Iodine-catalyzed one-pot synthesis of amides from nitriles via Ritter reaction

Ritter reactions of alcohols and tert-butyl acetate with various nitriles were performed using iodine as a mild and effective catalyst under heating conditions to afford the corresponding amides in good to excellent yields.     

A Rapid Stability-Indicating LC Method for Ziprasidone Hydrochloride

A simple and rapid reversed-phase liquid chromatographic method was developed for the related substances determination and quantitative evaluation of ziprasidone hydrochloride, which is used as an antipsychotic agent. Forced degradation studies were performed on bulk sample of ziprasidone hydrochloride using acid, base, oxidative hydrolysis, thermal stress and photolytic degradation. Mild degradation of the drug substance was observed during thermal stress and considerable degradation observed during base hydrolysis. The chromatographic method was fine tuned using the samples generated from forced degradation studies. Good resolution between the peaks corresponds to synthetic impurities and degradation products from the analyte were achieved on YMC Pack Pro C18 column using the mobile phase consists of a mixture of 0.05% v/v of phosphoric acid in water and acetonitrile. The stressed test solutions were assayed against the qualified working standard of ziprasidone hydrochloride and the mass balance in each case was close to 99.7% indicating that the developed method was stability-indicating. Validation of the developed method was carried out as per ICH requirements.     

A validated stability-indicating RP-HPLC assay method for Amsacrine and its related substances

A validated specific stability indicating reversed-phase high-performance liquid chromatography method was developed for the quantitative determination of Amsacrine as well as its related substances determination in bulk samples, in presence of degradation products, and its process related impurities. Forced degradation studies were performed on bulk samples of Amsacrine as per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) prescribed stress conditions using acid, base, oxidative, thermal stress, and photolytic degradation to show the stability indicating power of the method. Significant degradation was observed during basic hydrolysis, slight degradation was observed in oxidative and thermal stress, and no degradation was observed in other stress conditions. The chromatographic method was optimized using the samples generated from forced degradation studies and the impurity spiked solution. Good resolution between the peaks corresponds to process-related impurities and degradation products from the analyte were achieved on Inertsil ODS column using the mobile phase consists a mixture of 1.0% triethyl amine in 20 mM potassium dihydrogen orthophosphate, with pH adjusted to 6.5, with ortho phosphoric acid in water and acetonitrile using a simple linear gradient. The detection was carried out at wavelength 248 nm. The mass balance in each case was in between 99.4% to 99.9%, indicating that the developed method was stability-indicating. Validation of the developed method was carried out as per ICH requirements. The developed method was found to be suitable to check the quality of bulk samples of Amsacrine at the time of batch release and also during its stability studies.     

Levitin–Polyak well-posedness for parametric quasivariational inequality problem of the Minty type

In this paper, we introduce the notions of Levitin?CPolyak (LP) well-posedness and Levitin?CPolyak well-posedness in the generalized sense, for a parametric quasivariational inequality problem of the Minty type. Metric characterizations of LP well-posedness and generalized LP well-posedness, in terms of the approximate solution sets are presented. A parametric gap function for the quasivariational inequality problem is introduced and an equivalence relation between LP well-posedness of the parametric quasivariational inequality problem and that of the related optimization problem is obtained.     

New substrates in the ferroin-catalyzed bromate system in aqueous-organic mixed media

A large number of substrates have hitherto been employed in the Belousov-Zhabotinsky (B-Z) oscillatory system in pure aqueous medium. A systematic study of aromatic bromate oscillators is limited by solubility problem relating to the compounds and the brominated derivatives. The use of aqueous-organic mixed media for the oscillatory study is found to be highly useful for the study of water insoluble substances. A comparative study of the oscillatory behavior of gallic acid as substrate in pure aqueous as well as in a number of mixed media have been made in order to ascertain the suitability of mixed media in oscillatory systems. The alteration of oscillatory characteristics in the presence of organic solvent can be understood in terms of the Field-Koros-Noyes (FKN) mechanism. The oscillatory behavior of seventeen new substrates in the ferroin-catalyzed bromate system in 20% (v) acetonitrile is also presented and discussed in this communication. The reactivity of structurally related substrates has been correlated to the structure in terms of the relevant oscillatory parameters. The use of aqueous-organic mixed media in oscillatory systems would enable the investigation of new classes of substrates since getting them into the solution phase would no longer be a limitation. © 1993 John Wiley & Sons, Inc.     

Determining the resolution of Laplace inversion spectrum

In experiments involving decaying signals, it is often desirable to analyze the data as a sum of exponential decays using the Laplace inversion method. However, Laplace inversion is an ill-conditioned problem, and it is difficult to ascertain the stability of the reconstruction method and resolution of the resulting spectrum. This paper provides an easily computed approximate bound of the resolution and offers guidelines on how to design experiments to improve the spectral resolution.     

Weak Clarke epiderivative in set-valued optimization

A new notion of weak Clarke epiderivative for a set-valued map is introduced using the concept of Clarke tangent cone. The existence, characterization and properties of weak Clarke epiderivative are then studied. Finally optimality criteria are established for a constrained set-valued optimization problem in terms of weak Clarke epiderivative.     

Computational fragment-based design of Wee1 kinase inhibitors with tricyclic core scaffolds

Wee1 is cell cycle protein comprising a kinase domain and is a validated cancer target. We have designed molecules with variable tricyclic core scaffolds [6-6-5] system and extended them based on the chemical space available in the active site of Wee1 kinase using de novo drug design. The core scaffolds and linking fragments were extracted from pharmacophore-based virtual screening of ZINC and PubChem databases and Ludi library. These molecules bind the hinge region of kinase active site and form hydrogen bonds as confirmed from molecular docking, molecular dynamics simulations, and MM_PBSA calculations. When compared with reference inhibitors, AZD1775 and PHA-848125, the de novo designed molecules also show good docking scores and stability, retained non-covalent interactions, and high binding free energies contributed from active site residues.