Thienopyrimidinone compounds

Patent metadata

Field	Value
Publication number	US-10584133-B2
Application number	US-201916368409-A
Country	US
Kind code	B2
Filing date	Mar 28, 2019
Priority date	Mar 30, 2018
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

The present disclosure provides compounds that modulate protein function and/or restore protein homeostasis. The disclosure provides methods of modulating protein-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other therapeutic agents, are provided.

First claim

What is claimed is:

1. A compound of: Formula (I):

or a pharmaceutically acceptable salt or solvate thereof, wherein:
Q 1 is CR 1 or —S—;
Q 2 is CR 2 or —S—;
Q 3 is CR 3 or —S—;
wherein one of Q 1 , Q 2 , and Q 3 is —S—;
each is a single or double bond;
each of R 1 , R 2 , and R 1 is independently hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, a substituted or unsubstituted amino, a substituted or unsubstituted C-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted ester, a substituted or unsubstituted urea, a substituted or unsubstituted C 1 -C 6 alkoxy, a substituted or unsubstituted C 1 -C 6 , alkyl, a substituted or unsubstituted C 2 -C 6 alkenyl, a substituted or unsubstituted C 2 -C 6 alkynyl, a substituted or unsubstituted C 1 -C 6 haloalkyl, a substituted or unsubstituted C 3 -C 8 cycloalkyl, a substituted or unsubstituted C 6 -C 10 aryl, a substituted or unsubstituted 3-10 membered heterocyclyl, or a substituted or unsubstituted 5-10 membered heteroaryl;
each of R 4 and R 5 is independently selected from the group consisting of hydrogen, deuterium, halogen, and a substituted or unsubstituted C 1 -C 6 alkyl;
R 6 is selected from the group consisting of hydrogen, deuterium, hydroxy, a substituted or unsubstituted C 1 -C 6 alkyl, and a substituted or unsubstituted C 1 -C 6 alkoxy;
X is O, NH, or S; and
n is 1, 2, or 3.

2. A compound of Formula (II):

or a pharmaceutically acceptable salt or solvate thereof, wherein:
Q 1A is CR 1A or —S—;
Q 2A is CR 2A or —S—;
Q 3A is CR 3A or —S—;
each is a single or double bond;
wherein one of Q 1 , Q 2 , and Q 3 is —S—;
each of R 1A , R 2A , and R 3A is independently hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, a substituted or unsubstituted amino, a substituted or unsubstituted, C-amido, a substituted or unsubstituted, N-amido, a substituted or unsubstituted ester, a substituted or unsubstituted urea, a substituted or unsubstituted C 1 -C 6 alkoxy, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 2 -C 6 alkenyl, a substituted or unsubstituted C 2 -C 6 alkynyl, a substituted or unsubstituted C 1 -C 6 haloalkyl, a substituted or unsubstituted C 3 -C 8 cycloalkyl, a substituted or unsubstituted C 6 -C 10 aryl, a substituted or unsubstituted 3-10 membered heterocyclyl, a substituted or unsubstituted 5-10 membered heteroaryl,

wherein one of R 1A , R 2A , and R 3A is

each of R 4A and R 5A is independently selected from the group consisting of hydrogen, deuterium, halogen, and a substituted or unsubstituted C 1 -C 6 alkyl;
R 6A is selected from the group consisting of hydrogen, deuterium, hydroxy, a substituted or unsubstituted C 1 -C 6 alkyl, and a substituted or unsubstituted C 1 -C 6 alkoxy;
X A is O, NH, or S;
s is 1, 2, or 3;
each X 1A is independently O, NH, or S;
each X 2A is independently selected from the group consisting of —NR 9A —, —(CH 2 ) h —(NR 9A )—(CH 2 ) i —, —(CH 2 ) h —(NR 9A )—(CH 2 ) i —(NR 9A )—, —(CH 2 ) 1-5 —, —(CF 2 ) 1-5 —, —(CD 2 ) 1-5 —, —O—, —C(═O)—, and —S—;
each X 3A is independently selected from the group consisting of —(CH 2 ) t —(NR 9A )—(CH 2 ) j —, —(CH 2 ) t —(NR 9A )—(CH 2 ) j —(NR 9A )—, —(CH 2 ) 1-5 —, —(CF 2 ) 1-5 —, and —(CD 2 ) 1-5 —;
each m is independently 0, 1, 2; 3, 4, or 5;
each h, i, and j is independently 0, 1, 2, 3, 4, or 5;
each t is independently 1, 2, 3, 4, or 5;
each R 7A and R 8A is independently selected from the group consisting of a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 6 -C 10 aryl, a substituted or unsubstituted 5-10 membered heteroaryl, a substituted or unsubstituted 3-10 membered heterocyclyl, and a substituted or unsubstituted C 1 -C 10 alkyl; and
R 9A is hydrogen, or a substituted or unsubstituted C 1 -C 6 alkyl.

3. The compound of claim 2 , wherein each X 2A is independently selected from the group consisting of —NR 9A —, —(CH 2 ) h —(NR 9A )—(CH 2 ) i —, —(CH 2 ) h —(NR 9A )—(CH 2 ) i —(NR 9A )—, —(CH 2 ) 1-5 —, —(CF 2 ) 1-5 —, —(CD 2 ) 1-5 —, —O—, and —S—.

4. The compound of claim 2 , wherein the compound of Formula (II) is represented by Formula (IIa), (IIb), or (IIc),

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 2 , wherein s is 2.

6. The compound of claim 2 , wherein R 4A is hydrogen, halogen, or an unsubstituted C 1 -C 6 alkyl.

7. The compound of claim 2 , wherein R 5A is hydrogen, halogen, or an unsubstituted C 1 -C 6 alkyl.

8. The compound of claim 2 , wherein R 6A is hydrogen, or a substituted or unsubstituted C 1 -C 6 alkyl.

9. The compound of claim 2 , wherein X A is O.

10. The compound of claim 4 , wherein the compound of Formula (II) is represented by Formula (IIa), and wherein one of R 1A and R 2A is

and the other of R 1A and R 2A is hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, an unsubstituted amino, a substituted or unsubstituted C 1 -C 6 alkoxy, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted 4-6 membered heterocyclyl, or a substituted or unsubstituted 5 or 6 membered heteroaryl.

11. The compound of claim 10 , wherein one of R 1A and R 2A is

and the other of R 1A and R 2A is hydrogen.

12. The compound of claim 4 , wherein the compound of Formula (II) is represented by Formula (IIb), and wherein one of R 1A and R 3A is

and the other of R 1A and R 3A is hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, an unsubstituted amino, a substituted or unsubstituted C 1 -C 6 alkoxy, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted 4-6 membered heterocyclyl, or a substituted or unsubstituted 5 or 6 membered heteroaryl.

13. The compound of claim 12 , wherein one of R 1A and R 3A is

and the other of R 1A and R 3A is hydrogen.

14. The compound of claim 4 , wherein the compound of Formula (II) is represented by Formula (IIc), and wherein one of R 2A and R 3A is

and the other of R 2A and R 3A is hydrogen, deuterium

Assignees

• Biotheryx Inc

Inventors

• Chan Kyle W H
• Chourasia Aparajita Hoskote
• Erdman Paul E
• Fung Leah
• Lam Imelda
• Mercurio Frank
• Sullivan Robert
• Torres Eduardo

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D495/04 Primary

  Ortho-condensed systems · CPC title