Dioxolane analogues of cytidine for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-10144750-B2
Application number	US-201515506692-A
Country	US
Kind code	B2
Filing date	Aug 24, 2015
Priority date	Aug 25, 2014
Publication date	Dec 4, 2018
Grant date	Dec 4, 2018

Abstract

The invention provides compounds of the formula:

R 1 is OR 11 , or NR 5 R 5′ ;
R 2 is H or F;
R 5 is H, OH, C 1 -C 6 alkyl, OH, C(═O)R 6 , O(C═O)R 6 or O(C═O)OR 6 ;
R 5′ is H or C 1 -C 6 alkyl;
R 6 is C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl;
R 13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R 22 ;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.

First claim

The invention claimed is:

1. A compound represented by formula Ia:

wherein:
R 1 is NH 2 ;
R 2 is H;
R 13 is phenyl, optionally substituted with 1, 2 or 3 R 22 ;
R 15 is methyl;
R 16 is 2-pentyl;
each R 22 is independently selected from halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, phenyl, hydroxyC 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylcarbonyl, C 3 -C 6 cycloalkylcarbonyl, carboxyC 1 -C 6 alkyl, hydroxy, amino CN, and NO 2 , or any two R 22 groups attached to adjacent ring carbon atoms can combine to form —O—(CR 23 R 23′ ) 1-6 -O—;
R 23 and R 23′ are independently H or C 1 -C 3 alkyl;
or a pharmaceutically acceptable salt and/or solvate thereof.

2. A compound according to claim 1 wherein R 13 is substituted with one or two R 22 .

3. A compound according to claim 1 , wherein R 13 is unsubstituted phenyl.

4. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 in association with a pharmaceutically acceptable adjuvant, diluent or carrier.

5. A pharmaceutical combination comprising a therapeutically effective amount of compound according to claim 1 , further comprising one or more additional therapeutic agent(s) selected from the group consisting of chemotherapeutical agent, multi-drug resistance reversing agent and biological response modifier.

6. The pharmaceutical combination according to claim 5 , wherein the further therapeutic agent is a chemotherapeutical agent.

7. The compound of claim 1 , that is

8. The compound of claim 1 , that is

9. The compound of claim 1 that is

Assignees

• Medivir Ab

Inventors

• Bethell Richard
• Eneroth Anders
• Klasson Bjorn
• Oberg Fredrik

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P1/16

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

• C07F9/65586 Primary

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title