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
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Abstract
The invention relates to certain 1,5-benzothiazepine and 1,2,5-benzothiadiazepine derivatives as defined herein. 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.
Claims17
A method for treating a disease or disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I),
- wherein M, R1, R2, R3, R4 and R5 are as indicated in Table 1 below:
- TABLE 1
- M
- R1
- R2
- R3
- R4
- R5
- CH2
- CH2CH2CH2CH3
- CH2CH2CH2CH3
- F
- SCH3
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH3
- H
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH3
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH3
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH3
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH3
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH3
- F
- CH2
- CH2CH2CH3
- CH2CH3
- H
- SCH3
- H
- CH2
- CH2CH2CH3
- CH2CH3
- H
- SCH3
- F
- CH2
- CH(CH3)2
- CH2CH3
- H
- SCH3
- H
- CH2
- CH(CH3)2
- CH2CH3
- H
- SCH3
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH2CH3
- H
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH2CH3
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- H
- SCH2CH3
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- H
- SCH2CH3
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH2CH3
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH2CH3
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- H
- SCH2CH3
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- H
- SCH2CH3
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH2CH3
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- SCH2CH3
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- Cl
- H
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- Cl
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- H
- Cl
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- H
- Cl
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- Cl
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- Cl
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- H
- Cl
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- H
- Cl
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- Cl
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- Cl
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- N(CH3)2
- H
- CH2
- CH2CH2CH2CH3
- CH2CH3
- F
- N(CH3)2
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- H
- N(CH3)2
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- H
- N(CH3)2
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- N(CH3)2
- H
- NH
- CH2CH2CH2CH3
- CH2CH3
- F
- N(CH3)2
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- H
- N(CH3)2
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- H
- N(CH3)2
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- N(CH3)2
- H
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- F
- N(CH3)2
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- Cl
- SCH3
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- Cl
- SCH3
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- Cl
- SCH3
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- Cl
- Cl
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- Cl
- Cl
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- Cl
- Cl
- F
- CH2
- CH2CH2CH2CH3
- CH2CH3
- Cl
- N(CH3)2
- F
- NH
- CH2CH2CH2CH3
- CH2CH3
- Cl
- N(CH3)2
- F
- NCH3
- CH2CH2CH2CH3
- CH2CH3
- Cl
- N(CH3)2
- F
- or a pharmaceutically acceptable salt thereof, wherein the disease or disorder is selected from the group consisting of:
- a cardiovascular disease;
- a disorder of fatty acid metabolism;
- a glucose utilization disorder;
- a gastrointestinal disease or disorder;
- a liver disease or disorder;
- a hyperabsorption syndrome;
- hypervitaminosis and osteopetrosis;
- hypertension;
- glomerular hyperfiltration;
- or pruritus of renal failure.
Dependencies are inferred from the claim text.