9-substituted amino triazolo quinazoline derivatives as adenosine receptor antagonists, pharmaceutical compositions and their use

Patent metadata

Field	Value
Publication number	US-11312719-B2
Application number	US-201916695367-A
Country	US
Kind code	B2
Filing date	Nov 26, 2019
Priority date	Nov 30, 2018
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I):

and pharmaceutically acceptable salts thereof, wherein, ring A, R 1 and R 2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.

First claim

What is claimed is:

1. A compound having a structural Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from F, Cl, (C 1 -C 6 )alkyl, and O(C 1 -C 6 )alkyl;
R 2 is selected from H, F, Cl, (C 1 -C 6 )alkyl, and O(C 1 -C 6 )alkyl;
ring A is a moiety selected from:

R 3 is selected from pyrazolyl, triazolyl, and pyridinyl, wherein said pyrazolyl and said triazolyl, are substituted with 1 or 2 R 3A groups, and wherein said pyridinyl is substituted with 1, 2, or 3 R 3A groups, wherein:
each R 3A is independently selected from (C 1 -C 6 )alkyl, O(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-OH, (C 1 -C 6 )haloalkyl, O(C 1 -C 6 )haloalkyl, oxo, (C 1 -C 4 )alkylC(O)(C 1 -C 3 )alkyl, (C 1 -C 4 )alkylCH(OH)(C 1 -C 3 )alkyl, (C 1 -C 4 )alkylS(O) 2 (C 1 -C 3 )alkyl, —(CH 2 ) n (C 3 -C 7 )cycloalkyl, and —(CH 2 ) n 4-7 membered monocyclic heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from oxygen and nitrogen, wherein said (C 3 -C 7 )cycloalkyl, and said 4-7 membered monocyclic heterocycloalkyl are each unsubstituted or substituted with 1, 2, or 3 groups independently selected from F, Cl, OH, (C 1 -C 6 )alkyl, and (C 1 -C 6 )haloalkyl;
n is 0, 1, or 2;
R A1 is selected from H, and (C 1 -C 4 )alkyl;
R A2 is selected from H, F, and (C 1 -C 4 )alkyl;
R A3 is selected from H, F, and (C 1 -C 4 )alkyl;
R A4 is selected from H and OH; and
R A5 is selected from H, F, and (C 1 -C 4 )alkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is selected from F, Cl, and OCH 3 ; and
R 2 is selected from H, F, Cl, CH 3 , and OCH 3 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
ring A is a moiety selected from:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from

and
each R 3Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
ring A is the moiety:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from:

and
each R 3Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
ring A is the moiety:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from:

and
each R 3Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
ring A is the moiety:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from:

and
each R 3Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
ring A is the moiety:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from:

and
each R 3Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
ring A is the moiety:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from:

and each R 3Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
ring A is the moiety:

wherein:
R 3 is selected from

wherein:
each R 3A is a moiety selected from:

each R Aa is independently selected from (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, and O(C 1 -C 4 )haloalkyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from:

Assignees

• Merck Sharp & Dohme

Inventors

• Larsen Matthew A
• Ali Amjad
• Cumming Jared
• Demong Duane
• Deng Qiaolin
• Graham Thomas H
• Hennessy Elisabeth
• Hoover Andrew J
• Liu Ping
• Liu Kun
• Mansoor Umar Faruk
• Pan Jianping
• Plummer Christopher W
• Sather Aaron
• Swaminathan Uma
• Wang Huijun
• Zhang Yonglian

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title