# US 9,872,882 B2 · Aurantiamide dipeptide derivatives for treatment or prevention of angiogenesis-related diseases

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

- Number: US 9,872,882 B2
- Document ID: US9872882B2
- Status: Granted
- Kind: B2
- Application number: 14/981,178
- Filed: 2015-12-28
- Published: 2017-06-29
- Granted: 2018-01-23
- Earliest claimed: 2015-12-28
- Assignees: Mackay Medical College; Mackay Medical Foundation The Presbyterian Church In Taiwan Mackay Memorial Hospital; Chang Gung University
- Applicants: Mackay Medical College; MacKay Memorial Hospital of Taiwan Presbyterian Church and MacKay Memorial Social Work Foundation; Chang Gung University
- Inventors: Hung-I Yeh; Shih-Wei Wang; Ching-Hu Chung; Pei-Wen Hsieh
- Web page: https://patentgrep.com/patent/US9872882B2

## CPC

- A61K 38/05: Dipeptides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- G01N 2800/7014: (Neo)vascularisation - Angiogenesis
- G01N 2800/7028: Cancer
- G01N 2800/7042: Aging, e.g. cellular aging
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to a use of an aurantiamide dipepetide derivative in the treatment or prevention of angiogenesis-related diseases. Accordingly, aurantiamide dipeptide derivatives can be used as angiogenesis inhibitor, whereby preventing or treating invasive and metastatic cancer and ocular neovascularization (particularly macular degeneration such as pathological neovascularization of age-related macular degeneration (AMD)).

## Claims

### Claim 1

A method for ameliorating or treating ocular neovascularization, comprising administering an effective amount of a compound of the following Formula (I) to a subject,
wherein R is —(CH2)1-4phenyl wherein phenyl is unsubstituted or substituted by one to three hydroxyl, NH2, NO2 or alkyl; —(CH2)1-4indolyl; —(CH2)1-4naphthalenyl; or isopropyl,
or a tautomer, stereoisomer or enantiomer thereof, or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein R is —CH2phenyl, —CH2indolyl, —CH2naphthalenyl or isopropyl.

### Claim 3 (depends on 1)

The method of claim 1, wherein R is isopropyl.

### Claim 4 (depends on 1)

The method of claim 1, wherein the compound of formula (I) is selected from:
(9H-Fluoren-9-yl)methyl(S)-1-((S)-1-hydroxy-3-phenylpropan-2-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate;
(9H-Fluoren-9-yl)methyl(S)-1-((R)-1-hydroxy-3-phenylpropan-2-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate;
(9H-Fluoren-9-yl)methyl(S)-1-((S)-1-hydroxy-3-phenylpropan-2-ylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-ylcarbamate;
(9H-Fluoren-9-yl)methyl(S)-1-((R)-1-hydroxy-3-phenylpropan-2-ylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-ylcarbamate;
(9H-Fluoren-9-yl)methyl(S)-1-((S)-1-hydroxy-3-phenylpropan-2-ylamino)-3-(naphthalen-2-yl)-1-oxopropan-2-ylcarbamate;
(9H-Fluoren-9-yl)methyl(S)-1-((R)-1-hydroxy-3-phenylpropan-2-ylamino)-3-(naphthalen-2-yl)-1-oxopropan-2-ylcarbamate;
(9H-Fluoren-9-yl)methyl(S)-1-((S)-1-hydroxy-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-ylcarbamate; and
(9H-Fluoren-9-yl)methyl(S)-1-((R)-1-hydroxy-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-ylcarbamate;
or a tautomer, stereoisomer or enantiomer thereof, or a solvate, prodrug or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound is (9H-fluoren-9-yl)methyl (S)-1-((R)-1-hydroxy-3-phenylpropan-2-ylamino)-3-methyl-1-oxobutan-2-ylcarbamate,

### Claim 6 (depends on 1)

The method of claim 1, wherein the ocular neovascularization is macular degeneration.

### Claim 7 (depends on 6)

The method of claim 6, wherein the macular degeneration is wet macular degeneration.

### Claim 8 (depends on 7)

The method of claim 7, wherein the wet macular degeneration is age-related macular degeneration (AMD).

### Claim 9 (depends on 6)

The method of claim 6, wherein the administration is in an intravitreal, intraocular or periocular route.

### Claim 10 (depends on 6)

The method of claim 6, wherein the compound is formulated as an injection or eye drop.