C-Phosphorylation of Compounds with the Electron-Rich Double Carbon-Nitrogen Bond

Abstract

C-phosphorylation of N,N-dimethylhydrazones and N,N-dimethyl-N′-arylamidines by phosphorus tribromide was first accomplished. It directs to the formation of novel types of functional P(III) derivatives (1–3)     

Performance of global random search algorithms for large dimensions

We investigate the rate of convergence of general global random search (GRS) algorithms. We show that if the dimension of the feasible domain is large then it is impossible to give any guarantee that the global minimizer is found by a general GRS algorithm with reasonable accuracy. We then study precision of statistical estimates of the global minimum in the case of large dimensions. We show that these estimates also suffer the curse of dimensionality. Finally, we demonstrate that the use of quasi-random points in place of the random ones does not give any visible advantage in large dimensions.     

On the distribution of Farey fractions and hyperbolic lattice points

We derive an asymptotic formula for the number of pairs of consecutive fractions a0=q0 and a=q in the Farey sequence of order Q such that a=q; q=Q; and (Q - q0)=q lie each in prescribed subintervals of the interval [0; 1]. We deduce the leading term in the asymptotic formula for `the hyperbolic lattice point problem" for the modular group PSL(2; Z ), the number of images of a given point under the action of the group in a given circle in the hyperbolic plane.     

A Radon–Nikodým type theorem for orthosymmetric bilinear operators

A Radon–Nikodym type theorem for positive orthosymmetric bilinear operators is proved. The main tools are based upon homogeneous functional calculus on vector lattices and the concept of square of vector lattice.     

Branch and probability bound methods in multi-objective optimization

An approach to non-convex multi-objective optimization problems is considered where only the values of objective functions are required by the algorithm. The proposed approach is a generalization of the probabilistic branch-and-bound approach well applicable to complicated problems of single-objective global optimization. In the present paper the concept of probabilistic branch-and-bound based multi-objective optimization algorithms is discussed, and some illustrations are presented.     

Two-person game with nash equilibrium in optimal control problems

A two-person game with a Nash equilibrium is formulated for optimal control problems with a free right end and a linear differential system. The game is reduced to the calculation of a fixed point of an extremal mapping, which in turn is reduced to a variational inequality with linear constraints generated by systems of linear differential controllable processes. An extra-gradient iterative method is proposed for calculating the Nash equilibrium of the dynamic game. The convergence of the method is proved.     

Facile Access to 2-Selenoxo-1,2,3,4-tetrahydro-4-quinazolinone Scaffolds and Corresponding Diselenides via Cyclization between Methyl Anthranilate and Isoselenocyanates: Synthesis and Structural Features

A practical method for the synthesis of 2-selenoxo-1,2,3,4-tetrahydro-4-quinazolinone was reported. The latter compounds were found to undergo facile oxidation with H₂O₂ into corresponding diselenides. Novel organoselenium derivatives were characterized by the ¹H, ⁷⁷Se, and ¹³C NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, IR, elemental analyses (C, H, N), and X-ray diffraction analysis for several of them. Novel heterocycles exhibited multiple remarkable chalcogen bonding (ChB) interactions in the solid state, which were studied theoretically.     

New Multifunctional Agents Based on Conjugates of 4-Amino-2,3-polymethylenequinoline and Butylated Hydroxytoluene for Alzheimer’s Disease Treatment

New hybrids of 4-amino-2,3-polymethylenequinoline with different sizes of the aliphatic ring linked to butylated hydroxytoluene (BHT) by enaminoalkyl (7) or aminoalkyl (8) spacers were synthesized as potential multifunctional agents for Alzheimer’s disease (AD) treatment. All compounds were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. Lead compound 8c, 2,6-di-tert-butyl-4-{[2-(7,8,9,10- tetrahydro-6H-cyclohepta[b]quinolin-11-ylamino)-ethylimino]-methyl}-phenol exhibited an IC₅₀(AChE) = 1.90 ± 0.16 µM, IC₅₀(BChE) = 0.084 ± 0.008 µM, and 13.6 ± 1.2% propidium displacement at 20 μM. Compounds possessed low activity against carboxylesterase, indicating likely absence of clinically unwanted drug-drug interactions. Kinetics were consistent with mixed-type reversible inhibition of both cholinesterases. Docking indicated binding to catalytic and peripheral AChE sites; peripheral site binding along with propidium displacement suggest the potential of the hybrids to block AChE-induced β-amyloid aggregation, a disease-modifying effect. Compounds demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Conjugates 8 with amine-containing spacers were better antioxidants than those with enamine spacers 7. Computational ADMET profiles for all compounds predicted good blood-brain barrier distribution (permeability), good intestinal absorption, and medium cardiac toxicity risk. Overall, based on their favorable pharmacological and ADMET profiles, conjugates 8 appear promising as candidates for AD therapeutics.