Anticancer, Anti-inflammatory and Analgesic Activity Evaluation of Heterocyclic Compounds Synthesized by the Reaction of 4-Isothiocyanato-4-methylpentan-2-one with Substituted o-Phenylenediamines, o-Diaminopyridine and (Un)Substituted o

Abstract

4,5-Dimethyl-1,2-phenylenediamine and 4-chloro-1,2-phenylenediamine react with 4-isothiocyanato-4-methylpentan-2-one (15) to give compounds (3a) and (3b), respectively. 3,4-Diaminobenzoic acid reacts similarly with (15) to give a mixture of compounds, possibly (2a) and (2b), which could be cyclized at pH ~5 to compound (3c). 3,4-Diaminopyridine reacted with (15) in DMF to give compounds (5) and (6), whereas condensation of 5,6-diaminopyrimidine and 4,5,6-triaminopyrimidine sulfate under similar conditions gave compounds (8a) and (8b), respectively. Compounds (8a) and (8b) at pH ~4 gave a mixture of compounds (9a), (10a) and (9b), (10b), respectively. Condensation of 4,5-diamino-6-hydroxy-2-mercaptopyrimidine, 4,5-diamino-2,6-dimercapto-pyrimidine and 5,6-diamino-1,3-dimethyluracil hydrate with (15) gave corresponding mercaptopyrimidines (12a), (12b) and (14), respectively. The evaluation of (3a–c), (8a,b), (12a,b) and (14) aganist a small panel of six cancer cell lines, consisting of prostate (DU145), colon (HT29), melanoma (LOX), breast (MCF, MCF7/ADR), ovarian (OVCAR3) and CNS (U251) is reported. The most active was compound (8b), against colon (HT29) (44.2 &Mgr;). Anti-inflammatory and analgesic activity is also reported.