Crystalline forms of an antiviral compound

Patent metadata

Field	Value
Publication number	US-9862728-B2
Application number	US-201615387318-A
Country	US
Kind code	B2
Filing date	Dec 21, 2016
Priority date	Dec 23, 2013
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

Crystalline forms of the anti-HCV compound (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide (Compound I) were prepared and characterized in the solid state:

Also provided are processes of manufacture and methods of using the crystalline forms.

First claim

What is claimed is:

1. A crystalline form of compound I:

wherein, the crystalline form is:
an ethyl acetate solvate (Compound I Form II) characterized by an X-ray powder diffractogram comprising peaks (±0.2°) at 8.7, 13.0, and 17.4°2θ as determined on a diffractometer using Cu-Kα radiation.

2. Compound I Form II according to claim 1 , further comprising:
i) a peak at 15.4°±2θ±0.2°;
ii) a diffractogram substantially as shown in FIG. 6 ;
iii) a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 7 ;
iv) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG. 8 ;
v) a nuclear magnetic resonance spectrum ( 1 H NMR) substantially as shown in FIG. 9 ;
vi) a dynamic vapor sorption (DVS) curve substantially as shown in FIG. 10 ; or
vii) about 1 mole equivalents of ethyl acetate.

3. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable excipient.

Assignees

• Gilead Sciences Inc

Inventors

• Bringley Dustin
• Chan Johann
• Fung Peter
• Keaton Katie
• Lapina Olga
• Morrison Henry
• Pcion Dominika

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title