Method of reducing intraocular pressure in humans
AssigneeInotek Pharmaceuticals Corporation
InventorsNorman N. Kim, William K. McVicar, Thomas G. McCauley, Prakash Jagtap
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Abstract
Provided herein is a method of reducing intraocular pressure (IOP) in humans using N6-cyclopentyladenosine (CPA), CPA derivatives or prodrugs or enhanced cornea permeability formulations of CPA. In one embodiment, the invention is directed to CPA derivatives or prodrugs that are permeable to the cornea. In another embodiment, the invention is directed to uses of certain compounds in human subjects for reducing and/or controlling elevated or abnormally fluctuating IOPs in the treatment of glaucoma or ocular hypertension (OHT).
Claims19
A compound of Formula II
- or a pharmaceutically acceptable salt thereof,
- wherein R1 is selected from —(CO)C1-C6 alkyl, —(CO)CH(halo)2, —(CO)phenyl, a —(CO)C1-C10 optionally branched aliphatic, —(CO)C3-C8 cycloalkyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6, —(CO)aryl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6;
- and a —(CO)C3-C7 heterocyclyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH, wherein n is 1-6;
- R2 is selected from —H and halo;
- and R3 is selected from hydroxy, —O(CO)CH(halo)2, —O(CO)(CH2)2CH3, —O(CO)CH(CH3)2, and —O(CO)CH2C(CH3)3.
A compound of the formula 2a:
- or a pharmaceutically acceptable salt thereof.
A compound selected from the group consisting of formula 2b, 2c and 2h:
- or a pharmaceutically acceptable salt thereof.
An ophthalmic pharmaceutical composition comprising a compound of Formula II
- or a pharmaceutically acceptable salt thereof,
- wherein R1 is selected from —(CO)C1-C6 alkyl, —(CO)CH(halo)2, —(CO)phenyl, and a —(CO)C1-C10 optionally branched aliphatic, —(CO)C3-C8 cycloalkyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6, —(CO)aryl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6;
- and a —(CO)C3-C7 heterocyclyl heterocyclic which is optionally substituted with one or more of hydroxy or —(CH2)nOH, wherein n is 1-6;
- R2 is selected from —H and halo;
- and R3 is selected from hydroxy, —O(CO)CH(halo)2, —O(CO)(CH2)2CH3, —O(CO)CH(CH3)2, and —O(CO)CH2C(CH3)3, and a pharmaceutically acceptable carrier.
An ophthalmic pharmaceutical composition comprising compound 2a
- or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
An ophthalmic pharmaceutical composition comprising a compound selected from the group consisting of compound 2b, compound 2c and compound 2h:
- or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
A method of reducing intraocular pressure (IOP) in a human subject in need thereof by administering an effective amount of a compound of Formula II, or a pharmaceutically acceptable salt thereof, to an affected eye of the human subject,
- wherein R1 is selected from —(CO)C1-C6 alkyl, —(CO)CH(halo)2, —(CO)phenyl, and a —(CO)C1-C10 optionally branched aliphatic, —(CO)C3-C8 cycloalkyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6, —(CO)aryl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6;
- and a —(CO)C3-C7 heterocyclyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH, wherein n is 1-6;
- R2 is selected from —H and halo;
- and R3 is selected from hydroxy, —O(CO)CH(halo)2, —O(CO)(CH2)2CH3, —O(CO)CH(CH3)2, and —O(CO)CH2C(CH3)3.
A method of reducing IOP in a human subject in need thereof by administering an effective amount of Compound 2a,
- or a pharmaceutically acceptable salt thereof, to an affected eye of the human subject.
A method of treating diseases and conditions caused by elevated IOP in a human subject in need thereof by administering an effective amount of a compound of Formula II, or a pharmaceutically acceptable salt thereof, to an affected eye of the human subject,
- wherein R1 is selected from —(CO)C1-C6 alkyl, —(CO)CH(halo)2, —(CO)phenyl, and a —(CO)C1-C10 optionally branched aliphatic, —(CO)C3-C8 cycloalkyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6, —(CO)aryl which is optionally substituted with one or more of hydroxy or —(CH2)nOH where n is 1-6;
- and a —(CO)C3-C7 heterocyclyl which is optionally substituted with one or more of hydroxy or —(CH2)nOH, wherein n is 1-6;
- R2 is selected from —H and halo;
- and R3 is selected from hydroxy, —O(CO)CH(halo)2, —O(CO)(CH2)2CH3, —O(CO)CH(CH3)2, and —O(CO)CH2C(CH3)3.
A method of treating diseases and conditions caused by elevated IOP in a human subject in need thereof by administering an effective amount of Compound 2a,
- or a pharmaceutically acceptable salt thereof, to an affected eye of the human subject.
A method of reducing IOP in a human subject in need thereof by administering an effective amount of a compound selected from the group consisting of compound 2b, compound 2c and compound 2h:
- or a pharmaceutically acceptable salt thereof, to an affected eye of the human subject.
A method of treating diseases and conditions caused by elevated IOP in a human subject in need thereof by administering an effective amount of a compound selected from the group consisting of compound 2b, compound 2c and compound 2h:
- or a pharmaceutically acceptable salt thereof, to an affected eye of the human subject.
Dependencies are inferred from the claim text.