Back to results
US 2014/0275128 A1Published application
Method of providing ocular neuroprotection
AssigneeInotek Pharmaceuticals Corporation
InventorWilliam K. MCVICAR
Life of this patent
Estimating the term…
Abstract
Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for preventing, reducing or treating retinal ganglion cell damage comprising administering an effective amount of a purine derivative to a subject in need thereof.
Claims43
A method of preventing retinal ganglion cell damage in a subject in need thereof, comprising the step of:
- applying a pharmaceutical composition comprising an effective amount of a compound according to Formula I to an eye of the subject,
- or a pharmaceutically acceptable salt thereof,
- wherein
- A is —CH2ONO2, —CH2OH, —CH2OSO3H;
- B and C are —OH;
- D is
- A and B are trans with respect to each other;
- B and C are cis with respect to each other;
- C and D are cis or trans with respect to each other;
- R1 is —H, —C1-C10 alkyl, -aryl, -3- to 7-membered monocyclic heterocycle, -8- to 12-membered bicyclic heterocycle, —C3-C8 monocyclic cycloalkyl, —C3-C8 monocyclic cycloalkenyl, —C8-C12 bicyclic cycloalkyl, —C8-C12 bicyclic cycloalkenyl-(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), or —(CH2)n-aryl;
- R2 is —H, halo, —CN, —NHR4, —NHC(O)R4, —NHC(O)OR4, —NHC(O)NHR4, —NHNHC(O)R4, —NHNHC(O)OR4, —NHNHC(O)NHR4, or —NH—N═C(R6)R7;
- R4 is —C1-C15 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —C≡C—(C1-C10 alkyl) or —C≡C-aryl;
- R6 is —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), -phenylene-(CH2)nCOOH, or -phenylene-(CH2)nCOO—(C1-C10 alkyl);
- R7 is —H, —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl) or —(CH2)n—(C8-C12 bicyclic cycloalkyl);
- and each n is independently an integer ranging from 1 to 5, and a pharmaceutically acceptable vehicle.
12 more elements
A method of reducing retinal ganglion cell damage in a subject in need thereof, comprising the step of:
- applying a pharmaceutical composition comprising an effective amount of a compound according to Formula I to an affected eye of the subject,
- or a pharmaceutically acceptable salt thereof,
- wherein
- A is —CH2ONO2, —CH2OH— or —CH2OSO3H;
- B and C are —OH;
- D is
- A and B are trans with respect to each other;
- B and C are cis with respect to each other;
- C and D are cis or trans with respect to each other;
- R1 is —H, —C1-C10 alkyl, -aryl, -3- to 7-membered monocyclic heterocycle, -8- to 12-membered bicyclic heterocycle, —C3-C8 monocyclic cycloalkyl, —C3-C8 monocyclic cycloalkenyl, —C8-C12 bicyclic cycloalkyl, —C8-C12 bicyclic cycloalkenyl-(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), or —(CH2)n-aryl;
- R2 is —H, halo, —CN, —NHR4, —NHC(O)R4, —NHC(O)OR4, —NHC(O)NHR4, —NHNHC(O)R4, —NHNHC(O)OR4, —NHNHC(O)NHR4, or —NH—N═C(R6)R7;
- R4 is —C1-C15 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —C≡C—(C1-C10 alkyl) or —C≡C-aryl;
- R6 is —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), -phenylene-(CH2)nCOOH, or -phenylene-(CH2)nCOO—(C1-C10 alkyl);
- R7 is —H, —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl) or —(CH2)n—(C8-C12 bicyclic cycloalkyl);
- and each n is independently an integer ranging from 1 to 5, and a pharmaceutically acceptable vehicle.
12 more elements
A method of preventing reducing or treating retinal ganglion cell damage in a subject by administering a pharmaceutical composition comprising effective amount of a selective adenosine A1 agonist to an eye of the subject.
A method of providing ocular neuroprotection in a subject in need thereof, comprising the step of:
- applying a pharmaceutical composition comprising an effective amount of a compound according to Formula I to an eye of the subject,
- or a pharmaceutically acceptable salt thereof,
- wherein
- A is —CH2ONO2, —CH2OH, —CH2OSO3H;
- B and C are —OH;
- D is
- A and B are trans with respect to each other;
- B and C are cis with respect to each other;
- C and D are cis or trans with respect to each other;
- R1 is —H, —C1-C10 alkyl, -aryl, -3- to 7-membered monocyclic heterocycle, -8- to 12-membered bicyclic heterocycle, —C3-C8 monocyclic cycloalkyl, —C3-C8 monocyclic cycloalkenyl, —C8-C12 bicyclic cycloalkyl, —C8-C12 bicyclic cycloalkenyl-(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), or —(CH2)n-aryl;
- R2 is —H, halo, —CN, —NHR4, —NHC(O)R4, —NHC(O)OR4, —NHC(O)NHR4, —NHNHC(O)R4, —NHNHC(O)OR4, —NHNHC(O)NHR4, or —NH—N═C(R6)R7;
- R4 is —C1-C15 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —C≡C—(C1-C10 alkyl) or —C≡C-aryl;
- R6 is —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), -phenylene-(CH2)nCOOH, or -phenylene-(CH2)nCOO—(C1-C10 alkyl);
- R7 is —H, —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl) or —(CH2)n—(C8-C12 bicyclic cycloalkyl);
- and each n is independently an integer ranging from 1 to 5, and a pharmaceutically acceptable vehicle.
12 more elements
A method of providing ocular neuroprotection in a subject by administering a pharmaceutical composition comprising an effective amount of a selective adenosine A1 agonist to an eye of the subject.
Dependencies are inferred from the claim text.