US 7,732,475 B2Granted

Histone deacetylase inhibitors

AssigneeTakeda San Diego, Inc.

InventorsJerome C. Bressi, Anthony R. Gangloff, Lily Kwok

Life of this patent

Estimating the term…

Abstract

Compounds, pharmaceutical compositions, kits and methods are provided for use with HDAC that comprise a compound selected from the group consisting of: wherein the substituents are as defined herein.

Claims30

Dependent claims

A compound of a formula selected from the group consisting of:

or a pharmaceutically acceptable salt thereof, mixture of stereoisomers or a single stereoisomer thereof;
wherein:
m is selected from the group consisting of 0, 1, 2, 3 and 4;
n is selected from the group consisting of 0, 1, 2, 3 and 4;
p is selected from the group consisting of 0, 1, 2, 3 and 4;
each R4 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted;
R7 is selected from the group consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted;
each R9 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted, or any two R9 may be taken together to form a substituted or unsubstituted ring;
and
each R12 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted, or R12 and R7 or R11 may be taken together to form a substituted or unsubstituted ring.

7 more elements

A compound selected from the group consisting of:

4-((1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;
4-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;
4-((5-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;
N-(2-aminophenyl)-4-((5-nitro-1H-indazol-1-yl)methyl)benzamide;
4-((5-benzamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;
4-((5-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;
N-(2-aminophenyl)-4-((5-nitro-2H-indazol-2-yl)methyl)benzamide;
4-((5-benzamido-2H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;
2-Methoxyethyl 2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;
Methyl 2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;
2-Methoxyethyl 1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;
Methyl 1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;
Benzyl 1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;
Benzyl 2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;
N-(4-Amino-biphenyl-3-yl)-4-(5-nitro-indazol-2-ylmethyl)-benzamide;
N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide;
N-(1-(4-((2-Aminophenyl)carbamoyl)benzyl)-1H-indazol-5-yl)morpholine-4-carboxamide;
2-Morpholinoethyl 1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;
Pyridin-3-ylmethyl 1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;
N-(4-Amino-biphenyl-3-yl)-4-indazol-2-ylmethyl-benzamide;
N-(2-aminophenyl)-4-((5-fluoro-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((4-chloro-1H-indazol-1-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((4-chloro-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((4-fluoro-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((6-methoxy-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((3-chloro-2H-indazol-2-yl)methyl)benzamide;
4-((3-amino-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;
N-(2-aminophenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((5-methoxy-1H-indazol-1-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((5-methoxy-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((4-methoxy-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((4-methoxy-1H-indazol-1-yl)methyl)benzamide;
4-((6-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;
4-((6-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;
4-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;
N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;
N-(2-aminophenyl)-4-((5,6-dimethoxy-1H-indazol-1-yl)methyl)benzamide;
4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(thiophen-2-yl)phenyl)benzamide;
and
N-(2-aminophenyl)-4-((6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide.

40 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/457,260Filed 13 Jul 2006 · us provisional application
Priority: 14 Jul 2005
Published: US 2007/0015809 A118 Jan 2007
Granted: 8 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 231/12
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 17/00
Drugs for dermatological disorders
A61P 17/06
Drugs for dermatological disorders: antipsoriatics

Family

Application60/699,139Us provisional application · filed 14 Jul 2005
US 2007/0015809 A1Pre-grant publication · published 18 Jan 2007
US 7,732,475 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Compounds, pharmaceutical compositions, kits and methods are provided for use with HDAC that comprise a compound selected from the group consisting of: wherein the substituents are as defined herein.

A compound of a formula selected from the group consisting of:

or a pharmaceutically acceptable salt thereof, mixture of stereoisomers or a single stereoisomer thereof;
wherein:
m is selected from the group consisting of 0, 1, 2, 3 and 4;
n is selected from the group consisting of 0, 1, 2, 3 and 4;
p is selected from the group consisting of 0, 1, 2, 3 and 4;
each R4 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted;
R7 is selected from the group consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted;
each R9 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted, or any two R9 may be taken together to form a substituted or unsubstituted ring;
and
each R12 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C1-10)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, carbonyl(C1-3)alkyl, thiocarbonyl(C1-3)alkyl, sulfonyl(C1-3)alkyl, sulfinyl(C1-3)alkyl, amino(C1-10)alkyl, imino(C1-3)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, aryl, heteroaryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted, or R12 and R7 or R11 may be taken together to form a substituted or unsubstituted ring.

7 more elements

Facts

Application

11/457,260Filed 13 Jul 2006 · us provisional application

Priority

14 Jul 2005

Published

US 2007/0015809 A118 Jan 2007

Granted

8 Jun 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 231/12
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 17/00
Drugs for dermatological disorders
A61P 17/06
Drugs for dermatological disorders: antipsoriatics