Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole.
| Title: | Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. |
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| Authors: | Amnerkar ND; Department of Medicinal Chemistry, Sharad Pawar College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 441 110, Maharashtra, India. nikhilamnerkar@gmail.com; Bhusari KP |
| Source: | European journal of medicinal chemistry [Eur J Med Chem] 2010 Jan; Vol. 45 (1), pp. 149-59. Date of Electronic Publication: 2009 Sep 30. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Paris : Editions Scientifiques Elsevier; Original Publication: Paris, S.E.C.T. [etc.] |
| MeSH Terms: | Quantitative Structure-Activity Relationship*; Alkenes/*chemistry ; Anticonvulsants/*chemistry ; Anticonvulsants/*pharmacology ; Benzothiazoles/*chemistry ; Benzothiazoles/*pharmacology ; Pyrazoles/*chemistry; Alanine Transaminase/blood ; Anticonvulsants/chemical synthesis ; Anticonvulsants/toxicity ; Aspartate Aminotransferases/blood ; Behavior, Animal/drug effects ; Benzothiazoles/chemical synthesis ; Benzothiazoles/toxicity ; Liver/drug effects ; Animals ; Female ; Male ; Mice ; Models, Molecular ; Molecular Conformation ; Rats ; Software |
| Abstract: | 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 ED50 of 25.49 micromol/kg, TD50 of 123.87 micromol/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 (r2=0.9220, q2=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.; (Copyright 2009 Elsevier Masson SAS. All rights reserved.) |
| Substance Nomenclature: | 0 (Alkenes); 0 (Anticonvulsants); 0 (Benzothiazoles); 0 (Pyrazoles); 0 (aminobenzothiazole compound); AUG1H506LY (propylene); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase) |
| Entry Date(s): | Date Created: 20091027 Date Completed: 20100429 Latest Revision: 20121115 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.ejmech.2009.09.037 |
| PMID: | 19853976 |
| Database: | MEDLINE |
Journal Article