# US 2019/0315679 A1 · Solid forms of an adamantyl compound, compositions and uses thereof

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- Number: US 2019/0315679 A1
- Document ID: US20190315679A1
- Status: Published application
- Kind: A1
- Application number: 16/343,165
- Filed: 2017-11-02
- Published: 2019-10-17
- Earliest claimed: 2016-11-03
- Assignees: North & South Brother Pharmacy Investment Company Limited
- Applicants: Sunshine Lake Pharma Co., Ltd.
- Inventors: Huiqing Ye; Jinchao Xu; Bifei He; Guangyuan Liu; Yuping Fan; Zhongqing Wang; Zhonhhua Luo
- Web page: https://patentgrep.com/patent/US20190315679A1

## CPC

- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07C 271/24: with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
- A61K 31/4748: forming part of bridged ring systems (strychnine A61K31/475; morphinan derivatives A61K31/485)
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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
- A61K 31/27: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/473: ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07C 2603/74: Adamantanes
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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

Provided herein are crystalline forms of (((((1r, 3R, 5S, 7r)-3, 5-dimethyladamantan-1-yl)carbamoyl) oxy) methyl benzoate (Compound (I)): Also provided are compositions comprising the crystalline forms of Compound (I), processes of manufacture and methods of using the crystalline forms of Compound (I).

## Claims

### Claim 1

A crystalline form of Compound (I)
selected from
crystalline Form I characterized by an X-ray powder diffraction pattern comprising at least three peaks selected from the peaks expressed as 2θ at 7.7±0.2°, 8.9±0.2°, 10.7±0.2°, 13.1±0.2°, 14.2±0.2°, 15.4±0.2°, 18.0±0.2°, 18.7±0.2°, 21.4±0.2°, 21.6±0.2°, 22.4±0.2°, 22.8±0.2°, 23.9±0.2°, 25.5±0.2°, 26.5±0.2°, and 27.0±0.2°, or
crystalline Form II characterized by an X-ray powder diffraction pattern comprising at least three peaks selected from the peaks expressed as 2θ at 9.6±0.20, 13.8±0.2°, 14.7±0.2°, 15.0±0.2°, 16.1±0.2°, 16.8±0.2°, 17.8±0.2°, 18.5±0.2°, 19.0±0.2°, 19.4±0.2°, 20.4±0.2°, 21.7±0.2° and 22.6±0.2°.

### Claim 2 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form exists in substantially anhydrous form.

### Claim 3 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form I characterized by an X-ray powder diffraction pattern comprising at least one group of peaks expressed as 2θ selected from the groups consisting of: (A) 7.7±0.2°, 8.9±0.2°, and 10.7±0.2°; (B) 13.1±0.2°, 15.4±0.2°, and 18.0±0.2°; (C) 21.6±0.2°, 22.8±0.2°, and 23.9±0.2°; and (D) 25.5±0.2°, 26.5±0.2°, and 27.0±0.2°.

### Claim 4 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form I characterized an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 14.2±0.2°, 15.4±0.2°, 18.0±0.2°, and 18.7±0.2°.

### Claim 5 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form I characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 14.2±0.2°, 15.4±0.2°, 18.0±0.2°, 18.7±0.2°, 21.4±0.2°, 21.6±0.2° and 22.4±0.2°.

### Claim 6 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form I characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 7.7±0.2°, 8.9±0.2°, 14.2±0.2°, 15.4±0.2°, 16.7±0.2°, 17.7±0.2°, 18.0±0.2°, 18.7±0.2°, 19.2±0.2°, 21.4±0.2°, 21.6±0.2°, 22.4±0.2°, and 22.8±0.2°.

### Claim 7

(canceled)

### Claim 8 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form I characterized by a differential scanning calorimetry thermogram comprising an endothermic peak at 91.55° C.±2° C.

### Claim at position 9

-10. (canceled)

### Claim 11 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form II characterized by an X-ray powder diffraction pattern comprising at least one group of peaks expressed as 2θ selected from the groups consisting of: (A) 9.6±0.2°, 13.8±0.2°, and 14.7±0.2°; (B) 15.0±0.2°, 16.1±0.2°, and 16.8±0.2°; (C) 17.8±0.2°, 18.5±0.2°, and 19.0±0.2°; and (D) 19.4±0.2°, 20.4±0.2°, and 21.7±0.2°.

### Claim 12 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form II characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 13.8±0.2°, 14.7±0.2°, 15.0±0.2°, 16.1±0.2°, 16.8±0.2°, 18.5±0.2°, 19.4±0.2°, 21.7±0.2° and 22.6±0.2°.

### Claim 13 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form II characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 13.8±0.10, 14.7±0.10, 15.0±0.10, 16.1±0.10, 16.8±0.10, 18.5±0.1°, 19.4±0.1°, 21.7±0.10 and 22.6±0.10.

### Claim 14 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form II characterized by an X-ray powder diffraction pattern comprising peaks expressed as 2θ at 9.6±0.20, 13.8±0.2°, 14.7±0.2°, 15.0±0.2°, 16.1±0.2°, 16.8±0.2°, 17.8±0.2°, 18.5±0.2°, 19.0±0.2°, 19.4±0.2°, 20.4±0.2°, 21.7±0.2°, 22.6±0.2°, 23.2±0.2°, and 24.5±0.2°.

### Claim 15

(canceled)

### Claim 16 (depends on 1)

The crystalline form of Compound (I) according to claim 1, wherein the crystalline form is crystalline Form II characterized by a differential scanning calorimetry thermogram comprising an endothermic peak at 80.53° C.±2° C.

### Claim at position 16

-18. (canceled)

### Claim 19 (depends on 1)

A pharmaceutical composition comprising crystalline Form I or II of Compound (I) according to claim 1 or a combination thereof, and a pharmaceutically acceptable excipient.

### Claim 20 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the pharmaceutical composition further comprises a cholinesterase inhibitor.

### Claim 21 (depends on 20)

The pharmaceutical composition according to claim 20, wherein the cholinesterase inhibitor is tacrine, donepezil, huperzine-A, galanthamine, or rivastigmine, or a combination thereof.

### Claim at position 20

-25. (canceled)

### Claim 26 (depends on 1)

A method for preventing, treating or lessening a central nervous system disease, a neurodegenerative disease, or a symptom of diabetes in a subject in need thereof, comprising administering to the subject the crystalline form according to claim 1.

### Claim 27 (depends on 26)

The method according to claim 26, wherein the central nervous system disease is Parkinson syndrome, Alzheimer's disease, Huntington's disease, atrophic myelitis, AIDS dementia, vascular dementia, seizures, neuralgia, or abstinence symptoms.

### Claim 28 (depends on 26)

The method of claim 26, further comprising administering to the subject a cholinesterase inhibitor.

### Claim 29 (depends on 28)

The method of claim 28, wherein the cholinesterase inhibitor is tacrine, donepezil, huperzine-A, galanthamine, or rivastigmine, or a combination thereof.

### Claim 30

(canceled)