Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): ##STR00001##
wherein R is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; and n is 0 or 1, or a salt thereof, including a step of subjecting a compound represented by the formula (2): ##STR00002##
wherein R and n are as defined above, or a salt thereof, to an oxidation reaction.

The present invention relates to a process for the synthesis of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-1H-1,2,4-triazol-3-amine in two hydrated crystalline forms and in one anhydrous crystalline form. The present invention further relates to methyl (Z)-4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)-N-cyanopiperidine-1-carbimidothioate which is an intermediate in this process.

The present invention relates to a process for the synthesis of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-1H-1,2,4-triazol-3-amine in two hydrated crystalline forms and in one anhydrous crystalline form. The present invention further relates to methyl (Z)-4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)-N-cyanopiperidine-1-carbimidothioate which is an intermediate in this process.

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

A preparation method according to the present invention makes it possible to industrially produce large amounts of highly pure optically active tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate in high yield by use of commercially available reagents and solvents. In addition, the use of novel intermediates according to the present invention makes it possible to produce highly pure optically active tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate in high yield.

A preparation method according to the present invention makes it possible to industrially produce large amounts of highly pure optically active tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate in high yield by use of commercially available reagents and solvents. In addition, the use of novel intermediates according to the present invention makes it possible to produce highly pure optically active tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate in high yield.

The present disclosure relates generally to eukaryotic initiation factor 2B modulators of formula A, or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof and methods of making and using thereof.

##STR00001##

3,5-Diarylidenyl-N-substituted-piperid-4-one analogs, and pharmaceutically acceptable derivatives thereof, are useful in the treatment or prevention of disorders including cancer, autoimmune disorders, inflammatory disorders, and fibrotic disorders. The compounds are included in pharmaceutical compositions, and are useful for treating disorders, such as cancer associated with aberrant Stat3 pathway activity. The compositions further include another therapeutic agent, such as an anticancer drug. Such compounds or compositions thereof are used to treat resistant and/or metastatic cancers. Methods also inhibit Stat3 pathway activity in a cell. Other methods are useful for making the pharmaceutical compounds. Synthetic methods are also useful for making the compounds. The compounds and compositions are useful as a fluorescent probe.

An improved method is used for preparing triacetone amine while recycling the by-products. This involves treating the crude product from triacetone amine preparation, which leads to an increase in the content of compounds which react readily with ammonia. This method enables efficient recycling of the by-products formed in the synthesis of triacetone amine.