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

Patent metadata

Field	Value
Publication number	US-10149849-B2
Application number	US-201715641383-A
Country	US
Kind code	B2
Filing date	Jul 5, 2017
Priority date	Oct 6, 2014
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

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 compound of formula (If)

wherein:
R 1 is substituted or unsubstituted cycloalkylalkyl, or substituted 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 selected from substituted or unsubstituted C 1-3 alkyl, CN, and —OR′, wherein each R′ is independently substituted or unsubstituted C 1-3 alkyl;
when a C 1-3 alkyl group is substituted, it is independently substituted with 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, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aryloxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, B(OH) 2, or O(alkyl)aminocarbonyl; and
when a group, with the exception of a C 1-3 alkyl group, is substituted, it is independently substituted with 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, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aryloxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, oxygen (═O), B(OH) 2 , O(alkyl)aminocarbonyl, cycloalkyl, heterocyclyl, heteroaryl, aryloxy, aralkyloxy, heterocyclyloxy, or heterocyclyl alkoxy.

2. A compound of formula (Ig)

wherein:
R 1 is substituted or unsubstituted cycloalkylalkyl, or substituted 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 selected from substituted or unsubstituted C 1-3 alkyl, CN, and —OR′, wherein each R′ is independently substituted or unsubstituted C 1-3 alkyl; and
R # is C 1-2 alkyl;
when a C 1-2 or C 1-3 alkyl group is substituted, it is independently substituted with 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, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aryloxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, B(OH) 2, or O(alkyl)aminocarbonyl; and
when a group, with the exception of a C 1-2 or C 1-3 alkyl group, is substituted, it is independently substituted with 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, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aryloxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, oxygen (═O), B(OH) 2 , O(alkyl)aminocarbonyl, cycloalkyl, heterocyclyl, heteroaryl, aryloxy, aralkyloxy, heterocyclyloxy, or heterocyclyl alkoxy.

3. A compound of formula (Im)

wherein:
R 1 is substituted or unsubstituted cycloalkylalkyl, or substituted 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 selected from substituted or unsubstituted C 1-3 alkyl, CN, and —OR′, wherein each R′ is independently substituted or unsubstituted C 1-3 alkyl; and
P is Rink-H resin;
when a C 1-3 alkyl group is substituted, it is independently substituted with 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, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aryloxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, B(OH) 2 , or O(alkyl)aminocarbonyl; and
when a group, with the exception of a C 1-3 alkyl group, is substituted, it is independently substituted with 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, ketone, aldehyde, ester, urea, urethane, oxime, hydroxyl amine, alkoxyamine, aryloxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, oxygen (═O), B(OH) 2 , O(alkyl)aminocarbonyl, cycloalkyl, heterocyclyl, heteroaryl, aryloxy, aralkyloxy, heterocyclyloxy, or heterocyclyl alkoxy.

Assignees

• Signal Pharm Llc

Inventors

• Alexander Matthew
• Hansen Joshua
• Huang Dehua
• Hubbard Robert
• Raheja Raj K
• Schwarz Kimberly
• Sloss Marianne
• Torres Eduardo
• Zhao Jingjing

Classifications

• C07D473/32 Primary

  Nitrogen atom · CPC title

• A61K31/5377

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/52 Primary

  Purines, e.g. adenine · CPC title

• C07D239/50

  Three nitrogen atoms · CPC title