Microwave-Assisted Synthesis of Benzimidazoles and …

Synthesis of bioactive molecule fluoro benzothiazole comprising potent hetrocyclic moieties for biological and pharmacological screening, Res Rev Biomed Biotech1(1),issue (1);2010,24-30

this paper include a review of the synthesis, ..

T1 - Synthesis of 1-methyl-2-(2-hydrazino-4-thiazolyl)-benzimidazole and its hydrazones

describes the synthesis of benzimidazole ..

GSK-3 is involved in a large number of key cellular processes and exhibits dysregulation in a wide variety of disease states. Accordingly, modulation of GSK-3 activity has been deemed an important approach for therapy and imaging. As shown in this limited review, a very large number of GSK-3 inhibitors have been synthesized. However, as reflected in the slow progress of these inhibitors toward clinical translation, a number of challenges remain. Adverse effects caused by off-target activity of GSK-3 inhibitors were determined after the screening of compounds that bind to the ATP-competitive binding site conserved across a broad range of kinases. Therefore, it would be extremely advantageous to design and develop GSK-3 inhibitors that can selectively target individual pathways and differentiate between the phosphorylated and non-phosphorylated forms of GSK-3. In this regard, parallel development of a therapeutic molecule with a closely related imaging biomarker may allow early evaluation of drug candidates based on noninvasive imaging measurements of the target-to-background ratios. Imaging can also be instrumental in defining the brain uptake patterns of GSK inhibitors intended for brain-related disorders, which would allow for the early dismissal of candidates that show poor brain penetration or retention. Alternative approaches to ligand design may be needed to improve GSK-3 targeting specificity for both therapy and imaging purposes.

synthesis of benzimidazole derivatives are ..

In recent years drug stereochemistry has become a significant issue for both the pharmaceutical industry and the regulatory authorities. The significance of stereoisomerism in antimicrobial agents is addressed in this review using examples drawn from the β-lactams, as being representative of semisynthetic agents, and the quinolones, as examples of synthetic agents. Within these two groups of compounds it is clear that stereochemical considerations are of significance for an understanding of concentration effect relationships, selectivity in both action and inactivation and for an appreciation of the mode of action at a molecular level.

T1 - Synthesis of benzimidazoles condensed with, or linked to, nitroxides or heterocyclic N-oxides
T1 - Electrochemical synthesis of benzimidazole derivative using carbon electrode in aqueous medium

Synthesis, reactions, and spectroscopic properties ..

Glycogen synthase kinase-3 (GSK-3) is associated with various key biological processes, including glucose regulation, apoptosis, protein synthesis, cell signaling, cellular transport, gene transcription, proliferation, and intracellular communication. Accordingly, GSK-3 has been implicated in a wide variety of diseases and specifically targeted for both therapeutic and imaging applications by a large number of academic laboratories and pharmaceutical companies. Here, we review the structure, function, expression levels, and ligand-binding properties of GSK-3 and its connection to various diseases. A selected list of highly potent GSK-3 inhibitors, with IC50 50

Imidazole and benzimidazole synthesis - Organic …

The enzymes of the mevalonate-independent biosynthetic pathway to isoprenoids are attractive targets for the development of new drug candidates, in particular against malaria and tuberculosis, because they are present in major human pathogens but not in humans. Herein, the structure-based design, synthesis, and biological evaluation of a series of inhibitors featuring a central imidazole or benzimidazole scaffold for the kinase IspE from E. coli, a model for the corresponding malarial enzyme, are described. Optimization of the binding preferences of the hydrophobic sub-pocket at the substrate-binding site allowed IC50 values in the lower micromolar range to be reached. Structure-activity relationship studies using a 1,2-disubstituted imidazole central core revealed that alicyclic moieties fit the sub-pocket better than acyclic aliphatic and aromatic residues. The phosphate-binding region in the ATP-binding site of IspE, a neutral glycine-rich loop, was addressed for the first time by an additional vector attached to the central core. Polar functional groups, such as trifluoromethyl or nitriles, were introduced to undergo orthogonal dipolar interactions with the amide groups in the loop. Alternatively, small hydrogen-bond-accepting heterocyclic residues, capable of binding to the convergent NH groups in the loop, were explored. The biological data showed slightly improved inhibitory potency in some cases and confirmed the challenges in addressing, with gain in binding affinity, the highly water-exposed sections of enzyme active sites, such as the glycine-rich loop of IspE.

The Chemistry of the Benzimidazoles

This review highlights recent reports of antimicrobial, anticancer, antiviral, antiparasitic, antihypertensive as well as anti-inflammatory activities of the benzimidazoles.