Certain chemical entities, compositions, and methods

Patent metadata

Field	Value
Publication number	US-11208388-B2
Application number	US-201916702936-A
Country	US
Kind code	B2
Filing date	Dec 4, 2019
Priority date	Aug 15, 2016
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

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 (Ib):

or a pharmaceutically acceptable salt thereof, wherein:

is selected from the group consisting of

X 15 is N or CR 43 ;
X 16 is N or CR 44 ;
X 17 is Nor CR 45 ;
X 18 is N or CR 46 ;
X 19 is N or CR 47 ;
R 43 , R 44 , R 45 , R 46 and R 47 are independently selected 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 independently selected from the group consisting of:

and
R 1 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.

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 R 1 and R 6 are independently selected from the group consisting of hydrogen, cyano, halo, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted amino.

4. The compound or salt of claim 1 , wherein:

is selected from the group consisting of

R 1 is selected from the group consisting of hydrogen, cyano, halo, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted amino; and
R 6 is selected from hydrogen and —NH 2 .

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

6. A method of treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of the compound or salt of claim 1 , wherein the cancer is diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic lymphoma, chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplamacytic lymphoma/Waldenström macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B cell lymphoma, nodal marginal zone B cell lymphoma, mantle cell lymphoma, mediastinal (thymic) large B cell lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, burkitt lymphoma/leukemia, or lymphomatoid granulomatosis, and wherein the treatment does not comprise prophylactic treatment.

7. The compound or salt of claim 1 , wherein E is independently selected from the group consisting of

8. The compound or salt of claim 1 , wherein R 1 and R 6 are independently selected from the group consisting of hydrogen, optionally substituted aryl, and optionally substituted amino.

9. The compound or salt of claim 1 , wherein R 1 and R 6 are independently selected from the group consisting of hydrogen and optionally substituted amino.

10. The compound or salt of claim 1 , wherein R 1 is selected from hydrogen and —NH 2 .

11. The compound or salt of claim 1 , wherein R 1 is hydrogen.

12. The compound or salt of claim 1 , wherein R 6 is selected from hydrogen and —NH 2 .

13. The compound or salt of claim 1 , wherein R 6 is hydrogen.

14. The compound or salt of claim 1 , wherein

is selected from the group consisting of

15. The compound or salt of claim 1 , wherein

is

16. The compound or salt of claim 1 , wherein the compound is selected from the group consisting of:
N-(3-(2,6-diphenylquinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(2-chlorophenyl)-2-phenylquinazolin-8-yl)phenyl)acrylamide,
N-(3-(2-amino-6-(2-chlorophenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-phenylquinazolin-8-yl)phenyl)acrylamide,
N-(3-(2-amino-6-phenylquinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(pyridin-4-yl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(pyridin-3-yl)quinazolin-8-yl)phenyl)acrylamide,
4-(8-(3-acrylamidophenyl)quinazolin-6-yl)-N-(pyridin-2-yl)benzamide,
N-(3-(6-(6-methylpyridin-3-yl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(3-((3-(trifluoromethyl)phenyl)amino)phenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(2-chlorophenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(4-amino-6-phenylquinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(3-(phenylamino)phenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(2-(trifluoromethyl)pyridin-4-yl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(4-((3-(trifluoromethyl)phenyl)amino)phenyl)quinazolin-8-yl)phenyl)acrylamide,
1-(3-(6-phenylquinazolin-8-yl)piperidin-1-yl)prop-2-en-1-one,
N-(3-(4-amino-6-(3-(phenylamino)phenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(4-phenoxyphenyl)quinazolin-8-yl)phenyl)acrylamide,
N-(3-(6-(4-(phenylamino)phenyl)quinazolin-8-yl)phenyl)acrylamide,
1-(3-(2-amino-6-(4-phenoxyphenyl)quinazolin-8-yl)piperidin-1-yl)prop-2-en-1-one,
1-(3-(6-(3-((3-(trifluoromethyl)phenyl)amino)phenyl)quinazolin-8-yl)piperidin-1-yl)prop-2-en-1-one,
1-(3-(4-amino-6-(4-phenoxyphenyl)quinazolin-8-yl)piperidin-1-yl)prop-2-en-1-one,
1-(3-(6-(pyridin-3-yl)quinazolin-8-yl)piperidin-1-yl)prop-2-en-1-one,
1-(3-(4-amino-6-phenylquinazolin-8-yl

Assignees

• Neupharma Inc

Inventors

• Qian Xiangping
• Zhu Yong-Liang

Classifications

• C07D473/32

  Nitrogen atom · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• C07D401/12

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

• C07D239/84

  Nitrogen atoms · CPC title