# US 10,370,406 B2 · Salts and polymorphs of SCY-078

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- Number: US 10,370,406 B2
- Document ID: US10370406B2
- Status: Granted
- Kind: B2
- Application number: 16/203,273
- Filed: 2018-11-28
- Published: 2019-05-23
- Granted: 2019-08-06
- Earliest claimed: 2015-01-19
- Assignees: Scynexis, Inc.
- Applicants: Scynexis, Inc.
- Inventors: Yi Zhang
- Web page: https://patentgrep.com/patent/US10370406B2

## CPC

- C07J 71/0005: {Oxygen-containing hetero ring}
- A61P 31/10: Antimycotics
- C07C 59/265: Citric acid
- C07D 405/14: containing three or more hetero rings
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07J: STEROIDS (seco-steroids C07C)
- 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

SCY-078 is a glucan synthase inhibitor with antimicrobial activity. Novel salts and polymorph forms of SCY-078 are disclosed herein. The disclosure also relates to pharmaceutical compositions, methods of use, and methods of preparing the novel salts and polymorphs of SCY-078.

## Claims

### Claim 1

A method of treating a fungal infection in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising an effective amount of a pharmaceutically acceptable salt of compound 1:
wherein the pharmaceutically acceptable salt is selected from citrate, hippurate, mesylate, and fumarate, and wherein the pharmaceutically acceptable salt of compound 1 used to prepare the pharmaceutical composition has a water sorption of from 2% to 7% at 25° C. and 80% relative humidity as determined by DVS.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and wherein the pharmaceutical composition is suitable for injection into the patient.

### Claim 3 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and wherein the pharmaceutically acceptable salt of compound 1 is dissolved in the pharmaceutically acceptable carrier prior to administering the pharmaceutical composition to the patient.

### Claim 4 (depends on 3)

The method of claim 3, wherein the administering comprises administration by intravenous injection.

### Claim 5 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt of compound 1 used to prepare the pharmaceutical composition has a water sorption of from 3% to 7% at 25° C. and 80% relative humidity as determined by DVS.

### Claim 6 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt of compound 1 used to prepare the pharmaceutical composition has a water sorption of from 6% to 7% at 25° C. and 80% relative humidity as determined by DVS.

### Claim 7 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt of compound 1 is a citrate salt of compound 1.

### Claim 8 (depends on 1)

The method of claim 1, wherein the fungal infection is a Candida and/or Aspergillus fungal infection.

### Claim 9 (depends on 1)

The method of claim 1, wherein the fungal infection is Invasive Candidiasis and/or Invasive Aspergillosis.

### Claim 10

A method of treating a fungal infection in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising an effective amount of a citrate salt of compound 1:
wherein the citrate salt of compound 1 used to prepare the pharmaceutical composition comprises at least one of Type A, Type B, Type E, Type F, Type M, Type N, Type O, Type Q, Type R, and Type S citrate crystal forms.

### Claim 11 (depends on 10)

The method of claim 10, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and the pharmaceutical composition is suitable for injection into the patient.

### Claim 12 (depends on 10)

The method of claim 10, wherein the citrate salt of compound 1 is dissolved in a pharmaceutically acceptable carrier prior to administering the pharmaceutical composition to the patient.

### Claim 13 (depends on 12)

The method of claim 12, wherein the administering comprises administration by intravenous injection.

### Claim 14 (depends on 10)

The method of claim 10, wherein the citrate salt of compound 1 used to prepare the pharmaceutical composition comprises Type A.

### Claim 15 (depends on 10)

The method of claim 10, wherein the citrate salt of compound 1 used to prepare the pharmaceutical composition consists essentially of Type A.

### Claim 16 (depends on 10)

The method of claim 10, wherein the citrate salt of compound 1 used to prepare the pharmaceutical composition comprises at least 98% Type A.

### Claim 17 (depends on 10)

The method of claim 10, wherein the citrate salt of compound 1 used to prepare the pharmaceutical composition comprises at least 99% Type A.

### Claim 18 (depends on 14)

The method of claim 14, wherein the Type A has an XRPD pattern comprising peaks at d-spacing of 11.86, 6.71, and 5.90 Angstroms.

### Claim 19 (depends on 14)

The method of claim 14, wherein the Type A has an XRPD pattern comprising peaks at d-spacing of 11.86, 7.70, 7.09, 6.71, 5.90, and 5.29 Angstroms.

### Claim 20 (depends on 14)

The method of claim 14, wherein the Type A has an XRPD pattern comprising peaks at degrees 2 theta of 7.45, 11.49, 12.49, 13.19, 15.02, and 16.75.

### Claim 21 (depends on 14)

The method of claim 14, wherein the Type A has an XRPD pattern comprising peaks at degrees 2 theta of 7.45, 13.19, and 15.02.

### Claim 22 (depends on 14)

The method of claim 14, wherein the Type A is stable for at least 1 week when stored at 60° C.

### Claim 23 (depends on 14)

The method of claim 14, wherein the Type A is stable for at least 1 week when stored at 25° C. and 60% relative humidity.

### Claim 24 (depends on 14)

The method of claim 14, wherein the Type A is stable for at least 1 week when stored at 40° C. and 75% relative humidity.

### Claim 25 (depends on 14)

The method of claim 14, wherein the Type A has an equilibrium solubility of 38 mg/mL in non-buffered water at room temperature.

### Claim 26 (depends on 14)

The method of claim 14, wherein the Type A has an approximate solubility of from 40 mg/mL to 42 mg/mL at room temperature in at least one solvent selected from methanol, isopropyl alcohol, acetic acid, tetrahydrofuran, 2-methyl-tetrahydrofuran, 1,4-dioxane, n-methyl-2-pyrrolidone, dimethyl sulfoxide, and dimethylacetamide.

### Claim 27 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 4 mg/mL at 4 hours in dextrose buffer at pH 5.5.

### Claim 28 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 8 mg/mL at 24 hours in dextrose buffer at pH 5.5.

### Claim 29 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 5 mg/mL at 4 hours in phosphate buffer at pH 6.0.

### Claim 30 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 8 mg/mL at 24 hours in phosphate buffer at pH 6.0.

### Claim 31 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 21 mg/mL at 1 hour in SGF media.

### Claim 32 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 4 mg/mL at 24 hours in FeSSIF media.

### Claim 33 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 10 mg/mL at 1 hour in FaSSIF media.

### Claim 34 (depends on 14)

The method of claim 14, wherein the Type A has a kinetic solubility of 21 mg/mL at 4 hours in FaSSIF media.

### Claim 35 (depends on 14)

The method of claim 14, wherein the Type A has a water sorption of 6% at 25° C. and 80% relative humidity as determined by DVS.

### Claim 36 (depends on 10)

The method of claim 10, wherein the fungal infection is a Candida and/or Aspergillus fungal infection.

### Claim 37 (depends on 10)

The method of claim 10, wherein the fungal infection is Invasive Candidiasis and/or Invasive Aspergillosis.