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US 4,906,662 AGranted
Phenol derivatives, their preparation and the use thereof
AssigneeOtsuka Pharmaceutical Factory, Inc.
InventorsKinji Hashimoto, Kiyoto Goto, Ken-ichi Kanai, Yoshiaki Tsuda
Life of this patent
Estimating the term…
Abstract
Disclosed are phenol derivatives of the formula ##STR1## wherein R.sup.1 is a substituted phenyl group, R.sup.2 and R.sup.3 are C.sub.1 -C.sub.6 alkyl group and of the formula ##STR2## wherein R.sup.8, R.sup.9 and R.sup.10 are C.sub.1 -C.sub.6 alkyl and the like and A is H, C.sub.1 -C.sub.6 alkylsulfonyl and the like substituents. These compounds and some related compounds have anti-inflammatory activity and lipoxygenase inhibitory activity.
Claims11
A compound selected from the group consisting of:
- (1) a compound of the formula ##STR105## wherein R.sup.1 represents a phenyl group having 1-3 substituents selected from the class consisting of cyano group, carbamoyl group, nitro group, sulfamoyl group, hydroxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 -alkyoxycarbonyl-Cl-C.sub.6 alkyl group, carboxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 haloalkyl group, C.sub.1 -C.sub.6 alkylthio group, phenylthio group ad C.sub.1 -C.sub.6 alkysulfonyl group, and a salt thereof;
- (2) a compound of the formula ##STR106## wherein R.sup.2 and R.sup.3 are as defined above and R.sup.4 represents a tri(C.sub.1 -C.sub.6 alkoxy) phenyl group, dihalophenyl group or a group of the formula ##STR107## wherein R.sup.5 is hydroxy-C.sub.1 -C.sub.6 alkyl or carboxyl-C.sub.1 -C.sub.6 alkyl group and R.sub.6 is hydroxyl group, halogen atom or C.sub.1 -C.sub.6 alkyl group, and a salt thereof;
- (3) a compound of the formula ##STR108## wherein R.sup.7 represents a phenyl group having a substituent selected from the class consisting of fluoro, 2-chloro, C.sub.1 -C.sub.6 alkoxy, carboxyl, n-butyl, amino, hydroxyl and N,N-di(C.sub.1 -C.sub.6 alkyl) amino groups, or R.sup.7 represents a phenyl group having carboxyl and C.sub.1 -C.sub.6 alkyl groups as the substituent, a phenyl group having carboxyl and hydroxyl groups as the substituent, a phenyl group having carboxyl group and halogen atom as the substituent, a phenyl group having hydroxyl group and halogen atom as the substituent, or a phenyl group having C.sub.1 -C.sub.6 alkoxy and hydroxy group as the substituent, and a salt thereof;
- and
- (4) a compound of the formula ##STR109## wherein R.sup.8 and R.sup.9 are the same and each represent tertbutyl group, R.sup.10 represents hydrogen atom or C.sub.1 -C.sub.6 alkyl group, or R.sup.9 and R.sup.10, taken together with the phenyl ring to which they are attached, form a fused ring of the formula ##STR110## and A represents:
- a hydrogen atom,
- C.sub.1 -C.sub.6 alkylsulfonyl group,
- C.sub.1 -C.sub.6 alkoxycarbonyl group,
- piperidinocarbonyl group,
- phenyl-C.sub.1 -C.sub.6 alkylcarbamoyl group,
- C.sub.1 -C.sub.12 alkylcarbamoyl group,
- C.sub.3 -C.sub.8 cycloalkylcarbamoyl group,
- C.sub.2 -C.sub.6 alkenyl group having a substituent selected from the class consisting of C.sub.1 -C.sub.6 alkoxy-carbonyl, carboxyl, C.sub.1 -C.sub.6 acyl, C.sub.1 -C.sub.6 alkylcarbamoyl and C.sub.3 -C.sub.8 cycloalkylcarbamoyl groups,
- C.sub.1 -C.sub.6 alkyl group having a substituent selected from the class consisting of C.sub.3 -C.sub.8 cycloalkyl-carbamoyl, C.sub.1 -C.sub.6 alkylcarbamoyl, phenyl-C.sub.1 -C.sub.6 alkyl-carbamoyl, piperidinocarbonyl, morpholinocarbonyl and hydrazinocarbonyl groups,
- carboxy-C.sub.1 -C.sub.6 alkyl group,
- C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group,
- C.sub.1 -C.sub.6 alkyl group,
- carboxyl group,
- C.sub.1 -C.sub.6 alkoxy group,
- halogen atom, or
- a group --NR.sup.11 R.sup.12, wherein R.sup.11 is hydrogen atom or C.sub.1 -C.sub.6 alkyl group, and R.sup.12 is C.sub.1 -C.sub.6 alkyl group having a phenyl group as the substituent, phenyl group, benzoyl group which may optionally have C.sub.1 -C.sub.6 alkyl group as the substituent, C.sub.1 -C.sub.6 acyl group which may optionally have C.sub.1 -C.sub.6 alkoxycarbonyl group as the substituent, C.sub.1 -C.sub.6 alkylsulfonyl group or phenylsulfonyl group;
- with the proviso that when R.sup.10 is hydrogen atom, the group A does not represent hydrogen atom, carboxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkyl group, carboxyl group, C.sub.1 -C.sub.6 alkoxy group or halogen atom;
- and a salt thereof.
20 more elements
A method for treating inflammation in a patient comprising administering to said patient an effective amount of at least one compound selected from the group consisting of:
- (a) a compound of the formula ##STR111## wherein R.sup.1a represents unsubstituted phenyl group or a phenyl group having 1-3 substituents selected from the class consisting of cyano group, carbamoyl group, nitro group, sulfamoyl group, hydroxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group, carboxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 haloalkyl group, C.sub.1 -C.sub.6 acyl group, C.sub.1 -C.sub.6 alkylthio group, phenylthio group, C.sub.1 -C.sub.6 alkylsulfonyl group, amino group, C.sub.1 -C.sub.6 alkoxy group, hydroxyl group, C.sub.1 -C.sub.6 alkyl group and halogen atom, and R.sup.2 and R.sup.3 are the same or different and represent C.sub.1 -C.sub.6 alkyl group and a salt thereof;
- and
- (b) a compound of the formula ##STR112## wherein R.sup.8, R.sup.9 and R.sup.10 are as defined in the formula (4) above, and Aa represents:
- a hydrogen atom,
- C.sub.1 -C.sub.6 alkylsulfonyl group,
- C.sub.1 -C.sub.6 alkoxycarbonyl group,
- piperidinocarbonyl group,
- phenyl-C.sub.1 -C.sub.6 alkylcarbamoyl group,
- C.sub.1 -C.sub.12 alkylcarbamoyl group,
- C.sub.3 -C.sub.8 cycloalkylcarbamoyl group,
- C.sub.2 -C.sub.6 alkenyl group having a substituent selected from the class consisting of C.sub.1 -C.sub.6 alkoxycarbonyl, carboxyl, C.sub.1 -C.sub.6 acyl, C.sub.1 -C.sub.6 alkylcarbamoyl and C.sub.3 -C.sub.8 cycloalkylcarbamoyl groups,
- C.sub.1 -C.sub.6 alkyl group having a substituent selected from the class consisting of C.sub.3 -C.sub.8 cycloalkylcarbamoyl, C.sub.1 -C.sub.6 alkylcarbamoyl, phenyl-C.sub.1 -C.sub.6 alkylcarbamoyl, piperidinocarbonyl, morpholinocarbonyl and hydrazinocarbonyl groups,
- carboxy-C.sub.1 -C.sub.6 alkyl group,
- C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group,
- C.sub.1 -C.sub.6 alkyl group,
- carboxy group,
- C.sub.1 14 C.sub.6 alkoxy group,
- halogen atom, or
- a group --NR.sup.11 R.sup.12a (wherein R.sup.11 is hydrogen atom or C.sub.1 -C.sub.6 alkyl group, and R.sup.12a is C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkyl group having a phenyl group as the substituent, phenyl group, benzoyl group which may optionally have C.sub.1 -C.sub.6 alkyl as the substituent, C.sub.1 -C.sub.6 acyl group which may optionally have C.sub.1 -C.sub.6 alkoxycarbonyl group as the substituent, C.sub.1 -C.sub.6 alkylsulfonyl group or phenylsulfonyl group);
- with the proviso that when R.sup.10 is hydrogen atom, the group Aa does not represent hydrogen atom, carboxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkyl group, carboxyl group, C.sub.1 -C.sub.6 alkoxy group or halogen atom, and a salt thereof.
17 more elements
A method for inhibiting lipoxygenase in a patient comprising administering to said patient an effective amount of at least one compound selected from the group consisting of:
- (a) a compound of the formula ##STR113## wherein R.sup.1b represents unsubstituted phenyl group or a phenyl group having 1-3 substituents selected from the class consisting of carboxyl group, cyano group, carbamoyl group, nitro group, sulfamoyl group, hydroxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkoxycarbonyl C.sub.1 -C.sub.6 -alkyl group, carboxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 haloalkyl group, C.sub.1 -C.sub.6 acyl group, C.sub.1 -C.sub.6 alkylthio group, phenylthio group, C.sub.1 -C.sub.6 alkylsulfonyl group, amino group, C.sub.1 -C.sub.6 alkoxy group, hydroxyl group, C.sub.1 -C.sub.6 alkyl group and halogen atom, and R.sup.2 and R.sup.3 each are the same or different and represent C.sub.1 -C.sub.6 alkyl group and a salt thereof;
- and
- (b) a compound of the formula ##STR114## wherein R.sup.8, R.sup.9 and R.sup.10 are as defined in the formula (4) above, and Aa represents:
- a hydrogen atom,
- C.sub.1 -C.sub.6 alkylsulfonyl group,
- C.sub.1 -C.sub.6 alkoxycarbonyl group,
- piperidinocarbonyl group,
- phenyl-C.sub.1 -C.sub.6 alkylcarbamoyl group,
- C.sub.1 -C.sub.12 alkylcarbamoyl group,
- C.sub.3 -C.sub.8 cycloalkylcarbamoyl group,
- C.sub.2 -C.sub.6 alkenyl group having a substituent selected from the class consisting of C.sub.1 -C.sub.6 alkoxycarbonyl, carboxyl, C.sub.1 -C.sub.6 acyl, C.sub.1 -C.sub.6 alkylcarbamoyl and C.sub.3 -C.sub.8 cycloalkylcarbamoyl groups,
- C.sub.1 -C.sub.6 alkyl group having a substituent selected from the class consisting of C.sub.3 -C.sub.8 cycloalkylcarbamoyl, C.sub.1 -C.sub.6 alkylcarbamoyl, phenyl-C.sub.1 -C.sub.6 alkylcarbamoyl, piperidinocarbonyl, morpholinocarbonyl and hydrazinocarbonyl groups,
- carboxy-C.sub.1 -C.sub.6 alkyl group,
- C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group,
- C.sub.1 -C.sub.6 alkyl group,
- carboxyl group,
- C.sub.1 -C.sub.6 alkoxy group,
- halogen atom, or
- a group --NR.sup.11 R.sup.12a (wherein R.sup.11 is hydrogen atom or C.sub.1 -C.sub.6 alkyl group, and R.sup.12a is C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkyl group having a phenyl group as the substituent, phenyl group, benzoyl group which may optionally have C.sub.1 -C.sub.6 alkyl group as the substituent, C.sub.1 -C.sub.6 acyl group which may optionally have C.sub.1 -C.sub.6 alkoxycarbonyl group as the substituent, C.sub.1 -C.sub.6 alkylsulfonyl group or phenylsulfonyl group);
- with the proviso that when R.sup.10 is hydrogen atom, the group Aa does not represent hydrogen atom, carboxy-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkoxycarbonyl-C.sub.1 -C.sub.6 alkyl group, C.sub.1 -C.sub.6 alkyl group, carboxyl group, C.sub.1 -C.sub.6 alkoxy group or halogen atom, and a salt thereof.
17 more elements
Dependencies are inferred from the claim text.