Benzothiazole or benzoxazole compounds as SUMO activators
AssigneeIcahn School of Medicine at Mount Sinai
InventorsRussell Dahl, Ah Young Lee, Changwon Kho, Roger J. Hajjar
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 method of treating heart failure, cardiac hypertrophy, myocarditis, myocardial infarction, ischemia, cardiac arrhythmias, vascular rhexis, cardiac arrhythmia, valvulopathy, diastolic dysfunction, hypertension, neurodegenerative disorders, viral infection, liver disease, or inflammation in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of Formula II:
- or a pharmaceutically acceptable salt thereof;
- wherein:
- Ar is aryl or heteroaryl, each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1a groups;
- W is S or O;
- Y is O;
- each X is N;
- Z is O, S, or NRA;
- RA is H or C1-4 alkyl;
- R1, R2, R3, and R4 are each independently selected from hydrogen, 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(C1-4alkyl)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-C1-4alkylaminosulfonylamino;
- 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(C1-4alkyl)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 hydrogen.
A method of treating heart failure, cardiac hypertrophy, myocarditis, myocardial infarction, ischemia, cardiac arrhythmias, vascular rhexis, cardiac arrhythmia, valvulopathy, diastolic dysfunction, hypertension, neurodegenerative disorders, viral infection, liver disease, or inflammation in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of Formula II:
- or a pharmaceutically acceptable salt thereof;
- wherein:
- Ar is aryl or heteroaryl, each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1a groups;
- W is S or O;
- Y is O;
- each X is N;
- Z is O, S, or NRA;
- RA is H or C1-4 alkyl;
- R1, R2, R3, and R4 are each hydrogen;
- each R1a is independently selected from halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6 heteroaryl, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-4-alkylamino, carboxy, carbamyl, C1-6 alkylcarbamyl, di(C1-4alkyl)carbamyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6alklaminosulfonyl, di-C1-4 alklaminosulfonyl, aminosulfonylamino C1-6 alkylaminosulfonylamino, and di-C1-4alkylaminosulfonylamino;
- wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6 heteroaryl, 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, alkylamino, and di-C1-3-alkylamino;
- or
- two adjacent R1a taken together with the atoms to which they are attached can form a 3-7 membered carbocyclic or 4-6 membered heterocyclic ring, each of which is optionally substituted with 1, 2, 3, or 4 C1-3 alkyl groups.
A method of treating heart failure, cardiac hypertrophy, myocarditis, myocardial infarction, ischemia, cardiac arrhythmias, vascular rhexis, cardiac arrhythmia, valvulopathy, diastolic dysfunction, hypertension, neurodegenerative disorders, viral infection, liver disease, or inflammation in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of 5-(4 chlorophenyl)-N-(6-methoxybenzo[d]thiazol-2-yl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.