic compounds; Molecular model; Pyrazole derivatives; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.09.037

A series of 6-substituted-[3-substituted-prop-2-eneamido]benzothiazole 9– 32 and 6-substituted-2-[(1-acetyl-5-substituted)-2-pyrazolin-3-yl]aminobenzothiazole 33– 56 were synthesized using appropriate synthetic route and evaluated experimentally against maximal electroshock test. Selected compounds were evaluated for neurotoxicity, hepatotoxicity and behavioral study. The most active compound, 6-methyl-2-[(1-acetyl-5-(4-chlorophenyl))-2-pyrazolin-3-yl]aminobenzothiazole 52 exhibited an ED 50 of 25.49 μmol/kg, TD 50 of 123.87 μmol/kg and high protective index (PI) of 4.86 compared to standard drug phenytoin. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power ( r 2 = 0.9220, q 2 = 0.8144) was achieved. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may aids in the design of potent aminobenzothiazole derivatives as anticonvulsant agents. [Display omitted] Synthesis of series of aminobenzothiazole derivatives and their anticonvulsant activity with statistically reliable PHASE 3D-QSAR model ( r 2 = 0.9220, q 2 = 0.8144) are reported.