2,4-diaminoquinazoline derivatives and medical uses thereof

Patent metadata

Field	Value
Publication number	US-11597704-B2
Application number	US-201916977043-A
Country	US
Kind code	B2
Filing date	Feb 28, 2019
Priority date	Mar 1, 2018
Publication date	Mar 7, 2023
Grant date	Mar 7, 2023

Abstract

This application relates to quinazoline derivatives of formula (I), pharmaceutical compositions comprising the compounds of formula (I), and the use of the compounds of formula (I) in the treatment or prevention of a viral infection, of a virus-induced disease, of cancer or of an allergy. In formula (I), R 1 is a C 3-8 alkyl, optionally substituted by one or more substituents independently selected from fluorine, hydroxyl, amino, nitrile, ester, amide, C 1-3 alkyl, or C 1-3 alkoxy, 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, 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.

First claim

The invention claimed is:

1. A compound of formula (I)

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.

2. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is of formula (II):

wherein n is 0, 1, or 2.

3. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, 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.

4. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is fluorine or chlorine.

5. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, 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.

6. The compound of claim 1 , which is chosen from among compounds 1-34:

Compound

number

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

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

• A61P31/12

  Antivirals · CPC title

• 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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title