Bis dihydropyrimidine: synthesis and antimycobacterial activity.
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.
Ali
Mohamed Ashraf
MA
New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar, Rajasthan, India. asraf80med@rediffmail.com
Manogaran
Elumalai
E
Govindasamy
Jeyabalan
J
Sellappan
Velmurugan
V
Pandian
Suresh
S
D000090:Acetoacetates / Q000737:chemistry; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000737:chemistry; D003622:Dapsone / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy
D000090:Acetoacetates; D000995:Antitubercular Agents; D001557:Benzenesulfonates; D011743:Pyrimidines; D003622:Dapsone; C029501:4-toluenesulfonic acid; D007538:Isoniazid