A novel pyrimidine derivatives with aryl urea, thiourea and sulfonamide moieties: Synthesis, anti-inflammatory and antimicrobial evaluation

• Published in: Bioorganic & medicinal chemistry letters 2012-05, Vol.22 (10), p.3445-3448
• Main Authors: Keche, Ashish P., Hatnapure, Girish D., Tale, Rajesh H., Rodge, Atish H., Birajdar, Satish S., Kamble, Vandana M.
• Format: Article
• Language: English
• Subjects: Anti-bacterial; Anti-fungal; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Anti-inflammatory; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Biological and medical sciences; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Pyrimidine; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Sulfonamides - chemistry; Thiourea - chemistry; Thiourea and sulfonamide derivatives; Urea; Urea - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.03.092

A novel series of pyrimidine derivatives containing urea, thiourea and sulfonamide have been designed, synthesized and evaluated for anti-inflammatory activity (TNF-α and IL-6 inhibitory activity) and antimicrobial (antifungal and antibacterial) activities against pathogenic bacteria and fungi. A series of novel 4-(3-(trifluoromethyl)phenylamino-6-(4-(3-arylureiodo/arylthioureido/arylsulfonamido)-pyrimidine derivatives of biological interest were prepared by the sequential Suzuki cross coupling, acid amination, reduction followed by reaction of resulting amine with different arylisocyantes or arylisothiocyantes or arylsulfonyl chlorides. All the synthesized compounds (1–25) were screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological data revealed that among all the compounds screened, compounds 5, 6, 11, 12, 16 and 20 were found to have moderate to potent anti-inflammatory activity (up to 48–78% TNF-α and 56–96% IL-6 inhibitory activity) with reference to standard dexamethasone at 10μM. The compounds 10, 12, 13, 18, 20, 22, 24 and 25 found to have promising antimicrobial activity against all the selected pathogenic bacteria and fungi.