Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.

The invention relates to new benzonitrile derivatives of the formula (I) wherein R.sup.1 to R.sup.3 and A are as defined in the description and Claims, to their medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

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The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.

This invention provides an isolated compound having the structure:

##STR00001##

or a salt thereof.

The invention also provides for a process for preparing 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-4-ol, 1-(3,3-bis(3-(methylsulfonyl)phenyl)propyl)-4-(3-(methylsulfonyl) phenyl)piperidone, 1,4-bis((3-(1-propylpiperidin-4-yl)phenyl)sulfonyl)butane, (3R,4S)-4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-3-ol, 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidine 1-oxide, 1-(2-methylpentyl)-4-(3-(methylsulfonyl)phenyl)piperidine, 4-(3-(methylsulfinyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine, and 4-(3-(methylsulfonyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine.

This invention also provides an impurity or a salt thereof for use, as a reference standard to detect trace amounts of the impurity in a pharmaceutical composition comprising pridopidine or a pharmaceutically acceptable salt thereof. This invention further provides a process for producing a pridopidine drug product comprising obtaining a pridopidine drug substance and. mixing the pridopidine drug substance with suitable excipients so as to produce the pridopidine drug product. This invention also provides a process for producing a pridopidine drug product. This invention also provides a process of distributing a pridopidine drug product.

This invention provides an isolated compound having the structure:

##STR00001##

or a salt thereof.

The invention also provides for a process for preparing 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-4-ol, 1-(3,3-bis(3-(methylsulfonyl)phenyl)propyl)-4-(3-(methylsulfonyl) phenyl)piperidone, 1,4-bis((3-(1-propylpiperidin-4-yl)phenyl)sulfonyl)butane, (3R,4S)-4-(3-(methylsulfonyl)phenyl)-1-propylpiperidin-3-ol, 4-(3-(methylsulfonyl)phenyl)-1-propylpiperidine 1-oxide, 1-(2-methylpentyl)-4-(3-(methylsulfonyl)phenyl)piperidine, 4-(3-(methylsulfinyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine, and 4-(3-(methylsulfonyl)phenyl)-1-propyl-1,2,3,6-tetrahydropyridine.

This invention also provides an impurity or a salt thereof for use, as a reference standard to detect trace amounts of the impurity in a pharmaceutical composition comprising pridopidine or a pharmaceutically acceptable salt thereof. This invention further provides a process for producing a pridopidine drug product comprising obtaining a pridopidine drug substance and. mixing the pridopidine drug substance with suitable excipients so as to produce the pridopidine drug product. This invention also provides a process for producing a pridopidine drug product. This invention also provides a process of distributing a pridopidine drug product.

The compound of the formula (I-1):

##STR00001##

wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1P.sub.2 antagonistic activity. The compound may therefore be used as a therapeutic agent for S1P.sub.2-mediated diseases such as diseases resulting from vascular constriction, fibrosis, and respiratory diseases.

The compound of the formula (I-1):

##STR00001##

wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1P.sub.2 antagonistic activity. The compound may therefore be used as a therapeutic agent for S1P.sub.2-mediated diseases such as diseases resulting from vascular constriction, fibrosis, and respiratory diseases.

The invention provides a novel synthetic route for the preparation of the Chk-1 inhibitor compound:

##STR00001##

as well as novel process intermediates per se.

The invention provides a novel synthetic route for the preparation of the Chk-1 inhibitor compound:

##STR00001##

as well as novel process intermediates per se.