Red Blood Cell Transfusion in the Emergency Department: An Observational Cross-Sectional Multicenter Study.

Background: We aimed to describe red blood cell (RBC) transfusions in the emergency department (ED) with a particular focus on the hemoglobin (Hb) level thresholds that are used in this setting.

Methods: This was a cross-sectional study of 12 EDs including all adult patients that received RBC transfusion in January and February 2018. Descriptive statistics were reported.

4-Oxo-1,4-dihydropyridines as selective CB₂ cannabinoid receptor ligands. Part 2: discovery of new agonists endowed with protective effect against experimental colitis.

Further on to our earlier work on the 4-oxo-1,4-dihydropyridine, we describe herein our strategy to get access to potent selective CB₂ receptor agonists. Thus, we designed and synthesized 29 compounds, evaluated on both hCB₁ and hCB₂ cannabinoid receptors, and assessed 11 of them in the TNBS-induced colitis model in mice. Compound 48 was found to be the most efficient of our series, exhibiting an exquisite protection against experimental colitis, superior to the one observed after treatment with Pentasa.

Potent farnesyltransferase inhibitors with 1,4-diazepane scaffolds as novel destabilizing microtubule agents in hormone-resistant prostate cancer.

A new class of potent farnesyltransferase inhibitors based on a 1,4-diazepane scaffold was synthesized with protein farnesyltransferase inhibition potencies in the low nanomolar range. The compounds block the growth on two hormone-resistant tumor prostatic cell lines (DU145 and PC3). The advanced cellular evaluation of the more potent farnesyltransferase inhibitors was explored and revealed a disorganization of tubulin in PC3 cells.

Design, synthesis and biological evaluation of substituted dioxodibenzothiazepines and dibenzocycloheptanes as farnesyltransferase inhibitors.

A new series of FTase inhibitors containing a tricyclic moiety--dioxodibenzothiazepine or dibenzocycloheptane--has been designed and synthesized. Among them, dioxodibenzothiazepine 18d displayed significant inhibitory FTase activity (IC(50)=17.3 nM) and antiproliferative properties.

In vitro and in vivo evaluation of two rational-designed nonpeptidic farnesyltransferase inhibitors on HT29 human colon cancer cell lines.

FTase inhibitors constitute a new class of potential cancer therapeutics, especially in colorectal cancer where K-ras-selective mutations exist and have a role in tumorigenesis. The synthesis and biological evaluation of two nonpeptidic molecules (13 and 16) designed on the basis of a zinc chelator imidazole linked to two aromatic fragments able to fit in the "exit groove" and in the "A2 binding site" of FTase are described. These molecules are characterized respectively by a flexible phenylmethyl chain and a more constrained scaffold so as to evaluate their respective influences on site recognition.

Novel N-(4-Piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity.

Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.

Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective sigma1 ligands. Part 2.

Herein is described a new class of selective sigma1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 1a has high affinity (IC50 = 16 nM) for sigma1 receptor and is selective in a large panel of therapeutic targets. This study presents structural changes on the side chain of the Tic-hydantoin core.

Synthesis of a novel conformationally restricted Val-Phe dipeptidomimetic.

A method for the synthesis of (3(R,S),6S,11b(R,S))-1,3,4,6,7,11b-hexahydro-4-oxo-3-phthalimidopyrido[2,1-a]isoquinoline-6-carboxylic acid 2 as a new conformationally restricted dipeptidomimetic of Val-Phe is reported. It involved cyclisation via an intramolecular electrophilic addition at the reactive bridgehead carbon. This new scaffold can be used as a building block in the preparation of libraries of peptidomimetics.

Potent and selective farnesyl transferase inhibitors.

We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure--activity relationships revealed that replacement of cysteine by substituted benzylimidazoles provided nanomolar FTIs with in vitro activities (18e, IC(50) = 4.