Substituted aminopurine compounds, compositions thereof, and methods of treatment therewith

Patent metadata

Field	Value
Publication number	US-11590139-B2
Application number	US-202117147127-A
Country	US
Kind code	B2
Filing date	Jan 12, 2021
Priority date	Oct 6, 2014
Publication date	Feb 28, 2023
Grant date	Feb 28, 2023

Abstract

Provided herein are Aminopurine Compounds having the following structures:

wherein R 1 , R 2 , and R 3 are as defined herein, compositions comprising an effective amount of an Aminopurine Compound, and methods for treating or preventing a cancer, for example, melanoma.

First claim

What is claimed is:

1. A method for treating melanoma, comprising administering to a patient having melanoma an effective amount of a compound of formula (II):

or a pharmaceutically acceptable salt or tautomer thereof,
wherein:
R 1 is substituted or unsubstituted C 1-8 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, or substituted or unsubstituted non-aromatic heterocyclyl;
R 2 is H or substituted or unsubstituted C 1-3 alkyl;
R 3 is phenyl, substituted with one or more halogen, optionally further substituted with one or more substituents independently selected from substituted or unsubstituted C 1-3 alkyl, CN, and —OR′, wherein each R′ is independently substituted or unsubstituted C 1-3 alkyl;
wherein when an alkyl group is substituted, it is substituted with a substituent selected from the group consisting of chloro; iodo; bromo; fluoro; alkyl; hydroxyl; alkoxy; alkoxyalkyl; amino; alkylamino; carboxy; nitro; cyano; thiol; thioether; imine; imide; amidine; guanidine; enamine; aminocarbonyl; acylamino; phosphonate; phosphine; thiocarbonyl; sulfinyl; sulfone; sulfonamide; acyl; ester; urea; urethane; oxime; hydroxyl amine; alkoxyamine; aryloxyamine, aralkoxyamine; N-oxide; hydrazine; hydrazide; hydrazone; azide; isocyanate; isothiocyanate; cyanate; thiocyanate; B(OH) 2 ; and O(alkyl)aminocarbonyl;
wherein when a group other than an alkyl group is substituted, it is substituted with a substituent selected from the group consisting of chloro; iodo; bromo; fluoro; alkyl; hydroxyl; alkoxy; alkoxyalkyl; amino; alkylamino; carboxy; nitro; cyano; thiol; thioether; imine; imide; amidine; guanidine; enamine; aminocarbonyl; acylamino; phosphonate; phosphine; thiocarbonyl; sulfinyl; sulfone; sulfonamide; acyl; ester; urea; urethane; oxime; hydroxylamine; alkoxyamine; aryloxyamine; aralkoxyamine; N-oxide; hydrazine; hydrazide; hydrazone; azide; isocyanate; isothiocyanate; cyanate; thiocyanate; oxo; B(OH) 2 , O(alkyl)aminocarbonyl; cycloalkyl, which may be monocyclic or fused or non-fused polycyclic, or a heterocyclyl, which may be monocyclic or fused or non-fused polycyclic; monocyclic or fused or non-fused polycyclic aryl or heteroaryl; aryloxy; aralkyloxy; heterocyclyloxy; and heterocyclylalkoxy; and
provided that the compound is not
4-[2-[(1-methylethyl)amino]-8-[(2,4,6-trifluorophenyl)amino]-9H-purin-9-yl]-cis-cyclohexanecarboxamide, or
4-[8-[(2,4-difluorophenyl)amino]-2-[(trans-4-hydroxycyclohexyl)amino]-9H-purin-9-yl]-cis-cyclohexanecarboxamide.

2. The method of claim 1 , wherein R 1 is substituted or unsubstituted C 1-8 alkyl.

3. The method of claim 2 , wherein R 1 is substituted or unsubstituted methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 2-methylpentyl, 3-methylpentyl, isopentyl, or neopentyl.

4. The method of claim 2 , wherein R 1 is substituted with one or more substituents independently selected from halogen and OR, wherein each R is independently H or substituted or unsubstituted C 1-3 alkyl.

5. The method of claim 2 , wherein R 1 is substituted with one or more substituents independently selected from F, OH, and OCH 3 .

6. The method of claim 2 , wherein R 1 is ethyl, isopropyl, isobutyl, tert-butyl, CH 2 CH 2 F, CH 2 CHF 2 , CH 2 CF 3 , CH 2 CH(CH 3 )OH, CH 2 CH(CH 3 )OCH 3 , CH(CH 3 )CH 2 OH, CH(CH 3 )CH 2 OCH 3 , CH 2 C(F 2 )CH 2 OH, CH 2 C(F 2 )CH 2 OCH 3 , CH(CF 3 )CH 2 OH, CH(CF 3 )CH 2 OCH 3 , CH(CH 2 OH)CH 2 CH 3 , CH(CH 2 OCH 3 )CH 2 CH 3 , CH 2 C(CH 3 ) 2 CH 2 OH, or CH 2 C(CH 3 ) 2 CH 2 OCH 3 .

7. The method of claim 2 , wherein R 1 is isopropyl, isobutyl, tert-butyl, CH 2 CF 3 , CH 2 CH(CH 3 )OH, CH(CH 3 )CH 2 OH, CH(CH 3 )CH 2 OCH 3 , CH 2 C(F 2 )CH 2 OH, CH(CF 3 )CH 2 OH, CH(CH 2 OH)CH 2 CH 3 , or CH 2 C(CH 3 )2CH 2 OH.

8. The method of claim 1 , wherein R 1 is substituted or unsubstituted cycloalkyl.

9. The method of claim 8 , wherein R 1 is substituted or unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl.

10. The method of claim 8 , wherein R 1 is substituted with one or more substituents independently selected from halogen, OR, SO 2 R′, substituted or unsubstituted C 1-3 alkyl, and substituted or unsubstituted heterocyclyl, wherein each R is independently H or substituted or unsubstituted C 1-3 alkyl, and each R′ is independently substituted or unsubstituted C 1-3 alkyl.

11. The method of claim 8 , wherein R 1 is substituted with one or more substituents independently selected from F, OH, OCH 3 , SO 2 CH 3 , methyl, and a substituted or unsubstituted 5-membered heterocyclyl.

12. The method of claim 11 , wherein the 5-membered heterocylyl is pyrroldinedionyl, or oxadiazolyl.

13. The method of claim 8 , wherein R 1 is cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, optionally substituted with one or more substituents independently selected from F, OH, OCH 3 , SO 2 CH 3 , methyl, pyrrolidinedionyl, and oxadiazolyl.

14. The method of claim 1 , wherein R 1 is substituted or unsubstituted cycloalkylalkyl.

15. The method of claim 14 , wherein R 1 is substituted or unsubstituted (C 1-3 alkyl)-(C 1-8 cycloalkyl).

16. The method of claim 14 , wherein R 1 is substituted or unsubstituted CH 2 -cyclopropyl, CH 2 -cyclobutyl, CH 2 -cyclopentyl, CH 2 -cyclohexyl, or CH 2 -cycloheptyl.

17. The method of claim 14 , wherein R 1 is substituted with one or more substituents independently selected from (C 1-3 alkyl)OR or OR, wherein each R is independently H or substituted or unsubstituted C 1-3 alkyl.

18. The method of claim 14 , wherein R 1 is CH 2 -cyclopropyl, CH 2 -cyclobutyl, CH 2 -cyclopentyl, or CH 2 -cyclohexyl, optionally substituted with one or more CH 2 OH or OH.

19. The method of claim 1 , wherein R 1 is substituted or unsubstituted non-aromatic heterocyclyl.

20. The method of claim 19 wherein R 1 is substituted or unsubstituted oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydro-thiopyrandioxide, piperidyl, oxepanyl, or oxaspiroheptyl.

21. The method of claim 19 wherein R 1 is substituted with one or more substituents independently selected from halogen, OR, SO 2 R 4 , C(═O)R 5 , C(═O)OR 6 , C(═O)NRR 7 , substituted or unsubstituted C 1-3 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted or alkylaryl, wherein each R is independently H or substituted or unsubstituted C 1-3 alkyl; R 4 is substituted or unsubstituted C 1-3 alkyl, or substituted or unsubstituted aryl; R 5 is substituted or unsubstituted C 1-3 alkyl; R 6 is substituted or unsubstituted C 1-6 alkyl; and R 7 is substituted or unsubstituted C 1-3 alkyl, or substituted or unsubstituted aryl.

22. The method of claim 19 wherein R 1 is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydro-thiopyrandioxide, piperidyl, oxepanyl, or oxaspiroheptyl, optionally substituted with one or more substituents independently selected from F, OH, SO 2 CH 3 , SO 2 -tosyl, C(═O)CH 3 , C(═O)OCH 3 , C(═O)O-tert-butyl, C(═O)O-isopropyl, C(═O)NHCH 3 , C(═O)NH-phenyl, methyl, ethyl, isopropyl, CH 2 OH, phenyl, pyridyl, or benzyl.

23. The method of claim 1 , wherein R 2 is H.

24. The method of claim 1 , wherein R 2 is CH 3 .

25. The method of claim 1 ,

Assignees

• Signal Pharm Llc

Inventors

• Alexander Matthew
• Bahmanyar Sogole
• Boylan John Frederick
• Hansen Joshua
• Huang Dehua
• Hubbard Robert
• Jeffy Brandon
• Leisten Jim
• Moghaddam Mehran
• Raheja Raj K
• Raymon Heather
• Schwarz Kimberly
• Sloss Marianne
• Torres Eduardo
• Tran Tam Minh
• Xu Shuichan
• Zhao Jingjing

Classifications

• C07D473/32 Primary

  Nitrogen atom · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/52 Primary

  Purines, e.g. adenine · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D239/50

  Three nitrogen atoms · CPC title