this paper include a review of the synthesis, ..
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.