Substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines as potential inhibitors of H+/K+ ATPase

Abstract

A series of substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines were synthesized as potential inhibitors of the acid secretory enzyme H+/K+ ATPase. Substitutions on the aniline nitrogen atom resulted in potent enzyme inhibition in vitro but weak activity in gastric fistula dogs. Electron-donating substituents on the aniline ring enhanced in vitro and in vivo potency relative to the unsubstituted analogue. The potency showed a correlation to the calculated pKa of the aniline nitrogen atom. Substitutions on the aniline and benzimidazole rings did not further enhance potency. Di- and trisubstituted aniline derivatives were potent inhibitors of the enzyme system. The preferred combination of substituents were a methoxy group on the benzimidazole ring and a single alkyl group on the aniline ring. One such compound, 76, was an effective inhibitor of acid secretion in the dog and was selected for further pharmacological study.

Clinical treatment for hepatitis C reverses CYP2C19 inhibition

“…Previous studies, carried out in vitro , report the relationship between HCV replication and its influence on the activity of membrane transporters and CYP isoforms, and emphasises the importance of confirming these results in vivo 13 . HCV infection, the progression of hepatic fibrosis and the presence of cirrhosis may be accompanied by the induction of pro‐inflammatory cytokines, which may result in the inhibition of CYP enzymes and inhibition/induction of expression of the membrane transporters involved in absorption, distribution and elimination of several drugs used in the treatment of chronic hepatitis C. The present investigation covers for the first time the effect of chronic hepatitis C on the activity of 1,21,22 using omeprazole (OME) 23,24 as a probe drug in patients with HCV evaluated before and after the treatment.…”

Tandem [3 + 2] Cycloaddition/1,4-Addition Reaction of Azomethine Ylides and Aza-o-quinone Methides for Asymmetric Synthesis of Imidazolidines

“…The 1,4-addition reactions of ao-QMs with Grignard reagent or alcohol were extensively studied. In 1988, a thio etherification of 2-mercaptobenzimidazole with o -aminobenzyl halides protected with electron-withdrawing groups under meutral or acidic conditions was reported to give the sulfides . In 2014, Scheidt presented the reaction of benzyl chloride and benzaldehyde in the presence of NHC and DBU to yield the ketone .…”

Facile synthesis and antimicrobial properties of 2-(substituted-benzylsulfanyl)-1h-benzimidazoles

“…Some of them like thiabendazole, mebendazole and albendazole are widely used as antihelmintic drugs [2]. Similarly, benzimidazole-2-thiol and its derivatives have also been reported to have potent biological activities, such as proton pump inhibitors [3] antiulcer activity [4], inhibitors of H + /K + ATP ase [5].…”

“…In this regard, literature survey revealed that these compounds can be prepared by the reaction of 2-mercaptobenzimidazole with alkyl or aryl halides in the presence of bases such as NaH/DMF (8%) [6], K 2 CO 3 /EtOH (20%) [5], DMF/K 2 CO 3 [3b] (35 %), in low yields. In some instances, the formation of both the S and N benzyl derivatives have been reported even by the use of aq.…”