An Expedient Approach for the Synthesis of Bioactive Pyrazole,Isoxazole and Benzodiazepine‐Substituted Quinolin‐2(1H)‐one Derivatives

A sequence of functionalized pyrazole, isoxazole and benzodiazepine‐substituted quinolone derivatives were synthesized in good yield starting from readily available starting precursors. These approaches lead to the synthesis of hitherto unknown compounds with a varied substitution pattern by both conventional and microwave‐assisted method. A good number of analogues were evaluated for their in vitro cytotoxicity against human cervical and colon cancer cell lines by MTT protocol. Almost all the selected compounds showed remarkable cytotoxic activities. Among them, compound 4g and 4i emerged as the most promising scaffolds. These scaffolds will be used for further molecular level studies.     

Poly(oxanorbornenedicarboximide)s dendronized with amphiphilic poly(alkyl ether) dendrons

Attaching dendritically branched side chains to each repeat unit of a linear polymer produces molecular building blocks of nanometer‐sized dimensions called dendronized polymers. The structure of these complex molecular architectures is highly tunable and, therefore, of interest for a wide range of potential applications. The first examples of dendronized polymers prepared by living ring‐opening metathesis polymerization of oxanorbornenedicarboximide macromonomers with poly(alkyl ether) dendrons are reported. Small‐angle X‐ray scattering experiments on bulk samples confirm that the diameter of the individual cylindrical polymers can be tailored by the choice of dendron generation or the length of the hydrocarbon peripheral group. Analysis of the SAXS data based on a core‐shell model indicates that although the diameter of the cylinder increases with generation, the size of the core does not change; this suggests that these dendrons only loosely encapsulate the polymer backbone. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3221–3239     

Simultaneous Chemo/Enantioseparation and Assay of R-(+)-Rabeprazole and Related Impurities in Pharmaceutical Formulations

Simultaneous chiral and chemoseparation of R-(+)-rabeprazole and related (enantio)impurities was achieved on a cellulose tris-(3,5-dichlorophenylcarbamate) stationary phase chemically bonded to silica gel (Chiralpak IC). A gradient elution was applied in the reverse-phase separation mode. The mobile phase consisted of a mixture of acetonitrile and aqueous phosphate buffer at pH 7. The other operational parameters were flow rate of 1 mL min⁻¹, column temperature of 35 °C and ultraviolet (UV) detection at 282 nm. Quantification limits for R-(+)-rabeprazole and the related impurities ranged in the interval of 0.02–0.03 %. Linear response intervals of 0.02–0.66 % were obtained with UV detection. Validation of the proposed method was achieved according to current regulations in force. For better understanding of the R-(+)-rabeprazole impurity profile, (+)-EMS/MS and MS/MS detection were also used.

     

High-purity Zirconium under Niobium ion implantation: possibility of a dynamic precipitation?

High-purity (6N purity) Zirconium was subjected to different Niobium ion (Nb⁺) fluences in a particle accelerator. Grazing incidence X-ray diffraction confirmed subsurface phase transformation. While an approximate scaling was noted between Nb⁺ fluence and quantum of phase transformation, the sample subjected to the highest ion irradiation also showed significant subsurface shear residual stresses (τ₁₃). Molecular dynamics simulations, considering momentum transfer, revealed a drop in τ₁₃ beyond a critical displacements per atom or Nb⁺ fluence. High-resolution cross-sectional transmission electron microscopy (HRXTEM) confirmed formation of bcc (body-centred cubic) β phase and also linked τ₁₃ with such transformation. HRXTEM revealed, at about 100 nm depth, presence of 10–15% β with 2–15 nm size. The β particles and the surrounding α also had significant microscopic shear strains. The dynamic nature of the Nb implantation is expected to create fluctuations in temperature, Nb concentration and relative lattice damage. Such fluctuation, on the other hand, is/was hypothesized to dynamically alter the critical nuclei size: a clear possibility of ‘dynamic precipitation’.     

L-Proline catalyzed three component synthesis of pyrano[2,3-c]pyrazole-5-carbonitrile derivatives and in vitro antimalarial evaluation

An efficient one-pot synthesis of 6-amino-4-(2-chloroquinolin-3-yl)-3-methyl-2, 4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile derivatives (4a–f)(5a–f) by three component reactions of 2-chloroquinolin-3-carbaldehyde derivatives, malanonitrile, and 3-methyl pyrazolin-5-one derivatives catalyzed by L-proline in ethanol medium under mild conditions is established. The synthesized compounds were evaluated for antimalarial activity and the LC₅₀/LC₉₀ values were described. Compounds 4d, 5d, and 5f exhibits good antimalarial activity when compared to other pyrano[2,3-c]pyrazole scaffolds.