TW202015699A - 苯并噻(二)氮呯(benzothia(di)azepine)化合物及其作為膽汁酸調節劑之用途 - Google Patents

Info

Publication number

TW202015699A

TW202015699A TW108119554A TW108119554A TW202015699A TW 202015699 A TW202015699 A TW 202015699A TW 108119554 A TW108119554 A TW 108119554A TW 108119554 A TW108119554 A TW 108119554A TW 202015699 A TW202015699 A TW 202015699A

Authority

TW

Taiwan

Prior art keywords

tetrahydro

oxy

phenyl

ethyl

dioxanyl

Prior art date

2018-06-05

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003613 bile acid Substances 0.000 title claims abstract description 102
• 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 title claims abstract description 59
• 150000001538 azepines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 302
• 210000004185 liver Anatomy 0.000 claims abstract description 62
• 238000011282 treatment Methods 0.000 claims abstract description 49
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 34
• 208000019423 liver disease Diseases 0.000 claims abstract description 25
• 208000035475 disorder Diseases 0.000 claims abstract description 10
• 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 abstract description 9
• 208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 8
• 239000008103 glucose Substances 0.000 claims abstract description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 156
• 150000003839 salts Chemical class 0.000 claims description 149
• -1 cyano, nitro, amino Chemical group 0.000 claims description 118
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 111
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 110
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 79
• 206010016654 Fibrosis Diseases 0.000 claims description 71
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 61
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 61
• 201000002150 Progressive familial intrahepatic cholestasis Diseases 0.000 claims description 43
• 125000000217 alkyl group Chemical group 0.000 claims description 41
• 206010008635 Cholestasis Diseases 0.000 claims description 36
• 206010010774 Constipation Diseases 0.000 claims description 34
• 230000007870 cholestasis Effects 0.000 claims description 32
• 231100000359 cholestasis Toxicity 0.000 claims description 32
• 230000007882 cirrhosis Effects 0.000 claims description 32
• 239000001257 hydrogen Substances 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• 208000006454 hepatitis Diseases 0.000 claims description 25
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
• 201000010099 disease Diseases 0.000 claims description 21
• 210000002966 serum Anatomy 0.000 claims description 21
• 229960001541 benzthiazide Drugs 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 208000004930 Fatty Liver Diseases 0.000 claims description 17
• 206010061218 Inflammation Diseases 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 17
• 230000004054 inflammatory process Effects 0.000 claims description 17
• 150000002500 ions Chemical class 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 208000011580 syndromic disease Diseases 0.000 claims description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
• 229940079593 drug Drugs 0.000 claims description 13
• 238000002054 transplantation Methods 0.000 claims description 13
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
• 206010019708 Hepatic steatosis Diseases 0.000 claims description 12
• 210000000013 bile duct Anatomy 0.000 claims description 12
• 206010010317 Congenital absence of bile ducts Diseases 0.000 claims description 11
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
• 208000003251 Pruritus Diseases 0.000 claims description 11
• 201000005271 biliary atresia Diseases 0.000 claims description 11
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• 239000011737 fluorine Substances 0.000 claims description 11
• 229910052731 fluorine Inorganic materials 0.000 claims description 11
• 230000001965 increasing effect Effects 0.000 claims description 11
• 238000003786 synthesis reaction Methods 0.000 claims description 11
• 201000001493 benign recurrent intrahepatic cholestasis Diseases 0.000 claims description 10
• 150000002431 hydrogen Chemical class 0.000 claims description 10
• 210000003405 ileum Anatomy 0.000 claims description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• 206010010356 Congenital anomaly Diseases 0.000 claims description 8
• 125000003118 aryl group Chemical group 0.000 claims description 8
• 210000004369 blood Anatomy 0.000 claims description 8
• 239000008280 blood Substances 0.000 claims description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 230000007812 deficiency Effects 0.000 claims description 8
• 231100000283 hepatitis Toxicity 0.000 claims description 8
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 231100000240 steatosis hepatitis Toxicity 0.000 claims description 7
• 210000001519 tissue Anatomy 0.000 claims description 7
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 6
• 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 claims description 6
• 206010072268 Drug-induced liver injury Diseases 0.000 claims description 6
• 101000955481 Homo sapiens Phosphatidylcholine translocator ABCB4 Proteins 0.000 claims description 6
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 6
• 102100039032 Phosphatidylcholine translocator ABCB4 Human genes 0.000 claims description 6
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 6
• 210000003445 biliary tract Anatomy 0.000 claims description 6
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 6
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 5
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 5
• 102100028282 Bile salt export pump Human genes 0.000 claims description 5
• 102000006395 Globulins Human genes 0.000 claims description 5
• 108010044091 Globulins Proteins 0.000 claims description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 5
• 101000724352 Homo sapiens Bile salt export pump Proteins 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 5
• 206010023126 Jaundice Diseases 0.000 claims description 5
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• 238000010521 absorption reaction Methods 0.000 claims description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
• 230000002440 hepatic effect Effects 0.000 claims description 5
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
• 201000011374 Alagille syndrome Diseases 0.000 claims description 4
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 4
• 208000031229 Cardiomyopathies Diseases 0.000 claims description 4
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
• 201000004408 Hypobetalipoproteinemia Diseases 0.000 claims description 4
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
• 206010022489 Insulin Resistance Diseases 0.000 claims description 4
• 201000005099 Langerhans cell histiocytosis Diseases 0.000 claims description 4
• 206010033645 Pancreatitis Diseases 0.000 claims description 4
• 240000009305 Pometia pinnata Species 0.000 claims description 4
• 235000017284 Pometia pinnata Nutrition 0.000 claims description 4
• 206010036186 Porphyria non-acute Diseases 0.000 claims description 4
• 208000006011 Stroke Diseases 0.000 claims description 4
• 208000004622 abetalipoproteinemia Diseases 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 4
• 206010003119 arrhythmia Diseases 0.000 claims description 4
• 230000006793 arrhythmia Effects 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 230000007547 defect Effects 0.000 claims description 4
• 201000008220 erythropoietic protoporphyria Diseases 0.000 claims description 4
• 201000000544 familial hypobetalipoproteinemia 1 Diseases 0.000 claims description 4
• 208000001130 gallstones Diseases 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 230000001771 impaired effect Effects 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 150000003904 phospholipids Chemical class 0.000 claims description 4
• 230000000750 progressive effect Effects 0.000 claims description 4
• 208000010157 sclerosing cholangitis Diseases 0.000 claims description 4
• 206010004637 Bile duct stone Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 210000004204 blood vessel Anatomy 0.000 claims description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• 230000003111 delayed effect Effects 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 201000007270 liver cancer Diseases 0.000 claims description 3
• 208000014018 liver neoplasm Diseases 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 210000000496 pancreas Anatomy 0.000 claims description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• 230000035935 pregnancy Effects 0.000 claims description 3
• 206010067092 AIDS cholangiopathy Diseases 0.000 claims description 2
• 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 2
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 206010003658 Atrial Fibrillation Diseases 0.000 claims description 2
• 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 2
• 208000023514 Barrett esophagus Diseases 0.000 claims description 2
• 208000023665 Barrett oesophagus Diseases 0.000 claims description 2
• 208000019256 Benign recurrent intrahepatic cholestasis type 2 Diseases 0.000 claims description 2
• 208000029655 Caroli Disease Diseases 0.000 claims description 2
• 208000002177 Cataract Diseases 0.000 claims description 2
• 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 2
• 108010004103 Chylomicrons Proteins 0.000 claims description 2
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
• 208000008960 Diabetic foot Diseases 0.000 claims description 2
• 206010013003 Dilatation intrahepatic duct congenital Diseases 0.000 claims description 2
• 201000010374 Down Syndrome Diseases 0.000 claims description 2
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
• 108010010234 HDL Lipoproteins Proteins 0.000 claims description 2
• 102000015779 HDL Lipoproteins Human genes 0.000 claims description 2
• 206010019280 Heart failures Diseases 0.000 claims description 2
• 208000027761 Hepatic autoimmune disease Diseases 0.000 claims description 2
• 208000005176 Hepatitis C Diseases 0.000 claims description 2
• 208000005331 Hepatitis D Diseases 0.000 claims description 2
• 206010019728 Hepatitis alcoholic Diseases 0.000 claims description 2
• 206010019799 Hepatitis viral Diseases 0.000 claims description 2
• 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
• 206010020915 Hypervitaminosis Diseases 0.000 claims description 2
• 206010065973 Iron Overload Diseases 0.000 claims description 2
• 101150072399 LSC1 gene Proteins 0.000 claims description 2
• 206010025282 Lymphoedema Diseases 0.000 claims description 2
• 206010054805 Macroangiopathy Diseases 0.000 claims description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
• GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 2
• 206010051606 Necrotising colitis Diseases 0.000 claims description 2
• 206010056528 Neonatal cholestasis Diseases 0.000 claims description 2
• 208000030053 Opioid-Induced Constipation Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 208000031481 Pathologic Constriction Diseases 0.000 claims description 2
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 2
• 206010063985 Phytosterolaemia Diseases 0.000 claims description 2
• 206010057969 Reflux gastritis Diseases 0.000 claims description 2
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 2
• 208000017442 Retinal disease Diseases 0.000 claims description 2
• 206010038923 Retinopathy Diseases 0.000 claims description 2
• 208000002227 Sitosterolemia Diseases 0.000 claims description 2
• 208000026214 Skeletal muscle atrophy Diseases 0.000 claims description 2
• 208000007718 Stable Angina Diseases 0.000 claims description 2
• 201000009594 Systemic Scleroderma Diseases 0.000 claims description 2
• 206010042953 Systemic sclerosis Diseases 0.000 claims description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
• 208000007814 Unstable Angina Diseases 0.000 claims description 2
• 206010048215 Xanthomatosis Diseases 0.000 claims description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
• 230000002159 abnormal effect Effects 0.000 claims description 2
• 230000005856 abnormality Effects 0.000 claims description 2
• 208000002353 alcoholic hepatitis Diseases 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
• 201000001490 benign recurrent intrahepatic cholestasis 1 Diseases 0.000 claims description 2
• 201000001488 benign recurrent intrahepatic cholestasis 2 Diseases 0.000 claims description 2
• 208000026586 benign recurrent intrahepatic cholestasis type 1 Diseases 0.000 claims description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
• 230000002490 cerebral effect Effects 0.000 claims description 2
• 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
• 208000003167 cholangitis Diseases 0.000 claims description 2
• 208000020832 chronic kidney disease Diseases 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
• 125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
• 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
• 238000009826 distribution Methods 0.000 claims description 2
• 201000008865 drug-induced hepatitis Diseases 0.000 claims description 2
• 208000009866 extrahepatic cholestasis Diseases 0.000 claims description 2
• 239000000194 fatty acid Substances 0.000 claims description 2
• 229930195729 fatty acid Natural products 0.000 claims description 2
• 150000004665 fatty acids Chemical class 0.000 claims description 2
• 208000010706 fatty liver disease Diseases 0.000 claims description 2
• 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 2
• 230000001434 glomerular Effects 0.000 claims description 2
• 230000014101 glucose homeostasis Effects 0.000 claims description 2
• 235000011187 glycerol Nutrition 0.000 claims description 2
• 208000019622 heart disease Diseases 0.000 claims description 2
• 208000005252 hepatitis A Diseases 0.000 claims description 2
• 208000002672 hepatitis B Diseases 0.000 claims description 2
• 201000010284 hepatitis E Diseases 0.000 claims description 2
• 201000001421 hyperglycemia Diseases 0.000 claims description 2
• 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 2
• 201000008980 hyperinsulinism Diseases 0.000 claims description 2
• 206010021198 ichthyosis Diseases 0.000 claims description 2
• 208000001024 intrahepatic cholestasis Diseases 0.000 claims description 2
• 230000007872 intrahepatic cholestasis Effects 0.000 claims description 2
• 201000002161 intrahepatic cholestasis of pregnancy Diseases 0.000 claims description 2
• 208000028867 ischemia Diseases 0.000 claims description 2
• 230000000302 ischemic effect Effects 0.000 claims description 2
• 208000017169 kidney disease Diseases 0.000 claims description 2
• 201000006370 kidney failure Diseases 0.000 claims description 2
• 208000002502 lymphedema Diseases 0.000 claims description 2
• 208000030159 metabolic disease Diseases 0.000 claims description 2
• 201000006417 multiple sclerosis Diseases 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 208000004995 necrotizing enterocolitis Diseases 0.000 claims description 2
• 201000001119 neuropathy Diseases 0.000 claims description 2
• 230000007823 neuropathy Effects 0.000 claims description 2
• 208000002865 osteopetrosis Diseases 0.000 claims description 2
• 235000016236 parenteral nutrition Nutrition 0.000 claims description 2
• 208000000689 peptic esophagitis Diseases 0.000 claims description 2
• 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 claims description 2
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
• 230000002980 postoperative effect Effects 0.000 claims description 2
• 238000010992 reflux Methods 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 201000000306 sarcoidosis Diseases 0.000 claims description 2
• 230000025185 skeletal muscle atrophy Effects 0.000 claims description 2
• 210000002435 tendon Anatomy 0.000 claims description 2
• 230000001988 toxicity Effects 0.000 claims description 2
• 231100000419 toxicity Toxicity 0.000 claims description 2
• 201000001862 viral hepatitis Diseases 0.000 claims description 2
• 230000029663 wound healing Effects 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• 206010002388 Angina unstable Diseases 0.000 claims 1
• 208000015163 Biliary Tract disease Diseases 0.000 claims 1
• 208000002249 Diabetes Complications Diseases 0.000 claims 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N N-butylamine Natural products CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims 1
• 208000034189 Sclerosis Diseases 0.000 claims 1
• 201000004525 Zellweger Syndrome Diseases 0.000 claims 1
• 230000001476 alcoholic effect Effects 0.000 claims 1
• 206010002022 amyloidosis Diseases 0.000 claims 1
• 229910052788 barium Inorganic materials 0.000 claims 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims 1
• 201000001883 cholelithiasis Diseases 0.000 claims 1
• LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 claims 1
• WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 claims 1
• 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
• 230000036039 immunity Effects 0.000 claims 1
• 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
• 208000007232 portal hypertension Diseases 0.000 claims 1
• 230000002401 inhibitory effect Effects 0.000 abstract description 10
• 102100021711 Ileal sodium/bile acid cotransporter Human genes 0.000 abstract description 5
• 230000004129 fatty acid metabolism Effects 0.000 abstract description 4
• CICPSCXBPAGDJY-UHFFFAOYSA-N 1,2,5-benzothiadiazepine Chemical class S1N=CC=NC2=CC=CC=C12 CICPSCXBPAGDJY-UHFFFAOYSA-N 0.000 abstract description 3
• 108091006614 SLC10A2 Proteins 0.000 abstract description 3
• KJFRSZASZNLCDF-UHFFFAOYSA-N 1,5-benzothiazepine Chemical compound S1C=CC=NC2=CC=CC=C12 KJFRSZASZNLCDF-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 311
• 239000011541 reaction mixture Substances 0.000 description 244
• 239000000543 intermediate Substances 0.000 description 226
• 238000000034 method Methods 0.000 description 176
• 239000000243 solution Substances 0.000 description 160
• 235000019439 ethyl acetate Nutrition 0.000 description 155
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 145
• 238000006243 chemical reaction Methods 0.000 description 143
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 129
• 239000011734 sodium Substances 0.000 description 116
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
• 239000007787 solid Substances 0.000 description 114
• 238000004809 thin layer chromatography Methods 0.000 description 105
• 239000012044 organic layer Substances 0.000 description 103
• 239000013058 crude material Substances 0.000 description 100
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 88
• 239000000203 mixture Substances 0.000 description 83
• 238000005481 NMR spectroscopy Methods 0.000 description 77
• 239000012267 brine Substances 0.000 description 76
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 76
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
• 239000010410 layer Substances 0.000 description 61
• 239000003795 chemical substances by application Substances 0.000 description 58
• 238000004440 column chromatography Methods 0.000 description 58
• 239000000741 silica gel Substances 0.000 description 57
• 229910002027 silica gel Inorganic materials 0.000 description 57
• 239000012043 crude product Substances 0.000 description 52
• 238000000746 purification Methods 0.000 description 50
• 239000004698 Polyethylene Substances 0.000 description 49
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 44
• 230000004761 fibrosis Effects 0.000 description 40
• 239000003112 inhibitor Substances 0.000 description 40
• 230000035772 mutation Effects 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 37
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 36
• 239000000090 biomarker Substances 0.000 description 33
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• 108090000623 proteins and genes Proteins 0.000 description 21
• 229920006395 saturated elastomer Polymers 0.000 description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
• 102000001479 Member 11 Subfamily B ATP Binding Cassette Transporter Human genes 0.000 description 17
• 108010093662 Member 11 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 17
• 208000018191 liver inflammation Diseases 0.000 description 17
• 238000003756 stirring Methods 0.000 description 17
• 101000701363 Homo sapiens Phospholipid-transporting ATPase IC Proteins 0.000 description 16
• 239000000706 filtrate Substances 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 16
• 206010067125 Liver injury Diseases 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 230000009467 reduction Effects 0.000 description 15
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 15
• BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 14
• 102100030448 Phospholipid-transporting ATPase IC Human genes 0.000 description 14
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
• 239000012973 diazabicyclooctane Substances 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 13
• 102000030904 bile acid binding Human genes 0.000 description 13
• 108091022863 bile acid binding Proteins 0.000 description 13
• 229920002674 hyaluronan Polymers 0.000 description 13
• 229960003160 hyaluronic acid Drugs 0.000 description 13
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 13
• 238000005160 1H NMR spectroscopy Methods 0.000 description 12
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 239000007864 aqueous solution Substances 0.000 description 11
• 230000007423 decrease Effects 0.000 description 11
• FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 11
• 231100000753 hepatic injury Toxicity 0.000 description 11
• 238000002953 preparative HPLC Methods 0.000 description 11
• 210000000813 small intestine Anatomy 0.000 description 11
• 238000013456 study Methods 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 10
• 230000009977 dual effect Effects 0.000 description 10
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 10
• ZHPUJTGFHOCWAD-UHFFFAOYSA-N methyl 3-bromo-2,2-difluoropropanoate Chemical compound COC(=O)C(F)(F)CBr ZHPUJTGFHOCWAD-UHFFFAOYSA-N 0.000 description 10
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 10
• 235000018102 proteins Nutrition 0.000 description 10
• 102000004169 proteins and genes Human genes 0.000 description 10
• 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 9
• 108010082126 Alanine transaminase Proteins 0.000 description 9
• 108010003415 Aspartate Aminotransferases Proteins 0.000 description 9
• 102000004625 Aspartate Aminotransferases Human genes 0.000 description 9
• 239000007788 liquid Substances 0.000 description 9
• 235000016709 nutrition Nutrition 0.000 description 9
• 230000035764 nutrition Effects 0.000 description 9
• 239000003208 petroleum Substances 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 229940083542 sodium Drugs 0.000 description 9
• 208000024891 symptom Diseases 0.000 description 9
• POAWTYXNXPEWCO-OWOJBTEDSA-N (e)-3-bromoprop-2-enoic acid Chemical compound OC(=O)\C=C\Br POAWTYXNXPEWCO-OWOJBTEDSA-N 0.000 description 8
• 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
• 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 8
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
• 210000000941 bile Anatomy 0.000 description 8
• 239000003833 bile salt Substances 0.000 description 8
• 229910052801 chlorine Inorganic materials 0.000 description 8
• 230000001419 dependent effect Effects 0.000 description 8
• 210000003494 hepatocyte Anatomy 0.000 description 8
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 8
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 8
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 8
• 239000012528 membrane Substances 0.000 description 8
• 239000013589 supplement Substances 0.000 description 8
• 241000400611 Eucalyptus deanei Species 0.000 description 7
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 7
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 7
• 239000007821 HATU Substances 0.000 description 7
• BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 7
• 239000000556 agonist Substances 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 210000003240 portal vein Anatomy 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 7
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 229920002472 Starch Polymers 0.000 description 6
• 238000009825 accumulation Methods 0.000 description 6
• 235000012000 cholesterol Nutrition 0.000 description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
• 238000012317 liver biopsy Methods 0.000 description 6
• 239000008107 starch Substances 0.000 description 6
• 229940032147 starch Drugs 0.000 description 6
• 235000019698 starch Nutrition 0.000 description 6
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 6
• 230000032258 transport Effects 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 5
• 102000015696 Interleukins Human genes 0.000 description 5
• 108010063738 Interleukins Proteins 0.000 description 5
• 101150005380 Myo5b gene Proteins 0.000 description 5
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 5
• 239000002202 Polyethylene glycol Substances 0.000 description 5
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 5
• 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 5
• 102000005353 Tissue Inhibitor of Metalloproteinase-1 Human genes 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 239000005557 antagonist Substances 0.000 description 5
• 229940093761 bile salts Drugs 0.000 description 5
• 239000011230 binding agent Substances 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 208000010643 digestive system disease Diseases 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 150000002632 lipids Chemical class 0.000 description 5
• 238000002595 magnetic resonance imaging Methods 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 5
• 239000000523 sample Substances 0.000 description 5
• 230000007863 steatosis Effects 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 238000004808 supercritical fluid chromatography Methods 0.000 description 5
• 239000003451 thiazide diuretic agent Substances 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• YIKWKLYQRFRGPM-UHFFFAOYSA-N 1-dodecylguanidine acetate Chemical compound CC(O)=O.CCCCCCCCCCCCN=C(N)N YIKWKLYQRFRGPM-UHFFFAOYSA-N 0.000 description 4
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
• JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
• 102100038495 Bile acid receptor Human genes 0.000 description 4
• 108010074051 C-Reactive Protein Proteins 0.000 description 4
• 102100032752 C-reactive protein Human genes 0.000 description 4
• 108010078791 Carrier Proteins Proteins 0.000 description 4
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 4
• 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 4
• 101000785523 Homo sapiens Tight junction protein ZO-2 Proteins 0.000 description 4
• 229920000881 Modified starch Polymers 0.000 description 4
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 4
• 108091006611 SLC10A1 Proteins 0.000 description 4
• 102100026637 Tight junction protein ZO-2 Human genes 0.000 description 4
• 102000009618 Transforming Growth Factors Human genes 0.000 description 4
• 108010009583 Transforming Growth Factors Proteins 0.000 description 4
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
• 230000009102 absorption Effects 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 4
• 239000011248 coating agent Substances 0.000 description 4
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 4
• 238000002091 elastography Methods 0.000 description 4
• 230000010235 enterohepatic circulation Effects 0.000 description 4
• 238000005187 foaming Methods 0.000 description 4
• 210000000232 gallbladder Anatomy 0.000 description 4
• 231100000234 hepatic damage Toxicity 0.000 description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
• 230000008818 liver damage Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 229920003145 methacrylic acid copolymer Polymers 0.000 description 4
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• 230000001052 transient effect Effects 0.000 description 4
• 102000003390 tumor necrosis factor Human genes 0.000 description 4
• RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 3
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
• QWCGXANSAOXRFE-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanamine Chemical compound COCCOCCN QWCGXANSAOXRFE-UHFFFAOYSA-N 0.000 description 3
• IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 102220505876 Bile salt export pump_R1153C_mutation Human genes 0.000 description 3
• 102220505883 Bile salt export pump_R1268Q_mutation Human genes 0.000 description 3
• 102000001187 Collagen Type III Human genes 0.000 description 3
• 108010069502 Collagen Type III Proteins 0.000 description 3
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
• 238000002965 ELISA Methods 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 102100025353 G-protein coupled bile acid receptor 1 Human genes 0.000 description 3
• 239000004471 Glycine Substances 0.000 description 3
• 206010019663 Hepatic failure Diseases 0.000 description 3
• 208000037262 Hepatitis delta Diseases 0.000 description 3
• 241000724709 Hepatitis delta virus Species 0.000 description 3
• 101000857733 Homo sapiens G-protein coupled bile acid receptor 1 Proteins 0.000 description 3
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
• 206010022998 Irritability Diseases 0.000 description 3
• 108090001030 Lipoproteins Proteins 0.000 description 3
• 102000004895 Lipoproteins Human genes 0.000 description 3
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
• 102220580017 Phospholipid-transporting ATPase IC_G1040R_mutation Human genes 0.000 description 3
• 102100021988 Sodium/bile acid cotransporter Human genes 0.000 description 3
• 102000004357 Transferases Human genes 0.000 description 3
• 108090000992 Transferases Proteins 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000012190 activator Substances 0.000 description 3
• 229940083712 aldosterone antagonist Drugs 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 150000001413 amino acids Chemical group 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 3
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
• 239000001273 butane Substances 0.000 description 3
• 229920002678 cellulose Chemical class 0.000 description 3
• 239000001913 cellulose Chemical class 0.000 description 3
• 235000010980 cellulose Nutrition 0.000 description 3
• 230000004087 circulation Effects 0.000 description 3
• 239000011247 coating layer Substances 0.000 description 3
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
• 238000009585 enzyme analysis Methods 0.000 description 3
• 210000002919 epithelial cell Anatomy 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 229940126013 glucocorticoid receptor antagonist Drugs 0.000 description 3
• 239000003850 glucocorticoid receptor antagonist Substances 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
• 229960003943 hypromellose Drugs 0.000 description 3
• 150000003949 imides Chemical class 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 230000000968 intestinal effect Effects 0.000 description 3
• 210000000936 intestine Anatomy 0.000 description 3
• SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 208000007903 liver failure Diseases 0.000 description 3
• 231100000835 liver failure Toxicity 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 238000012045 magnetic resonance elastography Methods 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 239000002773 nucleotide Substances 0.000 description 3
• 125000003729 nucleotide group Chemical group 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 239000004014 plasticizer Substances 0.000 description 3
• 108010034596 procollagen Type III-N-terminal peptide Proteins 0.000 description 3
• 230000009103 reabsorption Effects 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 239000012748 slip agent Substances 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 229960003080 taurine Drugs 0.000 description 3
• 210000005239 tubule Anatomy 0.000 description 3
• NPBCMXATLRCCLF-IRRLEISYSA-N (2s,4r)-4-[(3r,5s,6r,7r,8r,9s,10s,12s,13r,14s,17r)-6-ethyl-3,7,12-trihydroxy-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]2C[C@H](O)[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 NPBCMXATLRCCLF-IRRLEISYSA-N 0.000 description 2
• QYYDXDSPYPOWRO-JHMCBHKWSA-N (3r)-3-[(3r,5s,7s,8r,9s,10s,13r,14s,17r)-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]butanoic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CC(O)=O)C)[C@@]2(C)CC1 QYYDXDSPYPOWRO-JHMCBHKWSA-N 0.000 description 2
• VDSBXXDKCUBMQC-HNGSOEQISA-N (4r,6s)-6-[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohexen-1-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C1=C(F)C(C)=CC(C=2CC(C)(C)CC(C)(C)C=2\C=C\[C@H]2OC(=O)C[C@H](O)C2)=C1 VDSBXXDKCUBMQC-HNGSOEQISA-N 0.000 description 2
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• HEAHLTGDUHXTTO-UHFFFAOYSA-N 1,3-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCNC1 HEAHLTGDUHXTTO-UHFFFAOYSA-N 0.000 description 2
• SQHNOPNELDVHHZ-UHFFFAOYSA-N 1,5-dibromo-2-[(2,4-dibromo-5-methoxyphenyl)disulfanyl]-4-methoxybenzene Chemical compound BrC1=C(C=C(C(=C1)Br)OC)SSC1=C(C=C(C(=C1)OC)Br)Br SQHNOPNELDVHHZ-UHFFFAOYSA-N 0.000 description 2
• DFORINBGYOWVRP-UHFFFAOYSA-N 2-(bromomethyl)-2-ethylhexanoic acid Chemical compound CCCCC(CC)(CBr)C(O)=O DFORINBGYOWVRP-UHFFFAOYSA-N 0.000 description 2
• VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 2
• VGCZHWYJBWOYMT-UHFFFAOYSA-N 2-[(2-amino-4-chloro-5-methoxyphenyl)sulfanylmethyl]-2-ethylhexanoic acid Chemical compound CCCCC(CC)(C(O)=O)CSC1=CC(OC)=C(Cl)C=C1N VGCZHWYJBWOYMT-UHFFFAOYSA-N 0.000 description 2
• WPIVKBKABZRZRO-UHFFFAOYSA-N 2-[(2-amino-5-methoxyphenyl)sulfanylmethyl]-2-ethylbutanoic acid Chemical compound NC1=C(C=C(C=C1)OC)SCC(C(=O)O)(CC)CC WPIVKBKABZRZRO-UHFFFAOYSA-N 0.000 description 2
• PHAHKRPOVINHPT-UHFFFAOYSA-N 2-[(2-amino-5-methoxyphenyl)sulfanylmethyl]-2-ethylhexanoic acid Chemical compound NC1=C(C=C(C=C1)OC)SCC(C(=O)O)(CCCC)CC PHAHKRPOVINHPT-UHFFFAOYSA-N 0.000 description 2
• APNXKIWWMDDWSL-UHFFFAOYSA-N 2-ethyl-1-n-phenylhexane-1,2-diamine Chemical compound CCCCC(N)(CC)CNC1=CC=CC=C1 APNXKIWWMDDWSL-UHFFFAOYSA-N 0.000 description 2
• LICJKQOCYUWRJF-UHFFFAOYSA-N 3,3-dibutyl-2-[(4-methoxyphenyl)methyl]-7-methylsulfanyl-1,1-dioxo-5-phenyl-4h-1$l^{6},2,5-benzothiadiazepin-8-ol Chemical compound C12=CC(SC)=C(O)C=C2S(=O)(=O)N(CC=2C=CC(OC)=CC=2)C(CCCC)(CCCC)CN1C1=CC=CC=C1 LICJKQOCYUWRJF-UHFFFAOYSA-N 0.000 description 2
• WSLXLABOEWJWJL-UHFFFAOYSA-N 5-chloro-6-methoxy-1,3-benzothiazol-2-amine Chemical compound C1=C(Cl)C(OC)=CC2=C1N=C(N)S2 WSLXLABOEWJWJL-UHFFFAOYSA-N 0.000 description 2
• KZHGPDSVHSDCMX-UHFFFAOYSA-N 6-methoxy-1,3-benzothiazol-2-amine Chemical compound COC1=CC=C2N=C(N)SC2=C1 KZHGPDSVHSDCMX-UHFFFAOYSA-N 0.000 description 2
• DGINSASEOQQAMM-UHFFFAOYSA-N 7-bromo-3,3-dibutyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-ol Chemical compound BrC=1C(=CC2=C(N(CC(NS2(=O)=O)(CCCC)CCCC)C2=CC=CC=C2)C=1)O DGINSASEOQQAMM-UHFFFAOYSA-N 0.000 description 2
• 101150048692 ABCB11 gene Proteins 0.000 description 2
• 102000014156 AMP-Activated Protein Kinases Human genes 0.000 description 2
• 108010011376 AMP-Activated Protein Kinases Proteins 0.000 description 2
• 229920002126 Acrylic acid copolymer Polymers 0.000 description 2
• 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• 241000208340 Araliaceae Species 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• 102100020683 Beta-klotho Human genes 0.000 description 2
• 102100036849 C-C motif chemokine 24 Human genes 0.000 description 2
• 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 2
• 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 2
• 229920001268 Cholestyramine Polymers 0.000 description 2
• 206010057573 Chronic hepatic failure Diseases 0.000 description 2
• 229920002905 Colesevelam Polymers 0.000 description 2
• 229920002785 Croscarmellose sodium Polymers 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• 102100035762 Diacylglycerol O-acyltransferase 2 Human genes 0.000 description 2
• 101710167503 Diacylglycerol O-acyltransferase 2 Proteins 0.000 description 2
• 208000010334 End Stage Liver Disease Diseases 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 239000001856 Ethyl cellulose Substances 0.000 description 2
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
• 108091008794 FGF receptors Proteins 0.000 description 2
• 108010039731 Fatty Acid Synthases Proteins 0.000 description 2
• 108010087894 Fatty acid desaturases Proteins 0.000 description 2
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
• 102000001214 HSP47 Heat-Shock Proteins Human genes 0.000 description 2
• 108010055039 HSP47 Heat-Shock Proteins Proteins 0.000 description 2
• 241000700721 Hepatitis B virus Species 0.000 description 2
• 206010019837 Hepatocellular injury Diseases 0.000 description 2
• 101001139095 Homo sapiens Beta-klotho Proteins 0.000 description 2
• 101000713078 Homo sapiens C-C motif chemokine 24 Proteins 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 108020004485 Nonsense Codon Proteins 0.000 description 2
• 108091028043 Nucleic acid sequence Proteins 0.000 description 2
• 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 2
• 235000003140 Panax quinquefolius Nutrition 0.000 description 2
• 108090000279 Peptidyltransferases Proteins 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 229920002845 Poly(methacrylic acid) Polymers 0.000 description 2
• 239000004372 Polyvinyl alcohol Substances 0.000 description 2
• 108091006277 SLC5A1 Proteins 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 102000058090 Sodium-Glucose Transporter 1 Human genes 0.000 description 2
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 2
• 229920002125 Sokalan® Polymers 0.000 description 2
• 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 description 2
• 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 2
• 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229940123464 Thiazolidinedione Drugs 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 2
• QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
• 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• 239000003858 bile acid conjugate Substances 0.000 description 2
• 238000001574 biopsy Methods 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 229920002301 cellulose acetate Polymers 0.000 description 2
• 229960005110 cerivastatin Drugs 0.000 description 2
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
• 208000011444 chronic liver failure Diseases 0.000 description 2
• 229960005049 clofibride Drugs 0.000 description 2
• CXQGFLBVUNUQIA-UHFFFAOYSA-N clofibride Chemical compound CN(C)C(=O)CCCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 CXQGFLBVUNUQIA-UHFFFAOYSA-N 0.000 description 2
• 229960001152 colesevelam Drugs 0.000 description 2
• 239000008119 colloidal silica Substances 0.000 description 2
• 238000002591 computed tomography Methods 0.000 description 2
• 229920001577 copolymer Polymers 0.000 description 2
• 229960001681 croscarmellose sodium Drugs 0.000 description 2
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 229950003040 dalvastatin Drugs 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
• RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
• FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
• 230000001079 digestive effect Effects 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 239000002158 endotoxin Substances 0.000 description 2
• UJTJVQIYRQALIK-ONEGZZNKSA-N ethyl (e)-3-bromoprop-2-enoate Chemical compound CCOC(=O)\C=C\Br UJTJVQIYRQALIK-ONEGZZNKSA-N 0.000 description 2
• SWNBPYRQCHSZSE-UHFFFAOYSA-N ethyl 2-aminobutanoate;hydrochloride Chemical compound Cl.CCOC(=O)C(N)CC SWNBPYRQCHSZSE-UHFFFAOYSA-N 0.000 description 2
• 235000019325 ethyl cellulose Nutrition 0.000 description 2
• 229920001249 ethyl cellulose Polymers 0.000 description 2
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 2
• 229960000815 ezetimibe Drugs 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• 235000008434 ginseng Nutrition 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
• 230000031891 intestinal absorption Effects 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 229960001375 lactose Drugs 0.000 description 2
• 210000002429 large intestine Anatomy 0.000 description 2
• YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 2
• 229920006008 lipopolysaccharide Polymers 0.000 description 2
• 231100000849 liver cell damage Toxicity 0.000 description 2
• CHHXEZSCHQVSRE-UHFFFAOYSA-N lobeglitazone Chemical compound C1=CC(OC)=CC=C1OC1=CC(N(C)CCOC=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=NC=N1 CHHXEZSCHQVSRE-UHFFFAOYSA-N 0.000 description 2
• 229950007685 lobeglitazone Drugs 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 210000000581 natural killer T-cell Anatomy 0.000 description 2
• 230000002956 necrotizing effect Effects 0.000 description 2
• 238000007481 next generation sequencing Methods 0.000 description 2
• ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic 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)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 2
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
• 239000000049 pigment Substances 0.000 description 2
• 229960005095 pioglitazone Drugs 0.000 description 2
• 239000004584 polyacrylic acid Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 229920002451 polyvinyl alcohol Polymers 0.000 description 2
• 230000000291 postprandial effect Effects 0.000 description 2
• FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
• 229940069328 povidone Drugs 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 229960004586 rosiglitazone Drugs 0.000 description 2
• 230000001568 sexual effect Effects 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
• QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 238000004611 spectroscopical analysis Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 230000008961 swelling Effects 0.000 description 2
• 230000001839 systemic circulation Effects 0.000 description 2
• ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 150000001467 thiazolidinediones Chemical class 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 238000002604 ultrasonography Methods 0.000 description 2
• 210000002700 urine Anatomy 0.000 description 2
• RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 2
• 229960001661 ursodiol Drugs 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 235000013343 vitamin Nutrition 0.000 description 2
• 239000011782 vitamin Substances 0.000 description 2
• 229940088594 vitamin Drugs 0.000 description 2
• 229930003231 vitamin Natural products 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• CRDAMVZIKSXKFV-FBXUGWQNSA-N (2-cis,6-cis)-farnesol Chemical compound CC(C)=CCC\C(C)=C/CC\C(C)=C/CO CRDAMVZIKSXKFV-FBXUGWQNSA-N 0.000 description 1
• 239000000260 (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol Substances 0.000 description 1
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
• GELVLHVQVRSFAY-FQEVSTJZSA-N (2S)-2-[(4-methyloxane-4-carbonyl)amino]-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CC1(CCOCC1)C(=O)N[C@H](C(=O)O)CCCCCCCC1=NC=2NCCCC=2C=C1 GELVLHVQVRSFAY-FQEVSTJZSA-N 0.000 description 1
• CWOFQJBATWQSHL-DEOSSOPVSA-N (2S)-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(quinazolin-4-ylamino)butanoic acid Chemical compound COCCN(CCCCc1ccc2CCCNc2n1)CC[C@H](Nc1ncnc2ccccc12)C(O)=O CWOFQJBATWQSHL-DEOSSOPVSA-N 0.000 description 1
• FONCZICQWCUXEB-RUZDIDTESA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(C)C=C(C=C1C)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 FONCZICQWCUXEB-RUZDIDTESA-N 0.000 description 1
• XFJAMQQAAMJFGB-ZQGJOIPISA-N (2s,3r,4r,5s,6r)-2-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-ethylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound C1=C(CC=2C=C3OCCOC3=CC=2)C(CC)=CC=C1[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XFJAMQQAAMJFGB-ZQGJOIPISA-N 0.000 description 1
• QKDRXGFQVGOQKS-CRSSMBPESA-N (2s,3r,4r,5s,6r)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](SC)O2)O)=CC=C1Cl QKDRXGFQVGOQKS-CRSSMBPESA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 description 1
• SHKXZIQNFMOPBS-OOMQYRRCSA-N (4r)-4-[(3s,5s,7r,8r,9s,10s,12s,13r,14s,17r)-7,12-dihydroxy-3-(icosanoylamino)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound O[C@H]1C[C@@H]2[C@@]3(C)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC)C[C@H]3C[C@@H](O)[C@H]2[C@@H]2CC[C@H]([C@H](C)CCC(O)=O)[C@]21C SHKXZIQNFMOPBS-OOMQYRRCSA-N 0.000 description 1
• MUBBPBZRFJGZEU-XSPPBVGUSA-N (e)-n-[1-[2-(dimethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]-4-[4-[[4-methoxy-2-propan-2-yl-5-[(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]phenyl]-2,2-dimethylbut-3-enamide Chemical compound C1=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C(OC)=CC(C(C)C)=C1CC1=CC=C(\C=C\C(C)(C)C(=O)NC(C)(C)C(=O)NCCN(C)C)C=C1 MUBBPBZRFJGZEU-XSPPBVGUSA-N 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
• HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
• XLQSXGGDTHANLN-UHFFFAOYSA-N 1-bromo-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Br)C=C1 XLQSXGGDTHANLN-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical class CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• NANJFPZFEUIDND-UHFFFAOYSA-N 13-ethyl-15-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1CCC2C3CCC(CC)(C(CC4O)=O)C4C3CCC2=C1 NANJFPZFEUIDND-UHFFFAOYSA-N 0.000 description 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
• ZRZCTHXIQSYCTI-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1$l^{6},2,5-benzothiadiazepine 1,1-dioxide Chemical compound O=S1(=O)NCCNC2=CC=CC=C12 ZRZCTHXIQSYCTI-UHFFFAOYSA-N 0.000 description 1
• SNJAKWDPQBWXFM-UHFFFAOYSA-N 2,3-dimethylhex-5-ene-2,3-diol Chemical compound CC(C)(O)C(C)(O)CC=C SNJAKWDPQBWXFM-UHFFFAOYSA-N 0.000 description 1
• QDFBFVIIHWEADT-UHFFFAOYSA-N 2,4-dibromo-5-methoxybenzenesulfonyl chloride Chemical compound COC1=CC(S(Cl)(=O)=O)=C(Br)C=C1Br QDFBFVIIHWEADT-UHFFFAOYSA-N 0.000 description 1
• LDBWFANYCMNLNH-UHFFFAOYSA-N 2-(bromomethyl)-2-ethylbutanoic acid Chemical compound CCC(CC)(CBr)C(O)=O LDBWFANYCMNLNH-UHFFFAOYSA-N 0.000 description 1
• FKGBFRNVTCFMGU-UHFFFAOYSA-N 2-[(5-tert-butyl-1,3-thiazol-2-yl)methyl-[[4-[4-[(4-heptan-4-ylphenoxy)methyl]phenyl]-1,3-thiazol-2-yl]methyl]amino]acetic acid Chemical compound C1=CC(C(CCC)CCC)=CC=C1OCC1=CC=C(C=2N=C(CN(CC(O)=O)CC=3SC(=CN=3)C(C)(C)C)SC=2)C=C1 FKGBFRNVTCFMGU-UHFFFAOYSA-N 0.000 description 1
• CMLUGNQVANVZHY-POURPWNDSA-N 2-[1-[2-[(3r,5s)-1-(3-acetyloxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-5h-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC([C@@H]2C3=CC(Cl)=CC=C3N(CC(C)(C)COC(C)=O)C(=O)[C@@H](CC(=O)N3CCC(CC(O)=O)CC3)O2)=C1OC CMLUGNQVANVZHY-POURPWNDSA-N 0.000 description 1
• KZSKGLFYQAYZCO-UHFFFAOYSA-N 2-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(N2CC(O)(C2)C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)=C1 KZSKGLFYQAYZCO-UHFFFAOYSA-N 0.000 description 1
• ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• FULDEIKIJMGEJQ-UHFFFAOYSA-N 3,3-dibutyl-5-(4-methoxyphenyl)-7-methylsulfanyl-1,1-dioxo-2,4-dihydro-1lambda6,5-benzothiazepin-8-ol Chemical compound C(CCC)C1(CS(C2=C(N(C1)C1=CC=C(C=C1)OC)C=C(C(=C2)O)SC)(=O)=O)CCCC FULDEIKIJMGEJQ-UHFFFAOYSA-N 0.000 description 1
• ZFSSIVGWZYCELO-UHFFFAOYSA-N 3,3-diethyl-7-iodo-8-methoxy-5-phenyl-2,4-dihydro-1,5-benzothiazepine Chemical class C(C)C1(CSC2=C(N(C1)C1=CC=CC=C1)C=C(C(=C2)OC)I)CC ZFSSIVGWZYCELO-UHFFFAOYSA-N 0.000 description 1
• MHXHDDPGIXRQQH-UHFFFAOYSA-N 3,3-diethyl-8-methoxy-2,5-dihydro-1,5-benzothiazepin-4-one Chemical compound C(C)C1(CSC2=C(NC1=O)C=CC(=C2)OC)CC MHXHDDPGIXRQQH-UHFFFAOYSA-N 0.000 description 1
• BQMMCRXYIIKAOB-UHFFFAOYSA-N 3-[6-chloro-2-cyclopropyl-1-(1-ethylpyrazol-4-yl)-7-fluoroindol-3-yl]sulfanyl-2-fluorobenzoic acid Chemical compound ClC1=CC=C2C(=C(N(C2=C1F)C=1C=NN(C1)CC)C1CC1)SC=1C(=C(C(=O)O)C=CC1)F BQMMCRXYIIKAOB-UHFFFAOYSA-N 0.000 description 1
• CKKFTRCSLCQDHF-UHFFFAOYSA-N 3-butyl-3-ethyl-7-iodo-8-methoxy-5-phenyl-2,4-dihydro-1,5-benzothiazepine Chemical class C(CCC)C1(CSC2=C(N(C1)C1=CC=CC=C1)C=C(C(=C2)OC)I)CC CKKFTRCSLCQDHF-UHFFFAOYSA-N 0.000 description 1
• HDSSJSHDSIAFEF-UHFFFAOYSA-N 3-butyl-7-chloro-3-ethyl-8-methoxy-2,5-dihydro-1,5-benzothiazepin-4-one Chemical compound CCCCC1(CC)CSC2=C(NC1=O)C=C(Cl)C(OC)=C2 HDSSJSHDSIAFEF-UHFFFAOYSA-N 0.000 description 1
• XQVCBOLNTSUFGD-UHFFFAOYSA-N 3-chloro-4-methoxyaniline Chemical compound COC1=CC=C(N)C=C1Cl XQVCBOLNTSUFGD-UHFFFAOYSA-N 0.000 description 1
• QMVAZEHZOPDGHA-UHFFFAOYSA-N 3-methoxybenzenethiol Chemical compound COC1=CC=CC(S)=C1 QMVAZEHZOPDGHA-UHFFFAOYSA-N 0.000 description 1
• OQDQIFQRNZIEEJ-UHFFFAOYSA-N 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloroindol-2-yl]butanoic acid Chemical compound C1=C2N=CSC2=CC(S(=O)(=O)N2C3=CC=C(Cl)C=C3C=C2CCCC(=O)O)=C1 OQDQIFQRNZIEEJ-UHFFFAOYSA-N 0.000 description 1
• BBGOSBDSLYHMRA-UHFFFAOYSA-N 4-[1-[4-cyclobutyl-2-methyl-5-(5-methyl-1h-1,2,4-triazol-3-yl)benzoyl]piperidin-4-yl]benzonitrile Chemical compound N1C(C)=NN=C1C1=CC(C(=O)N2CCC(CC2)C=2C=CC(=CC=2)C#N)=C(C)C=C1C1CCC1 BBGOSBDSLYHMRA-UHFFFAOYSA-N 0.000 description 1
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
• 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 1
• WIGIZIANZCJQQY-UHFFFAOYSA-N 4-ethyl-3-methyl-N-[2-[4-[[[(4-methylcyclohexyl)amino]-oxomethyl]sulfamoyl]phenyl]ethyl]-5-oxo-2H-pyrrole-1-carboxamide Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCC(C)CC2)C=C1 WIGIZIANZCJQQY-UHFFFAOYSA-N 0.000 description 1
• BVABFIZTUSTDDW-UHFFFAOYSA-N 5h-1,2-benzothiazepin-4-one Chemical compound S1N=CC(=O)CC2=CC=CC=C21 BVABFIZTUSTDDW-UHFFFAOYSA-N 0.000 description 1
• SDDSJMXGJNWMJY-BRHAQHMBSA-N 7-[(2r,4ar,5r,7ar)-2-[(3s)-1,1-difluoro-3-methylpentyl]-2-hydroxy-6-oxo-3,4,4a,5,7,7a-hexahydrocyclopenta[b]pyran-5-yl]heptanoic acid Chemical compound O1[C@](C(F)(F)C[C@@H](C)CC)(O)CC[C@@H]2[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]21 SDDSJMXGJNWMJY-BRHAQHMBSA-N 0.000 description 1
• UAYALICWRMRCEY-UHFFFAOYSA-N 7-bromo-3,3-dibutyl-8-methoxy-2-[(4-methoxyphenyl)methyl]-5-phenyl-4h-1$l^{6},2,5-benzothiadiazepine 1,1-dioxide Chemical compound C12=CC(Br)=C(OC)C=C2S(=O)(=O)N(CC=2C=CC(OC)=CC=2)C(CCCC)(CCCC)CN1C1=CC=CC=C1 UAYALICWRMRCEY-UHFFFAOYSA-N 0.000 description 1
• ISJDHCMJYMFOPI-UHFFFAOYSA-N 7-bromo-3,3-dibutyl-8-methoxy-5-[4-(trifluoromethyl)phenyl]-2,4-dihydro-1,5-benzothiazepine Chemical class BrC=1C(=CC2=C(N(CC(CS2)(CCCC)CCCC)C2=CC=C(C=C2)C(F)(F)F)C=1)OC ISJDHCMJYMFOPI-UHFFFAOYSA-N 0.000 description 1
• VQIWLYKSCOBNDO-UHFFFAOYSA-N 7-bromo-3,3-diethyl-8-methoxy-2,5-dihydro-1,5-benzothiazepin-4-one Chemical compound BrC=1C(=CC2=C(NC(C(CS2)(CC)CC)=O)C=1)OC VQIWLYKSCOBNDO-UHFFFAOYSA-N 0.000 description 1
• IYTQNTILFDHIBM-UHFFFAOYSA-N 7-bromo-3-butyl-3-ethyl-8-methoxy-2,5-dihydro-1,5-benzothiazepin-4-one Chemical compound N1C(=O)C(CCCC)(CC)CSC2=CC(OC)=C(Br)C=C21 IYTQNTILFDHIBM-UHFFFAOYSA-N 0.000 description 1
• 101150046889 ADORA3 gene Proteins 0.000 description 1
• 206010000087 Abdominal pain upper Diseases 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
• 229940122614 Adenosine receptor agonist Drugs 0.000 description 1
• 229940124232 Adiponectin receptor agonist Drugs 0.000 description 1
• 208000022309 Alcoholic Liver disease Diseases 0.000 description 1
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 241001312221 Anthurium Species 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 108091007065 BIRCs Proteins 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
• 208000017283 Bile Duct disease Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• KNCUZLUTDGZALS-NBVRZTHBSA-N C(/C1=CC=CC=C1)=N\C(C(=O)OCC)(CCCC)CC Chemical compound C(/C1=CC=CC=C1)=N\C(C(=O)OCC)(CCCC)CC KNCUZLUTDGZALS-NBVRZTHBSA-N 0.000 description 1
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• VZXMZBNOTKEQAU-UHFFFAOYSA-N CCCCOC(NNS(C)(=O)=O)=O Chemical compound CCCCOC(NNS(C)(=O)=O)=O VZXMZBNOTKEQAU-UHFFFAOYSA-N 0.000 description 1
• 101150008656 COL1A1 gene Proteins 0.000 description 1
• 101150072801 COL1A2 gene Proteins 0.000 description 1
• 101150066399 COL4A1 gene Proteins 0.000 description 1
• DNJVYWXIDISQRD-UHFFFAOYSA-N Cafestol Natural products C1CC2(CC3(CO)O)CC3CCC2C2(C)C1C(C=CO1)=C1CC2 DNJVYWXIDISQRD-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010062745 Chloride Channels Proteins 0.000 description 1
• 102000011045 Chloride Channels Human genes 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
• KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
• DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 description 1
• 240000001414 Eucalyptus viminalis Species 0.000 description 1
• LCDDAGSJHKEABN-MLGOLLRUSA-N Evogliptin Chemical compound C1CNC(=O)[C@@H](COC(C)(C)C)N1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F LCDDAGSJHKEABN-MLGOLLRUSA-N 0.000 description 1
• 229940124602 FDA-approved drug Drugs 0.000 description 1
• VLQTUNDJHLEFEQ-KGENOOAVSA-N Fexaramine Chemical compound COC(=O)\C=C\C1=CC=CC(N(CC=2C=CC(=CC=2)C=2C=CC(=CC=2)N(C)C)C(=O)C2CCCCC2)=C1 VLQTUNDJHLEFEQ-KGENOOAVSA-N 0.000 description 1
• 102100031734 Fibroblast growth factor 19 Human genes 0.000 description 1
• 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
• 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
• 229940126043 Galectin-3 inhibitor Drugs 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
• ZWPRRQZNBDYKLH-VIFPVBQESA-N Gemigliptin Chemical compound C([C@@H](N)CC(=O)N1CC2=C(C(=NC(=N2)C(F)(F)F)C(F)(F)F)CC1)N1CC(F)(F)CCC1=O ZWPRRQZNBDYKLH-VIFPVBQESA-N 0.000 description 1
• 229940123232 Glucagon receptor agonist Drugs 0.000 description 1
• 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
• 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
• 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
• 102100031132 Glucose-6-phosphate isomerase Human genes 0.000 description 1
• 108010070600 Glucose-6-phosphate isomerase Proteins 0.000 description 1
• 102000004366 Glucosidases Human genes 0.000 description 1
• 108010056771 Glucosidases Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 206010019842 Hepatomegaly Diseases 0.000 description 1
• 101001000686 Homo sapiens 4-aminobutyrate aminotransferase, mitochondrial Proteins 0.000 description 1
• 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 1
• 101001043352 Homo sapiens Lysyl oxidase homolog 2 Proteins 0.000 description 1
• 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 1
• 101000694615 Homo sapiens Membrane primary amine oxidase Proteins 0.000 description 1
• 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
• 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 1
• 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
• 208000028958 Hyperferritinemia Diseases 0.000 description 1
• 101710156096 Ileal sodium/bile acid cotransporter Proteins 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 206010062018 Inborn error of metabolism Diseases 0.000 description 1
• 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
• 238000008214 LDL Cholesterol Methods 0.000 description 1
• DUKURNFHYQXCJG-UHFFFAOYSA-N Lewis A pentasaccharide Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)OC1CO DUKURNFHYQXCJG-UHFFFAOYSA-N 0.000 description 1
• LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 1
• YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
• 108010019598 Liraglutide Proteins 0.000 description 1
• 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 description 1
• 229940126047 MET409 Drugs 0.000 description 1
• 102100025136 Macrosialin Human genes 0.000 description 1
• 102100027159 Membrane primary amine oxidase Human genes 0.000 description 1
• 102000003939 Membrane transport proteins Human genes 0.000 description 1
• 108090000301 Membrane transport proteins Proteins 0.000 description 1
• 102000005741 Metalloproteases Human genes 0.000 description 1
• 108010006035 Metalloproteases Proteins 0.000 description 1
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
• 229940121875 Mitochondrial pyruvate carrier inhibitor Drugs 0.000 description 1
• 239000004368 Modified starch Substances 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 description 1
• OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
• 101150027485 NR1H4 gene Proteins 0.000 description 1
• WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
• MJGJPHUUDJCUEC-UHFFFAOYSA-N OC(=O)C[Ca] Chemical compound OC(=O)C[Ca] MJGJPHUUDJCUEC-UHFFFAOYSA-N 0.000 description 1
• VYLOOGHLKSNNEK-PIIMJCKOSA-N OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 Chemical compound OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 VYLOOGHLKSNNEK-PIIMJCKOSA-N 0.000 description 1
• 102100037602 P2X purinoceptor 7 Human genes 0.000 description 1
• 101710189965 P2X purinoceptor 7 Proteins 0.000 description 1
• 229940125819 PF-06835919 Drugs 0.000 description 1
• 229940126021 PLN-74809 Drugs 0.000 description 1
• 229940126033 PPAR agonist Drugs 0.000 description 1
• 102000023984 PPAR alpha Human genes 0.000 description 1
• 108010016731 PPAR gamma Proteins 0.000 description 1
• 102000000536 PPAR gamma Human genes 0.000 description 1
• 229940124754 PPAR-alpha/gamma agonist Drugs 0.000 description 1
• 108700027412 Pegbelfermin Proteins 0.000 description 1
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
• 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
• 208000035965 Postoperative Complications Diseases 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 229940127101 SAR425899 Drugs 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
• 108091006216 SLC10 Proteins 0.000 description 1
• 101150061657 Slc10a2 gene Proteins 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 102000004589 Solute Carrier Proteins Human genes 0.000 description 1
• 108010042650 Solute Carrier Proteins Proteins 0.000 description 1
• 206010041660 Splenomegaly Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 241001085768 Stereolepis gigas Species 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• 108090000088 Symporters Proteins 0.000 description 1
• 102000003673 Symporters Human genes 0.000 description 1
• 101150005448 TJP2 gene Proteins 0.000 description 1
• 229940123876 Thyroid hormone receptor beta agonist Drugs 0.000 description 1
• 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 229940122954 Transcription factor inhibitor Drugs 0.000 description 1
• DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• XGIYOABXZNJOHV-APIYUPOTSA-N [(3r)-3-[(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]butyl] hydrogen sulfate 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)CCOS(O)(=O)=O)CC[C@H]21 XGIYOABXZNJOHV-APIYUPOTSA-N 0.000 description 1
• PIUZYOCNZPYXOA-ZHHJOTBYSA-N [(3s,8s,9s,10r,13r,14s,17r)-17-[(2r)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)(C)O)C)[C@@]1(C)CC2 PIUZYOCNZPYXOA-ZHHJOTBYSA-N 0.000 description 1
• WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 1
• VASSQWFTQQSDIS-UHFFFAOYSA-N [O-][N+](C=C1)=CC=CN1O Chemical compound [O-][N+](C=C1)=CC=CN1O VASSQWFTQQSDIS-UHFFFAOYSA-N 0.000 description 1
• 101150063830 abcB4 gene Proteins 0.000 description 1
• 208000020560 abdominal swelling Diseases 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 229960002632 acarbose Drugs 0.000 description 1
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
• 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 description 1
• 102000005421 acetyltransferase Human genes 0.000 description 1
• 108020002494 acetyltransferase Proteins 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 108700013806 aldafermin Proteins 0.000 description 1
• DAYKLWSKQJBGCS-NRFANRHFSA-N aleglitazar Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-NRFANRHFSA-N 0.000 description 1
• 229950010157 aleglitazar Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 229960001667 alogliptin Drugs 0.000 description 1
• ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 1
• LDXYBEHACFJIEL-HNNXBMFYSA-N anagliptin Chemical compound C=1N2N=C(C)C=C2N=CC=1C(=O)NCC(C)(C)NCC(=O)N1CCC[C@H]1C#N LDXYBEHACFJIEL-HNNXBMFYSA-N 0.000 description 1
• 229950009977 anagliptin Drugs 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 229910052789 astatine Inorganic materials 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 125000003828 azulenyl group Chemical group 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 229940049706 benzodiazepine Drugs 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 229950010015 bertilimumab Drugs 0.000 description 1
• 229950005357 bervastatin Drugs 0.000 description 1
• 229960000516 bezafibrate Drugs 0.000 description 1
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 235000010338 boric acid Nutrition 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
• 125000006309 butyl amino group Chemical group 0.000 description 1
• NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
• KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
• MVRXKXMBNDEGTE-UHFFFAOYSA-N butyl prop-2-ynoate Chemical group CCCCOC(=O)C#C MVRXKXMBNDEGTE-UHFFFAOYSA-N 0.000 description 1
• DNJVYWXIDISQRD-JTSSGKSMSA-N cafestol Chemical compound C([C@H]1C[C@]2(C[C@@]1(CO)O)CC1)C[C@H]2[C@@]2(C)[C@H]1C(C=CO1)=C1CC2 DNJVYWXIDISQRD-JTSSGKSMSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 229960001713 canagliflozin Drugs 0.000 description 1
• VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000004203 carnauba wax Substances 0.000 description 1
• 235000013869 carnauba wax Nutrition 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 229920003174 cellulose-based polymer Polymers 0.000 description 1
• PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 1
• 229950011033 cenicriviroc Drugs 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 230000003399 chemotactic effect Effects 0.000 description 1
• RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
• 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 229940070042 cilofexor Drugs 0.000 description 1
• 229960002174 ciprofibrate Drugs 0.000 description 1
• KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
• 229960001214 clofibrate Drugs 0.000 description 1
• KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
• 229950005980 cobiprostone Drugs 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 230000000112 colonic effect Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000008602 contraction Effects 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 229920006037 cross link polymer Polymers 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 1
• 229960003834 dapagliflozin Drugs 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 238000005906 dihydroxylation reaction Methods 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 229940127256 dual PPAR α/δ agonist Drugs 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 229950003693 dutogliptin Drugs 0.000 description 1
• 229950001279 elafibranor Drugs 0.000 description 1
• 229960003345 empagliflozin Drugs 0.000 description 1
• OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 1
• 229950000234 emricasan Drugs 0.000 description 1
• 238000001839 endoscopy Methods 0.000 description 1
• 230000037149 energy metabolism Effects 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 229950001310 ertiprotafib Drugs 0.000 description 1
• ZADJRRFMOOACHL-WQICJITCSA-N ethyl (e,3s,5r)-7-[4-(4-fluorophenyl)spiro[chromene-2,1'-cyclopentane]-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound C12=CC=CC=C2OC2(CCCC2)C(/C=C/[C@H](O)C[C@H](O)CC(=O)OCC)=C1C1=CC=C(F)C=C1 ZADJRRFMOOACHL-WQICJITCSA-N 0.000 description 1
• PUFPKUWTAGCFPT-UHFFFAOYSA-N ethyl 2-amino-2-ethylhexanoate Chemical compound CCCCC(N)(CC)C(=O)OCC PUFPKUWTAGCFPT-UHFFFAOYSA-N 0.000 description 1
• 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 229950011259 evogliptin Drugs 0.000 description 1
• 210000001808 exosome Anatomy 0.000 description 1
• 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 1
• 229940043259 farnesol Drugs 0.000 description 1
• 229930002886 farnesol Natural products 0.000 description 1
• 235000020937 fasting conditions Nutrition 0.000 description 1
• 230000002550 fecal effect Effects 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 229940125753 fibrate Drugs 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960003627 gemfibrozil Drugs 0.000 description 1
• 229960002458 gemigliptin Drugs 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• AFLFKFHDSCQHOL-IZZDOVSWSA-N gft505 Chemical compound C1=CC(SC)=CC=C1C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1 AFLFKFHDSCQHOL-IZZDOVSWSA-N 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• 229960001381 glipizide Drugs 0.000 description 1
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
• 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• 229940049654 glyceryl behenate Drugs 0.000 description 1
• 239000001087 glyceryl triacetate Substances 0.000 description 1
• 235000013773 glyceryl triacetate Nutrition 0.000 description 1
• QWEWGXUTRTXFRF-KBPBESRZSA-N gosogliptin Chemical compound C1C(F)(F)CCN1C(=O)[C@H]1NC[C@@H](N2CCN(CC2)C=2N=CC=CN=2)C1 QWEWGXUTRTXFRF-KBPBESRZSA-N 0.000 description 1
• 229950005754 gosogliptin Drugs 0.000 description 1
• 201000000079 gynecomastia Diseases 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 230000008676 import Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 208000016245 inborn errors of metabolism Diseases 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 229940125798 integrin inhibitor Drugs 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical compound IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 125000003010 ionic group Chemical group 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
• SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
• JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 238000012332 laboratory investigation Methods 0.000 description 1
• 229960001021 lactose monohydrate Drugs 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229960002397 linagliptin Drugs 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 230000003520 lipogenic effect Effects 0.000 description 1
• 229960002701 liraglutide Drugs 0.000 description 1
• XCOBTUNSZUJCDH-UHFFFAOYSA-B lithium magnesium sodium silicate Chemical compound [Li+].[Li+].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 XCOBTUNSZUJCDH-UHFFFAOYSA-B 0.000 description 1
• 210000005229 liver cell Anatomy 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• WGFOBBZOWHGYQH-MXHNKVEKSA-N lubiprostone Chemical compound O1[C@](C(F)(F)CCCC)(O)CC[C@@H]2[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]21 WGFOBBZOWHGYQH-MXHNKVEKSA-N 0.000 description 1
• 229960000345 lubiprostone Drugs 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 235000012245 magnesium oxide Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 235000012054 meals Nutrition 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 229950004994 meglitinide Drugs 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
• 229960003105 metformin Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 229950009116 mevastatin Drugs 0.000 description 1
• AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
• BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
• 229960001110 miglitol Drugs 0.000 description 1
• GVVUZBSCYAVFTI-IYARVYRRSA-N miricorilant Chemical compound FC(F)(F)C1=CC=CC(CC2=C(NC(=O)NC2=O)[C@H]2CC[C@@H](CC2)C2=CC=CC=C2)=C1 GVVUZBSCYAVFTI-IYARVYRRSA-N 0.000 description 1
• 235000019426 modified starch Nutrition 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 229950001135 muraglitazar Drugs 0.000 description 1
• 229950006780 n-acetylglucosamine Drugs 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 102000006255 nuclear receptors Human genes 0.000 description 1
• 108020004017 nuclear receptors Proteins 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 229950000074 omarigliptin Drugs 0.000 description 1
• MKMPWKUAHLTIBJ-ISTRZQFTSA-N omarigliptin Chemical compound C1([C@H]2OC[C@@H](C[C@@H]2N)N2CC3=CN(N=C3C2)S(=O)(=O)C)=CC(F)=CC=C1F MKMPWKUAHLTIBJ-ISTRZQFTSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 description 1
• 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 244000087877 pink gum Species 0.000 description 1
• 235000002651 pink gum Nutrition 0.000 description 1
• 229960002797 pitavastatin Drugs 0.000 description 1
• VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
• 206010036067 polydipsia Diseases 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 239000004323 potassium nitrate Substances 0.000 description 1
• 235000010333 potassium nitrate Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 210000000512 proximal kidney tubule Anatomy 0.000 description 1
• 210000005234 proximal tubule cell Anatomy 0.000 description 1
• 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940075993 receptor modulator Drugs 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 description 1
• 229960000804 ronifibrate Drugs 0.000 description 1
• AYJVGKWCGIYEAK-UHFFFAOYSA-N ronifibrate Chemical compound C=1C=CN=CC=1C(=O)OCCCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 AYJVGKWCGIYEAK-UHFFFAOYSA-N 0.000 description 1
• 229960000672 rosuvastatin Drugs 0.000 description 1
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
• 102200039916 rs2296651 Human genes 0.000 description 1
• MRWFZSLZNUJVQW-DEOSSOPVSA-N saroglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCN1C(C=2C=CC(SC)=CC=2)=CC=C1C MRWFZSLZNUJVQW-DEOSSOPVSA-N 0.000 description 1
• 229950006544 saroglitazar Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 229960004937 saxagliptin Drugs 0.000 description 1
• QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
• 108010033693 saxagliptin Proteins 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229950003181 selonsertib Drugs 0.000 description 1
• YIDDLAAKOYYGJG-UHFFFAOYSA-N selonsertib Chemical compound CC(C)N1C=NN=C1C1=CC=CC(NC(=O)C=2C(=CC(C)=C(C=2)N2C=C(N=C2)C2CC2)F)=N1 YIDDLAAKOYYGJG-UHFFFAOYSA-N 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 229950009513 simtuzumab Drugs 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 229960004034 sitagliptin Drugs 0.000 description 1
• MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910001415 sodium ion Inorganic materials 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• WINXNKPZLFISPD-UHFFFAOYSA-N sodium;1,1-dioxo-1,2-benzothiazol-3-one Chemical compound [Na+].C1=CC=C2C(=O)NS(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-N 0.000 description 1
• HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 229950005268 sotagliflozin Drugs 0.000 description 1
• 241000894007 species Species 0.000 description 1
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
• 239000004059 squalene synthase inhibitor Substances 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 150000003429 steroid acids Chemical class 0.000 description 1
• 150000005845 steroid sulfates Chemical class 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000004575 stone Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• WWJZWCUNLNYYAU-UHFFFAOYSA-N temephos Chemical compound C1=CC(OP(=S)(OC)OC)=CC=C1SC1=CC=C(OP(=S)(OC)OC)C=C1 WWJZWCUNLNYYAU-UHFFFAOYSA-N 0.000 description 1
• 229950000034 teneligliptin Drugs 0.000 description 1
• WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• XGTPDIIFEPTULX-UHFFFAOYSA-N tert-butyl prop-2-ynoate Chemical compound CC(C)(C)OC(=O)C#C XGTPDIIFEPTULX-UHFFFAOYSA-N 0.000 description 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
• CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
• 229950004704 tesaglitazar Drugs 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 description 1
• 238000005809 transesterification reaction Methods 0.000 description 1
• 229950010728 trelagliptin Drugs 0.000 description 1
• IWYJYHUNXVAVAA-OAHLLOKOSA-N trelagliptin Chemical compound C=1C(F)=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 IWYJYHUNXVAVAA-OAHLLOKOSA-N 0.000 description 1
• 229960002622 triacetin Drugs 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
• 239000001069 triethyl citrate Substances 0.000 description 1
• VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
• 235000013769 triethyl citrate Nutrition 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• WUJVPODXELZABP-FWJXURDUSA-N trodusquemine Chemical compound C([C@@H]1C[C@H]2O)[C@@H](NCCCNCCCCNCCCN)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](C(C)C)OS(O)(=O)=O)[C@@]2(C)CC1 WUJVPODXELZABP-FWJXURDUSA-N 0.000 description 1
• 229950004499 trodusquemine Drugs 0.000 description 1
• 229940070126 tropifexor Drugs 0.000 description 1
• 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 229960001254 vildagliptin Drugs 0.000 description 1
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1