Sodium (2r,5s,13ar)-7,9-dioxo-10-((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b]oxazepin-8-olate

Patent metadata

Field	Value
Publication number	US-2016016973-A1
Application number	US-201514744915-A
Country	US
Kind code	A1
Filing date	Jun 19, 2015
Priority date	Jun 20, 2014
Publication date	Jan 21, 2016
Grant date	—

Abstract

The present invention relates to sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepin-8-olate Form I.

First claim

What is claimed:

1 . A compound of Formula II:

2 . The compound of claim 1 , characterized by being crystalline.

3 . The compound of claim 2 , characterized by an x-ray powder diffraction (XRPD) pattern having peaks at about 5.5°, 16.1°, and 23.3° 2-θ±0.2° 2-θ.

4 . The compound of claim 3 , wherein the x-ray powder diffraction (XRPD) pattern has further peaks at about 22.1°, and 28.5° 2-θ±0.2° 2-θ.

5 . The compound of claim 4 , wherein the x-ray powder diffraction (XRPD) pattern has further peaks at about 22.5 and 19.5° 2-θ±0.2° 2-θ.

6 . The compound of claim 5 , wherein the x-ray powder diffraction (XRPD) pattern has further peaks at about 26.6° and 17.9° 2-θ±0.2° 2-θ.

7 . The compound of claim 2 , characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 1 .

8 . The compound of claim 2 , characterized by differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 2 .

9 . The compound of claim 2 , characterized by a dynamic vapor sorption (DVS) pattern substantially as set forth in FIG. 4 .

10 . The compound of any one of claims 1 to 9 , characterized in being partially or fully hydrated.

11 . The compound of any one of claims 1 to 9 , characterized in being anhydrous or essentially anhydrous.

12 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 11 , and a pharmaceutically acceptable carrier or excipient.

13 . The pharmaceutical composition of claim 12 , further comprising one to three additional therapeutic agents.

14 . The pharmaceutical composition of claim 13 , wherein the additional therapeutic agents are each anti-HIV drugs.

15 . The pharmaceutical composition of claim 13 or claim 14 , wherein the additional therapeutic agents are each independently selected from the group consisting of HIV protease inhibitors, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, and other drugs for treating HIV.

16 . The pharmaceutical composition of any one of claims 12 to 14 , wherein at least two of the additional therapeutic agents are each HIV nucleoside inhibitors of reverse transcriptase.

17 . The pharmaceutical composition of claim 12 , further comprising tenofovir disoproxil fumarate and emtricitabine.

18 . The pharmaceutical composition of claim 12 , further comprising tenofovir alafenamide and emtricitabine.

19 . The pharmaceutical composition of claim 12 , further comprising tenofovir alafenamide hemifumarate and emtricitabine.

20 . The pharmaceutical composition of any one of claims 12 to 18 , wherein the pharmaceutical composition is in a unit dosage form.

21 . The pharmaceutical composition of claim 20 , wherein the unit dosage form is a tablet.

22 . Use of a compound of any one of claims 1 to 11 for treating or prophylactically preventing an HIV infection.

23 . Use of a compound of any one of claims 1 to 11 for the manufacture of a medicament for treating or prophylactically preventing an HIV infection.

24 . A compound of any one of claims 1 to 11 for use in a method for treating or prophylactically preventing an HIV infection.

25 . A method for treating or prophylactically preventing an HIV infection in a human in need thereof, comprising administering to the human a therapeutically effective amount of a compound of any one of claims 1 to 11 .

Assignees

• Gilead Sciences Inc

Inventors

• Carra Ernest A
• Chen Irene
• Zia Vahid

Classifications

• A61P31/18

  for HIV · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• C07D498/14 Primary

  Ortho-condensed systems · CPC title