US2014121186A1PendingUtilityA1
Compounds, Compositions and Methods for Treating Ocular Conditions
Est. expiryJul 21, 2029(~3 yrs left)· nominal 20-yr term from priority
A61P 31/14C07F 9/65742A61P 31/20C07F 9/6512A61P 27/02A61P 31/22A61P 31/12A61K 47/32A61P 31/16A61K 9/0048Y02A50/30C07F 9/65125
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Claims
Abstract
The present invention provides methods of treating viral infection of the eye or posterior ocular condition including administering a pharmaceutical composition comprising a compound described in the present application. In some embodiments, the pharmaceutical composition is topically administered. In another embodiment, the pharmaceutical composition is orally administered or intraocularly administered.
Claims
exact text as granted — not AI-modifiedThat which is claimed is:
1 . An ophthalmic composition comprising: an ophthalmically acceptable carrier and a compound in an amount effective to treat a viral infection, wherein said compound has the structure of Formula II or III
wherein:
R 1 is a moiety selected from the group consisting of optionally substituted alkylglycerol, alkylpropanediol, 1-S-alkylthioglycerol, alkoxyalkanol and alkylethanediol, wherein R 1 is linked to —P(═O)— via oxygen of an available —OH of the moiety,
B is selected from the group consisting of hydrogen, F, CF 3 , —CH 2 CH 3 , —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)—CH 3 , —CH 2 F, —CH═CH 2 and —CH 2 N 3 ,
Z is a heterocyclic moiety, and
the symbol * indicates the point of attachment of the methylene moiety in Formula (II) or (III) to Z is via an available nitrogen of the heterocyclic moiety,
or a pharmaceutically acceptable salt thereof.
2 . The composition of claim 1 , wherein the compound is in the form of an enantiomer, diastereomer, racemate, stereoisomer, tautomer, rotamer or a mixture thereof.
3 . The composition of claim 1 or 2 , wherein R 1 is a moiety of
wherein R a and R b are independent selected from the group consisting of —H, optionally substituted —O(C 1 -C 24 )allyl, —O(C 2 -C 24 )alkenyl, —O(C 2 -C 24 )alkynyl, —O(C 1 -C 24 )acyl, —S(C 1 -C 24 )alkyl, —S(C 2 -C 24 )alkenyl, —S(C 2 -C 24 )alkynyl, or —S(C 1 -C 24 )acyl, —N(C 1 -C 24 )acyl, —NH(C 1 -C 24 )alkyl, —N(C 2 -C 24 )alkenyl, —N(C 2 -C 24 )alkynyl, —N((C 1 -C 24 )alkyl) 2 , oxo, halogen, —NH 2 , —OH and —SH.
4 . The composition of claim 1 or 2 , wherein R 1 is a moiety of
wherein R a and R b are independent selected from the group consisting of —H, optionally substituted —O(C 1 -C 24 )alkyl, —O(C 2 -C 24 )alkenyl, —O(C 2 -C 24 )alkynyl, —O(C 1 -C 24 )acyl, —S(C 1 -C 24 )alkyl, —S(C 2 -C 24 )alkenyl, —S(C 2 -C 24 )alkynyl or —S(C 1 -C 24 )acyl, —N(C 1 -C 24 )acyl, —NH(C 1 -C 24 )allyl, —N(C 2 -C 24 )alkenyl, —N(C 2 -C 24 )alkynyl, —N((C 1 -C 24 )alkyl) 2 , oxo, halogen, —NH 2 , —OH and —SH.
5 . The composition of claim 1 or 2 , wherein R 1 is a moiety of
wherein R a and R b are independent selected from the group consisting of —H, optionally substituted —O(C 1 -C 24 )alkyl, —O(C 2 -C 24 )alkenyl, —O(C 2 -C 24 )alkynyl, —O(C 1 -C 24 )acyl, —S(C 1 -C 24 )alkyl, —S(C 2 -C 24 )alkenyl, —S(C 2 -C 24 )alkynyl or —S(C 1 -C 24 )acyl, —N(C 1 -C 24 )acyl, —NH(C 1 -C 24 )alkyl, —N(C 2 -C 24 )alkenyl, —N(C 2 -C 24 )alkynyl, —N((C 1 -C 24 )alkyl) 2 , oxo, halogen, —NH 2 , —OH and —SH.
6 . The composition of claim 1 or 2 , wherein R 1 is —O—(CH 2 ) a —O—(CH 2 ) t —CH 3 , wherein a is 2 to 4 and t is 11 to 19.
7 . The composition of claim 6 wherein a is 3 and t is 15 or 17.
8 . The composition of claim 1 , wherein Z is selected from the group consisting of 6-alkylpurine, N 6 -alkylpurines, N 6 -acylpurines, N 6 -benzylpurine, 6-halopurine, N 6 -acetylenic purine, N 6 -acyl purine, N 6 -hydroxyalkyl purine, 6-thioalkyl purine, N 2 -alkylpurines, N 4 -alkylpyrimidines, N 4 -acylpyrimidines, 4-halopyrimidines, N 4 -acetylenic pyrimidines, 4-amino and N 4 -acyl pyrimidines, 4-hydroxyalkyl pyrimidines, 4-thioalkyl pyrimidines, thymine, cytosine, 6-azapyrimidine, including 6-azacytosine, 2- and/or 4-mercaptopyrimidine, uracil, C 5 -alkylpyrimidines, C 5 -benzylpyrimidines, C 5 -halopyrimidines, C 5 -vinylpyrimidine, C 5 -acetylenic pyrimidine, C 5 -acyl pyrimidine, C 5 -hydroxyalkyl purine, C 5 -amidopyrimidine, C 5 -cyanopyrimidine, C 5 -nitropyrimidine, C 5 -aminopyrimidine, N 2 -alkylpurines, N 2 -alkyl-6-thiopurines, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, and pyrazolopyrimidinyl.
9 . The composition of any of claims 1 - 7 , wherein Z is
wherein the symbol * in Formula A or B indicates the point of attachment of N to the methylene in Formula II or III.
10 . The composition of claim 1 or 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
11 . The composition of claim 1 or 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
12 . The composition of claim 1 or 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13 . The composition of any of claims 1 - 12 , wherein the composition comprises a topically ophthalmic acceptable carrier.
14 . The composition of claim 13 , wherein said topically ophthalmic acceptable carrier comprises an aqueous solution, a non aqueous solution, an oil, wax, grease, petrolatum, or a combination thereof.
15 . The composition of any of claims 1 - 14 , wherein the ophthalmic composition is in the form selected from the group consisting of an aqueous solution, a non-aqueous solution, a suspension, a solution/suspension, a gel, a cream, an ointment, and an emulsion.
16 . The composition of any of claims 1 - 15 further comprises at least one excipient selected from the group consisting of stabilizer, a penetrating enhancer, a pH adjusting agent, an antimicrobial preservative, a lubricant, a viscosifier, and a wetting agent.
17 . The composition of any of claims 1 - 16 , further comprises carbomer, triethanolamine, paraben, propylene glycol, and/or glycerin.
18 . The composition of any of claims 1 - 17 , wherein the amount of the compound is in the range of about 0.001% to 30% by weight.
19 . A method of treating a viral infection of the eye comprising administering an ophthalmic composition to a subject, wherein the composition comprising an ophthalmically acceptable carrier and a compound having the structure of Formula II or III
wherein:
R 1 is a moiety selected from the group consisting of optionally substituted alkylglycerol, alkylpropanediol, 1-S-alkylthioglycerol, alkoxyalkanol and alkylethanediol, wherein R 1 is linked to —P(═O)— via oxygen of an available —OH of the moiety,
B is selected from the group consisting of hydrogen, F, CF 3 , —CH 3 , —CH 2 CH 3 , —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)—CH 3 , —CH 2 F, —CH═CH 2 , and —CH 2 N 3 ,
Z is a heterocyclic moiety, and
the symbol * indicates the point of attachment of the methylene moiety in Formula (II) or (III) to Z is via an available nitrogen of the heterocyclic moiety,
or a pharmaceutically acceptable salt thereof.
20 . The method of claim 19 , wherein the compound is in the form of an enantiomer, diastereomer, racemate, stereoisomer, tautomer, rotamer or a mixture thereof.
21 . The method of claim 19 or 20 , wherein R 1 is —O—(CH 2 ) n —O—(CH 2 ) t —CH 3 , wherein a is 2 to 4 and t is 11 to 19.
22 . The method of claim 21 , wherein a is 3 and t is 15 or 17.
23 . The method of claim 21 , wherein Z is selected from the group consisting of 6-alkylpurine, N 6 -alkylpurines, N 6 -acylpurines, N 6 -benzylpurine, 6-halopurine, N 6 -acetylenic purine, N 6 -acyl purine, N 6 -hydroxyalkyl purine, 6-thioalkyl purine, N 2 -alkylpurines, N 4 -alkylpyrimidines, N 4 -acylpyrimidines, 4-halopyrimidines, N 4 -acetylenic pyrimidines, 4-amino and N 4 -acyl pyrimidines, 4-hydroxyalkyl pyrimidines, 4-thioalkyl pyrimidines, thymine, cytosine, 6-azapyrimidine, including 6-azacytosine, 2- and/or 4-mercaptopyrimidine, uracil, C 5 -alkylpyrimidines, C 5 -benzylpyrimidines, C 5 -halopyrimidines, C 5 -vinylpyrimidine, C 5 -acetylenic pyrimidine, C 5 -acyl pyrimidine, C 5 -hydroxyalkyl purine, C 5 -amidopyrimidine, C 5 -cyanopyrimidine, C 5 -nitropyrimidine, C 5 -aminopyrimidine, N 2 -alkylpurines, N 2 -alkyl-6-thiopurines, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, and pyrazolopyrimidinyl.
24 . The method of any of claims 19 - 22 , wherein Z is
wherein the symbol * in Formula A or B indicates the point of attachment of N to the methylene in Formula II or III.
25 . The method of claim 19 or 20 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
26 . The method of claim 19 or 20 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
27 . The method of claim 19 or 20 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
28 . The method of any of claims 19 - 27 , wherein said at least one viral infection is selected from the group consisting of influenza, herpes simplex virus (HSV), human herpes virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), orthopox virus, variola major and minor, vaccinia, cowpox, camelpox, monkeypox, papilloma virus, adenovirus, polyoma virus including JC virus, BK virus, SV40 and a combination thereof.
29 . The method of any of claims 19 - 27 , wherein said at least one viral infection is selected from the groups consisting of cytomegalovirus, varicella zoster virus, adenovirus, herpes simplex virus and Epstein-Barr virus.
30 . The method of any of claims 19 - 29 , wherein the composition is topically administered to the eye.
31 . The method of any of claims 19 - 30 , wherein the composition is topically administered to the cornea and/or conjunctiva of the subject.
32 . The method of any of claims 19 - 29 , wherein the composition is orally administered or intraocularly administered.
33 . The method of any of claims 19 - 29 wherein the composition is administered by retrobulbar, intravitreal, intraretinal or subconjuctival injection.
34 . A method of treating macular degeneration, retinopathy, or retinitis pigmentosa comprising administering a pharmaceutical composition to a subject, wherein the composition comprising a pharmaceutically acceptable carrier and a compound having the structure of Formula II or III
wherein:
R 1 is a moiety selected from the group consisting of optionally substituted alkylglycerol, alkylpropanediol, 1-S-alkylthioglycerol, alkoxyalkanol and alkylethanediol, wherein R 1 is linked to —P(═O)— via oxygen of an available —OH of the moiety,
B is selected from the group consisting of hydrogen, F, CF 3 , —CH 3 , —CH 2 CH 3 , —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)—CH 3 , —CH 2 F, —CH═CH 2 , and —CH 2 N 3 ,
Z is a heterocyclic moiety, and
the symbol * indicates the point of attachment of the methylene moiety in Formula (II) or (III) to Z is via an available nitrogen of the heterocyclic moiety,
or a pharmaceutically acceptable salt thereof.
35 . The method of claim 34 , wherein the compound is in the form of an enantiomer, diastereomer, racemate, stereoisomer, tautomer, rotamer or a mixture thereof.
36 . The method of claim 34 , wherein Z is selected from the group consisting of 6-alkylpurine, N 6 -alkylpurines, N 6 -acylpurines, N 6 -benzylpurine, 6-halopurine, N 6 -acetylenic purine, N 6 -acyl purine, N 6 -hydroxyalkyl purine, 6-thioalkyl purine, N 2 -alkylpurines, N 4 -alkylpyrimidines, N 4 -acylpyrimidines, 4-halopyrimidines, N 4 -acetylenic pyrimidines, 4-amino and N 4 -acyl pyrimidines, 4-hydroxyalkyl pyrimidines, 4-thioallyl pyrimidines, thymine, cytosine, 6-azapyrimidine, including 6-azacytosine, 2- and/or 4-mercaptopyrimidine, uracil, C 5 -alkylpyrimidines, C 5 -benzylpyrimidines, C 5 -halopyrimidines, C 5 -vinylpyrimidine, C 5 -acetylenic pyrimidine, C 5 -acyl pyrimidine, C 5 -hydroxyalkyl purine, C 5 -amidopyrimidine, C 5 -cyanopyrimidine, C 5 -nitropyrimidine, C 5 -aminopyrimidine, N 2 -alkylpurines, N 2 -alkyl-6-thiopurines, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, and pyrazolopyrimidinyl.
37 . The method of claim 34 or 35 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
38 . The method of claims 34 - 36 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
39 . The method of any of claims 34 - 38 , wherein the composition is intraocularly administered.
40 . The method of claim 39 , wherein the composition is administered by intraocular injection.
41 . The method of any of claims 34 - 38 , wherein the composition is administered by retrobulbar, intravitreal, intraretinal or subconjuctival injection.
42 . A pharmaceutical composition for intraocular administration comprising a pharmaceutically acceptable carrier and a compound in an amount effective to treat macular degeneration, retinopathy, or retinitis pigmentosa, wherein said compound having the structure of Formula II or III
wherein:
R 1 is a moiety selected from the group consisting of optionally substituted alkylglycerol, alkylpropanediol, 1-S-alkylthioglycerol, alkoxyalkanol and allylethanediol, wherein R 1 is linked to —P(═O)— via oxygen of an available —OH of the moiety,
B is selected from the group consisting of hydrogen, F, CF 3 , —CH 3 , —CH 2 CH 3 , —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)—CH 3 , —CH 2 F, —CH═CH 2 , and —CH 2 N 3 ,
Z is a heterocyclic moiety, and
the symbol * indicates the point of attachment of the methylene moiety in Formula (II) or (III) to Z is via an available nitrogen of the heterocyclic moiety,
or a pharmaceutically acceptable salt thereof.
43 . The composition of claim 42 , wherein the compound is in the form of an enantiomer, diastereomer, racemate, stereoisomer, tautomer, rotamer or a mixture thereof.
44 . The method of claim 42 , wherein Z is selected from the group consisting of 6-alkylpurine, N 6 -alkylpurines, N 6 -acylpurines, N 6 -benzylpurine, 6-halopurine, N 6 -acetylenic purine, N 6 -acyl purine, N 6 -hydroxyalkyl purine, 6-thioalkyl purine, N 2 -alkylpurines, N 4 -alkylpyrimidines, N 4 -acylpyrimidines, 4-halopyrimidines, N 4 -acetylenic pyrimidines, 4-amino and N 4 -acyl pyrimidines, 4-hydroxyalkyl pyrimidines, 4-thioalkyl pyrimidines, thymine, cytosine, 6-azapyrimidine, including 6-azacytosine, 2- and/or 4-mercaptopyrimidine, uracil, C 5 -alkylpyrimidines, C 5 -benzylpyrimidines, C 5 -halopyrimidines, C 5 -vinylpyrimidine, C 5 -acetylenic pyrimidine, C 5 -acyl pyrimidine, C 5 -hydroxyalkyl purine, C 5 -amidopyrimidine, C 5 -cyanopyrimdine, C 5 -nitropyrimidine, C 5 -aminopyrimidine, N 2 -alkylpurines, N 2 -alkyl-6-thiopurines, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, and pyrazolopyrimidinyl.
45 . The composition of claim 42 - 44 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
46 . The composition of claims 42 - 44 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
47 . The composition of any of claims 42 - 46 , wherein said composition is in the form selected from a solution, a gel, a cream and a suspension.
48 . The composition of any of claims 42 - 47 , wherein said composition comprises at least one viscosifier.
49 . A topical ophthalmic composition comprising an ophthalmic acceptable carrier and a compound in an amount of effective to treat a viral infection of the eye, wherein said compound having the structure of
or a pharmaceutically acceptable salt thereof.
50 . The composition of claim 49 , wherein the compound is in the form of an enantiomer, racemate, stereoisomer, or a mixture thereof.
51 . The composition of any of claims 49 - 50 , wherein the ophthalmic composition is in a form selected from the group consisting of an aqueous solution, a non-aqueous solution, a suspension, a solution/suspension, a gel, a cream, an ointment, and an emulsion.
52 . The composition of any of claims 49 - 51 further comprises at least one excipient selected from the group consisting of a stabilizer, a pH adjusting agent, an antimicrobial preservative, a lubricant and a wetting agent.
53 . The composition of any of claims 49 - 51 , further comprise at least one excipient selected from the group consisting of carbomer, triethanolamine, paraben, propylene glycol, and glycerin.
54 . The composition of any of claims 49 - 53 , wherein the amount of the compound is in the range of about 0.001% to 30% by weight of the total weight of the composition.
55 . The use of a compound as described herein for the preparation of a medicament for carrying out a method of treatment according to any of claims 19 - 41 .
56 . A compound as described herein for use in carrying out methods of treatment according to any of claims 19 - 41 .Cited by (0)
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