Uracyl spirooxetane nucleosides

• US 10,301,347 B2
• Filed: 12/06/2018
• Issued: 05/28/2019
• Est. Priority Date: 05/25/2012
• Status: Active Grant

• Current Assignee: Janssen Sciences Ireland Unlimited Company (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland Unlimited Company (Johnson & Johnson)
• Inventors: Houpis, Ioannis Nicolaos, Jonckers, Tim Hugo Maria, Raboisson, Pierre Jean-Marie Bernard, Tahri, Abdellah
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US16/212,554
• Publication Number:
  US 20190092804A1
• Time in Patent Office: 173 Days
• Field of Search: None
• 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 31/14 for RNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• 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 19/11 containing cyclic phosphate
• CPC Class Codes: C07H 19/24 Heterocyclic radicals containing oxygen or sulfur as ring hetero atom

Abstract

The present invention relates to compounds of the formula I:

including any possible stereoisomers thereof, wherein R⁹ has the meaning as defined herein, or a pharmaceutically acceptable salt or solvate thereof.

The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.

Claims

1. A method of preparing a compound of formula (7),

2. A method as claimed in claim 1, wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in the presence of triethylamine.

3. A method as claimed in claim 1, wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in the presence of N-methylimidazole.

4. A method as claimed in claim 1, wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in dichloromethane.

5. A method as claimed in claim 1, wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in the presence of triethylamine and N-methylimidazole in dichloromethane.

6. A method as claimed in claim 1, wherein R⁹ is C₁-C₆alkyl.

7. A method as claimed in claim 1, wherein R⁹ is C₃-C₇cycloalkyl.

8. A method as claimed in claim 1, wherein R⁹ is isopropyl.

9. A method as claimed in claim 1, wherein R⁹ is C₂-C₄alkyl.

10. A method as claimed in claim 1, wherein R⁹ is C₁-C₂alkyl substituted with phenyl.