Disclosed are methods of decreasing the concentration of a metal in a monomer composition including a bis(benzoyl)benzene, bis(benzoyl)benzene monomer compositions having a low total metal concentration, di-ketone polymers made from low metal bis(benzoyl)benzene monomers, and polymer compositions and shaped articles including the di-ketone polymers. It was surprisingly found that di-ketone polymers made by nucleophilic substitution of low metal bis(benzoyl)benzene monomers exhibit greater crystallinity, as compared with di-ketone polymers made with conventional monomers.

Disclosed are methods of decreasing the concentration of a metal in a monomer composition including a bis(benzoyl)benzene, bis(benzoyl)benzene monomer compositions having a low total metal concentration, di-ketone polymers made from low metal bis(benzoyl)benzene monomers, and polymer compositions and shaped articles including the di-ketone polymers. It was surprisingly found that di-ketone polymers made by nucleophilic substitution of low metal bis(benzoyl)benzene monomers exhibit greater crystallinity, as compared with di-ketone polymers made with conventional monomers.

A polysubstituted benzene compound, preparation method thereof, and method of using the same. The compound has a formula I or I′, where X represents carbon, sulfur, or oxygen; R.sup.1 represents a C.sub.1-16 alkyl, C.sub.2-16 alkenyl, or C.sub.2-10 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-16 alkyl, C.sub.2-16 alkenyl, or C.sub.2-10 alkynyl; or an aryl group or a substituted aryl group by 1-5 groups selected from halogen, C.sub.1-26 alkyl, C.sub.1-3 halogenated alkyl, O—C.sub.1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; or a heteroaryl group or a substituted heteroaryl group by 1-5 groups selected from halogen, C.sub.1-26 alkyl, C.sub.1-3 halogenated alkyl, O—C.sub.1-3 alkyl, hydroxyl, amino, nitro, cyano group, aldehyde group and ester group; the heteroaryl group is a 3-10-membered heteroaryl group including N, S, O, or a combination thereof.

The invention provides a method for synthesizing a compound of formula ##STR00001##
wherein each R independently represents an optionally substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, cyano, sulfo or sulfhydryl group, in ortho, meta or para position to the cycloalkylamine moiety; R.sup.1 and R.sup.2 each independently represents a hydrogen atom, a lower alkyl group or a cycloalkyl group; R.sup.3 represents a hydrogen group, substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy group; Y represents an oxygen atom, a sulfur atom, a NH group, a NR.sup.4 group or a CH.sub.2 group; R.sup.4 represents a hydrogen atom or an alkyl, aryl or a heteroaryl group; and n and m each independently represents an integer from 1 to 5; or a pharmaceutically acceptable salt thereof; or a precursor thereof; wherein the method comprises one or more of the following steps: (a) reacting a compound of formula (II) ##STR00002##
wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I) with an oxygenating agent, a first additive and a second additive in a solvent in a fluidic network or in a batch process under thermal and/or photochemical conditions to form a compound of formula (III): ##STR00003##
wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I), (b) reacting a compound of formula (III) with a nitrogen containing nucleophile in the presence of a third additive and/or a solvent in the fluidic network or in a batch process under thermal conditions to form a compound of formula (IV): ##STR00004##
wherein R, R.sub.1, R.sub.2, R.sub.3, Y, n and m are as defined above in relation to the compound of formula (I); and/or (c) reacting a compound of formula (IV) in a fluidic network or in a batch process, optionally in the presence of a fourth additive, under thermal conditions to form a compound of formula (I); wherein one or more of steps (a), (b) and/or (c) is carried out in a fluidic network that comprises micro- and/or meso-channels having an internal dimension of from 100 μm to 2000 μm.

The invention provides a method for synthesizing a compound of formula ##STR00001##
wherein each R independently represents an optionally substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, cyano, sulfo or sulfhydryl group, in ortho, meta or para position to the cycloalkylamine moiety; R.sup.1 and R.sup.2 each independently represents a hydrogen atom, a lower alkyl group or a cycloalkyl group; R.sup.3 represents a hydrogen group, substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy group; Y represents an oxygen atom, a sulfur atom, a NH group, a NR.sup.4 group or a CH.sub.2 group; R.sup.4 represents a hydrogen atom or an alkyl, aryl or a heteroaryl group; and n and m each independently represents an integer from 1 to 5; or a pharmaceutically acceptable salt thereof; or a precursor thereof; wherein the method comprises one or more of the following steps: (a) reacting a compound of formula (II) ##STR00002##
wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I) with an oxygenating agent, a first additive and a second additive in a solvent in a fluidic network or in a batch process under thermal and/or photochemical conditions to form a compound of formula (III): ##STR00003##
wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I), (b) reacting a compound of formula (III) with a nitrogen containing nucleophile in the presence of a third additive and/or a solvent in the fluidic network or in a batch process under thermal conditions to form a compound of formula (IV): ##STR00004##
wherein R, R.sub.1, R.sub.2, R.sub.3, Y, n and m are as defined above in relation to the compound of formula (I); and/or (c) reacting a compound of formula (IV) in a fluidic network or in a batch process, optionally in the presence of a fourth additive, under thermal conditions to form a compound of formula (I); wherein one or more of steps (a), (b) and/or (c) is carried out in a fluidic network that comprises micro- and/or meso-channels having an internal dimension of from 100 μm to 2000 μm.

The invention provides compounds and methods of treating autophagy mediated diseases and disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits.

A method of preparing a compound of Formula (I) comprising reacting the compound of Formula (A) with a base and a compound of Formula (B) to yield a compound of Formula (C).

##STR00001##

A method of preparing a compound of Formula (I) comprising reacting the compound of Formula (A) with a base and a compound of Formula (B) to yield a compound of Formula (C).

##STR00001##

The present invention is directed to inhibitors of tyrosinase, pharmaceutical compositions comprising such tyrosinase inhibitors, and methods of making and using the same. Specifically, included in the present invention are compositions of matter comprised of at least one 2,4-dihydroxybenzene analog, which inhibit the activity of tyrosinase and which inhibit the overproduction of melanin.

The present invention is directed to inhibitors of tyrosinase, pharmaceutical compositions comprising such tyrosinase inhibitors, and methods of making and using the same. Specifically, included in the present invention are compositions of matter comprised of at least one 2,4-dihydroxybenzene analog, which inhibit the activity of tyrosinase and which inhibit the overproduction of melanin.