Co-crystals, salts and solid forms of tenofovir alafenamide

Patent metadata

Field	Value
Publication number	US-9777028-B2
Application number	US-201615181213-A
Country	US
Kind code	B2
Filing date	Jun 13, 2016
Priority date	Jun 17, 2015
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

The present invention relates to co-crystals, salts and crystalline forms of tenofovir alafenamide and methods for preparation, use and isolation of such compounds.

First claim

The invention claimed is:

1. A solvate of tenofovir alafenamide sesquifumarate, wherein the solvate comprises a solvent selected from the group consisting of isopropanol, methyl ethyl ketone, tetrahydrofuran and acetone.

2. A crystal form of the sesquifumarate of claim 1 , wherein the solvent is isopropanol and the crystal form has an XRPD pattern comprising 2theta values of 4.5±0.2, 20.4±0.2, 26.5±0.2, and 26.9±0.2.

3. A crystal form of the sesquifumarate of claim 1 , wherein the solvent is isopropanol and the crystal form has a differential scanning calorimetry (DSC) comprising onset endotherms of 54±2° C. and 112±2° C.

4. A crystal form of the sesquifumarate of claim 1 , wherein the solvent is methyl ethyl ketone and the crystal form has a XRPD pattern comprising 2theta values of 4.6±0.2, 22.8±0.2, 27.4±0.2, and 27.8±0.2.

5. A crystal form of the sesquifumarate of claim 1 , wherein the solvent is tetrahydrofuran and the crystal form has a XRPD pattern comprising 2theta values of 4.5±0.2, 22.6±0.2, 27.2±0.2, and 27.7±0.2.

6. A crystal form of the sesquifumarate of claim 1 , wherein the solvent is acetone and the crystal form has a XRPD pattern comprising 2theta values of 4.6±0.2, 22.9±0.2, 27.6±0.2 and 28.0±0.2.

7. A crystal form of tenofovir alafenamide sesquifumarate, wherein the crystal form has a XRPD pattern comprising 2theta values of 5.0±0.2, 20.1±0.2, 22.7±0.2, and 25.2±0.2.

8. A crystal form of tenofovir alafenamide sesquifumarate, having differential scanning calorimetry (DSC) onset endotherms of 110±2° C. and 118±2° C.

9. A pharmaceutical composition comprising the crystal form of claim 7 and a pharmaceutically acceptable excipient.

10. A method for treating an HIV infection comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 4 .

11. A pharmaceutical composition comprising the crystal form of claim 8 and a pharmaceutically acceptable excipient.

12. A method for treating an HIV infection comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 11 .

Assignees

• Gilead Sciences Inc

Inventors

• Shi Bing
• Su Zhuoyi
• Wang Fang

Classifications

• A61P31/20

  for DNA viruses · CPC title

• A61P31/18

  for HIV · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C57/15

  Fumaric acid · CPC title

• C07F9/65616 Primary

  containing the ring system [IMAGE cpc-sch-C07F-1006.gif] having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs · CPC title