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US 2020/0270240 A1Published application
Benzothiazole and pyridothiazole compounds as sumo activators
AssigneeIcahn School of Medicine at Mount Sinai
InventorsRoger Hajjar, Robert Devita
Life of this patent
Estimating the term…
Abstract
Provided are SUMO activators, which can enhance SUMOylation of SERCA2a, which are useful in the treatment of heart failure, cardiovascular diseases, cancer, neurodegenerative disorders, viral infection, bacterial infection, liver disease, inflammation, and other diseases.
Claims16
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof;
- R1, R2, R3, and R4 are each independently selected from hydrogen, halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, and di-C1-4-alkylamino;
- each R5 is independently selected from halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, and di-C1-4-alkylamino;
- n is 0, 1, 2, or 3;
- R6 is selected from R6a—C(O)— and R6b—C1-4 alkylene-O—;
- R6a is selected from C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, and C1-6 heteroaryl, each of which are optionally substituted by 1, 2, 3, or 4 substituents selected from halo, CN, hydroxy, C1-3 alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino;
- R6b is selected from —C(O)ORa, —C(O)Rb, —C(O)NRcRd, —S(O)2NRcRd, —OC(O)Rb, —NRaC(O)Rb, —NRaS(O)2Rb, —NRaC(O)ORa, —OC(O)NRcRd, —NRaC(O)NRcRd, —NRaS(O)2NRcRd, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, and C1-6 heteroaryl, wherein said C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, and C1-6 heteroaryl are optionally substituted by 1, 2, 3, or 4 substituents selected from halo, CN, hydroxy, C1-3 alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino;
- each Ra, Rc, and Rd is independently selected from hydrogen, C1-4 alkyl, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, and C1-6 heteroaryl;
- wherein said C1-4 alkyl, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, and C1-6 heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents selected from halo, CN, hydroxy, C1-3 alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino;
- and
- each Rb is independently selected from C1-4 alkyl, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, and C1-6 heteroaryl;
- each of which is optionally substituted by 1, 2, 3, or 4 substituents independently selected from halo, CN, hydroxy, C1-3 alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino.
9 more elements
A compound of Formula II:
- or a pharmaceutically acceptable salt thereof;
- Ar is phenyl, which is optionally substituted with 1, 2, 3, 4, or 5 independently selected R1a groups;
- R1, R2, and R4 are each independently selected from hydrogen, halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-4-alkylamino, carboxy, carbamyl, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di-C1-4 alkylamino sulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, and di-C1-4 alkylaminosulfonylamino;
- wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, di-C1-4-alkylamino, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, and C1-6 alkylcarbonyl are each optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, hydroxy, C1-3 alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino;
- each R1a is independently selected from halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl-C1-3 alkylene, C2-6 heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, C1-6 heteroaryl-C1-3 alkylene, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6 heteroaryl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-4-alkylamino, carboxy, carbamyl, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di-C1-4 alkylaminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, and di-C1-4 alkylaminosulfonylamino;
- wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl-C1-3 alkylene, C2-6 heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, C1-6 heteroaryl-C1-3 alkylene, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6 heteroaryl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, and C1-6 alkylcarbonyl are each optionally substituted with 1, 2, or 3 groups independently selected R1b groups;
- and
- each R1b group is independently selected from halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl-C1-3 alkylene, C2-6 heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, C1-6 heteroaryl-C1-3 alkylene, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6 heteroaryl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-4-alkylamino, carboxy, carbamyl, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di-C1-4 alkylaminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, and di-C1-4 alkylaminosulfonylamino.
5 more elements
A compound selected from the group consisting of the compounds identified in Examples 3a, 3b, 3c, 8a, 8b, 12a, 12b, 12c, 12d, 15a, 15b, 15c, 15d, 16a, 16b, 16c, 16d, 16e, 18a, 18b, 18c, 18d, 18e, 18f, 20a, 20b, 20c, 20d, 20e, 20f, 26, 27, 31a, and 31b, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.