Title:Molecular Properties Prediction and Synthesis of Novel Pyrazoline Carboxamide Analogs as Antitubercular Agents
VOLUME: 10 ISSUE: 2
Author(s):Mohamed Jawed Ahsan, Jeyabalan Govinda Samy, Habibullah Khalilullah, Choudhary R. Kirit and Savita Soni
Affiliation:Department of Pharmaceutical Sciences, National Institute of Medical Sciences University, Jaipur 303 121, India.
Keywords:Pyrazolines, claisen schmidt condensation, antitubercular agents, molecular properties prediction, lipophilicity;
lipinski “rule of five”
Abstract:In the present investigation, a series of 3-substituted-N-aryl-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-
c]pyrazole-2-carboxamide analogs were synthesized based on the structure of known antitubercular drug thiacetazone and
were evaluated for antitubercular activity by two fold serial dilution technique. A computational study was carried out for
prediction of pharmacokinetic properties and none of the compounds violated Lipinski “Rule of Five”. The structures of
the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. All the newly synthesized
compounds showed low to good activity inhibitory activities against Mycobacterium tuberculosis H37Rv (MTB)
and isoniazid resistant M. tuberculosis (INHR-MTB). 3-(4-fluoromethyl)-N-(2-chlorophenyl)-6,7-dimethoxy-3a,4-
dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4c) was found to be the most promising compound active against M.
tuberculosis H37Rv and isoniazid resistant M. tuberculosis (INHR-MTB) with minimum inhibitory concentration 0.83 and
3.35 μM respectively.
