An Alternative Scalable Process for the Synthesis of the Key Intermediate of Omarigliptin

An alternative scalable process for the synthesis of the key intermediate of omarigliptin is described. The asymmetric synthesis relies on the initial diastereoselective alkylation and subsequent aluminum-catalyzed substrate-controlled Meerwein–Ponndorf–Verley reduction. A highly regioselective 5-exo-dig iodocyclization followed to afford <b>11b</b>, which was then subjected to ring-opening cycloetherification to give product <b>1</b> with >99:1 dr and >99% ee in 31.2% overall yield in nine steps. This synthetic strategy has been successfully applied for multikilogram scale production

Identification, Characterization, Synthesis, and Strategy for Minimization of Potential Impurities Observed in the Synthesis of Solithromycin

Potential causes for the formation of synthetic impurities that are present in solithromycin (<b>1</b>) during laboratory development are studied in the article. These impurities were monitored by HPLC, and their structures are identified on the basis of MS and NMR spectroscopy. In addition to the synthesis and characterization of these seven impurities, strategies for minimizing them to the level accepted by the International Conference on Harmonization (ICH) are also described

Identification, Characterization, Synthesis, and Strategy for Minimization of Potential Impurities Observed in the Synthesis of Solithromycin

Potential causes for the formation of synthetic impurities that are present in solithromycin (<b>1</b>) during laboratory development are studied in the article. These impurities were monitored by HPLC, and their structures are identified on the basis of MS and NMR spectroscopy. In addition to the synthesis and characterization of these seven impurities, strategies for minimizing them to the level accepted by the International Conference on Harmonization (ICH) are also described

Additional file 1: of Preclinical modeling and multimodality imaging of chronic myocardial infarction in minipigs induced by novel interventional embolization technique

Classic methods have been fully described by previous investigators and introduced. (DOCX 29 kb

3‑((<i>R</i>)‑4-(((<i>R</i>)‑6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4

The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues. After several rounds of modification, compound <b>58</b> (HEC72702), which had an (<i>R</i>)-morpholine-2-propionic acid at the C6 position of its dihydropyrimidine core ring, was found to display no induction of the CYP1A2, CYP3A4, or CYP2B6 enzyme at the high concentration of 10 μM. In particular, it demonstrated a good systemic exposure and high oral bioavailability and achieved a viral-load reduction greater than 2 log in a hydrodynamic-injected (HDI) HBV mouse model and has now been selected for further development