# US 10,765,651 B2 · Co-crystals of substituted glycine and uses thereof

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- Number: US 10,765,651 B2
- Document ID: US10765651B2
- Status: Granted
- Kind: B2
- Application number: 16/412,804
- Filed: 2019-05-15
- Published: 2019-08-29
- Granted: 2020-09-08
- Earliest claimed: 2017-02-13
- Assignees: SyneuRx International (Taiwan) Corp.
- Applicants: SyneuRx International (Taiwan) Corp.
- Inventors: Guochuan Emil Tsai; Ching-Cheng Wang; Tien-Lan Hsieh
- Web page: https://patentgrep.com/patent/US10765651B2

## CPC

- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- C07C 57/15: Fumaric acid
- C07C 59/255: Tartaric acid
- C07C 229/12: to carbon atoms of acyclic carbon skeletons
- C07D 307/62: Three oxygen atoms, e.g. ascorbic acid
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure provides co-crystals of a substituted glycine compound and a co-former compound of Formula (I): compositions comprising such, and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, suicidal ideation and/or behavior, obsessive compulsive disorder or Alzheimer's disease). Also provided herein are methods for preparing the co-crystals.

## Claims

### Claim 1

A co-crystal comprising N-trimethylglycine and a co-former, wherein the co-former is a compound of Formula (IB):
in which:
A and B are both H or both OH;
W is O;
X is H;
Z is OH;
C2C1 are C2═C1 or C2-C1; and
wherein the molecular ratio between the N-trimethylglycine and the co-former in the co-crystal ranges from 1:1 to 2:1.

### Claim 2 (depends on 1)

The co-crystal of claim 1, wherein the co-former is fumaric acid or a geometric isomer thereof, or tartaric acid.

### Claim 3 (depends on 2)

The co-crystal of claim 2, wherein the co-former is tartaric acid.

### Claim 4 (depends on 3)

The co-crystal of claim 3, wherein the tartaric acid is D-tartaric acid.

### Claim 5 (depends on 3)

The co-crystal of claim 3, wherein the tartaric acid is L-tartaric acid.

### Claim 6 (depends on 3)

The co-crystal of claim 3, wherein the molecular ratio between the N-trimethylglycine and the tartaric acid is 1:1.

### Claim 7 (depends on 2)

The co-crystal of claim 2, wherein the co-former is fumaric acid or the geometric isomer thereof.

### Claim 8 (depends on 7)

The co-crystal of claim 7, wherein the molecular ratio between the N-trimethylglycine and the fumaric acid or the geometric isomer is 1:1 or 2:1.

### Claim 9 (depends on 1)

A composition comprising a co-crystal of claim 1 and a carrier, wherein the composition is formulated in a solid dosage form or a gel form.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the composition is a pharmaceutical composition, a nutraceutical composition, a health food, or a medical food.

### Claim 11 (depends on 9)

A method of treating or reducing the risk for a neuropsychiatric disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of the composition of claim 9.

### Claim 12 (depends on 11)

The method of claim 11, wherein the neuropsychiatric disorder is selected from the group consisting of schizophrenia, psychotic disorders, Alzheimer's disease, dementia, frontotemporal dementia, mild cognitive impairment, benign forgetfulness, closed head injury, an autistic spectrum disorder, Asperger's disorder, attention deficit hyperactivity disorders, obsessive compulsive disorder, tic disorders, childhood learning disorders, premenstrual syndrome, depressions, suicidal ideation and/or behavior, bipolar disorders, anxiety disorders, post-traumatic stress disorder, chronic pain, eating disorders, addiction disorders, personality disorders, Parkinson's disorder, Huntington's disorder, and amyotrophic lateral sclerosis.

### Claim 13 (depends on 1)

A method for preparing a co-crystal of claim 1, the method comprising:
(i) mixing the N-trimethylglycine and the co-former in a solvent at a temperature of about 40-110° C. to form a saturated solution;
(ii) incubating the solution at a temperature of about 40-110° C. for 1-10 hours;
(iii) cooling the solution at a temperature of about 4-30° C. for 10-36 hours to allow formation of the co-crystal; and
(iv) collecting the co-crystal formed in (iii),
wherein the solvent is selected from the group consisting of methanol, ethanol, acetic acid, dimethyl sulfoxide, tetrahydrofuran, water, and diethyl ether, or a combination thereof.