TRIAZOLE-CONTAINING MACROLIDES AND OPHTHALMIC USES THEREFOR

1 . A method for treating an ocular disease in a host animal, the method comprising the step of topically administering to an eye of the host animal an effective amount of a composition comprising one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 10 is hydrogen or acyl;

X and Y are taken together with the attached carbon to form carbonyl;

V is C(O);

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, or C(O)NHS(O) 2 ;

B is C 0 to C 10 alkylene, C 2 to C 10 alkenylene, C 2 to C 10 alkynylene or C 4 to C 10 alkenylalkynylene; and

C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted.

2 . Use of one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating an ocular disease in a host animal, wherein:

R 10 is hydrogen or acyl;

X and Y are taken together with the attached carbon to form carbonyl;

V is C(O);

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, or C(O)NHS(O) 2 ;

B is C 0 to C 10 alkylene, C 2 to C 10 alkenylene, C 2 to C 10 alkynylene or C 4 to C 10 alkenylalkynylene; and

C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted.

3 . A pharmaceutical composition for treating an ocular disease in a host animal, the composition comprising an effective amount of one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 10 is hydrogen or acyl;

X and Y are taken together with the attached carbon to form carbonyl;

V is C(O);

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, or C(O)NHS(O) 2 ;

B is C 0 to C 10 alkylene, C 2 to C 10 alkenylene, C 2 to C 10 alkynylene or C 4 to C 10 alkenylalkynylene; and

C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted.

4 . A pharmaceutical formulation adapted for topical delivery to the eye, the formulation comprising one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 10 is hydrogen or acyl;

X and Y are taken together with the attached carbon to form carbonyl;

V is C(O);

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, or C(O)NHS(O) 2 ;

B is C 0 to C 10 alkylene, C 2 to C 10 alkenylene, C 2 to C 10 alkynylene or C 4 to C 10 alkenylalkynylene; and

C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted.

5 . The method, use, composition, or formulation of any one of claims 1 to 4 wherein the compound is solithromycin, or a salt thereof.

6 . The method, use, composition, or formulation of any one of claims 1 to 4 wherein the composition comprises boric acid or a salt thereof/

7 . The method, use, composition, or formulation of claim 6 wherein the composition further comprises a metal chelating agent.

8 . The method, use, composition, or formulation of any one of claims 1 to 4 wherein the composition comprises one or more polyethylene glycol esters.

9 . The method, use, composition, or formulation of claim 8 wherein the one or more polyethylene glycol esters are selected the group consisting of PEG castor oils and PEG stearates, and combinations thereof.

10 . The method, use, composition, or formulation of any one of claims 1 to 4 wherein the composition comprises one or more polyethylene glycols.

11 . The method, use, composition, or formulation of any one of claims 1 to 4 wherein the composition has a low viscosity.

12 . The method, use, composition, or formulation of any one of claims 1 to 4 wherein the composition has a midrange viscosity.

13 . The method, use, composition, or formulation of claim 12 wherein the composition comprises xanthan gum.

14 . The method, use, composition, or formulation of any one of claims 1 to 4 for treating conjunctivitis, neonatal conjunctivitis, or blinding trachoma.