title: 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 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.
authors.affiliation: New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar, Rajasthan, India. asraf80med@rediffmail.com
authors.forename: Mohamed Ashraf
authors.initials: MA
authors.lastname: Ali
authors.forename: Elumalai
authors.initials: E
authors.lastname: Manogaran
authors.forename: Jeyabalan
authors.initials: J
authors.lastname: Govindasamy
authors.forename: Velmurugan
authors.initials: V
authors.lastname: Sellappan
authors.forename: Suresh
authors.initials: S
authors.lastname: Pandian
mesh_terms: 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
chemical_list: D000090:Acetoacetates; D000995:Antitubercular Agents; D001557:Benzenesulfonates; D011743:Pyrimidines; D003622:Dapsone; C029501:4-toluenesulfonic acid; D007538:Isoniazid