# US 2006/0069016 A1 · Cyclosporin alkyne analogues and their pharmaceutical uses

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- Number: US 2006/0069016 A1
- Document ID: US20060069016A1
- Status: Published application
- Kind: A1
- Application number: 11/232,360
- Filed: 2005-09-21
- Published: 2006-03-30
- Earliest claimed: 2004-09-29
- Assignees: AMR Technology, Inc.
- Inventors: Bruce Molino; Zhicai Yang
- Web page: https://patentgrep.com/patent/US20060069016A1

## CPC

- C07K 7/645: {Cyclosporins; Related peptides}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 11/06: Antiasthmatics
- A61P 17/06: Antipsoriatics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The compounds of the present invention are represented by the chemical structure found in Formula I: or a pharmaceutically acceptable salt thereof, with X, R0, R1, and R2 defined herein.

## Claims

### Claim 1

A compound of Formula I:
wherein:
X is OH or OAc;
R0 is H, CH2OH, or CH2OR3;
R1 is hydrogen, deuterium, or methyl;
R2 is selected from the group consisting of:
hydrogen;
halogen;
C1-C6 saturated or unsaturated, straight or branched carbon chain;
C1-C6 saturated or unsaturated, straight or branched carbon chain containing a substitution or substitutions selected from the group consisting of deuterium, halogen, nitrogen, sulfur, and silicon;
C1-C6 saturated or unsaturated, straight or branched carbon chain containing a function group or function groups selected from the group consisting of alcohol, ether, aldehyde, ketone, carboxylic acid, ester, and amide;
C1-C6 saturated or unsaturated, straight or branched carbon chain containing a function group of oxime or hydrazone;
C1-C6 saturated or unsaturated, straight or branched carbon chain containing an aryl or a heteroaryl group;
C3-C6 substituted and unsubstituted cycloalkyl;
substituted and unsubstituted aryl; and
substituted and unsubstituted heteroaryl; and
R3 is selected from the group consisting of:
alkanoyl,
alkenoyl,
alkynoyl,
aryloyl,
arylalkanoyl,
alkylaminocarbonyl,
arylaminocarbonyl,
arylalkylaminocarbonyl,
alkyloxycarbonyl,
aryloxycarbonyl, and
arylalkyloxycarbonyl,
wherein the compound is a cis geometric isomer, a trans geometric isomer, or a mixture of the cis and the trans geometric isomers or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein X is OH or OAc, R0 is H, CH2OH, or CH2OAc, and R1 is H or D.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein R2 is H.

### Claim 4 (depends on 2)

The compound according to claim 2, wherein R2 is selected from the group consisting of CH3, CD3, CH2CH3, and CH2CH2CH3.

### Claim 5 (depends on 2)

The compound according to claim 2, wherein R2 is selected from the group consisting of CH═CH2, CH═CHCH3, C≡CH, and —C≡C—CH3.

### Claim 6 (depends on 2)

The compound according to claim 2, wherein R2 is selected from the group consisting of F, Cl, Br, and I.

### Claim 7 (depends on 2)

The compound according to claim 2, wherein R2 is cyclopropyl.

### Claim 8 (depends on 2)

The compound according to claim 2, wherein R2 is selected from the group consisting of CH2OH, CH(OH)CH3, CH2OCH3, CH2OCH2CH3, CHO, and C(═O)CH3.

### Claim 9 (depends on 2)

The compound according to claim 2, wherein R2 is selected from the group consisting of CH═N—OCH3, CH═N—OCH2CH3, CH═N—NHCH3, and CH═N—N(CH3)2.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 1.

### Claim 11 (depends on 1)

A method of suppressing or reducing immune response in a mammal comprising:
administering a therapeutically effective amount of the compound of claim 1 to said mammal under conditions effective to suppress immune response in a mammal.

### Claim 12 (depends on 1)

A method of treating a mammal with a chronic inflammatory or autoimmune disease comprising:
administering a therapeutically effective amount of the compound of claim 1 to the mammal under conditions effective to treat the chronic inflammatory or autoimmune disease.

### Claim 13 (depends on 12)

The method of claim 12, wherein the chronic inflammatory or autoimmune disease is selected from the group consisting of asthma, rheumatoid arthritis, multiple sclerosis, psoriasis, and ulcerative colitis.

### Claim 14 (depends on 1)

A method of treating a mammal with ocular allergy and dry eye comprising:
administering a therapeutically effective amount of the compound of claim 1 to the mammal under conditions effective to treat ocular allergy and dry eye.