# US 7,410,995 B1 · N-linked sulfonamide of heterocyclic thioesters for vision and memory disorders

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,410,995 B1
- Document ID: US7410995B1
- Status: Granted
- Kind: B1
- Application number: 09/134,421
- Filed: 1998-08-14
- Granted: 2008-08-12
- Earliest claimed: 1998-08-14
- Assignees: GPI NIL Holdings, Inc.
- Inventors: Douglas T. Ross; Hansjörg Sauer; Gregory S. Hamilton; Joseph P. Steiner
- Web page: https://patentgrep.com/patent/US7410995B1

## CPC

- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 27/12: for cataracts
- A61P 31/12: Antivirals
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to pharmaceutical compositions and methods for treating a vision disorder, improving vision, treating memory impairment, or enhancing memory performance using N-linked sulfonamides of heterocyclic thioesters.

## Claims

### Claim 1

A method for improving naturally-occurring vision in an animal, in the absence of any opthalmologic disorder, disease, or injury or treating a nerve-related vision disorder in a mammal in need thereof, which comprises administering to said mammal an effective amount of an N-linked sulfonamide of a heterocyclic thioester compound, wherein the nerve-related vision disorder is selected from the group consisting of the following,
visual impairments;
orbital disorders;
disorders of the lacrimal apparatus;
disorders of the eyelids;
disorders of the conjunctiva;
disorders of the cornea;
cataract;
disorders of the uveal tract;
disorders of the retina;
disorders of the optic nerve or visual pathways;
free radical induced eye disorders and disease;
immunologically-mediated eye disorders and diseases;
nerve-related physical injury affecting vision; and
nerve-related symptoms and complications of eye disease, nerve-related symptoms and complications of eye disorders, and nerve-related symptoms and complications of physical injury affecting vision.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound is immunosuppressive.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound has an affinity for an FKBP-type immunophilin.

### Claim 4 (depends on 3)

The method of claim 3, wherein the FKBP-type immunophilin is FKBP-12.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound is of formula I:
or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
A and B, taken together with the nitrogen and carbon atoms to which they are respectively attached, form a 5-7 membered saturated or unsaturated heterocyclic ring containing any combination of CH2, C, S, SO, SO2, N, NH, or NR2 in any chemically stable oxidation state;
X is either O or S;
Y is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
R2 is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkynyl, and C1-C4 bridging alkyl,
wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring;
wherein said ring is optionally fused to an Ar group;
Ar is an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring;
wherein the ring is either unsubstituted or substituted with one or more substituent(s),
wherein the individual ring size is 5-8 members,
wherein the heterocyclic ring contains 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S,
and wherein an aromatic or tertiary alkyl amine is optionally oxidized to a corresponding N-oxide;
Z is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
C and D are independently hydrogen, Ar, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C3-C8 cycloalkyl, C5-C7 cycloalkenyl, hydroxy, carbonyl oxygen, Ar, C1-C6 alkyl, C2-C6 alkenyl, hydroxy, amino, halo, thioalkyl, thiocarbonyl, ester, thioester, alkyoxy, alkenoxy, cyan, nitro, imino, alkylammo, aminoalkyl, sulfhydryl, thioalkyl, and sulfonyl,
wherein said cycloalkyl or cycloalkenyl is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, hydroxy, amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, thialkyl, or sulfonyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with oxygen to form a carbonyl, or
wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2; and
R1 is selected from the group consisting of Ar, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl, and C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of Ar, C3-C8 cycloalkyl, amino, halo, haloalkyl, hydroxy, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, carbonyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, and sulfonyl, or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound is of formula II:
or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein: E, P, G and J are independently CH2, O, S, SO, SO2, NH or NR2;
X is either O or S;
Y is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
R2 is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C1-C4 straight or branched chain alkenyl or alkynyl, and C1-C4 bridging alkyl
wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring,
wherein said ring is optionally fused to an group;
z is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
Ar is an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring, wherein the ring is either unsubstituted or substituted with one or more substituent(s),
wherein the individual ring size is 5-8 members,
wherein the heterocyclic ring contains 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S,
and wherein an aromatic or tertiary alkyl amine is optionally oxidized to a corresponding N-oxide,
C and D are independently hydrogen, Ar, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C3-C8 cycloalkyl, C5-C7 cycloalkenyl, hydroxy, carbonyl oxygen, Ar, C1-C4 alkyl, C2-C4 alkenyl, and hydroxy,
wherein said cycloalkyl or cycloalkenyl is optionally substituted with C1-C4 alkyl, C2-C4 alkenyl, or hydroxy,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with oxygen to form a carbonyls,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2; and
R1 is selected from the group consisting of Ar, C3-C8 cycloalkyl, C1-C6,
straight or branched chain alkyl, and C2-C6 straight or branched chain alkenyl, wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of Ar and C3-C8 cycloalkyl.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound is of formula III:
or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
E, F, and G are independently CH2, O, S, SO, SO2, NH or NR2;
X is either O or S;
Y is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
R2 selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkynyl, and C3-C4 bridging alkyl,
wherein a bridge, is formed between the nitrogen; and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring,
wherein said ring is optionally fused to an Ar group;
Ar is an alicyclic or aromatic, mono-, bi- or tricyclic, carbo or heterocyclic ring, wherein the ring is either unsubstituted or substituted with one or more substituent(s),
wherein the individual ring size is 5-8 members,
wherein the heterocyclic ring contains 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S,
and wherein an aromatic or tertiary alkyl amine is optionally oxidized to a corresponding N-oxide;
Z is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any atom of said alkyl or alkenyl is optionally replaced with O, NH, NR, S, SO, or SO2;
R2, is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkenyl, and C1-C4 bridging alkyl
wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring,
wherein said ring is optionally fused to an Ar group;
C and D are independently hydrogen, Ar, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C3-C8 cycloalkyl, C5-C7 cycloalkenyl, hydroxy, carbonyl oxygen, Ar, C1-C4 alkyl, C2-C4 alkenyl, and hydroxy,
wherein said cycloalkyl or cycloalkenyl is optionally substituted with C1-C4 alkyl, C2-C4 alkenyl, or hydroxy,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2; and
R1 is selected from the group consisting of Ar, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl, and C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of Ar and C3-C8 cycloalkyl.

### Claim 8 (depends on 1)

The method of claim 1, wherein the compound is of formula IV:
or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein: n is 1, 2 or 3;
X is either O or S;
Y is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
R2 is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkynyl, and C1-C4 bridging alkyl
wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring,
wherein said ring is optionally fused to an Ar group;
Z is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl
or wherein any atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
R2 is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkenyl, and C1-C4 bridging alkyl
wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring,
wherein said ring is optionally fused to an Ar group;
Ar is an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring,
wherein the ring is either unsubstituted or substituted with one or more substituent(s),
wherein the individual ring size is 5-8 members,
wherein the heterocyclic ring contains 1-5 heteroatom(s) independently selected from the group consisting of O, N, and S,
and wherein an aromatic or tertiary alkyl amine is optionally oxidized to a corresponding N-oxide;
C and D are independently hydrogen, Ar, C3-C6 straight or branched chain alkyl, or C-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C3-C8 cycloalkyl, Cs-C7 cycloalkenyl, hydroxy, carbonyl oxygen, Ar, C,-C4 alkyl, C2-C4 alkenyl, and hydroxyl,
wherein said cycloalkyl or cycloalkenyl is optionally substituted with C1-C4 alkyl, C2-C4 alkenyl, or hydroxy,
wherein any carbon atoms of said alkyl or alkenyl is optionally substituted in one or more position(s) with oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2; and
R1, is selected from the group consisting of Ar, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl, and C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of Ar and C3-C8 cycloalkyl.

### Claim 9 (depends on 5)

The method of claim 5, wherein the mono- or bicyclic, carbo- or heterocyclic ring is selected from the group consisting of phenyl, benzyl, naphthyl, indolyl, pyridyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, purinyl, quinolinyl, isoquinolinyl, furyl, fluorenyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, and thienyl.

### Claim 10 (depends on 5)

The method of claim 5, wherein:
A and B are taken together, with the nitrogen and carbon atoms to which they are respectively attached, to form a 6 membered saturated or unsaturated heterocyclic ring; and
R2 is C4-C7 branched chain alkyl, C4-C7 cycloalkyl, phenyl, or 3,4,5-trimethoxyphenyl.

### Claim 11 (depends on 5)

The method of claim 5, wherein the compound is selected from the group consisting of:
3-(para-Methoxyphenyl)-1-propylmercaptyl (2S)—N-(benzenesulfonyl)pyrrolidine-2-carboxylate;
3-(para-Methoxyphenyl)-1-propylmercaptyl (2S)—N-(-toluenesulfonyl)pyrrolidine-2-carboxylate;
3-(para-Methoxyphenyl)-1-propylmercaptyl (2S)—N-(-toluenesulfonyl)pyrrolidine-2-carboxylate;
1,5-Diphenyl-3-pentylmercaptyl N-(para-toluenesulfonyl)pipecolate; and pharmaceutically acceptable salts, esters, and solvates thereof.

### Claim 12 (depends on 6)

The method of claim 6, wherein the mono- or bicyclic, carbo- or heterocyclic ring is selected from the group consisting of phenyl, benzyl, naphthyl, indolyl, pyridyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, purinyl, quinolinyl, isoquinolinyl, furyl, fluorenyl; thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, and thienyl.

### Claim 13 (depends on 7)

The method of claim 7, wherein the mono- or bicyclic, carbo- or heterocyclic ring is selected from the group consisting of phenyl, benzyl, naphthyl, indolyl, pyridyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, purinyl, quinolinyl, isoquinolinyl, furyl, fluorenyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, and thienyl.

### Claim 14 (depends on 8)

The method of claim 8, wherein the mono- or bicyclic, carbo- or heterocyclic ring is selected from the group consisting of phenyl, benzyl, naphthyl, indolyl, pyridyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, purinyl, quinolinyl, isoquinolinyl, furyl, fluorenyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, and thienyl.

### Claim 15 (depends on 1)

The method of claim 1 wherein the compound is administered to said animal in combination with an effective amount of one or more neopsic factor(s) useful in treating vision disorders, or improving vision, in an animal.

### Claim 16 (depends on 15)

The method of claim 15, wherein the one or more neopsic factor(s) is/are selected from the group consisting of immunosuppressants for treating autoimmune, inflammatory, and immunologically-mediated disorders; wound healing agents for treating wounds resulting from injury or surgery; antiglaucomatous medications for treating abnormally elevated intraocular pressure; neurotrophic factors and growth factors for treating neurodegenerative disorders or stimulating neurite outgrowth; compounds effective in limiting or preventing hemorrhage or neovascularization for treating muscular degeneration; and antioxidants for treating oxidative damage to eye tissues.

### Claim 17 (depends on 1)

The method of claim 1, wherein the compound is non-immunosuppressive.

### Claim 18

A method for treating a nerve-related vision disorder, improving vision in a mammal in need thereof, which comprises administering to said animal an effective amount of an N-linked sulfonamide of a compound of formula V:
or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
V is C, N, or S;
A and B, taken together with the nitrogen and carbon atoms to which they are respectively attached, form a 5-7 membered saturated or unsaturated heterocyclic ring containing any combination of CH2, O, S, SO, SO2, N, NH, or NR2 in any chemically stable oxidation state;
X is either O or S;
Y is a direct bond, C1-C6 straight or branched chains alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
R2 is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkynyl, and Q-C4 bridging alkyl,
wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom for form a ring,
wherein said ring is optionally fused to an Ar group;
Ar is an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring,
wherein the ring is either unsubstituted or substituted with one or more substituent(s),
wherein the individual ring size is 5-8 members,
wherein the heterocyclic ring contains 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S,
and wherein an aromatic or tertiary alkyl amine is optionally oxidized to a corresponding N-oxide;
Z is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
or wherein any atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
C and D are independently hydrogen, Ar, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl, wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C3-C8 cycloalkyl, C5-C7; cycloalkenyl, hydroxy, carbonyl oxygen, Ar, C1-C6 alkyl, C2-C6 alkenyl, hydroxy, amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, and sulfonyl,
wherein said cycloalkyl or cycloalkenyl is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, hydroxy, amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, or sulfonyl,
wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with oxygen to form a carbonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2; and
R1 is selected from the group consisting of Ar, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl, and C2-C6 straight or branched chain alkenyl,
wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of Ar, C3-C8 cycloalkyl, amino, halo, haloalkyl, hydroxy, trifluoromenthyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, carbonyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, and sulfonyl,
or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2,
wherein the nerve-related vision disorder is selected from the group consisting of visual impairments; orbital disorders; disorders of the lacrimal apparatus; disorders of the eyelids; disorders of the conjunctiva; disorders of the cornea; cataract; disorders of the uveal tract; disorders of the retina; disorders of the optic nerve or visual pathways; free radical induced eye disorders and diseases; immunologically-mediated eye disorders and diseases: eye injuries; and symptoms and complications of eye disease, eye disorder, and eye injury.

### Claim 19 (depends on 1)

The method of claim 1, wherein the mammal is human.

### Claim 20 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is retinal.

### Claim 21 (depends on 20)

The method of claim 20, wherein the retinal ischemia is selected from the group consisting of degeneration of retinal ganglion cells, degeneration of optic nerve axons, degeneration of myelin sheaths, ischemic optic neopathy, and retinal vascular blockage.

### Claim 22 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is optic nerve transection.

### Claim 23 (depends on 22)

The method of claim 22, wherein the optic nerve transection is selected from the group consisting of ganglion cell death after optic nerve transection and myelin degeneration after optic nerve transection.

### Claim 24 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is diabetes.

### Claim 25 (depends on 24)

The method of claim 24, wherein the diabetes is selected from the group consisting of diabetes from degeneration and diabetic retinopathy.

### Claim 26 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is macular degeneration.

### Claim 27 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is glaucoma related degeneration.

### Claim 28 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is cataract related degeneration.

### Claim 29 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is a detached retina.

### Claim 30 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is inflammation related degeneration.

### Claim 31 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is photoreceptor degeneration.

### Claim 32 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is optic neuritis.

### Claim 33 (depends on 1)

The method of claim 1, wherein the nerve-related vision disorder is dry eye degeneration.