A Systematic Review of Congenital Insensitivity to Pain, a Rare Disease.

Introduction: Pain perception, far from being a pathological mechanism, is a crucial protective stimulus to prevent additional injuries. Any disturbance in this complex system poses significant risks to individuals, affecting their quality of life and even their survival.

Objective: This review aims to explore congenital insensitivity to pain, an extremely rare genetic disorder with an autosomal recessive pattern that results in the inability to perceive pain.

Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1-pyrazol-1-yl)methyl)phosphonate (BMS-820132).

Glucokinase (GK) is a key regulator of glucose homeostasis, and its small-molecule activators represent a promising opportunity for the treatment of type 2 diabetes. Several GK activators have been advanced into clinical trials and have demonstrated promising efficacy; however, hypoglycemia represents a key risk for this mechanism. In an effort to mitigate this hypoglycemia risk while maintaining the efficacy of the GK mechanism, we have investigated a series of amino heteroaryl phosphonate benzamides as ''partial" GK activators.

Synthesis of isohasubanan alkaloids via enantioselective ketone allylation and discovery of an unexpected rearrangement.

A synthesis of the hasubanan alkaloids hasubanonine, runanine, and aknadinine via a unified route was attempted. Construction of key phenanthrene intermediates by a Suzuki coupling-Wittig olefination-ring-closing metathesis sequence allowed a convergent and flexible approach. Conversion of the phenanthrenes into the target structures was projected to involve six steps including phenolic oxidation, ketone allylation, anionic oxy-Cope rearrangement, and acid-promoted cyclization.