Oxazole and thiazole compounds as β-catenin modulators and uses thereof
AssigneeNew York University
InventorsRamanuj Dasgupta, Foster Gonsalves
Life of this patent
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Abstract
A series of oxazole and thiazole compounds are shown herein to be small molecule inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of β-cat oxazole and thiazole compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and others.
Claims18
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound according to formula I:
- wherein A is A1;
- A1 is
- x is 1;
- L1 is S, SO or SO2;
- m1 is 1, 2 or 3;
- n is 1, 2, 3, 4 or 5;
- each R1, R2a, R2b, R2c, and R2d is independently selected from hydrogen, halo, and substituted or unsubstituted C1-C6 alkyl;
- R3 is NR3aR3b;
- and
- one of R3a and R3b is substituted or unsubstituted alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenethyl, cycloheptyl, cyclohexyl, cyclohexyl substituted with methyl or dimethyl, substituted or unsubstituted cyclopentyl, substituted or unsubstituted cyclobutyl, or substituted or unsubstituted cyclopropyl;
- and the other is H or substituted or unsubstituted alkyl;
- or
- NR3aR3b is:
- and wherein R3c is H or alkyl;
- each R4 is independently selected from alkyl, substituted alkyl, acyl, substituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkythio, substituted or unsubstituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted arylsulfonyl, azido, carboxy, substituted or unsubstituted carbamoyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol;
- and
- a pharmaceutically acceptable salt, solvate or prodrug thereof;
- and stereoisomers, isotopic variants and tautomers thereof.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound, wherein the compound is according to formula XIa, XIb, XIc or XId:
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound, wherein the compound is selected from Table 1.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound, wherein the compound is selected from Table 2.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound, wherein the compound is selected from Table 4.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound according to formula I:
- wherein A is A1;
- A1 is
- x is 1;
- L1 is S, SO or SO2;
- m1 is 1, 2 or 3;
- n is 1, 2, 3, 4 or 5;
- each R1, R2a, R2b, R2c, and R2d is independently selected from hydrogen, halo, and substituted or unsubstituted C1-C6 alkyl;
- R3 is NR3aR3b;
- and
- one of R3a and R3b is substituted or unsubstituted alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenethyl, substituted or unsubstituted cyclopentyl, substituted or unsubstituted cyclobutyl, or substituted or unsubstituted cyclopropyl;
- and the other is H or substituted or unsubstituted alkyl;
- or
- NR3aR3b is:
- and wherein R3c is H or alkyl;
- each R4 is independently selected from alkyl, substituted alkyl, acyl, substituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkythio, substituted or unsubstituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted arylsulfonyl, azido, carboxy, substituted or unsubstituted carbamoyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol;
- and
- a pharmaceutically acceptable salt, solvate or prodrug thereof;
- and stereoisomers, isotopic variants and tautomers thereof.
Dependencies are inferred from the claim text.