The weekend factor: the effect on healthcare quality. A medico-legal, retrospective study.

Background: In the healthcare system, in the last 30 years, the prognostically negative value of the so-called Weekend Effect (WE) has been internationally recognized. The WE is regarded as the increased risk a patient might incur when hospitalized during non-working days, of enduring severe complications in comparison to the same hospitalization that occur on working days. The aim of this study was to retrospectively verify whether, once a mistake was made during weekends or on holidays, in comparison to a mistake occurred on workdays, it subsequently implied a higher risk of complications, death included, in a statistical and medico-legal way.

Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.

Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2.

Rational design based on a pharmacophore of CCR2 antagonists reported in the literature identified lead compound 9a with potent inhibitory activity against human CCR2 (hCCR2) but moderate activity against murine CCR2 (mCCR2). Modification on 9a led to the discovery of a potent CCR2 antagonist 21 (INCB3344) with IC(50) values of 5.1 nM (hCCR2) and 9.

General scope of 1,4-diastereoselective additions to a 2(3H)-quinazolinone: practical preparation of HIV therapeutics.

The practical and highly diastereoselective syntheses of CF(3)-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2).