Substituted Di-t-Butylphenols

Claim 2

A process for preparing a compound of the formula comprising combining 3,5-di-t-butyl-4-hydroxybenzoyl chloride with an amine of the formula in an inert solvent, accompanied by gentle heating if necessary; wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, tri­fluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms, or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage, or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom.

Claim 3

A process for preparing a compound of the formula comprising preferentially hydrolyzing the -CN group of a compound of the formula wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-­carbon bond; an alkylene group containing one to about seven carbon atoms, or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage, or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom.

Claim 4

A process for preparing a compound of the formula comprising preferentially hydrolyzing the -CN group of a compound of the formula wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-­carbon bond; an alkylene group containing one to about seven carbon atoms, or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage, or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom.

Claim 5

A process for preparing a compound of the formula comprising combining a compound of the formula with sodium azide, ammonium chloride and lithium chloride in the presence of a polar solvent, wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido.

Claim 6

A process for preparing a compound of the formula comprising combining a compound of the formula with sodium azide, ammonium chloride and lithium chloride in the presence of a polar solvent, wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido.

Claim 7

A process for preparing a compound of the formula comprising combining 3,5-di-t-butyl-4-hydroxybenzoyl chloride and a compound of the formula in the presence of an inert solvent; wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido.

Claim 8

A process for preparing a compound of the formula comprising combining 3,5-di-t-butyl-4-hydroxybenzoyl chloride and a compound of the formula in the presence of an inert solvent; wherein R is hydrogen or lower alkyl; Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy; and B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido.

Claim 9

Use of a compound of the formula wherein x is carbonyl or N-R, and y is carbonyl or N-R; with the proviso that when x is carbonyl, y is N-R, and when x is N-R, y is carbonyl; further provided that: 1) when x is N-R, R is hydrogen, Rʹ is hydrogen, B is a carbon-carbon bond, Ar is phenyl or cyclohexyl, and E is tetrazolyl or carboxyl, with the proviso that when Ar is cyclohexyl, E is carboxyl and is alpha to the carbonyl-cyclohexyl bond; and 2) when x is carbonyl, R is hydrogen or lower alkyl, Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, Ar is phenyl, E is carboxyl, tetrazolyl, or N-methyltetrazolyl, and B is as follows: when E is carboxyl, B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms; or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; or when E is tetrazolyl or N-methyltetrazolyl, B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido; or a derivative of said compound wherein E is carboxyl, selected from the group consisting of a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, an ester of glycolamide, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt; or a derivative of said compound wherein E is tetrazolyl, selected from a pharmaceutically acceptable alkali metal or alkaline earth salt of the tetrazolyl moiety in a process for preparing a medicament for inhibiting bronchoconstriction due to an allergic response in a mammal.

Claim 10

Use of a compound of the formula wherein x is carbonyl or N-R, and y is carbonyl or N-R; with the proviso that when x is carbonyl, y is N-R, and when x is N-R, y is carbonyl; further provided that: 1) when x is N-R, R is hydrogen, Rʹ is hydrogen, B is a carbon-carbon bond, Ar is phenyl or cyclohexyl, and E is tetrazolyl or carboxyl, with the proviso that when Ar is cyclohexyl, E is carboxyl and is alpha to the carbonyl-cyclohexyl bond; and 2) when x is carbonyl, R is hydrogen or lower alkyl, Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, Ar is phenyl, E is carboxyl, tetrazolyl, or N-methyltetrazolyl, and B is as follows: when E is carboxyl, B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms; or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; or when E is tetrazolyl or N-methyltetrazolyl, B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido; or a derivative of said compound wherein E is carboxyl, selected from the group consisting of a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, an ester of glycolamide, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt; or a derivative of said compound wherein E is tetrazolyl, selected from a pharmaceutically acceptable alkali metal or alkaline earth salt of the tetrazolyl moiety in a process for preparing a medicament for inhibiting bronchoconstriction due to an allergic response in a mammal.

Claim 11

Use of a compound of the formula wherein x is carbonyl or N-R, and y is carbonyl or N-R; with the proviso that when x is carbonyl, y is N-R, and when x is N-R, y is carbonyl; further provided that: 1) when x is N-R, R is hydrogen, Rʹ is hydrogen, B is a carbon-carbon bond, Ar is phenyl or cyclohexyl, and E is tetrazolyl or carboxyl, with the proviso that when Ar is cyclohexyl, E is carboxyl and is alpha to the carbonyl-cyclohexyl bond; and 2) when x is carbonyl, R is hydrogen or lower alkyl, Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, Ar is phenyl, E is carboxyl, tetrazolyl, or N-methyltetrazolyl, and B is as follows: when E is carboxyl, B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms; or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; or when E is tetrazolyl or N-methyltetrazolyl, B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido; or a derivative of said compound wherein E is carboxyl, selected from the group consisting of a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, an ester of glycolamide, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt; or a derivative of said compound wherein E is tetrazolyl, selected from a pharmaceutically acceptable alkali metal or alkaline earth salt of the tetrazolyl moiety in a process for preparing a medicament for inhibiting leukotriene biosynethesis in a mammal

Claim 12

Use of a compound of the formula wherein x is carbonyl or N-R, and y is carbonyl or N-R; with the proviso that when x is carbonyl, y is N-R, and when x is N-R, y is carbonyl; further provided that: 1) when x is N-R, R is hydrogen, Rʹ is hydrogen, B is a carbon-carbon bond, Ar is phenyl or cyclohexyl, and E is tetrazolyl or carboxyl, with the proviso that when Ar is cyclohexyl, E is carboxyl and is alpha to the carbonyl-cyclohexyl bond; and 2) when x is carbonyl, R is hydrogen or lower alkyl, Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, Ar is phenyl, E is carboxyl, tetrazolyl, or N-methyltetrazolyl, and B is as follows: when E is carboxyl, B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms; or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; or when E is tetrazolyl or N-methyltetrazolyl, B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido; or a derivative of said compound wherein E is carboxyl, selected from the group consisting of a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, an ester of glycolamide, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt; or a derivative of said compound wherein E is tetrazolyl, selected from a pharmaceutically acceptable alkali metal or alkaline earth salt of the tetrazolyl moiety in a process for preparing a medicament for inhibiting leukotriene biosynethesis in a mammal

Claim 13

Use of a compound of the formula wherein x is carbonyl or N-R, and y is carbonyl or N-R; with the proviso that when x is carbonyl, y is N-R, and when x is N-R, y is carbonyl; further provided that: 1) when x is N-R, R is hydrogen, Rʹ is hydrogen, B is a carbon-carbon bond, Ar is phenyl or cyclohexyl, and E is tetrazolyl or carboxyl, with the proviso that when Ar is cyclohexyl, E is carboxyl and is alpha to the carbonyl-cyclohexyl bond; and 2) when x is carbonyl, R is hydrogen or lower alkyl, Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, Ar is phenyl, E is carboxyl, tetrazolyl, or N-methyltetrazolyl, and B is as follows: when E is carboxyl, B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms; or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; or when E is tetrazolyl or N-methyltetrazolyl, B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido; or a derivative of said compound wherein E is carboxyl, selected from the group consisting of a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, an ester of glycolamide, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt; or a derivative of said compound wherein E is tetrazolyl, selected from a pharmaceutically acceptable alkali metal or alkaline earth salt of the tetrazolyl moiety in a process of preparing a medicament for the therapeutic treatment of the human or animal body.

Claim 14

Use of a compound of the formula wherein x is carbonyl or N-R, and y is carbonyl or N-R; with the proviso that when x is carbonyl, y is N-R, and when x is N-R, y is carbonyl; further provided that: 1) when x is N-R, R is hydrogen, Rʹ is hydrogen, B is a carbon-carbon bond, Ar is phenyl or cyclohexyl, and E is tetrazolyl or carboxyl, with the proviso that when Ar is cyclohexyl, E is carboxyl and is alpha to the carbonyl-cyclohexyl bond; and 2) when x is carbonyl, R is hydrogen or lower alkyl, Rʹ is hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, Ar is phenyl, E is carboxyl, tetrazolyl, or N-methyltetrazolyl, and B is as follows: when E is carboxyl, B is a carbon-carbon bond; an alkylene group containing one to about seven carbon atoms; or an alkylene group containing one to about seven carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; or when E is tetrazolyl or N-methyltetrazolyl, B is a carbon-carbon bond; an alkylene group containing one to about four carbon atoms; an alkylene group containing one to about four carbon atoms and being either (a) interrupted by an ether linkage, a thioether linkage or a carbon-carbon double bond, or (b) attached to the phenyl ring by an oxygen atom or an unoxidized sulfur atom; an unoxidized sulfur atom; or carboxamido; or a derivative of said compound wherein E is carboxyl, selected from the group consisting of a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, an ester of glycolamide, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt; or a derivative of said compound wherein E is tetrazolyl, selected from a pharmaceutically acceptable alkali metal or alkaline earth salt of the tetrazolyl moiety in a process of preparing a medicament for the therapeutic treatment of the human or animal body.