This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold, as shown in Formula (I): ##STR00001##
Phosphonamidate compounds disclosed herein typically include a P-phenyl phosphonamidate moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phosphonamidate moiety may be optionally substituted at phosphorus with thio (S) instead of oxo (O), and/or with a thioxy group or a second amino group instead of an oxy group. One of the heteroatoms attached to phosphorus may be cyclically linked to the N-substituted nitrogen atom that is attached to the phosphorus to provide a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety, a favorable binding conformation may be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

There is provided a method for producing a 2,3-bisphosphinopyrazine derivative, the method comprising a first step of adding a base to a liquid comprising: 2,3-dihalogenopyrazine represented by the following general formula (1); a hydrogen-phosphine borane compound represented by the following general formula (2); and a deboranating agent, and allowing the resultant to react to thereby obtain the 2,3-bisphosphinopyrazine derivative represented by the following general formula (3). According to the present invention, a method for producing the industrially advantageous 2,3-bisphosphinopyrazine derivative can be provided.

##STR00001##

A phosphine-based compound and an organic electroluminescence device including the same, the phosphine-based compound being represented by the following Formula 1: ##STR00001##

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK.sub.1) receptor. The compounds have the general formula (I): ##STR00001##

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is OH or OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

In the method for producing an optically active 2,3-bisphosphinopyrazine derivative of the present invention, an optically active 2,3-bisphosphinopyrazine derivative represented by the following formula (3) is produced by the step of: preparing solution A containing 2,3-dihalogenopyrazine represented by the following formula (1)

##STR00001##

and a carboxylic acid amide coordinating solvent, lithiating an optically active R- or S-isomer of a hydrogen-phosphine borane compound represented by the following formula (2)

##STR00002##

to give a lithiated phosphine borane compound; adding solution B containing the lithiated phosphine borane compound to the solution A to perform an aromatic nucleophilic substitution reaction; and then performing a deboranation reaction.

##STR00003##

(For symbols in the formulas, see the description.)

The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

##STR00001##

The present invention relates to a compound which can be useful for the treatment or prevention of SPT-related diseases including cancer and congenital diseases associated with sphingolipid accumulation (including Niemann-Pick disease).

The present invention relates to a compound which can be useful for the treatment or prevention of SPT-related diseases including cancer and congenital diseases associated with sphingolipid accumulation (including Niemann-Pick disease).

The present invention relates to defined quinoxalin-2-one compounds or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. The compounds, salts or hydrates have a glucocorticoid receptor agonist activity, and are useful as a medicine, in particular as a prophylactic or therapeutic agent for a glucocorticoid receptor related disease.