The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

The present application falls within the field of drug synthesis, and in particular, the present application relates to a method for preparing ruxolitinib, and a method for preparing the intermediate and relevant intermediates used. The method comprises reacting a compound of formula II with a compound of formula IV or a salt thereof to obtain a compound of formula III, and then subjecting the compound of formula III to an acyl halogenation reaction, an amidation reaction, and a reaction dehydrating an amide to form a cyano group or removing the protecting group to prepare ruxolitinib. The method has the characteristics of brief steps, a high stereoselectivity, a high utilization ratio of atoms, mild reaction conditions and convenient post treatment. The method avoids using expensive asymmetric reaction catalysts, and is suitable for industrial production.

##STR00001##

The present application falls within the field of drug synthesis, and in particular, the present application relates to a method for preparing ruxolitinib, and a method for preparing the intermediate and relevant intermediates used. The method comprises reacting a compound of formula II with a compound of formula IV or a salt thereof to obtain a compound of formula III, and then subjecting the compound of formula III to an acyl halogenation reaction, an amidation reaction, and a reaction dehydrating an amide to form a cyano group or removing the protecting group to prepare ruxolitinib. The method has the characteristics of brief steps, a high stereoselectivity, a high utilization ratio of atoms, mild reaction conditions and convenient post treatment. The method avoids using expensive asymmetric reaction catalysts, and is suitable for industrial production.

##STR00001##

Disclosed herein are compounds for treating conditions related to oxidative stress/damage among other causes, with pharmaceutically accepted salts hydrate, solvate, optical isomer, or combination thereof, comprising lipophilic cation moieties linked to heterocyclics compounds of formula (I) and formula (8);

##STR00001##

wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 may be selected from the group consisting of

##STR00002##

wherein X, Y, and Z are selected from the group consisting of H, methyl, ethyl, propyl, butyl, substituted or unsubstituted aryl, and heteroaryls; n is an integer selected from 0-18, and E is a phosphorous or nitrogen atom.

Disclosed herein are compounds for treating conditions related to oxidative stress/damage among other causes, with pharmaceutically accepted salts hydrate, solvate, optical isomer, or combination thereof, comprising lipophilic cation moieties linked to heterocyclics compounds of formula (I) and formula (8);

##STR00001##

wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 may be selected from the group consisting of

##STR00002##

wherein X, Y, and Z are selected from the group consisting of H, methyl, ethyl, propyl, butyl, substituted or unsubstituted aryl, and heteroaryls; n is an integer selected from 0-18, and E is a phosphorous or nitrogen atom.

Provided are compounds that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the cytotoxicity of virus to cells. Other uses, compositions and methods of using same are also provided.

Provided are compounds that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the cytotoxicity of virus to cells. Other uses, compositions and methods of using same are also provided.

The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:

##STR00001##

which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:

##STR00001##

which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.