Stat3 transcription factor inhibitors and methods of using the same
AssigneeThe Regents of the University of Colorado
InventorsPhilip REIGAN, Donald S. BACKOS, Christopher J. MATHESON, Steffanie L. FURTEK, Craig T. JORDAN, Maria L. AMAYA
Life of this patent
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Abstract
Compounds that inhibit the activity of Signal transducer and activator of transcription 3 (STAT3), or pharmaceutically acceptable salts or prodrugs thereof, and methods of using these compounds to treat cancer and other diseases.
Claims24
A compound of Formula (I) or (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is H, C1-6 alkyl, substituted C1-6 alkyl, C1-6 alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, nitro, CN, SO3H, OR1S where R1S is H, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR1SaR1Sb where R1Sa and R1Sb are independently H, C1-8 alkyl, substituted C1-8 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, aryl such as a phenyl, substituted aryl, heteroaryl or substituted heteroaryl;
- R2 is H, C1-6 alkyl, substituted C1-6 alkyl, C1-6 alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, OR2S where R2S is H, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR2SaR2Sb where R2Sa and R2Sb are independently H, C1-8 alkyl, substituted C1-8 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, aryl such as a phenyl, substituted aryl, heteroaryl or substituted heteroaryl;
- R3 is H, C1-6 alkyl, substituted C1-6 alkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
- R4 is H, C1-6 alkyl, substituted C1-6 alkyl, C1-6 alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, nitro, OR4S where R4S is H, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR4SaR4Sb where R4Sa and R4Sb are independently H, C1-8 alkyl, substituted C1-8 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, aryl such as a phenyl, substituted aryl, heteroaryl or substituted heteroaryl;
- R5 is H, C1-6 alkyl, substituted C1-6 alkyl, C1-6 alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, OR5S where R5S is H, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR5SaR5Sb where R5Sa and R5Sb are independently H, C1-8 alkyl, substituted C1-8 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, aryl such as a phenyl, substituted aryl, heteroaryl or substituted heteroaryl;
- and
- R6 is H, C1-6 alkyl, substituted C1-6 alkyl, C1-6 alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, OR6S, or —C(═O)—OR6S where R6S is H, C1-6 alkyl, —C(═O)—C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or NR6SaR6Sb where R6Sa and R6Sb are independently H, C1-8 alkyl, substituted C1-8 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, aryl such as a phenyl, substituted aryl, heteroaryl or substituted heteroaryl.
A compound of Formula (I) or (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is H, nitro, or NH2;
- R2 is halogen;
- R3 is H or C1-6 alkyl;
- R4 is halogen, nitro, or NH2;
- R5 is H, C6-C12 aryl, or 5- to 12-membered heteroaryl, wherein the C6-C12 aryl or 5- to 12-membered is optionally substituted with one or more R5S;
- each R5S independently is halogen, C1-6 alkyl, —OR5SS, —N(R5SS)2, —(C1-6 alkyl)-OR5SS, —(C1-6 alkyl)-N(R5SS)2, —C(═O)—R5SS, or —C(═O)—OR5SS;
- each R5SS independently is H or C1-6 alkyl;
- R6 is halogen, OR6S, or —C(═O)—OR6S;
- and
- R6S is H, C1-6 alkyl, or —C(═O)—C1-6 alkyl.
The compound of any one of the preceding claims, being of Formula (I) or (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is H, nitro, CN, SO3H, —C(═O)—OR1S, —(C═O)—N(R1S)2, or N(R1S)2;
- each R1S independently is H or C1-6 alkyl;
- R2 is halogen;
- R3 is H or C1-6 alkyl;
- R4 is halogen, nitro, or NH2;
- R5 is H, C6-C12 aryl, or 5- to 12-membered heteroaryl, wherein the C6-C12 aryl or 5- to 12-membered is optionally substituted with one or more R5S;
- each R5S independently is halogen, C1-6 alkyl, —OR5SS, —N(R5SS)2, —(C1-6 alkyl)-OR55S, —(C1-6 alkyl)-N(R5SS)2, —C(═O)—R5SS, or —C(═O)—OR5SS;
- each R5SS independently is H or C1-6 alkyl;
- R6 is halogen, OR6S, or —C(═O)—OR6S;
- and
- R6S is H, C1-6 alkyl, or —C(═O)—C1-6 alkyl.
The compound of any one of the preceding claims, being of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is nitro, CN, SO3H, —C(═O)—OR1S, —(C═O)—N(R1S)2, or N(R1S)2;
- each R1S independently is H or C1-6 alkyl;
- R2 is halogen;
- R3 is H or C1-6 alkyl;
- R4 is halogen;
- R5 is 5- to 12-membered heteroaryl optionally substituted with one or more R5S;
- each R5S independently is halogen, C1-6 alkyl, —OR5SS, —N(R5SS)2, —(C1-6 alkyl)-OR55S, —(C1-6 alkyl)-N(R5SS)2, —C(═O)—R5SS, or —C(═O)—OR5SS;
- each R5SS independently is H or C1-6 alkyl;
- R6 is OR6S or —C(═O)—OR6S;
- and
- R6S is H or —C(═O)—C1-6 alkyl.
The compound of any one of the preceding claims, being of Formula (I-a):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is nitro, CN, SO3H, —C(═O)—OR1S, —(C═O)—N(R1S)2, or N(R1S)2;
- each R1S independently is H or C1-6 alkyl;
- R5 is 5- to 12-membered heteroaryl optionally substituted with one or more R5S;
- each R5S independently is halogen, C1-6 alkyl, —OR5SS, —N(R5SS)2, —(C1-6 alkyl)-OR55S, —(C1-6 alkyl)-N(R5SS)2, —C(═O)—R5SS, or —C(═O)—OR5SS;
- and
- each R5SS independently is H or C1-6 alkyl.
The compound of any one of the preceding claims, wherein the compound is not niclosamide or a pharmaceutically acceptable salt thereof.
The compound of any one of the preceding claims, being selected from:
- prodrugs thereof, and pharmaceutically acceptable salts thereof.
The compound of any one of the preceding claims, being selected from:
- prodrugs thereof, and pharmaceutically acceptable salts thereof.
The compound of any one of the preceding claims, being
- or a pharmaceutically acceptable salt thereof.
The compound of any one of the preceding claims, being
- or a pharmaceutically acceptable salt thereof.
The compound of any one of the preceding claims, being
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a compound of any one of the preceding claims or a prodrug thereof, and at least one pharmaceutically-acceptable additive.
Dependencies are inferred from the claim text.