Certain chemical entities, compositions, and methods

Patent metadata

Field	Value
Publication number	US-12018002-B2
Application number	US-202117506367-A
Country	US
Kind code	B2
Filing date	Oct 20, 2021
Priority date	Aug 15, 2016
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.

First claim

What is claimed is:

1. A compound of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein:

is selected from the group consisting of phenyl, piperidine, and pyrrolidine, each of which is substituted with E;

is selected from the group consisting of

wherein b is a point of attachment for

and d is a point of attachment for

is selected from the group consisting of phenyl and pyridine;
X 3 is C—R 3 ;
X 4 is C—R 4 ;
X 5 is C—R 5 ;
R 1 , R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, oxo, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted cycloalkyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, and optionally substituted carbamimidoyl;
Q and Z are each independently selected at each occurrence from hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, oxo, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted cycloalkyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, and E;

E is selected from the group consisting of

m is 0, 1, 2, 3, or 4; and
n is 0, 1, 2, 3, 4, or 5.

2. The compound or salt of claim 1 , wherein

is selected from the group consisting of

3. The compound or salt of claim 1 , wherein

is

4. The compound or salt of claim 1 , wherein Z is independently selected at each occurrence from cyano, halo, optionally substituted aryloxy, optionally substituted amino, and optionally substituted aminocarbonyl.

5. A compound selected from the group consisting of:
4-(8-(1-acryloylpiperidin-3-yl)quinazolin-5-yl)-N-(pyridin-2-yl)benzamide,
4-(8-(3-acrylamidophenyl)quinazolin-5-yl)-N-(pyridin-2-yl)benzamide,
4-(8-(1-acryloylpyrrolidin-3-yl)quinazolin-5-yl)-N-(pyridin-2-yl)benzamide,
4-(8-(1-acryloylpyrrolidin-3-yl)-4-aminoquinazolin-5-yl)-N-(pyridin-2-yl)benzamide,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-N-(pyridin-2-yl)benzamide,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-N-(4-cyclopropylpyridin-2-yl)benzamide,
N-(3-(5-amino-6-(2-fluoro-4-(pyridin-2-yloxy)phenyl)quinazolin-8-yl)phenyl)acrylamide,
1-(3-(5-amino-6-(2-fluoro-4-(pyridin-2-yloxy)phenyl)quinazolin-8-yl)pyrrolidin-1-yl)prop-2-en-1-one,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-N-(4-cyanopyridin-2-yl)benzamide,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-3-fluoro-N-(pyridin-2-yl)benzamide,
4-(8-(3-acrylamidophenyl)-2,5-diaminoquinazolin-6-yl)-N-(pyridin-2-yl)benzamide,
N-(3-(5-amino-6-(4-(pyridin-2-yloxy)phenyl)quinazolin-8-yl)phenyl)acrylamide,
1-(3-(5-amino-6-(4-(pyridin-2-yloxy)phenyl)quinazolin-8-yl)pyrrolidin-1-yl)prop-2-en-1-one,
N-(3-(5-amino-6-(4-phenoxyphenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(5-amino-6-(2-fluoro-4-((4-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(5-amino-6-(4-((4-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)quinazolin-8-yl)phenyl)acrylamide,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-3-chloro-N-(pyridin-2-yl)benzamide,
1-(3-(5-amino-6-(4-phenoxyphenyl)quinazolin-8-yl)pyrrolidin-1-yl)prop-2-en-1-one,
1-(3-(5-amino-6-(4-((4-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)quinazolin-8-yl)pyrrolidin-1-yl)prop-2-en-1-one,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-3-chloro-N-(4-cyclopropylpyridin-2-yl)benzamide,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-N-(4-cyclopropylpyridin-2-yl)-3-fluorobenzamide,
N-(3-(5-amino-6-(2-chloro-4-(pyridin-2-yloxy)phenyl)quinazolin-8-yl)phenyl)acrylamide,
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-N-(3-fluoropyridin-2-yl)benzamide,
4-(8-(1-acryloylpyrrolidin-3-yl)-5-aminoquinazolin-6-yl)-N-(3-fluoropyridin-2-yl)benzamide, and
4-(8-(3-acrylamidophenyl)-5-aminoquinazolin-6-yl)-3-chloro-N-(3-fluoropyridin-2-yl)benzamide,
or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound or salt of claim 1 .

7. The compound or salt of claim 1 , wherein R 1 and R 6 are each independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted amino.

8. The compound or salt of claim 1 , wherein R 1 and R 6 are each independently selected from the group consisting of hydrogen and —NH 2 .

9. The compound or salt of claim 1 , wherein R 3 and R 4 are each independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted amino.

10. The compound or salt of claim 1 , wherein R 3 and R 4 are each independently hydrogen.

11. The compound or salt of claim 1 , wherein R 5 is selected from the group consisting of cyano, halo, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted amino.

12. The compound or salt of claim 1 , wherein R 5 is —NH 2 .

13. The compound or salt of claim 1 , wherein is

14. The compound or salt of claim 1 , wherein is

Assignees

• Neupharma Inc

Inventors

• Qian Xiangping
• Zhu Yong-Liang

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D473/32

  Nitrogen atom · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title