PEG-400 mediated an efficient eco-friendly synthesis of new isoxazolyl pyrido[2,3-d]pyrimidines and their anti-inflammatory and analgesic activity

Abstract

Polyethylene glycol-400 (PEG-400) has been developed as an efficient and eco-friendly reaction medium for the synthesis of new isoxazolyl pyrido[2,3-d]pyrimidine derivatives 11 from isoxazolyl cyanoacetamide synthon 7. Compound 7 was employed with various aromatic aldehydes 8 and malononitrile 9 in the presence of triethylamine (Et₃N) to afford the corresponding (E)-6-amino-1-(3-methyl-5-styrylisoxazol-4-yl)-2-oxo-4-phenyl-1,2-dihydro- pyridine-3,5-dicarbonitrile 10 at room temperature by using PEG-400 as a solvent medium as well as catalyst. The intermediate 10 on treatment with thiourea in the presence of PEG-400 at 90?°C to give the target compounds isoxazolyl pyrido[2,3-d]pyrimidines 11 in good to excellent yields. The newly synthesized compounds 10 and 11 were characterized by IR, ¹H NMR, ¹³C NMR, and HRMS analysis. The target compounds 11a-x was screened for their anti-inflammatory and analgesic activities. Among the tested compounds, the compounds 11s, 11t, 11u, 11v, 11w, and 11x showed significant anti-inflammatory and potent analgesic activities as that of reference drugs. The advantages of this protocol are operational simplicity, catalyst free, environmental safety, wide substrate scope, good yields, and PEG-400 can be recovered and reused. Most significant of all, this protocol is green.     

Spherically symmetric inhomogeneous dust collapse in higher dimensional space-time and cosmic censorship hypothesis

We consider a collapsing spherically symmetric inhomogeneous dust cloud in higher dimensional space-time. We show that the central singularity of collapse can be a strong curvature or a weak curvature naked singularity depending on the initial density distribution.     

Scattering by small defects in the neighbourhood of a fluid-solid interface

The scattering of incident plane elastic waves by a varietyof different defects that lie upon a fluid-solid interface isconsidered here using matched asymptotic expansions. The expansionscheme is developed in terms of a parameter , the ratio of typicaldefect length scale to a typical wavelength of the incidentfield, taken to be small. Three different canonical situations occur and these are illustratedvia three specific examples treated here: a rigid strut, anedge crack, and a rigid strip. In each case the leading-ordermatching is performed to identify the leading-order contributionof the defect to the acoustic field in the far field. In particular,each defect is identified with a source of dipole response ininterfacial stress of displacement. It is shown in the limit as s<<s1 that in the inner problemsthe fluid and solid pieces uncouple in a particularly convenientmanner allowing analytical solutions to be deduced. These arethen matched with appropriate outer solutions.     

Scalable fine-grained parallelization of plane-wave-based ab initio molecular dynamics for large supercomputers

Many systems of great importance in material science, chemistry, solid-state physics, and biophysics require forces generated from an electronic structure calculation, as opposed to an empirically derived force law to describe their properties adequately. The use of such forces as input to Newton's equations of motion forms the basis of the ab initio molecular dynamics method, which is able to treat the dynamics of chemical bond-breaking and -forming events. However, a very large number of electronic structure calculations must be performed to compute an ab initio molecular dynamics trajectory, making the efficiency as well as the accuracy of the electronic structure representation critical issues. One efficient and accurate electronic structure method is the generalized gradient approximation to the Kohn-Sham density functional theory implemented using a plane-wave basis set and atomic pseudopotentials. The marriage of the gradient-corrected density functional approach with molecular dynamics, as pioneered by Car and Parrinello (R. Car and M. Parrinello, Phys Rev Lett 1985, 55, 2471), has been demonstrated to be capable of elucidating the atomic scale structure and dynamics underlying many complex systems at finite temperature. However, despite the relative efficiency of this approach, it has not been possible to obtain parallel scaling of the technique beyond several hundred processors on moderately sized systems using standard approaches. Consequently, the time scales that can be accessed and the degree of phase space sampling are severely limited. To take advantage of next generation computer platforms with thousands of processors such as IBM's BlueGene, a novel scalable parallelization strategy for Car-Parrinello molecular dynamics is developed using the concept of processor virtualization as embodied by the Charm++ parallel programming system. Charm++ allows the diverse elements of a Car-Parrinello molecular dynamics calculation to be interleaved with low latency such that unprecedented scaling is achieved. As a benchmark, a system of 32 water molecules, a common system size employed in the study of the aqueous solvation and chemistry of small molecules, is shown to scale on more than 1500 processors, which is impossible to achieve using standard approaches. This degree of parallel scaling is expected to open new opportunities for scientific inquiry.     

Agallochins J-L,new isopimarane diterpenoids from Excoecaria agallocha L

The ethyl acetate extract of Excoecaria agallocha L. furnished three more new isopimarane diterpenoids, 11alpha,14alpha-dihydroxy-7,15-isopimaradien-3-one, agallochin J (1), 3alpha, 1alpha,14alpha-trihydroxyisopimara-7,15-diene, agallochin K (2) and 6alpha,14alpha,17-trihydroxy-7,15-isopimaradien-3-one, agallochin L.     

On a Simple Nonisothermal Adsorption Experiment with Organic Vapors and an Inertial Microbalance To Study the Surface Properties of Hybrid (Organic/Inorganic) Porous Materials

A nonisothermal adsorption experiment using a controlled flow of cyclopentane in the 333-313 K range is used to simultaneously estimate the specific surface area and micropore volume of a hybrid (organic/inorganic) alcogel. For reference, the method is also applied to an all-inorganic material with a more rigid structure, namely, a high surface area SiO(2)-Al(2)O(3). The proposed data analysis provides guidelines to determine whether adsorption data on a certain adsorbate/adsorbent system can be modeled effectively as a convolution of BET (meso- and macropore) and Dubinin-Radushkevitch (DR, micropore) contributions. Copyright 2000 Academic Press.     

Synthesis and Characterization of Compounds Potentially Related to the Janus Kinase Inhibitor Baricitinib

Russian Journal of Organic Chemistry - Nine compounds potentially related to the Janus kinase inhibitor Baricitinib have been identified, synthesized by conventional methods, and characterized by...     

Working group report: Heavy-ion physics and quark-gluon plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of quark-gluon plasma believed to have created in heavy-ion collisions and in early Universe are reported.     

Retracted: Synthesis,Molecular Properties,and Biological Evaluation of Hybrid 1,2,3‐Triazolylpolyaza Heterocyclic Compounds

In this research article, a highly efficient, cost‐effective synthesis of various hybrid molecules possessing 1,2,3‐triazolyltetrazoles and evaluation of their biological activity have been addressed. The structure elucidation of these new library hybrid molecules has been carried out by IR, ¹H NMR, ¹³C NMR, and mass spectral analysis. The compounds have been screened for their anticancer activity against human colon cancer cell line Colo‐205 and human lung cancer cell line HOP‐205, and the results attest that most of the compounds have shown very good therapeutic nature. In particular, compounds 3d , 3j , 6a , and 6e were more cytotoxic than Adriamycin against all tested human cancer cell lines with 68%, 101.8%, 94%, and 104.5% growth, respectively. In the present investigation, a series of 3a – j and 6a – h were subjected to molecular properties prediction, drug likeness by Molinspiration, and toxicity risks by Molsoft software programs. All the 18 analogues were chosen on the basis of Lipinski “Rule of five” for the synthesis, screening their antibacterial and anticancer as oral bioavailable drugs/leads.