Microwave-assisted three component synthesis of novel bis-fused quinazolin-8(4H)-ones linked to aliphatic or aromatic spacer via amide linkages

Abstract

A novel series of bis(tetrahydro[1,2,4]triazolo[5,1-b]quinazolin-8-ones) and bis(tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolinones) containing amide linkages were regionselectively prepared via a three-component reaction of bis(aldehydes) with dimedone and 3-amino-1,2,4-triazole (or 2-aminobenzimidazole) under conventional heating as well as under microwave irradiation.     

Une nouvelle approche pour la gestion de la qualité de service dans les réseaux UMTS

The fast expansion of the applications and services in the 3G mobile networks and the competition between the operators have increased the need to improve the QoS either for the subscribers or for the service providers. The umts operators’ principal goal is to guarantee their maximal benefit and offer the best QoS to the subscribers. Our work is funded on the optimisation of the network parameters, especially bit-rate. Our proposal’s goal is to offer the best rate distribution between the subscribers (bit-rate balancing) and to guarantee the load balancing between the network cells. It is based on network and radio engineering concepts. We used the genetic algorithm for the optimisation of the bit-rate allocation and we proposed a new process for the bit-rate and load balancing. The differentiation of the services treatment has been done by the definition of a priority based on each service requirements in QoS. To show the contribution of this approach in the practice, we simulated it on a Tunisian operator’s test platform model. The gotten results showed an increase of the connected users, some very weak blocking and call-drop rates and a better load balancing between the cells.     

Adiabatic self-focusing in media with spatially variable nonlinearity

An optical medium whose nonlinearity can be spatially adjusted is considered to study beam reshaping. The concept is applied to perform adiabatic self-focusing of broad beams. Experimental results are obtained in a photorefractive lithium niobate crystal where the self-focusing nonlinearity is controlled over propagation by a temperature gradient. As a demonstration, gradual self-focusing is shown to transform an incoming beam into an output circular spot 10 times smaller over a 2 cm long crystal submitted to a 30 °C temperature gradient. Once formed, the adiabatic self-focused beam has inscribed a funnel waveguide in the crystal.     

Smoothing Methods for Nonlinear Complementarity Problems

In this paper, we present some new smoothing techniques to solve general nonlinear complementarity problems. Under a weaker condition than monotonicity as on the original problems, we prove convergence of our methods. We also present an error estimate under a general monotonicity condition. Some numerical tests confirm the efficiency of the proposed methods.     

Existence results for a nonlinear version of Rotenberg model with infinite maturation velocities

In this paper, we present some existence results on L¹ spaces of a nonlinear boundary value problem derived from a model introduced by Rotenberg (1983) describing the growth of a cell population. Each cell of this population is distinguished by its degree of maturity μ ∈ [0,1] and its maturation velocity v. The biological boundary at μ = 0 and μ = 1 are fixed and tightly coupled through the mitosis. At mitosis, daughter cells and mother cells are related by a general reproduction rule, which covers all known biological ones. In this work, the maturation velocity is allowed to be infinite, that is, v ∈ [0, + ∞ ). This hypothesis introduce some mathematical difficulties, which are overcomed by using a measure of weak noncompactness adapted to the problem and a recent fixed point theorem (Theorem 3.2) involving weakly compact operators on nonreflexive Banach spaces. Copyright © 2014 John Wiley & Sons, Ltd.     

Versatile Pectin Grafted Poly (N-isopropylacrylamide); Modulated Targeted Drug Release

This study describes synthesis and optimization of pectin grafted poly(N-isopropylacrylamide) hydrogels as vehicles for colon-targeted theophylline model drug release. The gels were prepared in the presence of N, N′–methylenebisacrylamide (MBAA) crosslinker and ceric ammonium nitrate (CAN) initiator under N₂ atmosphere. Optimum conditions, in terms of percent of grafting (%G), were determined as follows: pectin = 1.0 g, [NIPAAm] = 26.51 mM, [MBAA] = 0.65 mM, [CAN] = 0.073 mM, polymerization temperature = 30°C and time = 4.0 h. Hydrogels were characterized by FTIR, TGA, DSC, XRD and SEM. The formed hydrogel did not have a thermo-sensitivity behavior. The in vitro percent drug release was studied in terms of different percent of grafting and different polymerization temperatures under two pH values namely 5.5 and 7.4. Conclusively, the optimum colon-targeted vehicle properties that provide the least drug release at pH5.5 and the most drug release at pH7.4 were as follows: [NIPAAm] = 26.51 mM and [MBAA] = 0.56 mM, polymerization temperature = 30°C and %G = 55.5.     

Synthesis of functionalized cinnamaldehyde derivatives by an oxidative Heck reaction and their use as starting materials for preparation of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase inhibitors

Cinnamaldehyde derivatives were synthesized in good to excellent yields in one step by a mild and selective, base-free palladium(II)-catalyzed oxidative Heck reaction starting from acrolein and various arylboronic acids. Prepared α,β-unsaturated aldehydes were used for synthesis of novel α-aryl substituted fosmidomycin analogues, which were evaluated for their inhibition of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase. IC(50) values between 0.8 and 27.3 μM were measured. The best compound showed activity comparable to that of the most potent previously reported α-aryl substituted fosmidomycin-class inhibitor.     

Systematic synthesis of inhibitors of the two first enzymes of the bacterial heptose biosynthetic pathway: towards antivirulence molecules targeting lipopolysaccharide biosynthesis

L-Heptoses (L-glycero-D-manno-heptopyranoses) are constituents of the inner core of lipolysaccharide (LPS), a molecule playing key roles in the mortality of many infectious diseases as well as in the virulence of many human pathogens. The inhibition of the first enzymes of the bacterial heptose biosynthetic pathway is an almost unexplored field to date although it appears to be a very novel way for the development of antivirulence drugs. We report the synthesis of a series of D-glycero-D-manno-heptopyranose 7-phosphate (H7P) analogues and their inhibition properties against the isomerase GmhA and the the kinase HldE, the two first enzymes of the bacterial heptose biosynthetic pathway. The heptose structures have been modified at the 1-, 2-, 6- and 7-positions to probe the importance of the key structural features of H7P that allow a tight binding to the target enzymes; H7P being the product of GmhA and the substrate of HldE, the second objective was to find structures that could simultaneously inhibit both enzymes. We found that GmhA and HldE were extremely sensitive to structural modifications at the 6- and 7- positions of the heptose scaffold. To our surprise, the epimeric analogue of H7P displaying a D-glucopyranose configuration was found to be the best inhibitor of both enzymes but also the only molecule of this series that could inhibit GmhA (IC(50)=34 μM) and HldE (IC(50)=9.4 μM) in the low micromolar range. Noteworthy, this study describes the first inhibitors of GmhA ever reported, and paves the way to the design of a second generation of molecules targeting the bacterial virulence.     

β‐LiMoO2(AsO4)

A new non‐centrosymmetrical form of lithium molybdyl arsenate has been synthesized and grown as a single crystal. The structure of β‐LiMoO₂(AsO₄) is built up of corner‐sharing AsO₄ tetrahedra and MoO₆ octahedra which form a three‐dimensional framework containing tunnels running along the a axis, wherein the Li⁺ cations are located. This novel structure is compared with the compound LiMoO₂(AsO₄) of the same formula, and with those of AMO₂(XO₄) (A is Na, K, Rb or Pb, M is Mo or V, and X is P or As) and B(MoO₂)₂(XO₄)₂ (B is Ba, Pb or Sr).