Benzothia(di)azepine compounds and their use as bile acid modulators
AssigneeAlbireo AB
InventorsPer-Göran Gillberg, Ingemar Starke, Santosh S. Kulkarni
Life of this patent
Estimating the term…
Abstract
The invention relates to 1,5-benzothiazepine and 1,2,5-benzothiadiazepine derivatives of formula (I). These compounds are bile acid modulators having apical sodium-dependent bile acid transporter (ASBT) and/or liver bile acid transport (LBAT) inhibitory activity. The invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment of cardiovascular diseases, fatty acid metabolism and glucose utilization disorders, gastrointestinal diseases and liver diseases.
Claims20
-17. (canceled)
A compound of formula (I-a):
- wherein
- M is selected from the group consisting of —CH2—, —NH— and —NCH3—;
- R1 is C2-4 alkyl;
- R2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, amino, N—(C1-4 alkyl)amino, N,N-di(C1-4 alkyl)amino, C1-6 alkylcarbonylamino, C3-6 cycloalkylcarbonylamino, N—(C1-4 alkyl)aminocarbonyl, N,N-di(C1-4 alkyl)aminocarbonyl, C1-4 alkyloxycarbonylamino, C1-4 alkylsulfonamido and C3-6 cycloalkylsulfonamido;
- n is an integer 1 or 2;
- R3 is selected from the group consisting of hydrogen, halogen, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, amino, N—(C1-4 alkyl)amino and N,N-di(C1-4 alkyl)amino;
- R4 is hydrogen or fluoro;
- or a pharmaceutically acceptable salt thereof.
A method for treating a cholestatic liver disease or viral hepatitis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I-a):
- wherein
- M is selected from the group consisting of —CH2—, —NH— and —NCH3—;
- R1 is C2-4 alkyl;
- R2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, amino, N—(C1-4 alkyl)amino, N,N-di(C1-4 alkyl)amino, C1-6 alkylcarbonylamino, C3-6 cycloalkylcarbonylamino, N—(C1-4 alkyl)aminocarbonyl, N,N-di(C1-4 alkyl)aminocarbonyl, C1-4 alkyloxycarbonylamino, C1-4 alkylsulfonamido and C3-6 cycloalkylsulfonamido;
- n is an integer 1 or 2;
- R3 is selected from the group consisting of hydrogen, halogen, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, amino, N—(C1-4 alkyl)amino and N,N-di(C1-4 alkyl)amino;
- R4 is hydrogen or fluoro;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.