AMG 579 / Amgen - LARVOL DELTA

Nickel catalysed SET-induced oxygenation of (aryl)(N-heteroaryl)methanes with molecular oxygen. (PubMed, Org Biomol Chem) - "The current approach has been successfully applied for the synthesis of an intermediate of AMG 579, an investigational drug candidate. A slightly modified catalyst system enables the synthesis of benzoxazinones directly starting from (aryl)(N-heteroaryl)methanes."

Journal

Understanding Hole Generation on Thiophene-based for Covalent Triazine Frameworks the Photocatalytic Selective Oxidation of Toluene. (PubMed, Angew Chem Int Ed Engl) - "Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG-579 using a photocatalytic protocol."

Journal

The effects of the phosphodiesterase 10A inhibitor AMG579 on alcohol intake, locomotor activity, and place conditioning in mice (Neuroscience 2022) - "In conclusion, AMG579 showed pharmacological activity across the entire dose range. Based on the present results we are further studying the ability of AMG579 at doses under 300 nmol/kg to reduce alcohol intake without nonspecific locomotor suppression or place conditioning effects."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders

Effects of two PDE10A inhibitors on alcohol self-administration and striatal gene expression in naïve and post-dependent rats (Neuroscience 2021) - "To test our hypothesis, we studied ethanol post-dependent male and female adult Wistar rats in operant fixed-ratio self-administration of ethanol vs. water after 1-hr pretreatment with either MR1916 or AMG579 (i.p., 0, 0.4, 0.2, 0.1 and 0.05 µ mol/kg) (n = 10/drug/sex), two PDE10A inhibitors, in a within-subject manner...Additionally, MR1916 dose-dependently reduced self-administration of alcohol by post-dependent male rats in relation to whether they were high (>0.6 g/kg) vs. low drinker rats. Collectively, our study sheds light on the neurobiological role of PDE10A in distinct striatal circuits on post-dependent drinking behaviors as well as the potential impact of novel translatable PDE10A inhibitors to treat AUD.; Grant Support: Triton Research & Experiential Learning Scholars; NIH grant P60 AA006420; Pearson Center for Alcoholism and Addiction Research; Drugs were donated by Mochida Pharmaceutical and Amgen; NIH grant R01 AA028879"

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • ADORA2A • DRD2 • EGR1