Arylhydroxamates

Claim 2

A compound having the structure wherein R 1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, aralkyl, or (CH 2 ) n C-X wherein n is 1 to 4 and X is hydroxy, alkoxy, amino, C 1 -C 4 -alkylamino or C 1 -C 4 - dialkylamino; R 2 is hydrogen or lower alkyl; and R 3 is C 1 -C 20 alkyl, C 3 -C 20 alkenyl, aryl, aryl-alkyl, cycloalkyl, aryl-alkenyl, lower alkoxy, lower alkenyloxy, aryl-alkoxy, aryloxy or cycloalkyloxy, but when R 3 is aryl, R 1 is other than H, including pharmaceutically acceptable monobasic and dibasic salts thereof.

Claim 3

The compound as defined in Claim 1 O wherein R is alkyl or -(CH 2 ) n C-X.

Claim 4

The compound as defined in Claim 1 wherein R 1 is alkyl, R 2 is H and R 3 is alkyl.

Claim 5

The compound as defined in Claim 1 wherein R 1 is phenyl, phenylalkyl, phenylalkenyl, C 1 to C 20 alkyl or C 3 to C 20 alkenyl.

Claim 6

The compound as defined in Claim 1 having the name 4-decyl-N-hydroxy-N-methylbenzamide.

Claim 7

The compound as defined in Claim 1 having the name (Z)-4-[[4-(1-decenyl)benzoyl]-hydroxyamino]butanoic acid.

Claim 8

The compound as defined in Claim 1 having the name (Z)-4-[[4-(1-decenyl)benzoyl]-hydroxyamino]butanoic acid including all stereoisomers thereof.

Claim 9

The compound as defined in Claim 1 having the name 4-[(3-decylbenzoyl)hydroxyamino]-butanoic acid.

Claim 10

The compound as defined in Claim 1 having the name 4-[(2-decylbenzoyl)hydroxyamino]-butanoic acid or its dilithium salt.

Claim 11

The compound as defined in Claim 1 having the name 4-[(4-decylbenzoyl)hydroxyamino]-butanoic acid, ethyl ester.

Claim 12

The compound as defined in Claim 1 having the name (Z)-4-[[4-(1-decenyl)benzoyl]-methoxyamino]butanoic acid or its dicyclohexylamine salt(l:l) including all stereoisomers thereof.

Claim 13

The compound as defined in Claim 1 having the name N-(4-amino-4-oxobutyl)-4-decyl-N-hydroxybenzamide.

Claim 14

The compound as defined in Claim 1 having the name 4-[(4-decylbenzoyl)hydroxyamino]-butanoic acid.

Claim 15

The compound as defined in Claim 1 having the name 5-[(4-decylbenzoyl)hydroxyamino]-pentanoic acid.

Claim 16

The compound as defined in Claim 1 having the name (4-decyl-N-hydroxybenzamido)-acetic acid.

Claim 17

The compound as defined in Claim 1 having the name 4-[[3-(1-decenyl)benzoyl]hydroxy- amino]butanoic acid.

Claim 18

The compound as defined in Claim 1 having the name (Z)-4-(1-decenyl)-N-hydroxybenzamide, including all stereoisomers thereof.

Claim 19

18 ' . The compound as defined in Claim 1 having the name N-hydroxy-N-methyl-4-(4-phenylbutyl)benzamide.

Claim 20

The compound as defined in Claim 1 having the name N-hydroxy-N-methyl[1,1'-biphenylyl]-4-carboxamide.

Claim 21

The compound as defined in Claim 1 having the name N-hydroxy-N-methyl-4-(4-phenylbuten-l-yl)benzamide.

Claim 22

The compound as defined in Claim 1 having the name N-hydroxy-4-(4-phenylbutyl)-N-(phenylmethyl)benzamide.

Claim 23

The compound as defined in Claim 1 having the name N-hydroxy-N-phenyl-4-(4-phenylbutyl)benzamide.

Claim 24

The compound as defined in Claim 1 having the name N-(1,1-dimethylethyl)-N-hydroxy[1,1'-biphenylyl]-4-carboxamide.

Claim 25

The compound as defined in Claim 1 having the name N-cyclohexyl-N-hydroxy[1,1'-biphenylyl]-4-carboxamide.

Claim 26

The compound as defined in Claim 1 having the name N-hydroxy-N-methyl-4-pentylbenzamide.

Claim 27

The compound as defined in Claim 1 having the name 4-heptyl-N-hydroxy-N-methylbenzamide.

Claim 28

The compound as defined in Claim 1 having the name 4-(cyclohexyloxy)-N-hydroxy-N-methylbenzamide.

Claim 29

The compound as defined in Claim 1 having the name N-hydroxy-N-methyl-4-(3-phenyl- propoxy)benzamide.

Claim 30

The compound as defined in Claim 1 having the name N-(1,1-dimethylethyl)-N-hydroxy-4-(4-phenylbutyl)benzamide.

Claim 31

A process for preparing compounds having the formula wherein R 1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, aralkyl, or wherein n is 1 to 4 and X is hydroxy, alkoxy, amino, C 1 -C 4 -alkylamino or C 1 -C 4 - dialkylamino; R 2 is hydrogen or lower alkyl; and R 3 is C 1 -C 20 alkyl, C3-C20 alkenyl, aryl, aryl-alkyl, cycloalkyl, aryl-alkenyl, lower alkoxy, lower alkenyloxy, aryl-alkoxy, aryloxy or c y cloalk y lox y, but when R 3 is aryl, R 1 is other than H, including pharmaceutically acceptable monobasic and dibasic salts thereof which comprises A) when R 1 is lower alkyl, aryl, cycloalkyl, aralkyl or alkoxy, R 2 is hydrogen and R 3 is C 1 -C 20 alkyl, arylalkyl, cycloalkyloxy, lower alkoxy or aryloxy reacting a compound having the formula wherein R 3a is C 3- C 20 alkenyl, alkenyloxy, aryloxy, cycloalkyloxy or arylalkenyl with a compound having the formula C Hal-R 1a wherein Hal is I, Br, or Cl and R 1a is the same as R 1 wherein R 1 is lower alkyl, aryl, cycloalkyl, aralkyl or alkoxy to yield a compound having the formula and reacting compound III with hydrogen in the presence of palladium hydroxide on a carbon catalyst to form compounds of formula wherein R 1 , R 2 and R 3 are as defined in this subsection A and when B ) R 1 is (CH 2 ) ; in formula I, reacting a compound of formula IV when R 1 is (CH 2 ) n C0 2 alkyl with an alkali metal hydroxide in an organic solvent and when C) R 1 is when X is OH or alkoxy reacting a compound of the formula with hydrogen in the presence of palladium hydroxide on a carbon catalyst to form the compound of the formula and hydrolyzing the compound of formula IVa to the corresponding acid and when D) R is C 3 -C 20 alkenyl, arylalkenyl or lower alkenyl removing the tetrahydropyranyl or methoxymethyl protecting group from the compounds of formula III or IIIb with acetic acid or when the protecting group is methylthiomethyl, treating the compounds of formula III or IIIb with Cu0-CuCl 2 in aqueous acetone and and X is amino, alkylamino or dialkylamino reacting a compound of the formula with ammonium hydroxide when X is amino or with an alkylamine or dialkylamine when X is alkylamino or dialkylamino in the presence of an activating agent, organic base and organic solvent and removing a benzyl protecting group to form the compound wherein R 3 is alkyl and X is amino or alkylamino and removing a tetrahydropyranal protecting group wherein R 3 is alkenyl.

Claim 32

A process for preparing compounds having the formula wherein R 1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, aralkyl, or wherein n is 1 to 4 and X is hydroxy, alkoxy, amino, C 1 -C 4 -alkylamino or C 1 -C 4 - dialkylamino; R 2 is hydrogen or lower alkyl; and R 3 is C 1 -C 20 alkyl, C3-C20 alkenyl, aryl, aryl-alkyl, cycloalkyl, aryl-alkenyl, lower alkoxy, lower alkenyloxy, aryl-alkoxy, aryloxy or c y cloalk y lox y, but when R 3 is aryl, R 1 is other than H, including pharmaceutically acceptable monobasic and dibasic salts thereof which comprises A) when R 1 is lower alkyl, aryl, cycloalkyl, aralkyl or alkoxy, R 2 is hydrogen and R 3 is C 1 -C 20 alkyl, arylalkyl, cycloalkyloxy, lower alkoxy or aryloxy reacting a compound having the formula wherein R 3a is C 3- C 20 alkenyl, alkenyloxy, aryloxy, cycloalkyloxy or arylalkenyl with a compound having the formula C Hal-R 1a wherein Hal is I, Br, or Cl and R 1a is the same as R 1 wherein R 1 is lower alkyl, aryl, cycloalkyl, aralkyl or alkoxy to yield a compound having the formula and reacting compound III with hydrogen in the presence of palladium hydroxide on a carbon catalyst to form compounds of formula wherein R 1 , R 2 and R 3 are as defined in this subsection A and when B ) R 1 is (CH 2 ) ; in formula I, reacting a compound of formula IV when R 1 is (CH 2 ) n C0 2 alkyl with an alkali metal hydroxide in an organic solvent and when C) R 1 is when X is OH or alkoxy reacting a compound of the formula with hydrogen in the presence of palladium hydroxide on a carbon catalyst to form the compound of the formula and hydrolyzing the compound of formula IVa to the corresponding acid and when D) R is C 3 -C 20 alkenyl, arylalkenyl or lower alkenyl removing the tetrahydropyranyl or methoxymethyl protecting group from the compounds of formula III or IIIb with acetic acid or when the protecting group is methylthiomethyl, treating the compounds of formula III or IIIb with Cu0-CuCl 2 in aqueous acetone and and X is amino, alkylamino or dialkylamino reacting a compound of the formula with ammonium hydroxide when X is amino or with an alkylamine or dialkylamine when X is alkylamino or dialkylamino in the presence of an activating agent, organic base and organic solvent and removing a benzyl protecting group to form the compound wherein R 3 is alkyl and X is amino or alkylamino and removing a tetrahydropyranal protecting group wherein R 3 is alkenyl.

Claim 33

A process according to Claim 30 wherein R 1 is hydrogen prepared by removing the protecting group of compound II in the presence of an acid catalyst to form the compound wherein R 2 is hydrogen and R 3 is C 3 -C 20'

Claim 34

A process according to Claim 30 wherein R 2 is alkyl and R 3 is C 1 -C 20 alkyl or aryl-alkyl prepared by reacting a compound having the formula with halide C to form a compound of the formula wherein R 3a is C 3- C 20 alkenyl or aryl-alkenyl and where compound VI is reduced to form the corresponding compound wherein R 3 is C 3 -C 20 alkyl.

Claim 35

A process for preparing compounds of formula I wherein R 1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, aralkyl, or wherein is to 4 X is hydroxy, alkoxy, amino, C 1 -C 4 -alkylamino or C 1 -C 4 - dialkylamino; R 2 is hydrogen or lower alkyl; and R 3 is C 1 -C 20 alkyl, C 3 -C 20 alkenyl, aryl, aryl-alkyl, cycloalkyl, aryl-alkenyl, lower alkoxy, lower alkenyloxy, aryl-alkoxy, aryloxy or cycloalkyloxy, but when R 3 is aryl, R 1 is other than H, including pharmaceutically acceptable monobasic and dibasic salts thereof which comprises A) wherein R 2 is hydrogen reacting a compound with a compound of the formula to yield the compounds of the formula and B) when R 2 is alkyl reacting compounds of formula VII with a base and an alkyl halide.

Claim 36

A process for preparing compounds of formula I wherein R 1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkyl, aralkyl, or wherein is to 4 X is hydroxy, alkoxy, amino, C 1 -C 4 -alkylamino or C 1 -C 4 - dialkylamino; R 2 is hydrogen or lower alkyl; and R 3 is C 1 -C 20 alkyl, C 3 -C 20 alkenyl, aryl, aryl-alkyl, cycloalkyl, aryl-alkenyl, lower alkoxy, lower alkenyloxy, aryl-alkoxy, aryloxy or cycloalkyloxy, but when R 3 is aryl, R 1 is other than H, including pharmaceutically acceptable monobasic and dibasic salts thereof which comprises A) wherein R 2 is hydrogen reacting a compound with a compound of the formula to yield the compounds of the formula and B) when R 2 is alkyl reacting compounds of formula VII with a base and an alkyl halide.

Claim 37

A process for preparing compounds of formula I which comprises reacting a compound of with an amine salt of the formula to form a compound of the formula esterifying compound X and then deprotecting followed by hydrolysis to yield

Claim 38

A process for preparing compounds of formula I which comprises reacting a compound of with an amine salt of the formula to form a compound of the formula esterifying compound X and then deprotecting followed by hydrolysis to yield

Claim 39

A process according to Claims 30, 31 and 32 wherein the protecting group is benzyl, tetrahydropyranyl, methylthiomethyl or methoxymethyl.

Claim 40

A process according to Claim 33 wherein R 3 is aryl or cycloalkyl.

Claim 41

A process according to Claims 30, 31 and 32 wherein the reaction temperature is from 50° to 110°C.