Heterocyclic indoles for use in influenza virus infection

Patent metadata

Field	Value
Publication number	US-10626108-B2
Application number	US-201615779468-A
Country	US
Kind code	B2
Filing date	Nov 25, 2016
Priority date	Nov 27, 2015
Publication date	Apr 21, 2020
Grant date	Apr 21, 2020

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

The invention claimed is:

1. A compound of formula (I)

or a stereoisomeric form thereof, or a pharmaceutically acceptable salt thereof, wherein:
(a) X is N and Y is N; or
(b) X is C substituted by F and Y is C substituted by —F, —CH 3 , or —CN;
(1) Z is N, Q is —C—CH 3 , —C—COOH, —C—CF 3 , —CH-cyclopropyl, —CH 2 R 1 ,
or —CONR 1 R 1 , and M is CF;
wherein each R 1 is independently selected from hydrogen, halogen, cyano, oxo, alkyl, hydroxyl, and amino; or

(2) Z is N, Q is N, and M is CH; or
(3) Z is C, Q is N, and M is CH; and
R is C 3-8 cycloalkyl substituted by (i) carboxylic acid or (ii)—NH—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

or a pharmaceutically acceptable salt thereof.

3. A compound selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

4. A pharmaceutical composition comprising a compound of claim 1 together with one or more pharmaceutically acceptable excipients, diluents or carriers.

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

or a stereoisomeric form thereof, or a pharmaceutically acceptable salt thereof, wherein:
(a) X is N and Y is N; or
(b) X is C substituted by —F and Y is C substituted by —F, —Cl, —CH 3 , or —CN;
(1) Z is N, Q is —C—CH 3 , —C—COOH, —C—CF 3 , —CH-cyclopropyl, —CH 2 R 1 , or —CONR 1 R 1 , and M is CF;
wherein each R 1 is independently selected from hydrogen, halogen, cyano, oxo, alkyl, hydroxyl, and amino; or

(2) Z is N, Q is N, and M is CH; or
(3) Z is C, Q is N, and M is CH; and
R is C 3-8 cycloalkyl substituted by (i) carboxylic acid or (ii)—NH—C(O)—C 3-6 heterocycle
optionally substituted by C 1-6 alkyl or —COOH.

6. The method of claim 5 , further comprising co-administering an additional therapeutic agent.

7. The method of claim 6 , wherein the additional therapeutic agent is an antiviral agent or an influenza vaccine, or both.

8. The method of claim 7 , wherein the additional therapeutic agent is an antiviral agent.

9. The method of claim 5 , wherein the compound or the stereoisomeric form thereof, or the pharmaceutically acceptable salt thereof, is administered to the patient in a pharmaceutical composition together with one or more pharmaceutically acceptable excipients, diluents or carriers.

10. The method of claim 5 , wherein the compound is represented by the following structural formula (I):

or a stereoisomeric form thereof, or a pharmaceutically acceptable salt thereof.

Assignees

• Janssen Sciences Ireland Uc

Inventors

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

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · 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