Bhavinkumar Vavaiya^1,, Shivani Patel², Vrajlal Pansuriya³, Vanita Marvaniya⁴ and Popatbhai Patel^1,*

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: vavaiyabhavin@gmail.com

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.