Heterocyclic indoles for use in influenza virus infection

Patent metadata

Field	Value
Publication number	US-2018258074-A1
Application number	US-201615779468-A
Country	US
Kind code	A1
Filing date	Nov 25, 2016
Priority date	Nov 27, 2015
Publication date	Sep 13, 2018
Grant date	—

Abstract

The current invention relates to a compound of formula (I) which can be used for the treatment of, or against viral influenza infections.

First claim

1 . A compound of formula (I)

a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof, wherein
X is N and Y is N; or
X is C substituted by —F and Y is C substituted by —F, —Cl, —CH 3 , or —CN;
Z is N, Q is selected from —C—CH 3 , —C—COOH, —C—CF 3 , —CH-cyclopropyl, —CH 2 R 1 , or —CONR 1 R 1 and M is CF wherein R 1 is independently selected from hydrogen,
halogen, cyano, oxo, alkyl, hydroxyl, amino; or
Z is N, Q is N and M is CH; or
Z is C, Q is N and M is CH; and
R is C 3-8 cycloalkyl substituted by carboxylic acid, or —N—C(O)—C 3-6 heterocycle optionally substituted by C 1-6 alkyl or -COOH.

2 . A compound according to claim 1 having the structural formula

3 . A pharmaceutical composition comprising a compound of formula (I) or a stereo- isomeric form , a pharmaceutically acceptable salt, solvate or polymorph thereof according to claim 1 together with one or more pharmaceutically acceptable excipients, diluents or carriers.

4 . (canceled)

5 . (canceled)

6 . A method of treating influenza infection in a patient, said method comprising administering to the patient a compound represented by the following structural formula (I)

a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof, wherein
X is N and Y is N; or
X is C substituted by —F and Y is C substituted by —F, —Cl, —CH 3 , or —CN;
Z is N, Q is selected from —C—CH 3 , —C—COOH, —C—CF 3 , —CH-cyclopropyl, —CH 2 R 1 , or —CONR 1 R 1 and M is CF wherein R1 is independently selected from hydrogen, halogen, cyano, oxo, alkyl, hydroxyl, amino ; or
Z is N, Q is N and M is CH; or
Z is C, Q is N and M is CH; and
R is C 3-8 cycloalkyl substituted by carboxylic acid, or —N—C(O)—C 3-6 heterocycle optionally substituted by C 1-6 alkyl or —COOH.

7 . The method of claim 6 , further comprising co-administering an additional therapeutic agent.

8 . The method of claim 7 , wherein the additional therapeutic agent is selected from an antiviral agent or influenza vaccine, or both.

9 . The method of claim 8 , wherein the additional therapeutic agent is an antiviral agent.

10 . The method of claim 6 , wherein the compound, stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof is administered to the patient in a pharmaceutical composition together with one or more pharmaceutically acceptable excipients, diluents or carriers.

11 . The method of claim 6 , wherein the compound is represented by the following structural formula (I):

a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

Assignees

• Janssen Sciences Ireland Uc

Inventors

• Jonckers Tim Hugo Maria
• Mcgowan David Craig
• Guilllemont Jérôme Émile George
• Cooymans Ludwig Paul
• Embrechts Werner Constant Johan
• Buyck Christophe Francis Robert Nest
• Balemans Wendy Mia Albert
• Raboisson Pierre Jean-Marie Bernard

Classifications

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title