HCV polymerase inhibitors

Patent metadata

Field	Value
Publication number	US-9828408-B2
Application number	US-201615360360-A
Country	US
Kind code	B2
Filing date	Nov 23, 2016
Priority date	Sep 4, 2013
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The invention provides compounds of the formula:

wherein B is a nucleobase selected from the groups (a) to (d):

and the other variables are as defined in the claims,

which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

First claim

The invention claimed is:

1. A compound represented by formula I:

2. A process for the preparation of a compound of claim 1 comprising the step of reacting a diastereomenically pure compound of formula 1e with uracil, followed by removal of the hydroxy protecting groups as outlined in the scheme:

wherein
Pg 1 and Pg 2 are, the same or different, hydroxy protecting groups selected from triisopropylsilyl, acetyl, benzoyl, p-chlorobenzoyl or trityl;
Lg is a leaving group, selected from methylsulfonate, a halide or a phosphate ester.

3. The process of claim 2 , wherein Pg 1 and Pg 2 both are triisopropylsilyl or benzoyl.

4. The process of claim 3 , wherein Pg 1 and Pg 2 both are triisopropylsilyl.

5. The process of claim 2 , wherein Lg is methylsulfonate.

6. The process of claim 2 , wherein the reaction of compound 1e with uracil in step f is performed in the presence of hexamethyldisilazane and a Lewis acid.

7. The process of claim 6 , wherein the Lewis acid is TMS triflate.

8. The process of claim 2 , wherein removal the hydroxy protecting groups in step g is performed by treatment with an acid in an aqueous solution.

9. The process of claim 2 , wherein removal the hydroxy protecting groups is performed by treatment with aqueous acetic acid.

10. A diastereomerically pure compound of the formula:

11. A compound of the formula:

Assignees

• Medivir Ab

Inventors

• Kalayanov Genadiy
• Torssell Staffan
• Wahling Horst

Classifications

• C07H19/16

  Purine radicals · CPC title

• C07H19/073

  with 2-deoxyribosyl as the saccharide radical · CPC title

• A61K45/06

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

• A61K31/7072

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title

• C07H19/10

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title