Tetrahydroquinoline compositions as BET bromodomain inhibitors
AssigneeFORMA Therapeutics, Inc.
InventorsKenneth W. Bair, Torsten Herbertz, Goss S. Kauffman, Katherine J. Kayser-Bricker, George P. Luke, Matthew W. Martin, David S. Millan, Shawn E. R. Schiller, Adam C. Talbot
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Abstract
The present invention relates to inhibitors of bromo and extra terminal (BET) bromodomains that are useful for the treatment of cancer, inflammatory diseases, diabetes, and obesity, having Formula I: wherein W, X, Y, Z, R1, R2, R5, and R8 are as described herein.
Claims22
A method of treating a disease or disorder mediated by one or more BET-family bromodomains in a patient, comprising administering to the patient in need thereof a compound:
- or a pharmaceutically acceptable salt thereof.
A method of treating a disease or disorder mediated by one or more BET-family bromodomains in a patient, comprising administering to the patient in need thereof a compound of Formula IV:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- R4 is —O(CH2)nRd;
- R8 is C1-C6 alkyl, cycloalkyl, —O—C1-C6 alkyl, or —O-cycloalkyl;
- each Ra and Rb are independently hydrogen or C1-C6 alkyl;
- each Ra is independently —(CH2)nRa, —(CH2)nORa, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —S(O)2Ra, —S(O)2NRaRb, C1-C6 haloalkyl, C1-C6 haloalkoxy, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, cyano, or oxo, wherein cycloalkyl and heterocycloalkyl are optionally substituted with one or more Re;
- Rd is hydrogen, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from Ra, Rb, and Rc;
- each Re is independently hydrogen, halogen, —OH, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, oxo, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxy, or —S(O)2(C1-C6 alkyl);
- and
- n is 0, 1, or 2.
A method of treating cancer, comprising administering to a patient in need thereof a compound:
- or a pharmaceutically acceptable salt thereof.
A method of treating a disease or disorder mediated by one or more BET-family bromodomains in a patient, comprising administering to the patient in need thereof a compound of Formula IV:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- R4 is —O(CH2)nRd;
- R8 is C1-C6 alkyl, cycloalkyl, —O—C1-C6 alkyl, or —O-cycloalkyl;
- each Ra and Rb are independently hydrogen or C1-C6 alkyl;
- each Rc is independently —(CH2)nRa, —(CH2)nORa, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —S(O)2Ra, —S(O)2NRaRb, C1-C6 haloalkyl, C1-C6 haloalkoxy, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, cyano, or oxo, wherein cycloalkyl and heterocycloalkyl are optionally substituted with one or more Re;
- Rd is hydrogen, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from Ra, Rb, and Rc;
- each Re is independently hydrogen, halogen, —OH, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, oxo, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxy, or —S(O)2(C1-C6 alkyl);
- and
- n is 0, 1, or 2.
Dependencies are inferred from the claim text.