Bis dihydropyrimidine: synthesis and antimycobacterial activity

Abstract

A series of bis dihydropyrimidine compounds were synthesised by reacting dapsone with acetylacetoacetate to produce N1-4-[4-(2-oxopropylcarboxamido) phenylsulphonyl] phenyl-3-oxobutanamide, then treated with guanidine hydrochloride and an appropriate aldehyde with a catalytic amount of p-toluene sulphonic acid (PTSA) in the presence of methanol to afford the title compounds. The synthesised compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H₃₇Rv and isoniazid (INH) resistant M. tuberculosis. Among the synthesised compounds, compound N5-(4-4-[6-(4-fluorophenyl)-2-imino-4-methyl-1,2,3,4-tetrahydro-5-pyrimidinylcarboxamido ]phenylsulphonylphenyl)-6-(4-fluorophenyl)-2-imino-4-methyl-1,2,3,4-tetrahydro-5-pyrimidine carboxamide (3g) was found to be the most promising compound with activity against M. tuberculosis H₃₇Rv and INH resistant M. tuberculosis with a minimum inhibitory concentration (MIC) between 0.08 and 0.10 μM.

Keywords::

• Bis dihydropyrimidine
• dapsone
• antitubercular agents

Acknowledgements

Ashraf Ali would like to thank to V.K Agarwal, Sanjay Prakash Garg and Manju Agarwal for their valuable suggestions. We would also like to thank Alwar Pharmacy College, Alwar, Rajasthan, India for providing research facilities.

Declaration of interest

The authors report no conflict of interest.