L,2-dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-one analogs

Patent metadata

Field	Value
Publication number	US-11124518-B2
Application number	US-201816635348-A
Country	US
Kind code	B2
Filing date	Jul 31, 2018
Priority date	Aug 1, 2017
Publication date	Sep 21, 2021
Grant date	Sep 21, 2021

Abstract

Compounds of Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as breast cancer.

First claim

What is claimed is:

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:

wherein:
R 1 is selected from the group consisting of an optionally substituted C 1-4 alkyl, an optionally substituted C 2-4 alkenyl, an optionally substituted C 2-4 alkynyl, an optionally substituted C 3-6 cycloalkyl and an optionally substituted C 3-6 cycloalkyl(C 1-4 alkyl), wherein when substituted, the C 1-4 alkyl, the C 2-4 alkenyl and the C 2-4 alkynyl are independently substituted with one or more substituents selected from the group consisting of halogen, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, cyano, amino, mono-C 1-4 alkyl amine and di-C 1-4 alkyl amine, and wherein the ring(s) of the C 3-6 cycloalkyl and the C 3-6 cycloalkyl(C 1-4 alkyl) are independently substituted with one or more substituents selected from the group consisting of halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, cyano, amino, mono-C 1-4 alkyl amine and di-C 1-4 alkyl amine;
R 2 is an optionally substituted aryl or an optionally substituted heteroaryl, wherein when the aryl or the heteroaryl are substituted, the aryl and the heteroaryl are independently substituted with one or more substituents selected from the group consisting of an unsubstituted C 1-4 alkyl and

R 3 is hydrogen or an unsubstituted C 1-4 alkyl;
A 1 is CR 6A or N;
A 2 is CR 6B or N;
Z 1 is a single bond, —C(═O)— or an optionally substituted C 1-6 alkylene group, wherein one or two more methylene groups constituting the optionally substituted C 1-6 alkylene group are independently optionally replaced by an oxygen atom or carbonyl group, and wherein when the C 1-6 alkylene group is substituted, one or more methylene group are independently substituted with an unsubstituted C 1-6 alkyl group;
Z 2 is N or C, and when Z 2 is N, then R 4c is absent;
R 4a and R 4b are independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, an unsubstituted C 1-6 alkyl, an unsubstituted hydroxy(C 1-6 alkyl), an unsubstituted alkoxy(C 1-6 alkyl), an unsubstituted C 2-7 acyl, an unsubstituted —C-carboxy having 2-7 carbons, an unsubstituted —C-amido and an unsubstituted C 1-7 alkylsulfonyl; or
R 4a and R 4b together form an optionally substituted C 1-6 alkylene, wherein one or two more methylene groups constituting the C 1-6 alkylene group are independently optionally replaced by an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, a carbonyl group or —(NR 5 )—, and wherein when the C 1-6 alkylene group is substituted, one or more methylene group are independently substituted with a substituent selected from the group consisting of halogen and an unsubstituted C 1-6 alkyl; or
R 4a and R 4b together with Z 2 form an unsubstituted monocyclic C 3-6 cycloalkyl and an unsubstituted 4-, 5-, or 6-membered heterocyclyl;
R 4c is selected from the group consisting of halogen, hydroxy, an unsubstituted C 1-6 alkyl and an unsubstituted hydroxy(C 1-6 alkyl);
R 5 is hydrogen, an unsubstituted C 1-6 alkyl or an unsubstituted C 1-6 haloalkyl;
R 6A and R 6B are independently hydrogen, halogen or an unsubstituted C 1-4 alkyl; and
Ring B is an optionally substituted monocyclic C 5-7 cycloalkyl, an optionally substituted 5-7 membered monocyclic heterocyclyl or an optionally substituted 7-10 membered bicyclic heterocyclyl, wherein when Ring B is substituted, Ring B is substituted with one or more substituents selected from the group consisting of halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 1-6 haloalkyl, an optionally substituted C 3-6 cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C 1-6 alkyl), an optionally substituted heteroaryl(C 1-6 alkyl), an optionally substituted heterocyclyl(C 1-6 alkyl), an optionally substituted acyl, an optionally substituted -hydroxy(C 1-6 alkyl), an optionally substituted —C-amido, an optionally substituted —C-amido(C 1-6 alkyl), an optionally substituted —N-amido, an optionally substituted —N-amido(C 1-6 alkyl), an optionally substituted mono-substituted amine, an optionally substituted di-substituted amine, an optionally substituted mono-substituted amine(C 1-6 alkyl), an optionally substituted di-substituted amine(C 1-6 alkyl) and an optionally substituted sulfonyl.

2. The compound of claim 1 , wherein R 1 is an optionally substituted C 2-4 alkenyl.

3. The compound of claim 1 , wherein R 1 is an optionally substituted C 1-4 alkyl, an optionally substituted C 2-4 alkynyl, an optionally substituted C 3-6 cycloalkyl or an optionally substituted C 3-6 cycloalkyl(C 1-4 alkyl).

4. The compound of claim 1 , wherein R 2 is an optionally substituted heteroaryl.

5. The compound of claim 4 , wherein R 2 is substituted with

6. The compound of claim 5 , wherein Z 1 is a single bond and Z 2 is C.

7. The compound of claim 6 , wherein R 4a and R 4b are independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, an unsubstituted C 1-6 alkyl, an unsubstituted hydroxy(C 1-6 alkyl), an unsubstituted alkoxy(C 1-6 alkyl), an unsubstituted C 2-7 acyl, an unsubstituted —C-carboxy having 2-7 carbons, an unsubstituted —C-amido and an unsubstituted C 1-7 alkylsulfonyl.

8. The compound of claim 7 , wherein R 4a and R 4b are independently hydroxy or an unsubstituted C 1-6 alkyl.

9. The compound of claim 7 , wherein R 4c is an unsubstituted C 1-6 alkyl.

10. The compound of claim 1 , wherein R 3 is hydrogen.

11. The compound of claim 1 , wherein A 1 is CR 6A ; and A 2 is CR 6B .

12. The compound of claim 11 , wherein R 6A is hydrogen; and R 6B is hydrogen.

13. The compound claim 1 , wherein A 1 is N; and A 2 is CR 6B ; or A 1 is CR 6A ; and A 2 is N.

14. The compound of claim 13 , wherein R 6A is hydrogen; and R 6B is hydrogen.

15. The compound claim 1 , wherein Ring B is an optionally substituted monocyclic C 5-7 cycloalkyl.

16. The compound of claim 1 , wherein Ring B is an optionally substituted 5-7 membered monocyclic heterocyclyl or an optionally substituted 7-10 membered bicyclic heterocyclyl.

17. The compound of claim 16 , wherein Ring B is selected from the group consisting of:

wherein the asterisks indicate the points of attachment to ring

wherein each ring can be optionally substituted at a ring carbon, and wherein each ring can be optionally substituted at a ring nitrogen.

18. The compound of claim 1 , wherein the compound is selected from the group consisting of:

Assignees

• Recurium Ip Holdings Llc

Inventors

• Huang Peter Qinhua
• Boren Brant Clayton
• Bunker Kevin Duane
• Liu Hui
• Paliwal Sunil

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title