Substituted phosphonic acids and derivatives useful in treating bone wasting diseases

Claim 1

A compound represented by the general formula I: ##STR7## wherein R 1 and R 2 are the same or different and are selected from any of H, C 1 -C 4 alkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkyl NR 3 R 4 wherein R 3 and R 4 are the same or different and selected from either C 1 -C 4 alkyl or H, or aralkyl wherein the alkyl portion has 1 carbon atom and the aryl portion is optionally independently substituted with any of halo, nitro, C 1 -C 2 alkyl or methylsulfonyl; wherein AR is selected from any of aryl or substituted aryl wherein the substituents are independently selected from any of C 1 -C 4 alkoxy, C 1 -C 8 alkyl, cyano, halo, hydroxy, nitro, phenoxy, phenyl, or trifluoromethyl; wherein R 5 is independently selected from any of carboxyl, C 3 -C 7 cycloalkyl, aryl, COaryl, COalkyl, COcycloalkyl, or aralkyl, wherein aryl is phenyl, naphthyl or substituted aryl wherein the substituents are independently selected from any of amino, acylamino, C 1 -C 4 alkoxy, C 1 -C 8 alkyl, carboxy, C 1 -C 4 carboalkoxy, cyano, halo, hydroxy, methylsulfonamido, methylsulfonyl, phenylsulfonamido, phenylsulfonyl, nitro, phenoxy, phenyl or trifluoromethyl; wherein R 6 is selected from any of hydrogen, carboxy, carboalkoxy, C 3 -C 7 cycloalkyl, aryl, COaryl, COalkyl, COcycloalky (C 3 -C 7 ), or aralkyl, where aryl is phenyl, naphthyl or substituted aryl wherein the substituents are independently selected from any of amino, acylamino, C 1 -C 4 alkoxy, C 1 -C 8 alkyl, carboxy, C 1 -C 4 carboalkoxy, cyano, halo, hydroxy, methylsulfonamido, methylsulfonyl, phenylsulfonamido, phenylsulfonyl, nitro, phenoxy, phenyl, or trifluoromethyl; or the optical isomers, enantiomers, diastereomers, or pharmaceutically acceptable salts thereof: with the proviso the following compounds are excluded from the definition of formula I; a) R 1 R 2 are alkyl, AR is phenyl or phenyl substituted by halo, alkoxy, alkyl, trifluoromethyl, R 5 is carboxyl, phenyl, 1-naphthyl, substituted phenyl, 1-(4-NO 2 )-naphthyl, cyclopentyl or cyclohexyl, (CH2) n Aryl where aryl is phenyl and n=1 or 2, and R 6 =hydrogen and b) R 1 R 2 is hydrogen, AR is phenyl, R 5 is carboxyl, phenyl or (CH2)nAryl where Aryl is phenyl and n=1 or 2, and R 6 is hydrogen.

Claim 18

A method of treating a bone wasting disease comprising administering the compound represented by the general formula I: ##STR9## wherein R 1 and R 2 are the same or different and are selected from any of H, C 1 -C 4 alkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkyl NR 3 R 4 wherein R 3 and R 4 are the same or different and selected from either C 1 -C 4 alkyl or H, or aralkyl wherein the alkyl portion has 1 carbon atom and the aryl portion is optionally independently substituted with any of halo, nitro, C 1 -C 2 alkyl or methylsulfonyl; wherein AR is selected from any of aryl or substituted aryl wherein the substituents are independently selected from any of C 1 -C 4 alkoxy, C 1 -C 8 alkyl, cyano, halo, hydroxy, nitro, phenoxy, phenyl, or trifluoromethyl; wherein R 5 is independently selected from any of carboxyl, C 3 -C 7 cycloalkyl, aryl, COaryl, COalkyl, COcycloalkyl, or aralkyl, wherein aryl is phenyl, naphthyl or substituted aryl wherein the substituents are independently selected from any of amino, acylamino, C 1 -C 4 alkoxy, C 1 -C 8 alkyl, carboxy, C 1 -C 4 carboalkoxy, cyano, halo, hydroxy, methylsulfonamido, methylsulfonyl, phenylsulfonamido, phenylsulfonyl, nitro, phenoxy, phenyl or trifluoromethyl; wherein R 6 is selected from any of hydrogen, carboxy, carboalkoxy, C 3 -C 7 cycloalkyl, aryl, COaryl, COalkyl, COcycloalky (C 3 -C 7 ), or aralkyl, where aryl is phenyl, naphthyl or substituted aryl wherein the substituents are independently selected from any of amino, acylamino, C 1 -C 4 alkoxy, C 1 -C 8 alkyl, carboxy, C 1 -C 4 carboalkoxy, cyano, halo, hydroxy, methylsulfonamido, methylsulfonyl, phenylsulfonamido, phenylsulfonyl, nitro, phenoxy, phenyl, or trifluoromethyl; or the optical isomers, enantiomers, diastereomers, or pharmaceutically acceptable salts thereof, to an animal afflicted with said disease in an amount effective for treating the bone wasting disease.

Claim 19

A method of treating a bone wasting disease comprising administering the compound represented by the general formula I: ##STR9## wherein R 1 and R 2 are the same or different and are selected from any of H, C 1 -C 4 alkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkyl NR 3 R 4 wherein R 3 and R 4 are the same or different and selected from either C 1 -C 4 alkyl or H, or aralkyl wherein the alkyl portion has 1 carbon atom and the aryl portion is optionally independently substituted with any of halo, nitro, C 1 -C 2 alkyl or methylsulfonyl; wherein AR is selected from any of aryl or substituted aryl wherein the substituents are independently selected from any of C 1 -C 4 alkoxy, C 1 -C 8 alkyl, cyano, halo, hydroxy, nitro, phenoxy, phenyl, or trifluoromethyl; wherein R 5 is independently selected from any of carboxyl, C 3 -C 7 cycloalkyl, aryl, COaryl, COalkyl, COcycloalkyl, or aralkyl, wherein aryl is phenyl, naphthyl or substituted aryl wherein the substituents are independently selected from any of amino, acylamino, C 1 -C 4 alkoxy, C 1 -C 8 alkyl, carboxy, C 1 -C 4 carboalkoxy, cyano, halo, hydroxy, methylsulfonamido, methylsulfonyl, phenylsulfonamido, phenylsulfonyl, nitro, phenoxy, phenyl or trifluoromethyl; wherein R 6 is selected from any of hydrogen, carboxy, carboalkoxy, C 3 -C 7 cycloalkyl, aryl, COaryl, COalkyl, COcycloalky (C 3 -C 7 ), or aralkyl, where aryl is phenyl, naphthyl or substituted aryl wherein the substituents are independently selected from any of amino, acylamino, C 1 -C 4 alkoxy, C 1 -C 8 alkyl, carboxy, C 1 -C 4 carboalkoxy, cyano, halo, hydroxy, methylsulfonamido, methylsulfonyl, phenylsulfonamido, phenylsulfonyl, nitro, phenoxy, phenyl, or trifluoromethyl; or the optical isomers, enantiomers, diastereomers, or pharmaceutically acceptable salts thereof, to an animal afflicted with said disease in an amount effective for treating the bone wasting disease.