Showing papers by "Rhône-Poulenc published in 2010"

The Role of an α‐Amino Group on H+‐dependent Transepithelial Transport of Cephalosporins in Caco‐2 Cells

Abstract: The role of an alpha-amino group on interaction with the intestinal and renal peptide carriers (PEPT 1 and PEPT 2, respectively) has been the subject of much investigation. Studies have differed in their conclusions about the role of an alpha-amino group on carrier-mediated absorption. Most studies have used brush-border membrane vesicles or perfused intestinal segments. These techniques enable the determination of membrane uptake and luminal disappearance, respectively, but not transepithelial transport. Transepithelial transport should be more predictive of absorption because it includes basolateral efflux, which could be the rate-limiting process in drug absorption. The objective of this study was to evaluate the influence of an alpha-amino group on PEPT 1-mediated transepithelial transport in Caco-2 cells. The apical-to-basolateral permeability coefficients of cephalosporins with or without a free alpha-amino group were determined in the presence and absence of a pH gradient. Permeability coefficients obtained under these conditions were used to calculate a permeability ratio (i.e. P(app) (pH 6.0)/P(app) (pH 7.4)), which should indicate whether PEPT 1 is involved in transport. For cephalosporins with an alpha-amino group (cephalexin, cefaclor, cefadroxil, cephradine, cephaloglycin) the permeability ratios ranged between 1.77 and 2.77. In contrast, the permeability ratios for cephalosporins without an alpha-amino group were 1 (approx.; range = 0.74-1.26). These data suggest that the presence of an alpha-amino group on cephalosporins increases their PEPT 1-mediated transepithelial transport in Caco-2 monolayers.

Industrial Applications of Rare Earths: Which Way for the End of the Century?

Abstract: Several examples of the potential of rare earths for innovation are reviewed, through either the optimization of the starting materials for existing applications or the use of intrinsic properties of specific compounds. The influence of the quality of starting materials on applications like phosphors and catalysis is illustrated, as well as the potentiality of rare earth sulphides in the new pigment application.

Friedel-Crafts Synthesis of Benzophenone with Little Lewis Acid Catalyst. Factorial Design and Mechanism

Abstract: A series of benzene derivatives C6H5R with R ranging from the two extremes of the σ+ scale of H.C. Brown has been acylated with little FeCl3 catalyst at reflux temperature. Under these conditions the reaction is limited to activated substrates: with benzene and deactivated aromatics the yield is below 10%. A fractional factorial design is carried out with 5 parameters: temperature, % catalyst, time, ratio aromatic/acylation reagent and nature of catalyst in the case of acylation of benzene by benzoyl chloride with a Lewis acid catalyst (AlCl3 or FeCl3). The multivariate analysis shows that the important factors are: temperature, nature and ratio of catalysts; and also that the interaction % of catalyst-nature of catalyst and temperature-nature of catalyst are determinant. Acylation of benzene (and deactivated aromatics) with little Lewis acid catalyst will give acceptable yields if both a moderately active catalyst (FeCl3, ZnCl2) and a high temperature of reaction are used.

Organometallic Chemistry in Industrial Vitamin A and Vitamin E Synthesis

Abstract: This paper illustrates the concepts of short synthesis, high selectivity and reduce effluent for industrial processes in the field of vitamin A and E synthesis. We have selected four reactions to demonstrate how organometallic chemistry can improve industrial synthesis : isomerisation of methylbutynol 1 to prenal 2 ; Carbon - Carbon coupling and new access to geranylacetone ; Hydrogenation of a p-unsaturated aldehydes ; Oxidation and access to trimethylhydroquinone.

Similarity Measures for Rational Set Selection and Analysis of Combinatorial Libraries: The Diverse Property-Derived (DPD) Approach.

Abstract: The generation of new chemical leads for biological targets is a very challenging task for researchers in the pharmaceutical industry. The design of representative screening sets and combinatorial libraries is central to achieving this objective. In this paper, we describe a novel molecular descriptor, the Diverse Property-Derived (DPD) code, that contains information about key molecular and physicochemical properties of a molecule. The utility of this descriptor is explored through its application for the selection of a maximally diverse representative screening set, through the selection of secondary screening sets to obtain more information concerning the structure−activity relationships (SAR) of a particular target receptor, and through the profiling of combinatorial libraries. The usefulness of physicochemical/molecular property descriptors, such as the DPD code, is discussed critically.

Estimation of oral bioavailability in the rat by the accelerated infusion technique

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Étude des protéines sériques de malades traités avec la clorpromazine, par la méthode de l'èlectrophorèse différentielle, en clinique psychiatrique†

Abstract: Etude effectuee dans le cadre des recherches poursuivies a la clinique des Maladies Mentales et de l'Encephale de la Faculte de Medicine de Paris (Pr. Jean Delay) pour depister les modifications biologiques que pourrait entrainer l'administration prolongee de la clorpromazine, recherches qui seront l'objet d'un memoire d'ensemble ulterieur. L'electrophorese differentielle a ete pratiquee en meme temps sur des malades temoins sans traitement et sur des malades traites a la clorpromazine, examines soit avant et pendant le traitement, soit seulement en cours de traitement. L'absence de modifications significatives du chiffre des proteines seriques, au cours d'un traitement prolonge a la clorpromazine, permet de penser que ce medicament n'a pas d'action nocive marquee vis-a-vis des fonctions proteiques hepatiques.

“Diam-BINAP”; a Highly Efficient Monomer for the Synthesis of Heterogeneous Enantioselective Catalysts.

Abstract: The synthesis of a monomeric analogue of BINAP, diam-BINAP, is described. The polyaddition of this monomer with 2,6-diisocyanato toluene gave the corresponding oligomer, poly-NAP, with a polymerization degree of 8. The ruthenium complex of this polymer proved to be a very efficient heterogeneous catalyst for the hydrogenation of β-ketoesters (99% ee, 0.1 mol% of catalyst). Furthermore the catalyst could be easily reused four times by simple filtration without loss of activity or enantioselectivity.

Captodative Substituent Effects .49. Esr Study of Carbon Centered Transient Radicals Using Alpha-tert-butylthioacrylonitrile As Radical Trap

Abstract: A method for trapping of transient carbon centered radicals is proposed. The ESR spectra of radical adducts 4 deriving from α-tert.butylthioacrylonitrile 3a give more information concerning the scavenged radical 2 than the other known radical traps.

The Synthesis of RP 66471. A Potent Potassium Channel Opener.

Abstract: The potent, homochiral, potassium channel opener, RP 66471, has been synthesised and shown to possess the (1R, 2S) configuration.

Access to Polychlorophenols: Chemistry of Intermediates

Abstract: Publisher Summary The development of an efficient analytical method enables to detect the presence of polychlorinated gem-dichlorocyclohexadienones in chlorination reaction masses. An in-depth study conducted on reactivity demonstrated that polychlorinated gem-dichlorocyclohexadienones had a very high degree of reactivity, but it explained how the mechanisms related to these compounds—which may have sometimes a catalytic quality—worked. All the products formed from polychlorinated gem-dichlorocyclohexadienones in the presence of chlorophenols are indeed those identified in the chlorination of phenol. These results confirm our hypothesis, and prove the essential role of polychlorinated gem-dichlorocyclohexadienones as reaction intermediates which can react to give either noble products (chlorinated phenols in meta), or unwanted condensation products (polychloro phenoxy phenols, polychloro dihydroxy biphenyls, etc.).

Automation of Organic Synthesis in Industrial Research Laboratories

Abstract: The introduction of a workstation in the organic synthesis laboratory as a current tool is a challenge. On one hand, the capabilities of the new tool must be in accordance with the type of chemistry performed in the laboratory at that particular moment, and on the other hand chemists must be aware of the methodological changes its introduction may generate. We have, at Rhone-Poulenc, developed a methodology to access and to progress toward the realisation of various workstations. This methodology involves a step-by-step procedure, in which validation and/or intensive testing by chemists is required. The main steps are: (1) precise definition of the application: functional specifications; (2) analysis of the elementary automated tools needed; (3) development of as yet non-existing elementary tools; (4) progressive integration of the tools; (5) introduction of supervision capabilities and artificial intelligence. Examples of workstations developed at Rhone-Poulenc will be presented to illustrate this methodology. The use by chemists and the integration into the laboratories will be discussed.