Search

The reaction of 5-methyl-7-nitro-1H-indole-2-carbohydrazide with ethyl acetoacetate yielded the title molecule, C16H18N4O5, in which the indole ring is almost planar, with the greatest deviation from the mean plane being 0.006 (2) Å. The nine atoms of the indole ring are almost perpendicular to the mean plane through the ethyl acetate group, as indicated by the dihedral angle of 87.02 (4)° between them. In the crystal, centrosymmetric supramolecular dimers are formedviaN—H...O hydrogen bonds and eight-membered amide {...HNCO}2synthons. These are consolidated into a three-dimensional architecture by C—H...O contacts, and by π–π interactions between six-membered rings [inter-centroid distance = 3.499 (2) Å].

La conception des systemes mecaniques devient tres automatisee dans le cadre de la Conception Mecanique Assistee par Ordinateur (C.M.A.O.). La modelisation geometrique est effectuee de plus en plus avec l'aide des logiciels de Dessin Assiste par Ordinateur (D.A.O.). La modelisation des structures et la simulation numerique s'effectuent generalement par la Methode des Elements Finis (M.E.F.). Le couplage de ces deux techniques permet de donner une image concrete et realiste des resultats de calcul issus des methodes de discretisation (concentration des contraintes, repartition des charges, etc.). L'application qu'on presente concerne une boite de vitesse a arbres paralleles, comporte deux etages de reductions (reducteur de vitesse). La chaine cinematique est constituee d'arbres d'engrenages a dentures droites et de paliers a roulements a billes et a rouleaux qui realisent la liaison avec le carter. Le probleme pose dans cette application consiste a quantifier le comportement dynamique et vibratoire afin de qualifier la conception du reducteur.

International audience

International audience; The condensation of 7-nitroindole-2-carbohydrazide derivatives with acetylacetone lead to (pyrazol-1-yl)(7-nitroindol-2-yl)ketones.

International audience

We have examinated the addition of 7-aminoindoles with acetylacetone and we have shown by careful examination of spectroscopic data that this reaction does not lead to the previously described diazepinoindole.

In order to understand the performance of the PARIS (Photon Array for the studies with Radioactive Ion and Stable beams) detector, detailed characterization of two individual phoswich (LaBr3(Ce)-NaI(Tl)) elements has been carried out. The detector response is investigated over a wide range of Eγ = 0.6 to 22.6 MeV using radioactive sources and employing 11B(p,γ) reaction at Ep = 163 keV and Ep = 7.2 MeV . The linearity of energy response of the LaBr3(Ce) detector is tested upto 22.6 MeV using three different voltage dividers. The data acquisition system using CAEN digitizers is set up and optimized to get the best energy and time resolution. The energy resolution of ~ 2.1% at Eγ = 22.6 MeV is measured for the configuration giving best linearity up to high energy. Time resolution of the phoswich detector is measured with a 60Co source after implementing CFD algorithm for the digitized pulses and is found to be excellent (FWHM ~ 315 ps). In order to study the effect of count rate on detectors, the centroid position and width of the Eγ = 835 keV peak were measured upto 220 kHz count rate. The measured efficiency data with radioactive sources are in good agreement with GEANT4 based simulations. The total energy spectrum after the add-back of energy signals in phoswich components is also presented.

International audience

International audience; Benzimidazoles are heterocyclic compounds that have awakened great interest during the last few years because of their proven biological activity as antiviral, antimicrobial, and antitumoral agents. For this reason, the development of a systematic \NMR\ study of condensed benzimidazole compounds constitutes a significant tool in understanding the molecular dynamics and the structural parameters that govern their behavior. The 1H and 13C \NMR\ spectra of new imidazobenzodiazepines were investigated. Based on the study of \NMR\ chemical shifts, we discuss the environmental effect of the nucleus 13C. The correlation 1H-13C proved to be a useful method for distinguishing the assignment of carbon.

This study deals with the design of a new macrofilaricidal drug derived from melphalan and having a lymphotropism to avoid the hepatic first pass effect and enhance bioavailability after oral administration. Melphalan was linked to a ligand leading to a prodrug called 1,3-dp-melphalan which has structural analogy to triglycerides. The Molinema dessetae/Proechimys oris model was used for antiparasitic evaluation. Melphalan was macrofilaricidal in vitro against Molinema dessetae at 1mM, inactive in vivo after an oral single dose at 164 mumol/kg while the prodrug 1,3-dp-melphalan was active against adult worms after a single dose at 82 mumol/kg. After an oral administration of the prodrug to rats, the maximum concentration and the cumulated quantities of melphalan in lymph were about 45-fold higher than those observed with the free drug under the same conditions. Moreover, the plasma concentration of melphalan was 2-fold higher than those observed after the administration of the free drug. These results are in favor of lymphotropic targeting as a novel approach to develop new orally active macrofilaricides.

We have examinated the addition of 7-aminoindoles with acetylacetone and we have shown by careful examination of spectroscopic data that this reaction does not lead to the previously described diazepinoindole.

The novelty of this work derives from the use of nitrogenous heterocycles as building block in the synthesis of conjugate bile acid derivatives. New piperazinyl bile acid derivatives were synthesized and tested in vitro against various human cancer cells (GBM, KMS-11, HCT-116). The best pro-apoptotic activity was obtained with N-[4N-cinnamylpiperazin-1-yl)-3alpha,7beta-dihydroxy-5beta-cholan-24-amide (7b) and N-[4N-cinnamyllpiperazin-1-yl)- 3alpha,7alpha-dihydroxy-5beta-cholan-24-amide (7c) on these human cancer cell lines (IC(50): 8.5-31.4microM). This activity was associated with nuclear and DNA fragmentation, demonstrating that 7b induces cell death by an apoptotic process as 7c. This study shows the possibility of hydrid heterocycle-steroids as new anticancer agents with improved bioactivity and easy to synthesize.

Δ 7 -5-Desaturase catalyses one of the last steps in ergosterol biosynthesis in fungi. Moreover Δ 5 -unsaturation is necessary for the sparking function. Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as potential growth inhibitors. Preliminary results suggest that 6β-aminocholestanol is a potent antifungal agent.

Halogenation of 2-alkyl-5(6)-chloro(ormethyl)benzimidazoles occurs in 6(5) position and subsequent nitration affords the corresponding 7(4)-nitrobenzimidazoles.

6- and 7-(4-hydroxy-6-methyl-2-oxo-1-pyridyl)benzimidazoles and 1-(6- and 7-benzimidazolyl)-4-hydroxy-2-oxoquinolines were synthesized by reaction of aminobenzimidazoles with 4-hydroxy-6-methyl-2-pyrone and 4-hydroxycoumarine.

3β-Acetoxy-6-iodocholest-5-ene was prepared with a convenient method from cholesterol and used as a key intermediate for the synthesis of 6-arylated cholesterol derivatives using a Suzuki―Miyaura cross-coupling. This versatile and efficient synthesis way can widely be used in the synthesis of other 6-aryl or 6-heteroaryl steroids as potential drugs.

3β-Acetoxy-6-iodocholest-5-ene was prepared with a convenient method from cholesterol and used as a key intermediate for the synthesis of 6-arylated cholesterol derivatives using a Suzuki―Miyaura cross-coupling. This versatile and efficient synthesis way can widely be used in the synthesis of other 6-aryl or 6-heteroaryl steroids as potential drugs.

International audience; Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta-hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.

The stilbene derivative 1,2,3-trimethoxy-4-[(E)-2-phenylvinyl]benzene, C(17)H(18)O(3), (I), and its homocoupling co-product (E,E)-1,4-bis(2,3,4-trimethoxyphenyl)buta-1,3-diene, C(22)H(26)O(6), (II), both have double bonds in trans conformations in their conjugated linkages. In the structure of stilbene (I), the aromatic rings deviate significantly from coplanarity, in contrast with coproduct (II), the core of which is rigorously planar. The deviation in stilbene (I) seems to be driven by intermolecular electrostatic interactions. Diene (II) sits on a crystallographic inversion centre, which bisects the conjugated linkage.

Darier disease is an uncommon genodermatosis characterized by verrucous papules in a seborrheic distribution. The linear form of this disease is rare and could result from genetic mosaicism in this autosomal dominant disorder. We report a case of linear Darier disease that involved the right lower limb with a zosteriform distribution.

A nonempty subset

Functions counting the number of subsets of {1, 2, . . .

National audience

Let f and g be polynomials with integer coefficients. In this paper, we improve upon a theorem of Nieto. We show that if the content of g divides the content of f and g(n) divides f (n) for...

International audience

In this paper, a remote temperature control system has been proposed. The physical system is controlled in real time through the Internet network. For educational purpose, the students use only a web browser to tune and test a PID controller via shared user interface. The PID parameters are calculated using the basic experimental Ziegler—Nichols tuning rules. After hardware and software experiment description, the remote online experiment is tested and the results are given.

Two sterol families have been synthesized: the first one is nitrogenous sterols containing amino, N-hydroxyimino or cyano group and the second one is oxysterols such as ketosterol and hydroxysterols. These compounds were then evaluated in vitro against Leishmania donovani promastigotes and Trypanosoma brucei brucei trypomastigotes. The most active compounds against L. donovani promastigotes were 7beta-aminomethylcholesterol and 7alpha,beta-aminocholesterol (IC50 in a range from 1 to 3 microM, pentamidine: 2.8 microM). These compounds were active on intramacrophage amastigotes with IC50 of 1.3 microM. Such an activity justifies further in vivo antileishmanial evaluation. Against T. b. brucei, (24R,S)-24-hydroxy-24-methylcholesterol (MEC, 12.5 microM) was the most active compound from these series.

Whether chronic typical atrial flutter differs from paroxysmal atrial flutter regarding electrophysiological properties of reentry pathways and cardiac function remains unknown. If so, can remodeling due to long duration of persistently rapid atrial or ventricular rates explain these changes? The aim of the study was to compare RA local conduction velocities and heart function parameters between three groups: (1) chronic atrial flutter, (2) paroxysmal atrial flutter, and (3) controls. The study evaluated 52 patients undergoing radiofrequency ablation for typical atrial flutter. There were 35 patients with chronic atrial flutter (62.7 +/- 14 years) and 17 patients with paroxysmal atrial flutter (62.7 +/- 10 years). Underlying structural heart disease was present in 20 (57%) of 35 chronic atrial flutter patients and in 7 (41%) of 17 paroxysmal atrial flutter patients (P = 0.1). Chronic atrial flutter duration was 10.9 +/- 17 months and paroxysmal atrial flutter duration was 8.5 +/- 10 (P = 0.06). RA conduction velocity measurements were carried out before ablation during sinus rhythm under pacing (600-ms cycle length) with a 12-pole steerable catheter positioned in the high lateral RA (poles 11-12 [H6]), mid-lateral RA (poles 9-10 [H5]), and along the inferior vena caval tricuspid isthmus (poles 7-8 [H4]; 5-6 [H3]; 3-4 [H2]) with its distal electrode pair at the coronary sinus origin (pole 1-2 [H1]). Counter-clockwise RA conduction velocities were assessed from H6 to H1 and clockwise RA conduction velocities from H1 to H6. After successful ablation, RA and LA areas, LV volumes, LVEF, inferior vena caval tricuspid annulus, and coronary sinus tricuspid annulus (septal isthmus) lengths were measured by two-dimensional echocardiography. The control group included 12 patients without structural heart disease, referred for electrophysiological evaluation of AVN reentry. Counter-clockwise RA conduction velocities at the inferior vena caval tricuspid isthmus were lower in chronic atrial flutter than in paroxysmal atrial flutter (H4, 1.19 +/- 0.4 vs 1.89 +/- 1 m/s, P = 0.0051; H3, 1.14 +/- 0.4 vs 1.6 +/- 0.7 m/s, P = 0.0015; H2, 1.16 +/- 0.4 vs 1.53 +/- 0.5 m/s, P0.0056 and H1, 1.2 +/- 0.4 vs 1.5 +/- 0.4 m/s, P = 0.03, respectively). Counter-clockwise RA conduction velocities were identical at the high and mid-lateral RA. Counter-clockwise caval isthmus RA conduction velocities from H3 to H1 were significantly different between chronic atrial flutter and controls (H3, 1.14 +/- 0.4 vs 1.7 +/- 0.3 m/s, P = 0.0014; H2, 1.16 +/- 0.4 vs 1.83 +/- 0.4 m/s, P0.0001 and H1, 1.2 +/- 0.4 vs 1.94 +/- 0.4 m/s, P0.0001, respectively). A difference was found regarding clockwise isthmus RA conduction velocities between the two groups of atrial flutter and controls but not between chronic atrial flutter and paroxysmal atrial flutter. Respectively, chronic atrial flutter had greater RA and LA areas (24.5 +/- 5 vs 13 +/- 2 cm2; P0.0001 and 23 +/- 5 vs 16 +/- 3 cm2, P0.0001), LV end-systolic and end-diastolic volumes (50 +/- 25 vs 32 +/- 13 cm3, P = 0.0084 and 112 +/- 40 vs 85 +/- 25 cm3, P = 0.01), septal isthmus length (21 +/- 3 vs 13 +/- 2 mm, P0.0001), and inferior vena caval tricuspid isthmus length (39 +/- 6 vs 23 +/- 5 mm; P0.0001). Chronic common atrial flutter is characterized by more prolonged counter-clockwise conduction times and larger anatomic conduction pathways than the paroxysmal form, the causal relationship between electrophysiological and anatomic characteristics remains to be demonstrated.