Journal of Enzyme Inhibition and Medicinal Chemistry 2011-02-01

Bis dihydropyrimidine: synthesis and antimycobacterial activity.

Mohamed Ashraf Ali, Elumalai Manogaran, Jeyabalan Govindasamy, Velmurugan Sellappan, Suresh Pandian

Index: J. Enzyme Inhib. Med. Chem. 26(1) , 149-53, (2011)

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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 H(37)Rv 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 H(37)Rv and INH resistant M. tuberculosis with a minimum inhibitory concentration (MIC) between 0.08 and 0.10 μM.