Decreasing Hospital-acquired Pressure Injuries During the COVID-19 Pandemic: A 5-step Quality Improvement Approach.

Background: Hospital-acquired pressure injuries (HAPIs) are common adverse events with large burdens on patients and health systems. In 2020, during the initial waves of the COVID-19 pandemic, the incidence of admitted patients with HAPIs of stage II and above in our health system rose from 2.92% to 3.

Novel 4-(2-pyrimidinylamino)benzamide derivatives as potent hedgehog signaling pathway inhibitors.

A series of novel hedgehog signaling pathway inhibitors have been designed and synthesized based on our previously reported scaffold of 4-(2-pyrimidinylamino)benzamide. The Hh signaling pathway inhibitory activities were evaluated by Gli-luciferase reporter method and most compounds showed more potent inhibitory activities than vismodegib. Three compounds were picked out to evaluated in vivo for their PK properties, and compound 23b bearing a 2-pyridyl A-ring and (morpholin-4-yl)methylene at 3-position of D-ring demonstrated satisfactory PK properties.

Introduction of fluorine to phenyl group of 4-(2-pyrimidinylamino)benzamides leading to a series of potent hedgehog signaling pathway inhibitors.

In present study, a novel series of fluorine containing 4-(2-pyrimidinylamino)benzamide analogues were designed and synthesized. The hedgehog (Hh) signaling inhibitory activities for these compounds were evaluated by a luciferase reporter method. The preliminary SAR was discussed and many compounds showed potent Hh signaling inhibitory activities.

Synthesis and pharmacological evaluation of trifluoromethyl containing 4-(2-pyrimidinylamino)benzamides as Hedgehog signaling pathway inhibitors.

In present study, a series of novel containing trifluoromethyl 4-(2-pyrimidinylamino)benzamide derivatives were designed by the fluorine scan strategy. Their Hh signaling inhibitory activities were evaluated by Gli-luciferase reporter method. The comprehensive SAR was discussed and several derivatives were found to display more potent Hh signaling inhibitory activity than positive drug vismodegib.

Discovery of novel 4-(2-pyrimidinylamino)benzamide derivatives as highly potent and orally available hedgehog signaling pathway inhibitors.

A series of novel hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2-pyrimidinylamino)benzamide. The SAR for this series was described and many derivatives showed potent inhibitory activity. Among these compounds, compounds 12af and 12bf were identified to have high potency and optimal PK profiles.

Determination and characterization of two degradant impurities in bendamustine hydrochloride drug product.

Bendamustine hydrochloride is an alkylating antitumor agent with a good efficacy in the treatment of chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphoma (B-NHL). Under the stressed conditions, two degradant impurities in bendamustine hydrochloride drug product were detected by high-performance liquid chromatography. These two degradant impurities were isolated from preparative liquid chromatography, and were further characterized using Q-TOF/MS and nuclear magnetic resonance (NMR).

Five-membered heteroaromatic ring fused-pyrimidine derivatives: design, synthesis, and hedgehog signaling pathway inhibition study.

A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines have been identified to be potent inhibitors of hedgehog signaling pathway. The synthesis and SAR of these compounds are described. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation.

Design, synthesis, and evaluation of pyrrolo[2,1-f][1,2,4]triazine derivatives as novel hedgehog signaling pathway inhibitors.

A novel series of Hh signaling pathway inhibitors were designed by replacing the pyrimidine skeleton of our earlier reported lead compound 1 with pyrrolo[2,1-f][1,2,4]triazine scaffold. Starting from this new scaffold, SAR exploration was investigated based on structural modification on A-ring, C-ring and D-ring. And several much potent compounds were studies in vivo to profile their pharmacokinetic properties.