Synthesis of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines as a new class of antifilarial agents

• Published in: European journal of medicinal chemistry Vol. 43; no. 12; pp. 2717 - 2723
• Main Authors: Singh, B.K., Mishra, Mridul, Saxena, Nisha, Yadav, G.P., Maulik, P.R., Sahoo, M.K., Gaur, R.L., Murthy, P.K., Tripathi, R.P.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.12.2008; Elsevier
• Subjects: 1,4-Dihydropyrimidines; Alkylation; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifilarial; Antiparasitic agents; Biological and medical sciences; Brugia malayi; Brugia malayi - drug effects; Chemistry, Medicinal; Dihydropyrimidines; Dose-Response Relationship, Drug; Filaricides - chemical synthesis; Filaricides - chemistry; Filaricides - pharmacology; Life Sciences & Biomedicine; Medical sciences; Models, Molecular; Molecular Structure; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyrimidines - chemical synthesis; Pyrimidines - pharmacology; Science & Technology; Stereoisomerism; Tetrabutyl ammonium bromide; Tetrabutyl ammonium bromide; Antifilarial; Dihydropyrimidines; Brugia malayi; 1,4-Dihydropyrimidines; ANALOGS; ANTI-HIV-1 ACTIVITY; Meriones unguiculatus; Intraperitoneal administration; Nitrogen heterocycle; Alkylation; Structure activity relation; Six membered ring; Chemical synthesis; Nematoda; Rodentia; Benzene derivatives; Parasitosis; Helminthiasis; In vitro; Infection; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Nematode disease; Helmintha; Parasiticide; Nemathelminthia; Fluorine Organic compounds; Filariosis; Invertebrata
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2008.01.038

A series of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines ( 8– 21) were synthesized in good yields by alkylation of 5-methyl-6-phenyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ethyl esters ( 2– 7) with different alkyl or aralkyl halides in the presence of a combination of anhydrous K 2CO 3 and catalytic amount of tetrabutyl ammonium bromide. The title compounds were evaluated for their antifilarial activity against adult parasites of human lymphatic filarial parasite Brugia malayi (sub-periodic strain) in vitro and in vivo at various concentrations. One of the compounds ( 18) showed promising antifilarial activity. [Display omitted]