Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine as orally-active adhesion molecule inhibitors

Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.     

ORIENTATION OF RETINYLIDENE CHROMOPHORE OF HYPSORHODOPSIN IN FROG RETINA

Abstract— Hypsorhodopsin and bathorhodopsin were formed in the frog retina by irradiating rhodopsin at liquid He temperature (9 K) with orange light (> 520 nm) and blue light (437 nm), respectively. Hypsorhodopsin was converted to bathorhodopsin in the retina by warming above 32 K in the dark. Similar phenomena were observed in the rod outer segment suspension. A difference spectrum between hypsorhodopsin and bathorhodopsin in the retina produced by warming was almost identical with that in the rod outer segment suspension. This suggests that the transition dipole moment of hypsorhodopsin is parallel to the disk membrane plane which is also parallel to that of bathorhodopsin.     

Current oscillation and low-field colossal magnetoresistance effect in phase-separated manganites

Current-induced switching from a metallic to an insulating state is observed in phase-separated states of (La(1-y)Pr(y))0.7Ca0.3MnO3 (y=0.7) and Nd(0.5)Ca(0.5)Mn(1-z)Cr(z)O3 (z=0.03) crystals. The application of magnetic fields to this current-induced insulating state causes a pronounced low-field negative magnetoresistance effect [rho(H)/rho(0)=10(-3) at H=1 kOe]. The application of a constant voltage also causes the breakdown of the Ohmic relation above a threshold voltage. At voltages higher than this threshold value, oscillations in currents are observed. This oscillation is well reproduced by a simple model of local switching of a percolative conduction path.     

Dihedral coverings of algebraic surfaces and their application

In this article, we study dihedral coverings of algebraic surfaces branched along curves with at most simple singularities. A criterion for a reduced curve to be the branch locus of some dihedral covering is given. As an application we have the following:

Let be a reduced plane curve of even degree having only nodes and cusps. If 2d^2 - 6d + 6$">, then is non-abelian.

Note that Nori's result implies that is abelian, provided that .

     

Factorial moment of the photon counting distribution of gaussian-lorentzian light under various spatial coherence

The generating function of the photon counting distribution is studied under consideration of the spatial coherence. The high order factorial moments are induced from the generating function, and are found to be experimental proof for the theory. The behavior of the second factorial moment is investigated for the purpose of spectroscopy of Rayleigh scattered light. The factorial moment measurements are made by using a digitalized electric system. The spectral line shape is determined quantitatively under various spatial coherence conditions.     

The spectral profile of light scattered by particles in electrophoretic movement

The electrophoretic movements of polystyrene latex particles suspended in water and in electrolyte solutions have been investigated with an optical beating technique. When two kinds of particles in water move in the presence of an external electric field, it is observed that the laser light scattered by these particles exhibits a shifted spectrum with a single peak profile, even if the electrophoretic mobilities of the two kinds of particles are different to each other. However, when these particles are suspended in an electrolyte solution, two separate spectral lines are observed which correspond to the velocity of each kind of particles.     

Hydrolysis of alkenyl esters and ethers catalyzed by metal complexes

[reaction: see text] Various kinds of transition metals catalyzed the hydrolysis of alkenyl esters and ethers under buffer-free, high concentration conditions compared to usual biocatalysts. Hydrolytic kinetic resolution of cis-2-tert-butylcyclohexyl vinyl ether was achieved by chiral (salen)Co complexes with good selectivity (k(rel) = 10.0).     

S‐((Phenylsulfonyl)difluoromethyl)thiophenium Salts: Carbon‐Selective Electrophilic Difluoromethylation of β‐Ketoesters, β‐Diketones,and Dicyanoalkylidenes

S‐((Phenylsulfonyl)difluoromethyl)thiophenium salts were designed and prepared by a triflic acid catalyzed intramolecular cyclization of ortho‐ethynyl aryldifluoromethyl sulfanes. The thiophenium salts were found to be efficient as electrophilic difluoromehtylating reagents for introduction of a CF₂H group to sp³‐hybridized carbon nucleophiles such as of β‐ketoesters and dicyanoalkylidenes. The (phenylsulfonyl)difluoromethyl group can be readily transformed into CF₂H under mild reaction conditions. Enantioselective electrophilic difluoromethylation was also achieved in the presence of bis(cinchona) alkaloids.     

Magnetic-field induced competition of two multiferroic orders in a triangular-lattice helimagnet MnI2

Magnetic and dielectric properties with varying magnitude and direction of magnetic-field H have been investigated for a triangular-lattice helimagnet MnI_{2}. The in-plane electric polarization P emerges in the proper screw magnetic ground state below 3.5 K, showing the rearrangement of six possible multiferroic domains as controlled by the in-plane H. With every 60° rotation of H around the [001] axis, discontinuous 120° flop of the P vector is observed as a result of the flop of magnetic modulation vector q. With increasing the in-plane H above 3 T, however, the stable q direction changes from q‖(110[ ˉover 0]) to q‖(110), leading to a change of P-flop patterns under rotating H. At the critical field region (～3 T), due to the phase competition and resultant enhanced q flexibility, the P vector smoothly rotates clockwise twice while the H vector rotates counterclockwise once.