Solid forms of an antiviral compound

• US 9,340,568 B2
• Filed: 12/08/2014
• Issued: 05/17/2016
• Est. Priority Date: 12/23/2013
• Status: Expired due to Fees

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Casteel, Melissa Jean, Dashner, Kathleen, Jung, Hyuk-Jun, Seo, Mun Sik, Shi, Bing, Wang, Fang, Zia, Vahid
• Primary Examiner(s): LEWIS, PATRICK T
• Application Number:
  US14/563,639
• Publication Number:
  US 20150175646A1
• Time in Patent Office: 526 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07F 9/65586 at least one of the hetero rings does not contain nitrogen as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

Crystalline solid forms of the anti-HCV compound (S)-isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2- yl)methoxy)(phenoxy)phosphorylamino)propanoate (Compound I) are described

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

Claims

1. A crystalline Compound I

2. The crystalline compound of claim 1, wherein the XRPD spectrum further comprises a peak at 17.3 °

2θ

±

0.2°

2θ

.

9. A pharmaceutical composition comprising the crystalline compound of claim 1 and a pharmaceutically acceptable excipient.

10. A method of treating a human subject infected with hepatitis C virus comprising administering to the human subject a therapeutically effective amount of the crystalline compound of claim 1.

3. A crystalline Compound I

4. The crystalline compound of claim 3, wherein the ¹³C SSNMR spectrum further comprises peaks at 21.5, 68.7, 81.7, 102.8, and 151 ppm±

0.2 ppm.

5. A crystalline Compound I:

6. The crystalline compound of claim 5, wherein the XRPD spectrum further comprises peaks at 14.2, 15.6, 16.0, 17.5, 18.1, 19.8, and 25.6 °

2θ

±

0.2°

2θ

.

7. A crystalline Compound I:

8. The crystalline compound of claim 7, wherein the ¹³C SSNMR spectrum further comprises peaks at 22.2, 71.6, 78.8, 118.6 and 172.2 ppm±

0.2 ppm.