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 and R 2 are the same and are lower alkoxy of one to six carbon atoms, lower alkylthio of one to six 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 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(0) 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 r 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 when R 1 and R 2 are optionally substituted phenoxy or optionally substituted phenylthio, m is 0, 1, or 2; with the proviso that when W is an alkyl group of two to seven carbon atoms and R1 and R 2 are alkoxy of two to six carbon atoms, m is 0 or 2.

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 0 or 1.

Claim 5

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

Claim 6

The composition according to Claim 4 wherein R 1 and R 2 are the same and are phenoxy or phenylthio optionally substituted by one or more lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms or halo.

Claim 7

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 8

The composition of Claim 6 wherein R and R 2 are the same and are lower alkoxy of one to six carbon atoms or lower alkylthio of one to six carbon atoms.

Claim 9

The composition of Claim 6 wherein R and R 2 are the same and are 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 10

A compound of the formula wherein: R 1 and R 2 are the same and are lower alkoxy of one to six carbon atoms, lower alkylthio of one to six 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 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 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 or 1 when R 1 and R 2 are methoxy and W is methyl.

Claim 11

A compound of the formula wherein: R 1 and R 2 are the same and are lower alkoxy of one to six carbon atoms, lower alkylthio of one to six 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 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 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 or 1 when R 1 and R 2 are methoxy and W is methyl.

Claim 12

The compound of Claim 9 wherein m is 2.

Claim 13

A compound of Claim 9 of the formula wherein R 1 , R2 R 3 and W are as defined in Claim 9 and m is 0 or 1.

Claim 14

The compound according to Claim 11 wherein R 3 is selected from the group consisting of halo, cyano, and alkoxy of one to four carbon atoms.

Claim 15

The compound according to Claim 12 wherein R is selected from the group consisting of fluoro, chloro and bromo and m is 1.

Claim 16

The compound according to Claim 11 wherein R is cyano.

Claim 17

The compound of Claim 13 wherein W is alkyl of one to seven carbon atoms.

Claim 18

A compound of Claim 15 wherein R 1 and R 2 are the same and are 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 19

A compound of Claim 16 which is 6-chloro-2,3-diphenoxy-1,4-diacetyloxynaphthalene; 6-chloro-2,3-diphenoxy-1,4-di-n-propanoyloxynaphthalene; or 6-chloro-2,3-diphenoxy-l,4-di-n-butanoyloxynaphthtalene.

Claim 20

The compound of Claim 13 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 21

The compound of Claim 18 wherein R 1 and R 2 are the same and are lower alkoxy of one to six carbon atoms or lower alkylthio of one to six carbon atoms.

Claim 22

The compound of Claim 19 which is 6-chloro-2,3-dimethoxy-l,4-dibenzoyloxynaphthalene.

Claim 23

The compound of Claim 1 8 wherein R 1 and R 2 are the same and are 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 24

The compound of Claim 21 which is 6-chloro-2,3-diphenoxy-l,4-dibenzoyloxynaphthalene.

Claim 25

A process for the preparation of compounds of formula (I) wherein: R 1 and R 2 are the same and are lower alkoxy of one to six carbon atoms, lower alkylthio of one to six 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 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, halo, cyano, or S(0) 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 n is not 0 or 1 when R 1 and R 2 are methoxy and W is methyl. which comprises reacting a compound of the formula wherein: R 1 , R2, R 3 and m are as defined above with an acid anhydride. optionally followed by (a) 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 (b) converting a pharmaceutically acceptable acid addition salt of a compound of formula (I) wherein R 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 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; or (c) 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(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.

Claim 26

A process for the preparation of compounds of formula (I) wherein: R 1 and R 2 are the same and are lower alkoxy of one to six carbon atoms, lower alkylthio of one to six 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 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, halo, cyano, or S(0) 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 n is not 0 or 1 when R 1 and R 2 are methoxy and W is methyl. which comprises reacting a compound of the formula wherein: R 1 , R2, R 3 and m are as defined above with an acid anhydride. optionally followed by (a) 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 (b) converting a pharmaceutically acceptable acid addition salt of a compound of formula (I) wherein R 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 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; or (c) 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(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.