# US 11,306,082 B2 · Esters of dihydrotetrabenazine

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

- Number: US 11,306,082 B2
- Document ID: US11306082B2
- Status: Granted
- Kind: B2
- Application number: 16/762,747
- Filed: 2018-11-07
- Published: 2020-08-27
- Granted: 2022-04-19
- Earliest claimed: 2017-11-08
- Assignees: Foresee Pharmaceuticals Co., Ltd.
- Applicants: Foresee Pharmaceuticals Co., Ltd.
- Inventors: Yuhua Li; Chen-Chang Lee; Wen-Yen Huang
- Web page: https://patentgrep.com/patent/US11306082B2

## CPC

- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- C07D 455/06: containing benzo [a] quinolizine ring systems
- A61K 31/473: ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention relates to a compound of formula (I) including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof. wherein R1 is —C(═O)O-alkyl, carbonate ester, or —C(═O)-alkyl, ester, or —C(═O)N-alkyl, carbamate ester and wherein R2 is —CH3 or —CD3. The alkyl ester can contain saturated or unsaturated C12 to C26 alkyl carbon. The alkyl carbon chain can have either a straight, branched, noncyclic, cyclic, unsubstituted or substituted structure.

## Claims

### Claim 1

A compound of formula (I)
or a pharmaceutically acceptable salt thereof; wherein R1 is selected from the group consisting of —C(═O)O-alkyl, —C(═O)-alkyl, and —C(═O)N-alkyl, and wherein the alkyl is a saturated or unsaturated straight-chain alkyl group containing from 11 to 25 carbon atoms, and R2 is —CH3 or —CD3.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

The compound as claimed in claim 1, wherein the compound has a formula of (Ia)
or a pharmaceutically acceptable salt thereof; wherein R is a saturated or unsaturated straight-chain alkyl group containing from 11 to 25 carbon atoms.

### Claim 4

A compound of a formula of (Ib)
or a pharmaceutically acceptable salt thereof; wherein R is a saturated or unsaturated straight-chain alkyl group containing from 11 to 25 carbon atoms.

### Claim 5 (depends on 1)

The compound as claimed in claim 1 wherein R1 is palmitoyl.

### Claim 6 (depends on 1)

The compound as claimed in claim 1 wherein R1 is stearoyl.

### Claim 7 (depends on 1)

The compound as claimed in claim 1 wherein R1 is behenoyl.

### Claim 8 (depends on 1)

The compound as claimed in claim 1 wherein R1 is oleoyl.

### Claim 9 (depends on 1)

The compound as claimed in claim 1 wherein the VMAT2 inhibition IC50 of the compound is more than 200 fold than that of unconjugated parent compound as determined using Radioligand Binding Assays.

### Claim 10 (depends on 1)

The compound as claimed in claim 1 wherein the VMAT2 inhibition IC50 of the compound is more than 500 fold than that of unconjugated parent compound as determined using radioligand binding assays.

### Claim 11 (depends on 1)

The compound as claimed in claim 1 wherein the VMAT2 inhibition IC50 of the compound is more than 1000 fold than that of unconjugated parent compound as determined using radioligand binding assays.

### Claim 12 (depends on 1)

The compound as claimed in claim 1, wherein the compound results in lower solubility in aqueous solution comparing with unconjugated (+)-(α)-DHTBZ.

### Claim 13 (depends on 2)

The composition according to claim 2, wherein the pharmaceutical acceptable carrier is selected from the group consisting of DMSO, NMP, DMAc, benzyl alcohol (BA), benzyl benzoate (BB), ethanol, glycofurol, triacetin and glycerol.

### Claim 14 (depends on 2)

The composition according to claim 2, wherein the pharmaceutical acceptable carrier is selected from the group consisting of sesame oil, vegetable oil, corn oil, soybean oil, castor oil, cottonseed oil, peanut oil and olive oil.