Novel Structures Derived from 2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazole as Anti-Helicobacter pylori Agents, Part 1

Abstract

2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We have discovered five compounds with retained antibacterial potency and selectivity in which the overall framework of the sulfides 2 could be kept intact while structural modifications were made to remove PPI activity. These compounds, 2-[((2-methyl-3-(2-(2-(2-methoxyethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (79), 2-[((2-methyl-3-(2-(2-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (80), 2-[((2-methyl-3-((2-morpholino)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (86), 2-[[[2-methyl-3-[2-(2-methyl-5-nitroimidazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (88), and 2-[[[2-methyl-3-[2-(1,2,4-triazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (89), had minimum bactericidal concentrations (MBCs) of 0.5, 0.5, 1, 2, and 4 microg/mL, respectively. The reported compounds are bactericidal with MBCs within 1 order of magnitude of MBCs of clinically used antimicrobials such as clarithromycin (0.1 microg/mL) or metronidazole (2-4 microg/mL) but differ from these inasmuch that they have an extremely narrow spectrum activity and appear to be species specific.

Synthesis of some novel benzimidazole derivatives and it's biological evaluation

“…Benzimidazole derivatives shows a very good anti bacterial activities [10][11][12][13][14], we are comparing the synthesized new benzimidazole derivatives to the marketed chlorophenicol [15] which shows very good anti bacterial activity, here we are synthesizing the newly substituted benzimidazole derivatives for the studies of antibacterial activities by comparison with the drug molecule. In this studies compound 3f shows good bacterial activity, in which the tertiary butyl group is the electron releasing group, which is attached to the para position.…”

“…Literature survey has also revealed the importance of benzimidazoles as antimicrobial and antioxidant agents [10][11][12][13][14]. It has also been reported that certain substituted benzimidazole derivatives have a broad antimicrobial spectrum [11].…”

Nucleophilic ring opening of 1,4-disubstituted 2-pyrrolidones with hydrazine. Synthesis of azoles with a high antibacterial activity

“…Also, the compounds whose molecules possess an azole ring, such as pyrrole [11][12][13], 1,3,4-oxadiazole [14][15][16][17][18][19] and 1,2,4-triazole [19][20][21][22][23], are often characterized as good antimicrobial agents. In our previous works [24][25][26][27], we have reported that the heating under reflux of 4-(1H-benzimidazol-2-yl)-1-(substituted phenyl)pyrrolidin-2-ones in a 20% aqueous sodium hydroxide solution leads to the opening of the 2-pyrrolidinone cycle, followed by the formation of sodium salts of the corresponding N-substituted γ-amino acids.…”

Facile Synthesis of (2-Benzimidazolyl)-1-azaazulenes, (2-Benzothiazolyl)-1-azaazulenes, and Related Compouds and Evaluation of Their Anticancer in vitro Activity

“…Substituted benzothiazoles and benzimidazoles have found application in a wide range of therapeutic areas such as antiulcers, anticancers, antihistamics, antifungals, and antivirals to name a few. [1][2][3][4][5][6][7][8][9][10] The chemistry of azaazulenes 11 is of interest for their physiological properties 12,13 as well as physical and chemical properties. Therefore, it is expected that benzazolyl-1-azaazulenes have potential bioactivities.…”