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Papers of the Week

Papers: 1 Jul 2023 - 7 Jul 2023

Basic Science

Molecular/Cellular, Neurobiology, Pharmacology/Drug Development


2023 Jul 04

Bioorg Med Chem Lett


Novel series of tunable µOR modulators with enhanced brain penetration for the treatment of opioid use disorder, pain and neuropsychiatric indications.


Nerurkar A, Nguyen T, Wang S, Bhatt U, Li K, Li Y, Ding P, Seidl FJ, Holan M, Lee J, Widjaja T, Wei ZL, Sadlowski C, Sperandio D, McGee LR, Youngblood B, Schwartz N, Gehlert D, Medina JC


Structural optimization of a previously reported agonist of µOR, PZM21 is described resulting in the discovery of a novel series of amides with at least 4-folds enhanced CNS penetration in rat. Furthermore, these efforts yielded compounds with varying levels of efficacy on the receptor ranging from high efficacy agonists such as compound 20 to antagonists, such as 24. The correlation between in vitro activation of µOR and relative activity in models of analgesia for these compounds is discussed. The compelling results obtained in these studies demonstrate the potential utility of these newly discovered compounds in the treatment of pain and opioid use disorder.