7221-27-4Relevant articles and documents
Synthesis and biological evaluation of 1,3-dideazapurine-like 7-amino-5-hydroxymethyl-benzimidazole ribonucleoside analogues as aminoacyl-tRNA synthetase inhibitors
Aerschot, Arthur Van,Gadakh, Bharat,Lescrinier, Eveline,Nautiyal, Manesh,Pang, Luping,Rozenski, Jef,Strelkov, Sergei V.,Weeks, Stephen D.,Zhang, Baole,de Graef, Steff
, (2020/10/27)
Aminoacyl-tRNA synthetases (aaRSs) have become viable targets for the development of antimicrobial agents due to their crucial role in protein translation. A series of six amino acids were coupled to the purine-like 7-amino-5-hydroxymethylbenzimidazole nucleoside analogue following an optimized synthetic pathway. These compounds were designed as aaRS inhibitors and can be considered as 1,3-dideazaadenine analogues carrying a 2-hydroxymethyl substituent. Despite our intentions to obtain N1-glycosylated 4-aminobenzimidazole congeners, resembling the natural purine nucleosides glycosylated at the N9-position, we obtained the N3-glycosylated benzimidazole derivatives as the major products, resembling the respective purine N7-glycosylated nucleosides. A series of X-ray crystal structures of class I and II aaRSs in complex with newly synthesized compounds revealed interesting interactions of these “base-flipped” analogues with their targets. While the exocyclic amine of the flipped base mimics the reciprocal interaction of the N3-purine atom of aminoacyl-sulfamoyl adenosine (aaSA) congeners, the hydroxymethyl substituent of the flipped base apparently loses part of the standard interactions of the adenine N1 and the N6-amine as seen with aaSA analogues. Upon the evaluation of the inhibitory potency of the newly obtained analogues, nanomolar inhibitory activities were noted for the leucine and isoleucine analogues targeting class I aaRS enzymes, while rather weak inhibitory activity against the corresponding class II aaRSs was observed. This class bias could be further explained by detailed structural analysis.
Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents
Kumar, Kunal,Awasthi, Divya,Lee, Seung-Yub,Zanardi, Ilaria,Ruzsicska, Bela,Knudson, Susan,Tonge, Peter J.,Slayden, Richard A.,Ojima, Iwao
supporting information; experimental part, p. 374 - 381 (2011/03/18)
Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strai
Hydrogenation on palladium-containing granulated catalysts 3. Synthesis of aminobenzimidazoles by catalytic hydrogenation of dinitroanilines
Elkin,Tolkacheva,Chernysheva,Karmanova,Konyushkin,Semenov
, p. 1216 - 1226 (2008/09/19)
Efficient hydrogenation of o-aminonitrobenzenes on palladium-containing granulated carbon catalysts in carboxylic acid solutions was accompanied by cyclization into aminobenzimidazoles. A simple hydrogenation reactor with a fixed gauze holding a reusable granulated catalyst was designed. Acylated and sulfonylated 4(7)-aminobenzimidazoles were obtained. In terms of electronic and geometrical parameters, they are close analogs of biologically active imidazo[1,5,4-e,f ][1,5]benzodiazepines.
