Synthesis and Antitumor Activity Evaluation of 2,4-Substituted Py-rimidine Derivatives Containing Trifluoromethyl

Abstract

In order to find more effective antitumor drugs, a series of novel 2,4-substituted pyrimidine derivatives containing trifluoromethyl were designed, synthesized, and evaluated for antitumor activity aganist EC-109 (human esophageal cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell) and HepG-2 (human liver cancer cell). The results showed that some compounds displayed moderate to potent antitumor activity against PC-3. Among them, 2-(((4-((1methyl-1H-tetrazol-5-yl)thio)-6-(trifluoromethyl)pyrimidin-2-yl)thio)methyl)benzo[d]thiazole (13w) possesses strong antitumor activity against PC-3 with IC 50 value of 1.76 µmol•L-1 , and the antitumor activity is significantly better than the positive control drug of 5-fluorouracil.

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…Condensation of ethyl 4,4,4-trifluoro-3-oxobutanoate 1 with thiourea 221 provided 2-mercapto-6-(trifluoromethyl)pyrimidin-4-ol 373 which underwent nucleophilic substitution with 2chloromethylbenzazole derivatives 374 in the presence of aqueous KOH to furnish 2-((benzoazol-2-ylmethyl)thio)-6-(trifluoromethyl)pyrimidin-4-ols 375 in moderate to good yields (Scheme 129). [221,222] ). [223,224] Chlorination of 382 with POCl ).…”

“…Condensation of ethyl 4,4,4‐trifluoro‐3‐oxobutanoate 1 with thiourea 221 provided 2‐mercapto‐6‐(trifluoromethyl)pyrimidin‐4‐ol 373 which underwent nucleophilic substitution with 2‐chloromethylbenzazole derivatives 374 in the presence of aqueous KOH to furnish 2‐((benzoazol‐2‐ylmethyl)thio)‐6‐(trifluoromethyl)pyrimidin‐4‐ols 375 in moderate to good yields (Scheme 129). [221,222] Chlorination of 375 followed by introduction of N ‐Boc substituted piperazine 376 afforded compound 377 which by substitution at piperazine ring provided 2‐(((4‐(4‐methylpiperazin‐1‐yl)‐6‐(trifluoromethyl)pyrimidin‐2‐yl)thio)methyl)benzo[ d ]thiazoles 378 . Compounds 378 having R group pyrimidin‐2‐yl and pyridin‐2‐yl exhibited the most potent antitumor activity against PC‐3 cells with IC 50 values of 2.29 and 3.89 μmol/L, respectively.…”

Synthesis and Antitumor Evaluation of 2,4,6-Trisubstituted Pyrimidine Derivatives Containing Benzothiazole Moiety

“…Based on previous studies, 2-mercapto-4-hydroxy-6trifluoromethylpyrimidine was selected as the scaffold. [15,16] Then, benzothiazole and the substituted piperazines were introduced into the macropyrimidine to synthesize a series of compounds with multiple active moieties. Finally, the antitumor activities of the target compounds were determined using thiazolyl blue (MTT) method.…”

Synthesis and Antiproliferative Activity of 2,4,5,6-Tetrasubstituted Pyrimidine Derivatives Containing Anisole

“…Compounds with pyrimidine structural units have a wide range of pharmacological activities, such as anti-tumor, [5][6] anti-viral, [7][8] anti-inflammatory [9][10] and antibacterial, [11][12] so they are still a very active field in the design and synthesis of new drug molecules. In recent years, many pyrimidine compounds have been approved by the US Food and Drug Administration (FDA) for clinical treatment of cancer, including capecitabine (1), [13] rociletinib (2), [14] osimertinib (3), [15][16] imatinib (4) (Figure 1), [17] etc.…”