Nucleoside phosphoramidates

• US 9,284,342 B2
• Filed: 06/24/2013
• Issued: 03/15/2016
• Est. Priority Date: 05/20/2009
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Ross, Bruce S., Sofia, Michael Joseph, Pamulapati, Ganapati Reddy, Rachakonda, Suguna, Zhang, Hai-Ren, Chun, Byoung-Kwon, Wang, Peiyuan
• Primary Examiner(s): Olson, Eric
• Application Number:
  US13/925,078
• Publication Number:
  US 20130288997A1
• Time in Patent Office: 995 Days
• Field of Search: None
• US Class Current: 1/1
• 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: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07F 9/2479 Compounds containing the structure P(=X)n-N-acyl, P(=X)n-N-heteroatom, P(=X)n-N-CN (X = O, S, Se; n = 0, 1)
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds

Abstract

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

Claims

1. A crystalline compound represented by the formula (S_P-4):

2. A pharmaceutical composition comprising the crystalline compound according to claim 1 and a pharmaceutically acceptable medium.

3. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the crystalline compound according to claim 1.

4. The method according to claim 3 further comprising administering to the human another antiviral agent.

5. A process for preparing the crystalline compound according to claim 1 comprising:

exposing a second crystalline compound represented by the formula (S_P-4);

6. The process according to claim 5 further comprising:

grinding the first composition into a powder; and

allowing the powder to stand in an open vessel.

7. A process for preparing the crystalline compound according to claim 1 comprising:

suspending a second crystalline compound represented by the formula (S_P-4);

8. The process according to claim 7 further comprising heating the suspension.

9. The process according to claim 8 further comprising cooling the suspension.