Synthesis of 5‐Substituted 2‐Methylbenzimidazoles with Anticancer Activity

Abstract

A series of compounds comprising the thiocarboximidopyrazolyl 5, the phenylpyrazolyl 6, the dimethylpyrazolyl 7, the nitrophenylpyrazolyl 8, the dimethyloxazolyl 9, the benzoxazepinyl 10, and pyrimidyl 11 a-c derivatives of 3-(2-methyl-1H-benzimidazol-5-ylazo)pentane-2, 4-dione was synthesized. Moreover, 5-amino-2-methylbenzimidazole (3) was reacted with phthalic anhydride or maleic anhydride in acetic acid or in toluene to produce 12-15. Treating 5, 6-diamino-2-methylbenzimidazole (16) with ethyl cyanoacetate or diethyl malonate or acetyl acetone leads to the formation of the benzodiazepine derivatives 17-20. The cytotoxic activity of the compounds 2, 7, 9, 10, and 11 was tested against 60 types of human cancer cell lines. Compounds 7 and 9 were found to be the most potent.

Synthesis,in vitroandin vivoantitumor and antiviral activity of novel 1-substituted benzimidazole derivatives

“…Chemistry 2-Methyl-5-nitro-1H-benzimidazole 1, previously described by our group 17,18,20,41 , was used as a starting material to prepare benzimidazole derivatives. During transformation of compound 1 into 2, alkylation occurred using allyl bromide with stirring at room temperature in DMF and sodium hydride.…”

“…It was found that thiadiazole ring linked at position 1 to benzimidazole ring through a methylene group, I, has cytotoxicity against breast cancer (MCF-7; Figure 1) 17 . The 1-substituted-2-methyl benzimidazole derivative II was reported to be cytotoxic against non-small lung cancer and breast cancer 18 . It was evident that 1-(4-bromobenzyl) benzimidazole derivative III was the most potent androgen receptor antagonist for prostate cancer 19 .…”

Functionalized Benzimidazole Scaffolds: Privileged Heterocycle for Drug Design in Therapeutic Medicine

“…Compounds 96 and 97 possessed significant inhibitory activities against Burkitt's lymphoma promotion . Compounds 98 , 99 (log GI 50 = 5.61), and 100 had high cytotoxic activities against non‐small lung cancer while their result on breast cancer were 98 (log GI 50 = 5.77) and 99 (log GI 50 = 5.36) . Other benzimidazole templates with strong in vitro antitumor activities against various cancer cell lines include 101 – 105 (Fig.…”

1-Benzyl-2-[1-(5-methyl-1H-pyrazol-3-yl)-2-phenylethyl]benzimidazole

“…Benzimidazole derivatives are compounds that have received much attention because of their applications in several areas. They are used as antibacterial (Ö zden et al, 2004), anticancer (Easmon et al, 2001;Zhu et al, 1999), anti-inflammatory (Tewari & Mishra, 2001) and antiulcer agents (Shafik et al, 2004;El-Naem et al, 2003). They also have herbicidal, insecticidal and complexing properties (Sbai et al, 2003(Sbai et al, , 2002Attar et al, 2001).…”