Quinazoline inhibitors of activating mutant forms of epidermal growth factor receptor

Patent metadata

Field	Value
Publication number	US-9718806-B2
Application number	US-201615162816-A
Country	US
Kind code	B2
Filing date	May 24, 2016
Priority date	Mar 6, 2013
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

The invention relates to compounds of formula (I), or a pharmaceutically acceptable salt thereof:

which possess inhibitory activity against activating mutant forms of EGFR, and are accordingly useful for their anti-cancer activity and in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of the compounds, or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.

First claim

The invention claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof.

2. The pharmaceutically acceptable salt of the compound as claimed in claim 1 .

3. The compound of formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1 in crystalline form.

4. A pharmaceutical composition which comprises a compound of formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1 , in association with a pharmaceutically-acceptable diluent or carrier.

5. A compound of formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1 , in combination with an anti-tumour agent selected from:
(i) an anti-CTLA-4 antibody;
(ii) 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide or a pharmaceutically acceptable salt thereof;
(iii) an anti-PD-L1 antibody;
(iv) 1-[(1S)-1-(imidazo[1,2-a]pyridin-6-yl)ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine or a pharmaceutically acceptable salt thereof;
(v) an anti-PD-1 antibody;
or
(vi) an OX40 agonist antibody.

6. A method of treating non-small cell lung cancer, in a warm blooded animal in need of such treatment which comprises administering to said animal an effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt thereof.

7. The method of claim 6 , wherein the non-small cell lung cancer is metastatic non-small cell lung cancer.

8. The method of claim 7 , wherein the metastatic non-small cell lung cancer has metastasized to the brain.

9. The method of claim 7 , wherein the metastatic non-small cell lung cancer has metastasized to the meninges.

10. The method of claim 6 , wherein the compound of formula (I), or the pharmaceutically acceptable salt thereof, is in crystalline form.

11. The method of claim 6 , wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is provided in association with a pharmaceutically-acceptable diluent or carrier.

12. The method of claim 6 , wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is provided in combination with an anti-tumour agent selected from:
(i) an anti-CTLA-4 antibody;
(ii) 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide or a pharmaceutically acceptable salt thereof;
(iii) an anti-PD-L1 antibody;
(iv) 1-[(1 S)-1-(imidazo[1,2-a]pyri din-6-yl)ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine or a pharmaceutically acceptable salt thereof;
(v) an anti-PD-1 antibody;

or
(vi) an OX40 agonist antibody.

13. The method of claim 6 , wherein the warm blood animal is man.

Assignees

• Astrazeneca Ab

Inventors

• Li David Yunzhi
• Wang Jiabing
• Yang Zhenfan
• Zeng Qingbei
• Zhang Xiaolin

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D403/12 Primary

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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title