Vijay Potluri

Cannabinoid 1 (CB1) Receptor - Pharmacology, Role in Pain and Recent Developments in Emerging CB1 Agonists

Cannabinoids are antinociceptive in animal models of acute pain, tissue injury and nerve injury induced nociception and act via their cognate receptors, cannabinoid receptor 1 and 2. This review examines the underlying biology of the endocannabinoids and behavioural, neurophysiological, neuroanatomical evidence supporting the notion of pain modulation by these ligands with a focus on the current evidence encompassing the pharmacological characterization of CB1 agonists in this therapy. Separating the psychotropic effects of CB1 agonists from their therapeutic benefits is the major challenge facing researchers in the field today and with the discovery of peripherally acting agonists there seems to be a ray of hope emerging for the diverse potential therapeutic applications of this class of ligands.

Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists

Kappa opioid receptor (KOR) is an important mediator of pain signaling and it is targeted for the treatment of various pains. Pharmacophore based mining of databases led to the identification of 2-aminobenzimidazole derivative as KOR agonists with selectivity over the other opioid receptors DOR and MOR. A short SAR exploration with the objective of identifying more polar and hence less brain penetrant agonists is described herewith. Modeling studies of the recently published structures of KOR, DOR and MOR are used to explain the receptor selectivity. The synthesis, biological evaluation and SAR of novel benzimidazole derivatives as KOR agonists are described. The in vivo proof of principle for anti-nociceptive effect with a lead compound from this series is exemplified.

A facile synthesis of 7,12-dihydro-1,3,6,7,12-pentaazapleiadenes by domino reaction

Abstract: A tandem strategy for the synthesis of 7,12-dihydro-1,3,6,7,12-pentaazapleiadenes and 4-(2-aminophenoxy)pyrido[4,3-d]pyrimidin-5(6H)-ones from readily available starting materials has been developed.