Biodegradable intravitreal tyrosine kinase implants

1. A method of treating an ocular condition of an eye of a patient, comprising the step of placing a biodegradable intraocular implant into the vitreous of an eye of the patient, the implant comprising a TKI and a biodegradable polymer, wherein the implant degrades at a rate effective to sustain release of an amount of the TKI from the implant effective to treat the ocular condition, wherein the TKI is represented by the formula:

wherein R 1 is selected from the group consisting of halogen, NO 2 , CN, C 1 to C 4 alkyl and aryl; R 2 is selected from the group consisting of hydrogen, C 1 to C 8 alkyl, COCH 3 , CH 2 CH 2 OH, CH 2 CH 2 CH 2 OH and phenyl; R is selected from the group consisting of D, halogen, C 1 to C 8 alkyl, CF 3 , OCF 3 , OCF 2 H, CH 2 CN, CN, SR 2 , (CR 7 R 8 ) c C(O)OR 2 , C(O)N(R 2 ) 2 , (CR 7 R 8 ) c OR 2 , HNC(O)R 2 , HN—C(O)OR 2 , (CR 7 R 8 ) c N(R 2 ) 2 , SO 2 (CR 7 R 8 ) c N(R 2 ) 2 , OP(O)(OR 2 ) 2 , OC(O)OR 2 , OCH 2 O, HN—CH═CH, —N(COR 2 )CH 2 CH 2 , HC═N—NH, N═CH—S, O(CR 7 R 8 ) d —R 6 and (CR 7 R 8 ) c —R 6 , —NR 2 (CR 7 R 8 ) d R 6 wherein R 6 is selected from the group consisting of halogen, 3-fluoropyrrolidinyl, 3-fluoropiperidinyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyrrolinyl, pyrrolidinyl, methyl isonipecotate, N-(2-methoxyethyl)-N-methylamyl, 1,2,3,6-tetrahydropyridinyl, morpholinyl, hexamethyleneiminyl, piperazinyl-2-one, piperazinyl, N-(2-methoxyethyl)ethylaminyl, thiomorpholinyl, heptamethyleneiminyl, 1-piperazinylcarboxaldehyde, 2,3,6,7-tetrahydro-(IH)-1,4-diazepinyl-5 (4H)-one, N-methylhomopiperazinyl, (3-dimethylamino)pyrrolidinyl, N-(2-methoxyethyl)-N-propylaminyl, isoindolinyl, nipecotamidinyl, isonipecotamidinyl, 1-acetylpiperazinyl, 3 acetamidopyrrolidinyl, trans-decahydroisoquinolinyl, cis-decahydroisoquinolinyl, N-acetylhomopiperazinyl, 3-(diethylamino)pyrrolidinyl, 1,4-dioxa-8-azaspiro[4.5]decaninyl, 1-(2-methoxyethyl)-piperazinyl, 2-pyrrolidin-3-ylpyridinyl, 4-pyrrolidin-3-ylpyridinyl, 3-(methylsulfonyl)pyrrolidinyl, 3-picolylmethylaminyl, 2-(2-methylaminoethyl)pyridinyl, 1-(2-pyrimidyl)-piperazinyl, 1-(2-pyrazinyl)-piperazinyl, 2-methylaminomethyl-1,3-dioxolane, 2-(N-methyl-2-aminoethyl)-1,3-dioxolane, 3-(N-acetyl-N-methylamino)pyrrolidinyl, 2-methoxyethylaminyl, tetrahydrofurfurylaminyl, 4-aminotetrahydropyran, 2-amino-1-methoxybutane, 2-methoxyisopropylaminyl, 1-(3-aminopropyl)imidazole, histamyl, N,N-diisopropylethylenediaminyl, 1-benzyl-3-aminopyrrolidyl 2-(aminomethyl)-5-methylpyrazinyl, 2,2-dimethyl-1,3-dioxolane-4-methanaminyl, (R)-3-amino-1-N—BOC-pyrrolidinyl, 4-amino-1,2,2,6,6-pentamethylpiperidinyl, 4-aminomethyltetrahydropyran, ethanolamine and alkyl-substituted derivatives thereof and wherein when c is 1 said CH 2 may be

and CH 2 CH 2 CH 2 ; provided said alkyl or phenyl radicals may be substituted with one or two halo, hydroxy or lower alkyl amino radicals wherein R 7 and R 8 may be selected from the group consisting of H, F and C 1 -C 4 alkyl or CR 7 R 8 may represent a carbocyclic ring of from 3 to 6 carbons, preferably R 7 and R 8 are H or CH 3 ;

b is 0 or an integer of from 1 to 3;

a is 0 or an integer of from 1 to 5, preferably 1 to 3;

c is 0 or an integer of from 1 to 4,

d is an integer of from 2 to 5;

the wavy line represents a E or Z bond and pharmaceutically acceptable salts thereof.

2. The method of claim 1 , wherein the method is effective to treat a retinal ocular condition.

3. The method of claim 1 , wherein the ocular condition is glaucoma.

4. The method of claim 1 , wherein the ocular condition is proliferative vitreoretinopathy.

5. The method of claim 1 , wherein the method comprises administering the implant to the patient by at least one of intravitreal injection, subconjunctival injection, sub-tenon injections, retrobulbar injection, and suprachoroidal injection.

6. The method of claim 1 , wherein the implant is placed directly into a posterior chamber of the eye.

7. The method of claim 1 , wherein the implant is placed directly into the vitreous of the eye.