In silico and In vitro Antitubercular Studies for Nitrogen Rich Hybrids of homopiperazine-pyrimidine-Pyrazole Adducts

Bhavinkumar Vavaiya1,, Shivani Patel2, Vrajlal Pansuriya3, Vanita Marvaniya4 and Popatbhai Patel1,*

1Department of Chemistry, M.G. Science Institute, Navrangpura, Ahmedabad-380009, India

2Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Navrangpura, Ahmedabad-380009, India

3Department of Chemistry, School of Science, Gujarat University, Ahmedabad-380009, India

4Shree Swaminarayan Sanskar Pharmacy College, Zundal, Gandhinagar-382421, India

*Corresponding author: E-mail:


Novel homopiperazine-pyrimidine-pyrazole hybrids (3a-j) were synthesized using ethyl 2-cyanoacetate and 4,6-dichloropyrimidine as starting materials by a multi-step process to afford ethyl 5-amino-1-(6-chloropyrimidin-4-yl)-1H-pyrazole-4-carboxylate in good yields using polar protic media. The intermediate 1, in two steps, chloroamine condensation followed by acid amine coupling, furnished the title compounds ethyl 5-amino-1-(6-(4-substituted aryl-1,4-diazepan-1-yl)pyrimidin-4-yl)-1H-pyrazole- 4-carboxylate (3a-j). The synthesized compounds were docked in the crystal structure of Mycobacterium tuberculosis (PDB ID: 4TRO) to get insights into structural requirements for antitubercular activity. In vitro antitubercular activity against M. tuberculosis H37Rv strains showed that compounds 3a, 3d, 3e and 3g were found to be the most potent (Docking score: > -21; MIC = 1.6 μg/mL) among the synthesized molecules. All the synthesized compounds showed acceptable drug-like properties which make them suitable for further lead modification using in silico design approaches.


Pyrazole, Pyrimidine, Homopiperazine, Molecular docking, Antitubercular activity.

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