Beecham Group Plc

Carl J Rose

Alexander C Goudie

William G Cole

David Drysdale Miller

Anthony William Lake

Anthony T Ainsworth

4-(6'-Methoxy-2'-naphthyl) butan-2-one is described as having anti-inflammatory activity and an improved therapeutic ratio.

Aromatic compounds

Anti-inflammatory compositions are prepared which comprise a therapeutically effective amount of a compound of the formula ##STR1## wherein X is CO or CHOH; Y is CO; the dotted line represents a double bond which is present or absent; R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, methoxyl, hydroxyl, acetoxyl, nitro or amino; R.sub.3 is alkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, alkenyl of 3 to 8 carbon atoms, cycloalkenyl of 5 to 8 carbon atoms or phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, methoxyl, ethoxyl, benzyloyl, hydroxyl, acetoxyl, trifluoromethyl, nitro, amino, acetyl, methylthiol, methylsulphonyl, methylamino and dimethylamino. Compounds of formula I above are also novel.

Pharmaceutical compositions

The present invention relates to a process for the preparation of 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl)butan-2-one and to certain compounds for use in that process. British patent specification No. 1,474,377 discloses inter alia that 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl)butan-2-one possesses useful anti-inflammatory activity. A particularly favored process has now been discovered that can be used to produce 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl)butan-2-one in particularly good yield. The present invention provides a process for the preparation of 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl)butan-2-one which process comprises the hydrogenation of a compound of the formula (I): ##STR1## wherein Ar is a 6-methoxy-2-naphthyl group; X and Y are each hydrogen atoms or together represent a second bond between the carbon atoms to which they are attached; and R is a group such that --CO.sub.2 R represents an ester group convertible by hydrogenation to a CO.sub.2 H group.

Chemical process for the preparation of 4-(6.sup.1 -methoxy-2.sup.1

The present invention relates to a process for the preparation of 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl)butan-2-one and to certain compounds for use in that process. British Pat. Spec. No. 1,474,377 discloses inter alia that 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl) butan-2-one possesses useful anti-inflammatory activity. A particularly favored process has now been discovered that can be used to produce 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl) butan-2-one in particularly good yield. The present invention provides a process for the preparation of 4-(6.sup.1 -methoxy-2.sup.1 -naphthyl)butan-2-one which process comprises the hydrogenation of a compound of the formula (I): ##STR1## wherein Ar is a 6-methoxy-2-naphthyl group; X and Y are each hydrogen atoms or together represent a second bond between the carbon atoms to which they are attached; and R is a group such that --CO.sub.2 R represents an ester group convertible by hydrogenation to a CO.sub.2 H group.

Chemical Process

Anti-inflammatory compositions are prepared which comprise a therapeutically effective effective amount of a compound of the formula ##STR1## wherein X is CO; Y is an oxygen atom; the dotted line represents a double bond which is present or absent; R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen; and R.sub.3 is phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, methoxyl, ethoxyl, benzyloxyl, hydroxyl, acetoxyl, trifluoromethyl, nitro, amino, acetyl, methylthiol, methylsulphonyl, methylamino and dimethylamino; in combination with a pharmaceutically acceptable carrier. Methods of treating inflammation utilizing the compounds of formula (I) are part of the present invention together with the compounds themselves of the above formula.

Anti-inflammatory compositions are prepared which comprise a therapeutically effective amount of a compound of the formula ##STR1## wherein X is CO or CHOH; Y is CO, an oxygen atom or a direct bond; the dotted line represents a double bond which is optionally present when Y is an oxygen atom or a direct bond; R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, methoxyl, hydroxyl, acetoxyl, nitro or amino; R.sub.3 is alkyl of 3-8 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 3-8 carbon atoms, cycloalkenyl of 5-8 carbon atoms, phenyl or phenyl substituted by 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, methoxyl, ethoxyl, benzyloxyl, hydroxyl, acetoxyl, trifluoromethyl, nitro, amino, acetyl, methylthiol, methylsulphonyl, methylamino and dimethylamino. Compounds of the above formula are novel except that R.sub.1 must be methyl: when R.sub.3 -- Y is a 4-phenyl group, R.sub.2 is hydrogen and X is CO; when R.sub.3 -- Y is a 4-benzyl group and R.sub.2 is hydrogen; and also when R.sub.3 -- Y is a 3-benzoyl group, R.sub.2 is hydrogen and X is CO.

Phenyl butanones

Naphthalene derivatives having anti-inflammatory activity

Compounds of the formula (II): ##SPC1## wherein R.sub.1 is an aliphatic moiety of 1-12 carbon atoms, a cycloaliphatic moiety of 3-7 carbon atoms or said aliphatic moiety or said cycloaliphatic moiety substituted by halogen, carboxylic acid, esterified carboxylic acid, carboxamide, nitro, hydroxyl, etherified hydroxyl, acylated hydroxyl, amino, alkylamino, dialkylamino or acylated amino: R.sub.2 is a hydrocarbon of 1-7 carbon atoms: R.sub.3 is amino, lower alkylamino, di-lower alkylamino, anilino or lower alkoxyl; R.sub.4 is hydrogen, R.sub.5 or CO.R.sub.5 wherein R.sub.5 is a hydrocarbon of 1-7 carbon atoms, are useful for their anti-inflammatory activity.

Growing community of inventors

London, United Kingdom

Carl J Rose