A review of environmental odor quantification and qualification methods: The question of objectivity in sensory analysis.

For several years, various issues have up surged linked to odor nuisances with impacts on health and economic concerns. As awareness grew, recent development in instrumental techniques and sensorial analysis have emerged offering efficient and complementary approaches regarding environmental odor monitoring and control. While chemical analysis faces several obstacles, the sensory approach can help overcome them.

Objective odor analysis of incidentally emitted compounds using the Langage des Nez® method: application to the industrial zone of Le Havre.

Environmental odor studies are usually done using two approaches: nuisance impact assessment and source identification. The latter may be done using chemical analysis or sensory analysis. While sensory analyses offer many advantages, they also face the main obstacle: odor nature description still uses conventional methods based on subjective evocations as odor descriptors.

Discovery of SAR184841, a potent and long-lasting inhibitor of 11β-hydroxysteroid dehydrogenase type 1, active in a physiopathological animal model of T2D.

Starting from 11β-HSD1 inhibitors that were active ex vivo but with Cyp 3A4 liability, we obtained a new series of adamantane ureas displaying potent inhibition of both human and rodent 11β-HSD1 enzymes, devoid of Cyp 3A4 interactions, and rationally designed to provide long-lasting inhibition in target tissues. Final optimizations lead to SAR184841 with good oral pharmacokinetic properties showing in vivo activity and improvement of metabolic parameters in a physiopathological model of type 2 diabetes.

Pyrrolidine-pyrazole ureas as potent and selective inhibitors of 11β-hydroxysteroid-dehydrogenase type 1.

A High Throughput Screening campaign allowed the identification of a novel class of ureas as 11β-HSD1 inhibitors. Rational chemical optimization provided potent and selective inhibitors of both human and murine 11β-HSD1 with an appropriate ADME profile and ex vivo activity in target tissues.

Mutant 5-hydroxytryptamine 1A receptor D116A is a receptor activated solely by synthetic ligands with a rich pharmacology.

Like other biogenic amine G protein-coupled receptors, mutation of the conserved aspartatic residue into alanine at position 116 (D116A(3.32)) in the 5-hydroxytryptamine (5-HT)(1A) receptor greatly affects 5-HT binding and signal transduction. [(3)H]8-Hydroxy-2-dipropylaminotetralin (8-OH-DPAT) and [(3)H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100,635) are capable to bind the 5-HT(1A)-D116A mutant and, using these radioligands, we show here that this mutation dramatically reduces the affinities of the selective 5-HT(1A) agonists N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-[(5-methylpyridin-2-yl)-methylamino methyl]piperidine (F13640), 3-chloro-4-fluorophenyl-(4-fluorophenyl-4-{[(5-methyl-6 methylamino-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl-methanone (F13714), and 2-[5-[3-(4-methylsulfonylamino)benzyl-1,4-oxadiazol-5-yl]-1H-indole-3-yl]ethylamine (L694247) and that of 5-carboxamidotryptamine.