Design, synthesis and pharmacological activity of substituted 1,2,3,6-tetrahydropyrimidine-5-carbonitrile

Aim

The benzothiazole, pyrimidine and piperazine nucleuses having outstanding biological activates which prompted us to synthesis of substituted derivatives of N-(1,3-benzothiazol-2-yl)-2-[4-(5-cyano-6-imino-2-oxo1,2,3,4-tetrahydropyrimidin-4-yl)piperazin-1-yl]acetamide and to evaluate for anticancer and anti-inflammatory activity.

Method

Benzothiazole linked by acetamido bridge to 4-Imino-2 oxo-6-(piperazin-1-yl)1,2,3,4-tetrahydropyrimidine -5-carbonitrile to afforded a series of substituted N-(1,3-benzothiazol-2-yl)-2-[4-(5-cyano-6-imino-2-oxo1,2,3,4-tetrahydropyrimidin 4-yl)piperazin-1-yl]acetamide in good yield.

Results and discussion

The structures of compounds were in agreement with IR, ¹H NMR, and MASS spectral data. Three compounds were screened for in-vitro anticancer activity at the national cancer institute for anticancer activity against a panel of 60 different human tumor cell lines derived from nine neoplastic cancer types at NCI, and for in vitro anti-inflammatory activity by albumin denaturation technique. The compound (4b) with 6-chloro substitution was showed selective influence on cancer cell lines and compounds (4h), (4i), (4j) exhibited excellent anti-inflammatory activity.

Conclusion

New derivatives having significant in-vitro anti-inflammatory activity showed remarkable inhibitory effects against cancer. This observation may promote a further development of this novel series that may lead to compounds with better anticancer and anti-inflammatory profile.