Compounds of formula (I), wherein R.sub.1 is as defined in the claims, exhibit COMT enzyme inhibiting activity and are thus useful as COMT inhibitors. Methods of treatment and pharmaceutical dosage forms are also disclosed.

A class of water lean, organic solvents that can bind with various acid gasses to form acid gas bound molecules having a high degree of intramolecular hydrogen bonding which enables their use as regenerable solvents for acid gas capture. Unlike the other devices described in the prior art, the present invention takes advantage of shortened distances between the portions of the molecule that form hydrogen bonds within the structures when loaded with an acid gas so as to create a molecule with a higher internal bonding affinity and a reduced proclivity for agglomeration with other molecules.

The disclosure provides processes for synthesizing Compound I, and pharmaceutically acceptable salts thereof. ##STR00001##

The present invention relates to 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate, to processes for its preparation, to pharmaceutical compositions comprising it and to its use in the control of disorders.

The present invention relates to 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate, to processes for its preparation, to pharmaceutical compositions comprising it and to its use in the control of disorders.

A compound represented by formula (4) is produced by a step A of reacting a compound represented by formula (2): ##STR00001##
wherein R.sup.1 represents an ethyl group or the like, R represents a halogen atom or the like, n represents 0, 1, 2, or 3, and M represents potassium or the like, with thionyl chloride to obtain a compound represented by formula (1): ##STR00002##
a step B of reacting the compound represented by formula (1) with a compound represented by formula (5): ##STR00003##
wherein A.sup.1 represents a nitrogen atom or CH, R.sup.5 represents a trifluoromethyl group or the like, and m represents 1 or 2, to produce a compound represented by formula (3): ##STR00004##
or an acid salt thereof; and a step C of reacting the compound represented by formula (3) or an acid salt thereof in the presence of acid at 100 C. to 180 C. to obtain the compound represented by formula (4): ##STR00005##

A compound represented by formula (4) is produced by a step A of reacting a compound represented by formula (2): ##STR00001##
wherein R.sup.1 represents an ethyl group or the like, R represents a halogen atom or the like, n represents 0, 1, 2, or 3, and M represents potassium or the like, with thionyl chloride to obtain a compound represented by formula (1): ##STR00002##
a step B of reacting the compound represented by formula (1) with a compound represented by formula (5): ##STR00003##
wherein A.sup.1 represents a nitrogen atom or CH, R.sup.5 represents a trifluoromethyl group or the like, and m represents 1 or 2, to produce a compound represented by formula (3): ##STR00004##
or an acid salt thereof; and a step C of reacting the compound represented by formula (3) or an acid salt thereof in the presence of acid at 100 C. to 180 C. to obtain the compound represented by formula (4): ##STR00005##

The present invention is directed to compounds encompassed by the Formula (I), pharmaceutical compositions thereof, methods for inhibiting LTA-4 hydrolase, and methods for the treatment of a disease and disorder which is ameliorated by the inhibition of LTA4-h activity. Non-limiting examples of such diseases and conditions include inflammatory and autoimmune diseases and disorders.

The present invention is directed to compounds encompassed by the Formula (I), pharmaceutical compositions thereof, methods for inhibiting LTA-4 hydrolase, and methods for the treatment of a disease and disorder which is ameliorated by the inhibition of LTA4-h activity. Non-limiting examples of such diseases and conditions include inflammatory and autoimmune diseases and disorders.

The present invention relates to 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate, to processes for its preparation, to pharmaceutical compositions comprising it and to its use in the control of disorders.