JPWO2021110887A5 - - Google Patents
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- Publication number
- JPWO2021110887A5 JPWO2021110887A5 JP2022532833A JP2022532833A JPWO2021110887A5 JP WO2021110887 A5 JPWO2021110887 A5 JP WO2021110887A5 JP 2022532833 A JP2022532833 A JP 2022532833A JP 2022532833 A JP2022532833 A JP 2022532833A JP WO2021110887 A5 JPWO2021110887 A5 JP WO2021110887A5
- Authority
- JP
- Japan
- Prior art keywords
- tetrahydro
- oxy
- dioxide
- acetic acid
- benzothiazepin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 90
- 125000000217 alkyl group Chemical group 0.000 claims 15
- 206010010774 Constipation Diseases 0.000 claims 14
- 150000001875 compounds Chemical class 0.000 claims 14
- 206010008635 Cholestasis Diseases 0.000 claims 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 10
- 230000007870 cholestasis Effects 0.000 claims 9
- 231100000359 cholestasis Toxicity 0.000 claims 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 9
- 239000003613 bile acid Substances 0.000 claims 8
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 7
- 201000002150 Progressive familial intrahepatic cholestasis Diseases 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 210000004185 liver Anatomy 0.000 claims 6
- 201000001493 benign recurrent intrahepatic cholestasis Diseases 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- -1 cyano, nitro, amino Chemical group 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 5
- 208000019423 liver disease Diseases 0.000 claims 5
- 125000004414 alkyl thio group Chemical group 0.000 claims 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 208000011580 syndromic disease Diseases 0.000 claims 4
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 3
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 3
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 claims 3
- 206010010317 Congenital absence of bile ducts Diseases 0.000 claims 3
- 206010010356 Congenital anomaly Diseases 0.000 claims 3
- 206010072268 Drug-induced liver injury Diseases 0.000 claims 3
- 206010016654 Fibrosis Diseases 0.000 claims 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 3
- 206010019708 Hepatic steatosis Diseases 0.000 claims 3
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 3
- 208000004622 abetalipoproteinemia Diseases 0.000 claims 3
- 210000000941 bile Anatomy 0.000 claims 3
- 210000000013 bile duct Anatomy 0.000 claims 3
- 201000005271 biliary atresia Diseases 0.000 claims 3
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 201000001883 cholelithiasis Diseases 0.000 claims 3
- 230000007882 cirrhosis Effects 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 238000003786 synthesis reaction Methods 0.000 claims 3
- 238000002054 transplantation Methods 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 201000011374 Alagille syndrome Diseases 0.000 claims 2
- 208000010061 Autosomal Dominant Polycystic Kidney Diseases 0.000 claims 2
- 208000002814 Autosomal Recessive Polycystic Kidney Diseases 0.000 claims 2
- 208000017354 Autosomal recessive polycystic kidney disease Diseases 0.000 claims 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- 208000029448 Chylomicron retention disease Diseases 0.000 claims 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 2
- 206010020772 Hypertension Diseases 0.000 claims 2
- 201000004408 Hypobetalipoproteinemia Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 206010023126 Jaundice Diseases 0.000 claims 2
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010033645 Pancreatitis Diseases 0.000 claims 2
- 208000012347 Parenteral nutrition associated liver disease Diseases 0.000 claims 2
- 208000033147 Parenteral nutrition-associated cholestasis Diseases 0.000 claims 2
- 208000003251 Pruritus Diseases 0.000 claims 2
- 230000002159 abnormal effect Effects 0.000 claims 2
- 208000022185 autosomal dominant polycystic kidney disease Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 2
- 230000007547 defect Effects 0.000 claims 2
- 230000007812 deficiency Effects 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 201000008220 erythropoietic protoporphyria Diseases 0.000 claims 2
- 201000000544 familial hypobetalipoproteinemia 1 Diseases 0.000 claims 2
- 230000004129 fatty acid metabolism Effects 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 208000001130 gallstones Diseases 0.000 claims 2
- 208000006454 hepatitis Diseases 0.000 claims 2
- 231100000283 hepatitis Toxicity 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 208000001024 intrahepatic cholestasis Diseases 0.000 claims 2
- 230000007872 intrahepatic cholestasis Effects 0.000 claims 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 208000030761 polycystic kidney disease Diseases 0.000 claims 2
- 230000035935 pregnancy Effects 0.000 claims 2
- 208000010157 sclerosing cholangitis Diseases 0.000 claims 2
- 210000002966 serum Anatomy 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- 206010067092 AIDS cholangiopathy Diseases 0.000 claims 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 206010003210 Arteriosclerosis Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims 1
- 208000023514 Barrett esophagus Diseases 0.000 claims 1
- 208000023665 Barrett oesophagus Diseases 0.000 claims 1
- 208000019256 Benign recurrent intrahepatic cholestasis type 2 Diseases 0.000 claims 1
- 206010004593 Bile duct cancer Diseases 0.000 claims 1
- 206010051341 Bile duct stenosis Diseases 0.000 claims 1
- 206010004637 Bile duct stone Diseases 0.000 claims 1
- 102100028282 Bile salt export pump Human genes 0.000 claims 1
- 208000015163 Biliary Tract disease Diseases 0.000 claims 1
- 208000002177 Cataract Diseases 0.000 claims 1
- 206010053684 Cerebrohepatorenal syndrome Diseases 0.000 claims 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims 1
- 201000009331 Choledocholithiasis Diseases 0.000 claims 1
- 208000032170 Congenital Abnormalities Diseases 0.000 claims 1
- 208000011231 Crohn disease Diseases 0.000 claims 1
- 201000003883 Cystic fibrosis Diseases 0.000 claims 1
- 208000008960 Diabetic foot Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- 208000004930 Fatty Liver Diseases 0.000 claims 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 108010010234 HDL Lipoproteins Proteins 0.000 claims 1
- 102000015779 HDL Lipoproteins Human genes 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 208000027761 Hepatic autoimmune disease Diseases 0.000 claims 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 claims 1
- 206010019799 Hepatitis viral Diseases 0.000 claims 1
- 101000724352 Homo sapiens Bile salt export pump Proteins 0.000 claims 1
- 101000955481 Homo sapiens Phosphatidylcholine translocator ABCB4 Proteins 0.000 claims 1
- 101000671676 Homo sapiens U3 small nucleolar RNA-associated protein 4 homolog Proteins 0.000 claims 1
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims 1
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
- 206010020915 Hypervitaminosis Diseases 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 206010065973 Iron Overload Diseases 0.000 claims 1
- 101150072399 LSC1 gene Proteins 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 208000015924 Lithiasis Diseases 0.000 claims 1
- 206010025282 Lymphoedema Diseases 0.000 claims 1
- 206010054805 Macroangiopathy Diseases 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- 206010028289 Muscle atrophy Diseases 0.000 claims 1
- 206010051606 Necrotising colitis Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010030216 Oesophagitis Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 102100039032 Phosphatidylcholine translocator ABCB4 Human genes 0.000 claims 1
- 206010063985 Phytosterolaemia Diseases 0.000 claims 1
- 235000017284 Pometia pinnata Nutrition 0.000 claims 1
- 240000007653 Pometia tomentosa Species 0.000 claims 1
- 206010057969 Reflux gastritis Diseases 0.000 claims 1
- 208000001647 Renal Insufficiency Diseases 0.000 claims 1
- 208000017442 Retinal disease Diseases 0.000 claims 1
- 206010038923 Retinopathy Diseases 0.000 claims 1
- 208000002227 Sitosterolemia Diseases 0.000 claims 1
- 208000007718 Stable Angina Diseases 0.000 claims 1
- 102100036325 Sterol 26-hydroxylase, mitochondrial Human genes 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 1
- 206010042953 Systemic sclerosis Diseases 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 102100040072 U3 small nucleolar RNA-associated protein 4 homolog Human genes 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 201000004525 Zellweger Syndrome Diseases 0.000 claims 1
- 208000036813 Zellweger spectrum disease Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 208000002353 alcoholic hepatitis Diseases 0.000 claims 1
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims 1
- 206010002022 amyloidosis Diseases 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 210000001367 artery Anatomy 0.000 claims 1
- 230000003190 augmentative effect Effects 0.000 claims 1
- 208000021033 autosomal dominant polycystic liver disease Diseases 0.000 claims 1
- 201000001490 benign recurrent intrahepatic cholestasis 1 Diseases 0.000 claims 1
- 201000001488 benign recurrent intrahepatic cholestasis 2 Diseases 0.000 claims 1
- 208000026586 benign recurrent intrahepatic cholestasis type 1 Diseases 0.000 claims 1
- 208000026900 bile duct neoplasm Diseases 0.000 claims 1
- 208000006766 bile reflux Diseases 0.000 claims 1
- 210000003445 biliary tract Anatomy 0.000 claims 1
- 230000036765 blood level Effects 0.000 claims 1
- 210000001185 bone marrow Anatomy 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 208000001088 cerebrotendinous xanthomatosis Diseases 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 208000006990 cholangiocarcinoma Diseases 0.000 claims 1
- 208000003167 cholangitis Diseases 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 230000003111 delayed effect Effects 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 201000008865 drug-induced hepatitis Diseases 0.000 claims 1
- 208000006881 esophagitis Diseases 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 208000009866 extrahepatic cholestasis Diseases 0.000 claims 1
- 229930195729 fatty acid Natural products 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 150000004665 fatty acids Chemical class 0.000 claims 1
- 208000010706 fatty liver disease Diseases 0.000 claims 1
- 230000001434 glomerular Effects 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 230000014101 glucose homeostasis Effects 0.000 claims 1
- 230000002440 hepatic effect Effects 0.000 claims 1
- 208000005252 hepatitis A Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 201000001421 hyperglycemia Diseases 0.000 claims 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims 1
- 201000008980 hyperinsulinism Diseases 0.000 claims 1
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
- 206010021198 ichthyosis Diseases 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 208000016245 inborn errors of metabolism Diseases 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 208000015978 inherited metabolic disease Diseases 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 210000003228 intrahepatic bile duct Anatomy 0.000 claims 1
- 201000002161 intrahepatic cholestasis of pregnancy Diseases 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- 230000003902 lesion Effects 0.000 claims 1
- 208000002502 lymphedema Diseases 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 230000004060 metabolic process Effects 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 201000000585 muscular atrophy Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 208000002865 osteopetrosis Diseases 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000028589 polycystic liver disease Diseases 0.000 claims 1
- 208000007232 portal hypertension Diseases 0.000 claims 1
- 208000000876 primary bile acid malabsorption Diseases 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 230000033764 rhythmic process Effects 0.000 claims 1
- 201000000306 sarcoidosis Diseases 0.000 claims 1
- 230000001568 sexual effect Effects 0.000 claims 1
- 210000002027 skeletal muscle Anatomy 0.000 claims 1
- 231100000240 steatosis hepatitis Toxicity 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 claims 1
- 230000001988 toxicity Effects 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 201000001862 viral hepatitis Diseases 0.000 claims 1
- 230000029663 wound healing Effects 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN201911049985 | 2019-12-04 | ||
| IN201911049985 | 2019-12-04 | ||
| PCT/EP2020/084571 WO2021110887A1 (en) | 2019-12-04 | 2020-12-04 | Benzothiazepine compounds and their use as bile acid modulators |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2023504646A JP2023504646A (ja) | 2023-02-06 |
| JP2023504646A5 JP2023504646A5 (https=) | 2023-12-05 |
| JPWO2021110887A5 true JPWO2021110887A5 (https=) | 2023-12-05 |
| JP7665621B2 JP7665621B2 (ja) | 2025-04-21 |
Family
ID=82196618
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022532833A Active JP7665621B2 (ja) | 2019-12-04 | 2020-12-04 | ベンゾチアゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用 |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP4069362A1 (https=) |
| JP (1) | JP7665621B2 (https=) |
| CN (1) | CN114786773B (https=) |
| CA (1) | CA3158175A1 (https=) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4188541B1 (en) * | 2020-08-03 | 2024-12-25 | Albireo AB | Benzothia(di)azepine compounds and their use as bile acid modulators |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9800428D0 (en) * | 1998-01-10 | 1998-03-04 | Glaxo Group Ltd | Chemical compounds |
| EG26979A (en) * | 2000-12-21 | 2015-03-01 | Astrazeneca Ab | Chemical compounds |
| GB0121337D0 (en) * | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| JP6097695B2 (ja) * | 2010-11-08 | 2017-03-15 | アルビレオ アクチエボラグ | Ｉｂａｔ阻害剤および胆汁酸結合剤を含む薬学的組み合わせ |
-
2020
- 2020-12-04 CA CA3158175A patent/CA3158175A1/en active Pending
- 2020-12-04 EP EP20821144.1A patent/EP4069362A1/en active Pending
- 2020-12-04 JP JP2022532833A patent/JP7665621B2/ja active Active
- 2020-12-04 CN CN202080083824.3A patent/CN114786773B/zh active Active
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