# US 9,518,049 B2 · Salt forms of (S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate

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- Number: US 9,518,049 B2
- Document ID: US9518049B2
- Status: Granted
- Kind: B2
- Application number: 14/776,432
- Filed: 2014-03-14
- Published: 2016-02-11
- Granted: 2016-12-13
- Earliest claimed: 2013-03-15
- Assignees: Genzyme Corporation
- Applicants: Genzyme Corporation
- Inventors: Craig S. Siegel; Jin Zhao
- Web page: https://patentgrep.com/patent/US9518049B2

## CPC

- C07D 453/00: Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 59/245: containing hydroxy or O-metal groups
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to novel salt forms of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate useful as an inhibitor of glucosylceramide synthase (GCS) and for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

## Claims

### Claim 1

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peak measured using CuKα radiation: 18.095.

### Claim 2

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 18.095 and 17.493.

### Claim 3

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 18.095 and 19.516.

### Claim 4

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 18.095, 17.493, and 19.516.

### Claim 5

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 18.095, 17.493, 19.516 and 20.088.

### Claim 6

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 18.095, 17.493, 19.516 and 20.088 and 17.125.

### Claim 7

A crystalline Form B of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peak measured using CuKα radiation: 24.355.

### Claim 8

A crystalline Form B of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 24.355 and 21.167.

### Claim 9

A crystalline Form B of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 24.355, 21.167 and 27.343.

### Claim 10

A crystalline Form B of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 24.355, 21.167, 27.343 and 16.111.

### Claim 11

A crystalline Form B of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 24.355, 21.167, 27.343, 16.111 and 17.185.

### Claim 12

A crystalline Form B of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate malate, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 24.355, 21.167, 27.343, 16.111, 17.185 and 20.243.

### Claim 13

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate (S)-2-hydroxysuccinate salt, wherein said x-ray powder diffraction contains the following 2-theta peak measured using CuKα radiation: 17.162.

### Claim 14

A crystalline Form A of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate (S)-2-hydroxysuccinate salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 17.162 and 18.028.

### Claim 15

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate (S)-2-hydroxysuccinate salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 17.162 and 14.280.

### Claim 16

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate (S)-2-hydroxysuccinate salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 17.162, 18.028 and 14.280.

### Claim 17

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate (S)-2-hydroxysuccinate salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 17.162, 18.028, 14.280 and 18.153.

### Claim 18

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate (S)-2-hydroxysuccinate salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 17.162, 18.028, 14.280, 18.153 and 23.422.

### Claim 19

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate HCl salt, wherein said x-ray powder diffraction contains the following 2-theta peak measured using CuKα radiation: 18.087.

### Claim 20

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate HCl salt, wherein said x-ray powder diffraction contains the following 2-theta peak measured using CuKα radiation: 12.818.

### Claim 21

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate HCl salt, wherein said x-ray powder diffraction contains the following 2-theta peak measured using CuKα radiation: 25.722.

### Claim 22

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate HCl salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 12.818 and 25.722.

### Claim 23

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate HCl salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 12.818, 25.722 and 13.040.

### Claim 24

A crystalline form of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate HCl salt, wherein said x-ray powder diffraction contains the following 2-theta peaks measured using CuKα radiation: 12.818, 25.722, 13.040 and 28.910.