Catalytic Atroposelective Synthesis of -Aryl Quinoid Compounds.

Diarylamines and related scaffolds are among the most common chemotypes in modern drug discovery. While they can potentially possess two chiral axes, there are no studies on their enantioselective synthesis, as these axes typically possess lower stereochemical stabilities. Herein, we report a chiral phosphoric acid catalyzed atroposelective electrophilic halogenation of -aryl quinoids, a class of compounds that are analogous to diarylamines.

Atropisomerism in medicinal chemistry: challenges and opportunities.

Atropisomerism is a dynamic type of axial chirality that is ubiquitous in medicinal chemistry. There are several examples of stable atropisomeric US FDA-approved drugs and experimental compounds, and in each case the atropisomers of these compounds possess drastically different biological activities. Rapidly interconverting atropisomerism is even more prevalent, and while such compounds are typically considered achiral, they bind their protein targets in an atroposelective fashion, with the nonrelevant atropisomer contributing little to the desired activities.

A conjugate Lewis base-Brønsted acid catalyst for the sulfenylation of nitrogen containing heterocycles under mild conditions.

Catalysts that contain a thiourea tethered to a carboxylic acid were found to affect the sulfenylation of indoles and other N-heterocycles on the hour time scale at room temperature. The mild nature of these conditions allowed for the incorporation of diverse functionalities into more complex heterocycles.

Hype, harmony and human factors: applying user-centered design to achieve sustainable telehealth program adoption and growth.

Despite decades of international experience with the use of information and communication technologies in healthcare delivery, widespread telehealth adoption remains limited and progress slow. Escalating health system challenges related to access, cost and quality currently coincide with rapid advancement of affordable and reliable internet based communication technologies creating unprecedented opportunities and incentives for telehealth. In this paper, we will describe how Human Factors Engineering (HFE) and user-centric elements have been incorporated into the establishment of telehealth within a large academic medical center to increase acceptance and sustainability.

Comparison of differential gene expression of hot and cold thyroid nodules with primary epithelial cell culture models by investigation of co-regulated gene sets.

Both autonomously functioning thyroid nodules (AFTNs) and cold thyroid nodules (CTNs) are characterized by an increased proliferation, however, they have opposite functional activities. Therefore, with the aim to further understand the distinct molecular pathology of each entity and to discover common mechanisms like those leading to increased proliferation in both, AFTNs and CTNs, we now compared gene expression of AFTNs and CTNs with in vitro model systems (TSH-stimulated and ras-transfected primary cultures (PC)) whose gene expression patterns can be attributed to specific molecular alterations. Since combinations of co-regulated genes are more likely to reveal molecular mechanisms, we used a procedure which groups co-regulated genes within "gene sets".

Acidification of arterial blood enhances gastric mucosal injury induced by bile salts in dogs.

The influence of intraarterial infusion of hydrochloric acid on gastric mucosal injury induced by topical bile salts was assessed in a canine ex vivo model. Exposure of the gastric mucosa to 5.0 mM sodium taurocholate in acid bathing solution alone resulted in a slight but not significant reduction in intramural pH of gastric mucosa and mild mucosal damage.