Macrocyclic deaza-purinones for the treatment of viral infections

Patent metadata

Field	Value
Publication number	US-2016304531-A1
Application number	US-201414781291-A
Country	US
Kind code	A1
Filing date	Mar 28, 2014
Priority date	Mar 29, 2013
Publication date	Oct 20, 2016
Grant date	—

Abstract

This invention relates to macrocyclic deaza-purinones derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

First claim

1 . A compound having formula (I)

and pharmaceutically accepted salts thereof, wherein
n is 1, 2 or 3;
X is oxygen, nitrogen or sulfur;
Y represents an aromatic ring or heterocyclic ring comprising at least a nitrogen, optionally substituted by one or more substituents independently selected from the group consisting of C 1-6 alkyl, C 1-4 alkoxy, trifluoromethyl and halogen; and
Z represents C 1-10 saturated or unsaturated alkyl optionally substituted by an alkyl or alkylhydroxyl,
or Z represents C 1-6 alkyl —NH—C(O)— C 1-6 alkyl- , C 1-6 alkyl-NH— or C 1-6 alkyl —NH—C(O)— C 1-6 alkyl —O—,
or Z represents C 1-10 alkyl —O— wherein said alkyl is unsaturated or saturated and can optionally be substituted by an alkyl or alkylhydroxyl,
or Z represents C 1-6 alkyl-O—C 1-6 alkyl- wherein said alkyl is unsaturated or saturated and can optionally be substituted by an alkyl or alkylhydroxyl,
or Z represents C 1-6 alkyl-O—C 1-6 alkyl-O— wherein said alkyl is unsaturated or saturated and can optionally be substituted by an alkyl or alkylhydroxyl.

2 . A compound according to claim 1 selected from the group consisting of:

3 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt, solvate or polymorph thereof, together with one or more pharmaceutically acceptable excipients, diluents or carriers.

4 . (canceled)

5 . A method of treating a disorder involving the modulation of TLR 7, comprising administering a therapeutically effective amount of at least one compound of claim 1 .

6 . A compound selected from the group consisting of:

7 . The compound of claim 1 , wherein X is O or N.

8 . The compound of claim 1 , wherein Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen.

9 . The compound of claim 1 , wherein Y is phenyl optionally substituted with methoxy or fluorine.

10 . The compound of claim 1 , wherein Z is selected from the group consisting of C 1-10 alkyl, C 1-6 alkyl-NH—, and C 1-10 alkyl-O—, and wherein said alkyl is saturated or unsaturated.

11 . The compound of claim 1 , wherein
n is 1 or 2; X is O or N; Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen; and Z is selected from the group consisting of C 1-10 alkyl, C 1-6 alkyl-NH—C(O)—C 1-6 alkyl, C 1-6 alkyl-NH—, C 1-6 alkyl —NH—C(O)—C 1-6 alkyl-O—, C 1-10 alkyl-O—, C 1-6 alkyl-O—C 1-6 alkyl-, and C 1-6 alkyl-O—C 1-6 alkyl-O—, wherein said alkyl is saturated or unsaturated, and wherein said alkyl is optionally substituted with an alkyl or alkylhydroxyl.

12 . The compound of claim 1 wherein;
n is 1 or 2;
X is O or N; and
Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen.

13 . The compound of claim 1 , wherein
n is 1 or 2; X is O or N; Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen; and Z is selected from the group consisting of C 1-10 alkyl, C 1-6 alkyl-NH—, and C 1-10 alkyl-O—, and wherein said alkyl is saturated or unsaturated.

14 . The compound of claim 1 , wherein
n is 1 or 2; X is O or N; Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen; and Z is C 1-10 alkyl, wherein said alkyl is saturated or unsaturated.

15 . The compound of claim 1 , wherein
n is 1 or 2; X is O or N; Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen; and Z is C 1-10 alkyl-O—, wherein said alkyl is saturated or unsaturated.

16 . The compound of claim 1 , wherein
n is 1; X is O; Y is an aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of C 1-4 alkoxy and halogen; and Z is C 1-6 alkyl-NH—, wherein said alkyl is saturated or unsaturated.

17 . The compound of claim 1 , wherein
n is 1 or 2; X is O or N; Y is an aromatic ring optionally substituted with methoxy or fluorine; and Z is C 1-10 alkyl-O—, wherein said alkyl is saturated or unsaturated.

18 . A method of treating a viral infection comprising administering a therapeutically effective amount of at least one compound of claim 1 .

19 . A method of treating a viral infection comprising administering the pharmaceutical composition of claim 3 .

20 . A method of preparing the compound of claim 1 .

Assignees

• Janssen Sciences Ireland Uc

Inventors

• Bonfanti Jean-Francois
• Fortin Jerome Michel Claude
• Muller Philippe
• Doublet Frederic Marc Maurice
• Raboisson Pierre Jean-Marie Bernard
• Arnoult Eric Pierre Alexandre

Classifications

• A61P37/02

  Immunomodulators · CPC title

• C07D498/18

  Bridged systems · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P29/00 Primary

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D471/18

  Bridged systems · CPC title