Method of treating dry eye disorders and uveitis

1 . A method for the treatment of dry eye or uveitis in a mammal, which comprises topically administering to the eye of the mammal a composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of formula I:

wherein

R 1 is C 2 H 5 , CO 2 R, CONR 2 R 3 , CH 2 OR 4 , or CH 2 NR 5 R 6 , where:

R is H, C 1-6 straight chain or branched alkyl, C 3-6 cycloalkyl, or phenyl;

or R 1 is a carboxylate salt of formula CO 2 − R + , where R + is Li + , Na + , K + , or an ammonium moiety of formula + NR 10 R 11 R 12 R 13 ;

R 2 , R 3 are independently H, C 1-6 alkyl, C 3-6 cycloalkyl, benzyl, phenyl, OH, OCH 3 , or OC 2 H 5 , provided that at most only one of R 2 , R 3 is OH, OCH 3 , or OC 2 H 5 ;

R 4 is H, C(O)R 14 , C 1-6 alkyl, C 3-6 cycloalkyl, benzyl, or phenyl;

R 5 , R 6 are independently H, C(O)R 14 , C 1-6 alkyl, C 3-6 cycloalkyl, benzyl, phenyl, OH, OCH 3 , or OC 2 H 5 , provided that at most only one of R 2 , R 3 is OH, OCH 3 , or OC 2 H 5 ;

R 7 , R 8 , R 9 are independently H, CH 3 , C 2 H 5 , C(O)R 14 , or CO 2 R 15 ;

or R 7 and R 8 or R 8 and R 9 together constitute a carbonyl group;

or OR 8 R 1 together form a cyclic ester;

R 10 , R 11 , R 12 , R 13 are independently H or C 1-6 alkyl, each alkyl group optionally bearing an OH or OCH 3 substituent;

R 14 is H, C 1-6 alkyl, C 3-6 cycloalkyl, benzyl, or phenyl; and

R 15 is C 1-6 alkyl, C 3-6 cycloalkyl, benzyl, or phenyl.

2 . The method of claim 1 wherein for the compound of formula I:

R 1 is C 2 H 5 , CO 2 R, or CH 2 OR 4 ;

R is H, Na + , NH 4 + , CH 3 , C 2 H 5 , n-C 3 H 7 , or i-C 3 H 7 ;

R 4 is H, COCH 3 , or CH 3 ; and

R 7 , R 8 , R 9 are independently H, CH 3 , CH 3 CO;

or R 7 and R 8 or R 8 and R 9 together constitute a carbonyl group;

or OR 8 R 1 together form a cyclic ester.

3 . The method of claim 2 wherein the compound of formula I has the configuration:

4 . The method of claim 1 wherein the compound of formula I has the configuration:

5 . The method of claim 3 , wherein a compound of formula I is used to treat uveitis.

6 . The method of claim 3 , wherein a compound of formula I is used to treat dry eye.

7 . The method of claim 5 , wherein the compound is selected from the group consisting of:

8 . The method of claim 6 , wherein the compound is selected from the group consisting of:

9 . The method of claim 5 , wherein the pharmaceutically effective amount is from 0.1 to 1% (w/v).

10 . The method of claim 6 wherein the pharmaceutically effective amount is from 0.00003 to 0.001% (w/v).

11 . The method of claim 9 , wherein the pharmaceutically acceptable carrier comprises one or more ingredients selected from the group consisting of surfactants; tonicity agents; buffers; preservatives; co-solvents and viscosity building agents.

12 . The method of claim 10 , wherein the pharmaceutically acceptable carrier comprises one or more ingredients selected from the group consisting of surfactants; tonicity agents; buffers; preservatives; co-solvents and viscosity building agents.