# US 12,595,254 B2 · Crystal form of Resmetirom, preparation method therefor, and use thereof

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- Number: US 12,595,254 B2
- Document ID: US12595254B2
- Status: Granted
- Kind: B2
- Application number: 18/044,717
- Filed: 2021-08-30
- Published: 2023-12-28
- Granted: 2026-04-07
- Earliest claimed: 2020-09-10
- Assignees: Crystal Pharmaceutical (Suzhou) Co., Ltd.
- Applicants: Crystal Pharmaceutical (Suzhou) Co., Ltd.
- Inventors: Minhua Chen; Chunxiang Huang
- Web page: https://patentgrep.com/patent/US12595254B2

## CPC

- C07D 403/12: linked by a chain containing hetero atoms as chain links
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- 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 new crystal form of Resmetirom (referred to as “Compound I”) and a preparation method therefor, a pharmaceutical composition comprising the crystal form, and a use of the crystal form in preparing a THR-β selective agonist drug and a drug for treating NASH and HeFH. Compared with the prior art, the provided crystal form of the compound I has one or more improved properties, solves problems existing in the prior art, and has a great value for the optimization and development of drugs containing the compound I.

## Claims

### Claim 1

A crystalline form of Compound I, wherein the crystalline form is an anhydrate and has an X-ray powder diffraction pattern comprising characteristic peaks at 2θ values of 9.6°±0.2°, 10.1°±0.2°, 13.7°±0.2°, 18.9°±0.2°, 20.6°±0.2°, and 31.9°±0.2 using CuKα radiation,

### Claim 2 (depends on 1)

The crystalline form of Compound I according to claim 1, wherein the X-ray powder diffraction pattern comprises at least one characteristic peaks at 2θ values of 11.6°±0.2°, 19.5°±0.2°, and 23.3±0.2° using CuKα radiation.

### Claim 3 (depends on 1)

The crystalline form of Compound I according to claim 1, wherein the X-ray powder diffraction pattern using CuKα radiation is substantially as depicted in FIG. 1.

### Claim 4 (depends on 1)

A pharmaceutical composition, wherein said pharmaceutical composition comprises a therapeutically effective amount of crystalline form of Compound I according to claim 1, and pharmaceutically acceptable excipients.

### Claim 5 (depends on 1)

A process for preparing the crystalline form of Compound I according to claim 1, wherein the process comprises:
(1) adding Compound I into a nitrile or a solvent mixture of nitrile and water, stirring, separating and drying to obtain the crystalline form; or
(2) dissolving Compound I into a solvent mixture of a nitrile and water or a solvent mixture of a nitrile and an alcohol, filtering, cooling the filtrate, stirring to obtain solid, separating and drying to obtain the crystalline form.

### Claim 6 (depends on 5)

The process according to claim 5, in method (1), wherein the nitrile is acetonitrile, a volume ratio of acetonitrile and water in the solvent mixture is 95:5; in method (2), wherein the nitrile is acetonitrile, the alcohol is isopropanol, a volume ratio of acetonitrile and water in the solvent mixture is 95:5, and a volume ratio of acetonitrile and isopropanol in the solvent mixture is 1:1.

### Claim 7 (depends on 5)

The process according to claim 5, in method (1), wherein a stirring temperature is −20° C.-76° C., and a drying temperature is 10° C.-70° C.; in method (2), wherein a dissolving temperature is 40° C.-76° C., a cooling temperature is −20° C.-5° C., and a drying temperature is 10° C.-70° C.

### Claim 8 (depends on 7)

The process according to claim 7, in method (1), wherein the stirring temperature is −20° C.-30° C., and the drying temperature is 10° C.-40° C.; in method (2), wherein the cooling temperature is −20° C., and the drying temperature is 10° C.-40° C.

### Claim 9 (depends on 1)

A method for selectively activating THR-β, comprising administering the crystalline form of Compound I according to claim 1 to a subject in need thereof.

### Claim 10 (depends on 1)

A method for treating NASH and HeFH, comprising administering the crystalline form of Compound I according to claim 1 to a subject in need thereof.