Synthesis, In Silico and Kinetics Evaluation of -(β-d-glucopyranosyl)-2-arylimidazole-4(5)-carboxamides and -(β-d-glucopyranosyl)-4(5)-arylimidazole-2-carboxamides as Glycogen Phosphorylase Inhibitors.

Recently studied -(β-d-glucopyranosyl)-3-aryl-1,2,4-triazole-5-carboxamides have proven to be low micromolar inhibitors of glycogen phosphorylase (GP), a validated target for the treatment of type 2 . Since in other settings, the bioisosteric replacement of the 1,2,4-triazole moiety with imidazole resulted in significantly more efficient GP inhibitors, in silico calculations using Glide molecular docking along with unbound state DFT calculations were performed on -(β-d-glucopyranosyl)-arylimidazole-carboxamides, revealing their potential for strong GP inhibition. The syntheses of the target compounds involved the formation of an amide bond between per--acetylated β-d-glucopyranosylamine and the corresponding arylimidazole-carboxylic acids.

Design and Synthesis of 3-(β-d-Glucopyranosyl)-4-amino/4-guanidino Pyrazole Derivatives and Analysis of Their Glycogen Phosphorylase Inhibitory Potential.

Glycogen phosphorylase (GP) is a key regulator of glucose levels and, with that, an important target for the discovery of novel treatments against type 2 diabetes. β-d-Glucopyranosyl derivatives have provided some of the most potent GP inhibitors discovered to date. In this regard, -β-d-glucopyranosyl azole type inhibitors proved to be particularly effective, with 2- and 4-β-d-glucopyranosyl imidazoles among the most potent designed to date.

Mechanosensing in the Physiology and Pathology of the Gastrointestinal Tract.

Normal gastrointestinal function relies on sensing and transducing mechanical signals into changes in intracellular signaling pathways. Both specialized mechanosensing cells, such as certain enterochromaffin cells and enteric neurons, and non-specialized cells, such as smooth muscle cells, interstitial cells of Cajal, and resident macrophages, participate in physiological and pathological responses to mechanical signals in the gastrointestinal tract. We review the role of mechanosensors in the different cell types of the gastrointestinal tract.

The Role of Inflammatory Mediators in the Development of Gastrointestinal Motility Disorders.

Feeding intolerance and the development of ileus is a common complication affecting critically ill, surgical, and trauma patients, resulting in prolonged intensive care unit and hospital stays, increased infectious complications, a higher rate of hospital readmission, and higher medical care costs. Medical treatment for ileus is ineffective and many of the available prokinetic drugs have serious side effects that limit their use. Despite the large number of patients affected and the consequences of ileus, little progress has been made in identifying new drug targets for the treatment of ileus.