RU2019110780A - Комбинация агонистов fxr - Google Patents
Комбинация агонистов fxr Download PDFInfo
- Publication number
- RU2019110780A RU2019110780A RU2019110780A RU2019110780A RU2019110780A RU 2019110780 A RU2019110780 A RU 2019110780A RU 2019110780 A RU2019110780 A RU 2019110780A RU 2019110780 A RU2019110780 A RU 2019110780A RU 2019110780 A RU2019110780 A RU 2019110780A
- Authority
- RU
- Russia
- Prior art keywords
- disorder
- liver disease
- combination
- cholestasis
- disease
- Prior art date
Links
- 239000000556 agonist Substances 0.000 title 1
- 208000019423 liver disease Diseases 0.000 claims 7
- 206010008635 Cholestasis Diseases 0.000 claims 6
- 230000007870 cholestasis Effects 0.000 claims 5
- 231100000359 cholestasis Toxicity 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 5
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 3
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 3
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 claims 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 201000002150 Progressive familial intrahepatic cholestasis Diseases 0.000 claims 2
- 201000001883 cholelithiasis Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 229940002612 prodrug Drugs 0.000 claims 2
- 239000000651 prodrug Substances 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 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 class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 1
- VYLOOGHLKSNNEK-UHFFFAOYSA-N 2-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid Chemical group S1C2=CC(C(=O)O)=CC(F)=C2N=C1N1C(C2)CCC1CC2OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F VYLOOGHLKSNNEK-UHFFFAOYSA-N 0.000 claims 1
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 208000017283 Bile Duct disease Diseases 0.000 claims 1
- 206010056375 Bile duct obstruction Diseases 0.000 claims 1
- 208000021130 Bilirubin encephalopathy Diseases 0.000 claims 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 claims 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 claims 1
- 208000017667 Chronic Disease Diseases 0.000 claims 1
- 206010009208 Cirrhosis alcoholic Diseases 0.000 claims 1
- 201000003883 Cystic fibrosis Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 208000037319 Hepatitis infectious Diseases 0.000 claims 1
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 1
- 206010023138 Jaundice neonatal Diseases 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- 208000012868 Overgrowth Diseases 0.000 claims 1
- 208000012346 Venoocclusive disease Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 208000010002 alcoholic liver cirrhosis Diseases 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- 229940000425 combination drug Drugs 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 230000001856 erectile effect Effects 0.000 claims 1
- 229940011871 estrogen Drugs 0.000 claims 1
- 239000000262 estrogen Substances 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 208000001130 gallstones Diseases 0.000 claims 1
- 208000005252 hepatitis A Diseases 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 210000000936 intestine Anatomy 0.000 claims 1
- 208000006663 kernicterus Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 235000016709 nutrition Nutrition 0.000 claims 1
- 208000007232 portal hypertension Diseases 0.000 claims 1
- 201000002793 renal fibrosis Diseases 0.000 claims 1
- 208000010157 sclerosing cholangitis Diseases 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (8)
1. Фармацевтическая комбинация, содержащая агонист FXR, не являющийся производным желчной кислоты, и одно или несколько дополнительных терапевтических средств для одновременного, последовательного или раздельного введения, где дополнительное терапевтическое средство представляет собой ингибитор CCR2/5, например ценикривирок, и где агонист FXR представляет собой 2-[3-({5-циклопропил-3-[2-(трифторметокси)фенил]-1,2-оксазол-4-ил}метокси)-8-азабицикло[3.2.1]октан-8-ил]-4-фтор-1,3-бензотиазол-6-карбоновую кислоту, ее стереоизомер, энантиомер, фармацевтически приемлемую соль, пролекарство, и/или сложный эфир, или конъюгат с аминокислотой.
2. Комбинация по п. 1 для применения при лечении или предупреждении фиброзирующего или цирротического заболевания или нарушения, например, заболевания или нарушения печени, например, хронического заболевания или нарушения печени.
3. Комбинация по п. 1, где агонист FXR подлежит введению в дозе в диапазоне от приблизительно 3 мкг до приблизительно 100 мкг.
4. Комбинация по п. 1 или 3, где ценикривирок в свободной форме или в виде его фармацевтически приемлемой соли, сольвата, пролекарства или сложного эфира, подлежит введению в дозе в диапазоне от приблизительно 50 мг до приблизительно 250 мг.
5. Комбинация по любому из пп. 1-4, которая представляет собой комбинацию фиксированных доз.
6. Комбинация по любому из пп. 1-4, которая представляет собой произвольную комбинацию.
7. Применение комбинации по любому из пп. 1-6, при изготовлении лекарственного препарата, предназначенного для лечения или предупреждения фиброзирующего, цирротического заболевания или нарушения, например, заболевания или нарушения печени, например, хронического заболевания печени, например, заболевания или нарушения печени, выбранного из группы, состоящей из холестаза, внутрипеченочного холестаза, вызванного эстрогенами холестаза, холестаза, вызванного лекарственными средствами, холестаза беременных, холестаза, связанного с парентеральным питанием, первичного билиарного цирроза (PBC), первичного склерозирующего холангита (PSC), прогрессирующего семейного внутрипеченочного холестаза (PFIC), неалкогольного жирового заболевания печени (NAFLD), неалкогольного стеатогепатита (NASH), нарушения желчных протоков, вызванного лекарственными средствами, камней в желчном пузыре, цирроза печени, алкогольного цирроза, ассоциированного с муковисцидозом заболевания печени (CFLD), непроходимости желчных протоков, желчнокаменного заболевания, фиброза печени, фиброза почек, дислипидемии, атеросклероза, диабета, диабетической нефропатии, колита, желтухи новорожденных, предупреждения билирубиновой энцефалопатии, веноокклюзионного заболевания, портальной гипертензии, метаболического синдрома, гиперхолестеринемии, избыточного бактериального роста в кишечнике, эректильной дисфункции, прогрессирующего фиброза печени, вызванного любым из перечисленных выше заболеваний или инфекционным гепатитом, например NAFLD, NASH, фиброза печени или PBC.
8. Способ предупреждения, замедления или лечения заболевания или нарушения печени, определенных в п. 7, у пациента, нуждающегося в этом, включающий введение терапевтически эффективного количества комбинации по п. 1.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662394446P | 2016-09-14 | 2016-09-14 | |
| US62/394,446 | 2016-09-14 | ||
| PCT/IB2017/055503 WO2018051230A1 (en) | 2016-09-14 | 2017-09-12 | Combination of fxr agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2019110780A true RU2019110780A (ru) | 2020-10-15 |
| RU2019110780A3 RU2019110780A3 (ru) | 2020-11-30 |
Family
ID=60043251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019110780A RU2019110780A (ru) | 2016-09-14 | 2017-09-12 | Комбинация агонистов fxr |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20210290610A1 (ru) |
| EP (1) | EP3512558A1 (ru) |
| JP (1) | JP6878596B2 (ru) |
| KR (1) | KR102218498B1 (ru) |
| CN (1) | CN109689105A (ru) |
| AR (1) | AR109652A1 (ru) |
| AU (2) | AU2017328999B2 (ru) |
| BR (1) | BR112019004684A2 (ru) |
| CA (1) | CA3036760A1 (ru) |
| CL (1) | CL2019000625A1 (ru) |
| CO (1) | CO2019002245A2 (ru) |
| CR (1) | CR20190125A (ru) |
| EC (1) | ECSP19016844A (ru) |
| IL (1) | IL264628A (ru) |
| JO (1) | JOP20190040A1 (ru) |
| MX (1) | MX2019003021A (ru) |
| PE (1) | PE20190972A1 (ru) |
| PH (1) | PH12019500326A1 (ru) |
| RU (1) | RU2019110780A (ru) |
| SG (1) | SG11201900651PA (ru) |
| TW (1) | TW201811372A (ru) |
| WO (1) | WO2018051230A1 (ru) |
| ZA (1) | ZA201900528B (ru) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3051977A1 (en) * | 2017-02-24 | 2018-08-30 | Genfit | Pharmaceutical compositions for combination therapy |
| AU2019276955A1 (en) * | 2018-05-31 | 2020-12-03 | Novartis Ag | Combinations comprising tropifexor and cenicriviroc |
| CA3139750A1 (en) * | 2019-07-18 | 2021-01-21 | Jacky Vonderscher | Improved treatment using eyp001 |
| TW202135812A (zh) * | 2019-12-20 | 2021-10-01 | 瑞士商諾華公司 | 使用整聯蛋白抑制劑組合治療肝臟疾病 |
| CN112402430A (zh) * | 2020-12-11 | 2021-02-26 | 大连医科大学 | 泽泻醇b-23-醋酸酯在预防和治疗急性肾损伤中的应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6987121B2 (en) * | 2002-04-25 | 2006-01-17 | Smithkline Beecham Corporation | Compositions and methods for hepatoprotection and treatment of cholestasis |
| EP2370442B9 (en) * | 2008-11-26 | 2013-09-04 | Pfizer Inc. | 3-Aminocyclopentanecarboxamides as chemokine receptor modulators |
| US8383812B2 (en) | 2009-10-13 | 2013-02-26 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-A][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, a dual modulator of chemokine receptor activity, crystalline forms and processes |
| CU24152B1 (es) * | 2010-12-20 | 2016-02-29 | Irm Llc | 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr |
| KR102350357B1 (ko) * | 2013-11-05 | 2022-01-14 | 노파르티스 아게 | 파르네소이드 x 수용체의 조정을 위한 조성물 및 방법 |
| EP3116878A4 (en) * | 2014-03-13 | 2018-02-14 | Salk Institute for Biological Studies | Fxr agonists and methods for making and using |
| EP3777863A1 (en) * | 2014-09-12 | 2021-02-17 | Tobira Therapeutics, Inc. | Cenicriviroc combination therapy for the treatment of fibrosis |
| US20170368038A1 (en) * | 2014-12-18 | 2017-12-28 | Novartis Ag | Azabicyclooctane derivatives as fxr agonists for use in the treatment of liver and gastrointestinal diseases |
| SI3419624T1 (sl) * | 2016-02-22 | 2021-05-31 | Novartis Ag | Postopki za uporabo agonistov FXR |
-
2017
- 2017-09-12 RU RU2019110780A patent/RU2019110780A/ru not_active Application Discontinuation
- 2017-09-12 CR CR20190125A patent/CR20190125A/es unknown
- 2017-09-12 PE PE2019000497A patent/PE20190972A1/es unknown
- 2017-09-12 CN CN201780056097.XA patent/CN109689105A/zh active Pending
- 2017-09-12 JP JP2019535998A patent/JP6878596B2/ja not_active Expired - Fee Related
- 2017-09-12 AU AU2017328999A patent/AU2017328999B2/en not_active Ceased
- 2017-09-12 EP EP17781186.6A patent/EP3512558A1/en not_active Withdrawn
- 2017-09-12 BR BR112019004684A patent/BR112019004684A2/pt not_active IP Right Cessation
- 2017-09-12 US US16/332,446 patent/US20210290610A1/en not_active Abandoned
- 2017-09-12 CA CA3036760A patent/CA3036760A1/en not_active Abandoned
- 2017-09-12 MX MX2019003021A patent/MX2019003021A/es unknown
- 2017-09-12 KR KR1020197009426A patent/KR102218498B1/ko not_active Expired - Fee Related
- 2017-09-12 SG SG11201900651PA patent/SG11201900651PA/en unknown
- 2017-09-12 WO PCT/IB2017/055503 patent/WO2018051230A1/en not_active Ceased
- 2017-09-14 AR ARP170102541A patent/AR109652A1/es unknown
- 2017-09-14 TW TW106131530A patent/TW201811372A/zh unknown
-
2019
- 2019-01-25 ZA ZA2019/00528A patent/ZA201900528B/en unknown
- 2019-02-03 IL IL264628A patent/IL264628A/en unknown
- 2019-02-15 PH PH12019500326A patent/PH12019500326A1/en unknown
- 2019-03-10 JO JOP/2019/0040A patent/JOP20190040A1/ar unknown
- 2019-03-11 EC ECSENADI201916844A patent/ECSP19016844A/es unknown
- 2019-03-12 CL CL2019000625A patent/CL2019000625A1/es unknown
- 2019-04-15 CO CONC2019/0002245A patent/CO2019002245A2/es unknown
-
2020
- 2020-03-19 AU AU2020201980A patent/AU2020201980A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AR109652A1 (es) | 2019-01-09 |
| CN109689105A (zh) | 2019-04-26 |
| IL264628A (en) | 2019-02-28 |
| CR20190125A (es) | 2019-06-04 |
| JP2019526644A (ja) | 2019-09-19 |
| AU2020201980A1 (en) | 2020-04-09 |
| JP6878596B2 (ja) | 2021-05-26 |
| RU2019110780A3 (ru) | 2020-11-30 |
| PH12019500326A1 (en) | 2019-11-11 |
| SG11201900651PA (en) | 2019-04-29 |
| US20210290610A1 (en) | 2021-09-23 |
| ZA201900528B (en) | 2021-06-30 |
| CO2019002245A2 (es) | 2019-05-31 |
| CA3036760A1 (en) | 2018-03-22 |
| ECSP19016844A (es) | 2019-03-29 |
| WO2018051230A1 (en) | 2018-03-22 |
| BR112019004684A2 (pt) | 2019-05-28 |
| MX2019003021A (es) | 2019-09-26 |
| EP3512558A1 (en) | 2019-07-24 |
| KR102218498B1 (ko) | 2021-02-22 |
| JOP20190040A1 (ar) | 2019-03-10 |
| PE20190972A1 (es) | 2019-07-09 |
| AU2017328999A1 (en) | 2019-02-21 |
| TW201811372A (zh) | 2018-04-01 |
| KR20190044666A (ko) | 2019-04-30 |
| AU2017328999B2 (en) | 2019-12-19 |
| CL2019000625A1 (es) | 2019-05-17 |
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