2,4-diaminoquinazoline derivatives and medical uses thereof

Patent metadata

Field	Value
Publication number	US-2023278964-A1
Application number	US-202318159026-A
Country	US
Kind code	A1
Filing date	Jan 24, 2023
Priority date	Mar 1, 2018
Publication date	Sep 7, 2023
Grant date	—

Abstract

This application relates to quinazoline derivatives, processes for their preparation, pharmaceutical compositions, and medical uses thereof.

First claim

1 - 15 . (canceled)

16 . A method of agonizing TLR-8 receptors in a subject suffering from a viral infection, comprising administering an effective amount of compound of formula (I) to the subject in need thereof, wherein formula (I) is represented by:

or a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is of formula (II):

 wherein n is 0, 1, or 2;
or of formula (III):

 wherein n is 0, 1, or 2,
the carbon of R 1 bonded to the amine in the 4-position of the quinazoline is in (R)-configuration,
R 2 is hydrogen, deuterium, fluorine, chlorine, methyl, methoxy, cyclopropyl, trifluoromethyl, or carboxylic amide, wherein each of methyl, methoxy and cyclopropyl is optionally substituted by one or more substituents independently selected from fluorine and nitrile,
R 3 is hydrogen or deuterium,
R 4 is hydrogen, deuterium, fluorine, methyl, carboxylic ester, carboxylic amide, nitrile, cyclopropyl, C 4-7 heterocycle, or 5-membered heteroaryl group, wherein each of methyl, cyclopropyl, C 4-7 heterocycle and 5-membered heteroaryl group is optionally substituted by one or more substituents independently selected from fluorine, hydroxyl, or methyl,
and
R 5 is hydrogen, deuterium, fluorine, chlorine, methyl, or methoxy,
provided that at least one of R 2 , R 3 , R 4 and R 5 is not hydrogen.

17 . The method of claim 16 , wherein R 1 is formula (II):

wherein n is 0, 1, or 2.

18 . The method of claim 17 , wherein n is 1.

19 . The method of claim 17 , wherein R 2 is fluorine, chlorine or methyl, and wherein methyl is optionally substituted by one or more substituents independently selected from fluorine and nitrile.

20 . The method of claim 17 , wherein R 2 is fluorine or chlorine.

21 . The method of claim 17 , wherein R 4 is fluorine or methyl, and wherein methyl is optionally substituted by one or more substituents independently selected from fluorine, hydroxyl, or methyl.

22 . The method of claim 17 , wherein R 4 is fluorine.

23 . The method of claim 17 , wherein R 4 is hydrogen.

24 . The method of claim 17 , wherein R 3 and R 5 are hydrogen

25 . The method of claim 16 , wherein the compound of formula (I) is chosen from among compounds 1-34:

Compound

number

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Assignees

• Janssen Sciences Ireland Unlimited Co

Inventors

• Mc Gowan David Craig
• Embrechts Werner Constant Johan
• Guillemont Jérôme Émile Georges
• Cooymans Ludwig Paul
• Jonckers Tim Hugo Maria
• Raboisson Pierre Jean-Marie

Classifications

• C07D239/95 Primary

  with hetero atoms directly attached in positions 2 and 4 · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61P1/16

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

• A61P31/12

  Antivirals · CPC title

• A61P35/00

  Antineoplastic agents · CPC title