Naphthalene anti-psoriatic agents

Claim 2

A composition in a form suitable for topical administration for treating the condition of psoriasis which composition comprises a pharmaceutically acceptable, non-toxic carrier and a psoriasis relieving amount of a compound of the formula wherein: R 1 is alkoxy of one to twelve carbon atoms, alkylthio of one to twelve carbon atoms, phenoxy or phenylthio optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; R 2 is hydrogen, lower alkyl of one to six carbon atoms, phenyl or phenylalkyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; R 3 is lower alkyl of one to six carbon atoms, lower alkoxy of one to six carbon atoms, or halo and m is 0, 1 or 2 or R 3 is optionally substituted phenyl, optionally substituted phenyl lower alkyl, optionally substituted phenyl lower alkoxy, amino, lower alkylamino, lower dialk y lamino, cyano, or S(0? n R wherein R is lower alkyl of one to 3 ix carbon atoms; optionally substituted phenyl; optionally substituted phenyl lower alkyl; or heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano and the pharmaceutically acceptable acid addition salts thereof; and m is 1 and n is 0, 1 or 2; and W is alkyl of one to seven carbon atoms, phenyl or benzyl optionally substituted with one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo.

Claim 3

The composition of Claim 1 wherein m is 2.

Claim 4

The composition according to Claim 1 wherein the compound is wherein R 1 , R 2 , R 3 , and W are as defined in Claim 1 and m is 1.

Claim 5

The composition of Claim 3 wherein W is alkyl of one to seven carbon atoms.

Claim 6

The composition of Claim 3 wherein W is phenyl or benzyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo.

Claim 7

The composition of Claim 4 or 5 wherein R is alkoxy of one to twelve carbon atoms or alkylthio of one to twelve carbon atoms.

Claim 8

The composition of Claim 4 or 5 wherein R 1 is phenoxy or phenylthio optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo.

Claim 9

The composition of Claim 6 or 7 wherein R 2 is hydrogen.

Claim 10

The composition of Claim 6 or 7 wherein R 2 is lower alkyl of one to six carbon atoms, phenyl or phenylalkyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo.

Claim 11

A compound of the formula wherein R 1 , R 2 , R 3 , W, m and n are as defined in any one of claims 1 to 9, with the proviso that R 3 is not hydrogen when R 1 is methoxy or ethoxy and R 2 is hydrogen and W is methyl or R 1 is methoxy, R 2 is methyl or W is methyl.

Claim 12

A compound of Claim 10 of the formula wherein R 1 , R 2 , R 3 and W are as defined in Claim 1 0 and m is 1.

Claim 13

12 . A compound of Claim 11 wherein R 3 is selected from fluoro, chloro, bromo and cyano.

Claim 14

A process for preparation of compounds of the formula wherein: R is alkoxy of one to twelve carbon atoms, alkylthio of one to twelve carbon atoms, phenoxy or phenylthio optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; R 2 is hydrogen, lower alkyl of one to six carbon atoms, phenyl or phenylalkyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; R 3 is lower alkyl of one to six carbon atoms, lower alkoxy of one to six carbon atoms, or halo and m is 0, 1 or 2 or R 3 is optionally substituted phenyl, optionally substituted phenyl lower alkyl, optionally substituted phenyl lower alkoxy, amino, lower alkylamino, lower dialkylamino, cyano, or S(O) n R wherein R is lower alkyl of one to six carbon atoms; optionally substituted phenyl; optionally substituted phenyl lower alkyl; or heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano and the pharmaceutically acceptable acid addition salts thereof; and m is 1 and n is 0, 1 or 2; and W is alkyl of one to seven carbon atoms phenyl or benzyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; with the proviso that m is not 0 when R1 is methoxy or ethoxy, R 2 is hydrogen and W is methyl or R 1 is methoxy, R 2 is methyl or W is methyl. which comprises reacting a compound of the formula with an acid anhydride; optionally followed by (a) oxidizing a compound wherein R 3 is S(0) R wherein n is 0 or 1 and R is as defined above, to a compound wherein R 3 is S(O) n R wherein n is 1 or 2; or (b) converting the free compound of formula (I) wherein R 3 is S(O) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano, to a pharmaceutically acceptable acid addition salt; or (c) converting a pharmaceutically acceptable acid addition salt of a compound of formula (I) wherein R 3 is S(O) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano, to the free compound of formula (I) wherein R 3 is S(0) R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano; or (d) converting a pharmaceutically acceptable acid addition salt of a compound of formula (I) wherein R 3 is S(0) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano, to another pharmaceutically acceptable acid salt of a compound of formula (I) wherein R 3 is S(O) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano.

Claim 15

A process for preparation of compounds of the formula wherein: R is alkoxy of one to twelve carbon atoms, alkylthio of one to twelve carbon atoms, phenoxy or phenylthio optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; R 2 is hydrogen, lower alkyl of one to six carbon atoms, phenyl or phenylalkyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; R 3 is lower alkyl of one to six carbon atoms, lower alkoxy of one to six carbon atoms, or halo and m is 0, 1 or 2 or R 3 is optionally substituted phenyl, optionally substituted phenyl lower alkyl, optionally substituted phenyl lower alkoxy, amino, lower alkylamino, lower dialkylamino, cyano, or S(O) n R wherein R is lower alkyl of one to six carbon atoms; optionally substituted phenyl; optionally substituted phenyl lower alkyl; or heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano and the pharmaceutically acceptable acid addition salts thereof; and m is 1 and n is 0, 1 or 2; and W is alkyl of one to seven carbon atoms phenyl or benzyl optionally substituted by one or two lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo; with the proviso that m is not 0 when R1 is methoxy or ethoxy, R 2 is hydrogen and W is methyl or R 1 is methoxy, R 2 is methyl or W is methyl. which comprises reacting a compound of the formula with an acid anhydride; optionally followed by (a) oxidizing a compound wherein R 3 is S(0) R wherein n is 0 or 1 and R is as defined above, to a compound wherein R 3 is S(O) n R wherein n is 1 or 2; or (b) converting the free compound of formula (I) wherein R 3 is S(O) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano, to a pharmaceutically acceptable acid addition salt; or (c) converting a pharmaceutically acceptable acid addition salt of a compound of formula (I) wherein R 3 is S(O) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano, to the free compound of formula (I) wherein R 3 is S(0) R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano; or (d) converting a pharmaceutically acceptable acid addition salt of a compound of formula (I) wherein R 3 is S(0) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano, to another pharmaceutically acceptable acid salt of a compound of formula (I) wherein R 3 is S(O) n R wherein R is heterocyclic aryl of three to nine ring atoms containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the heterocyclic aryl is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo and cyano.