SA515370140B1 - مشتقات 11-هيدروكسيل- من الأحماض الصفراوية ومترافقات الحمض الأميني منها كمضمنات مستقبل فارنيسويد x - Google Patents
مشتقات 11-هيدروكسيل- من الأحماض الصفراوية ومترافقات الحمض الأميني منها كمضمنات مستقبل فارنيسويد x Download PDFInfo
- Publication number
- SA515370140B1 SA515370140B1 SA515370140A SA515370140A SA515370140B1 SA 515370140 B1 SA515370140 B1 SA 515370140B1 SA 515370140 A SA515370140 A SA 515370140A SA 515370140 A SA515370140 A SA 515370140A SA 515370140 B1 SA515370140 B1 SA 515370140B1
- Authority
- SA
- Saudi Arabia
- Prior art keywords
- hydroxyl
- compound
- disease
- cholestasis
- hydrogen
- Prior art date
Links
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 14
- 239000003613 bile acid Substances 0.000 title description 12
- 102100038495 Bile acid receptor Human genes 0.000 title description 3
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 210000004185 liver Anatomy 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
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- 239000000203 mixture Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 14
- 229910052739 hydrogen Inorganic materials 0.000 claims 11
- 239000001257 hydrogen Substances 0.000 claims 11
- 206010008635 Cholestasis Diseases 0.000 claims 10
- 125000000217 alkyl group Chemical group 0.000 claims 9
- 230000007870 cholestasis Effects 0.000 claims 9
- 231100000359 cholestasis Toxicity 0.000 claims 9
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 7
- 229910052736 halogen Inorganic materials 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 208000010157 sclerosing cholangitis Diseases 0.000 claims 5
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims 4
- 102100036325 Sterol 26-hydroxylase, mitochondrial Human genes 0.000 claims 4
- 208000001088 cerebrotendinous xanthomatosis Diseases 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 208000019423 liver disease Diseases 0.000 claims 4
- 230000035935 pregnancy Effects 0.000 claims 4
- 201000000742 primary sclerosing cholangitis Diseases 0.000 claims 4
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims 3
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 3
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 3
- 208000018565 Hemochromatosis Diseases 0.000 claims 3
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims 3
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 3
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 3
- 208000018839 Wilson disease Diseases 0.000 claims 3
- -1 alkyl hydroxyl Chemical class 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
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- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 230000008929 regeneration Effects 0.000 claims 2
- 238000011069 regeneration method Methods 0.000 claims 2
- 201000001862 viral hepatitis Diseases 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 206010004637 Bile duct stone Diseases 0.000 claims 1
- 201000009331 Choledocholithiasis Diseases 0.000 claims 1
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- 206010056533 Congenital hepatic fibrosis Diseases 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 claims 1
- 235000014820 Galium aparine Nutrition 0.000 claims 1
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- 241000257303 Hymenoptera Species 0.000 claims 1
- 102100030931 Ladinin-1 Human genes 0.000 claims 1
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- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010033302 Overgrowth bacterial Diseases 0.000 claims 1
- 244000089486 Phragmites australis subsp australis Species 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
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- 229910052799 carbon Inorganic materials 0.000 claims 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 208000010706 fatty liver disease Diseases 0.000 claims 1
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- 238000009472 formulation Methods 0.000 claims 1
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 208000001024 intrahepatic cholestasis Diseases 0.000 claims 1
- 230000007872 intrahepatic cholestasis Effects 0.000 claims 1
- 208000014861 isolated congenital hepatic fibrosis Diseases 0.000 claims 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 claims 1
- 239000002753 trypsin inhibitor Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
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- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 abstract 1
- 102000005962 receptors Human genes 0.000 description 16
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- 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 4
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- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[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)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- 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 1
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- 239000004471 Glycine Substances 0.000 description 1
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 1
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- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
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- 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
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- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[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 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 1
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Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
- C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361823169P | 2013-05-14 | 2013-05-14 | |
| PCT/EP2014/059896 WO2014184271A1 (en) | 2013-05-14 | 2014-05-14 | 11-hydroxyl-derivatives of bile acids and amino acid conjugates thereof as farnesoid x receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SA515370140B1 true SA515370140B1 (ar) | 2017-04-11 |
Family
ID=50721801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SA515370140A SA515370140B1 (ar) | 2013-05-14 | 2015-11-12 | مشتقات 11-هيدروكسيل- من الأحماض الصفراوية ومترافقات الحمض الأميني منها كمضمنات مستقبل فارنيسويد x |
Country Status (37)
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1392714T3 (da) | 2001-03-12 | 2006-01-09 | Intercept Pharmaceuticals Inc | Steroider som agonister for FXR |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| CN105377870B (zh) | 2013-05-14 | 2018-04-03 | 英特塞普特医药品公司 | 作为法尼醇x受体调节剂的胆汁酸的11‑羟基衍生物及其氨基酸共轭物 |
| US10077268B2 (en) | 2014-03-13 | 2018-09-18 | Salk Institute For Biological Studies | FXR agonists and methods for making and using |
| US10301268B2 (en) | 2014-03-13 | 2019-05-28 | The Salk Institute For Biological Studies | Analogs of fexaramine and methods of making and using |
| SI3626725T1 (sl) | 2014-05-29 | 2023-04-28 | Bar Pharmaceuticals S.R.L. | Derivati holana za uporabo pri zdravljenju in/ali preprečevanju bolezni, posredovanih s FXR in TGR5/GPBAR1 |
| BR112017009657A2 (pt) | 2014-11-06 | 2018-01-23 | Enanta Pharmaceuticals, Inc | análogos de ácidos biliares como agonistas de fxr/tgr5 e métodos de uso dos mesmos |
| JP6698085B2 (ja) | 2014-11-19 | 2020-05-27 | エヌゼットピー ユーケー リミテッド | ステロイドＦＸＲモジュレーター製造のための中間体としての６α−アルキル−６，７−ジオン−ステロイド |
| ES2748692T3 (es) | 2014-11-19 | 2020-03-17 | Nzp Uk Ltd | Esteroides 6.alfa.-alquil-3,7-diona como intermedios para la producción de moduladores FXR de esteroides |
| KR102526632B1 (ko) | 2014-11-19 | 2023-04-27 | 엔제트피 유케이 리미티드 | 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 5β-6-알킬-7-하이드록시-3-온 스테로이드 |
| EA033427B1 (ru) | 2014-11-19 | 2019-10-31 | Nzp Uk Ltd | 6-алкил-7-гидрокси-4-ен-3-оновые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr |
| WO2016086115A1 (en) | 2014-11-26 | 2016-06-02 | Enanta Pharmaceuticals, Inc. | Tetrazole derivatives of bile acids as fxr/tgr5 agonists and methods of use thereof |
| RU2017121457A (ru) | 2014-11-26 | 2018-12-26 | Энанта Фармасьютикалс, Инк. | Аналоги желчной кислоты в качестве агонистов fxr/tgr5 и способы их применения |
| US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| MA41094A (fr) * | 2014-12-02 | 2017-10-10 | Lilly Co Eli | Procédés de traitement de troubles rénaux |
| CN105348365A (zh) * | 2014-12-03 | 2016-02-24 | 四川百利药业有限责任公司 | 一种胆酸衍生物及其制备方法、药物组合物和用途 |
| CN104523703A (zh) * | 2014-12-24 | 2015-04-22 | 聂飚 | 一种游离脂肪酸转运蛋白小分子抑制物的应用 |
| ES2905872T3 (es) * | 2015-02-06 | 2022-04-12 | Intercept Pharmaceuticals Inc | Composiciones farmacéuticas para terapia combinada |
| AU2016219266A1 (en) | 2015-02-11 | 2017-08-10 | Enanta Pharmaceuticals, Inc. | Bile acid analogs as FXR/TGR5 agonists and methods of use thereof |
| JP2018507880A (ja) * | 2015-03-09 | 2018-03-22 | インターセプト ファーマシューティカルズ， インコーポレイテッド | 骨密度を調節する方法 |
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| US2080775A (en) * | 1934-08-22 | 1937-05-18 | Celanese Corp | Shedding mechanism for circular looms |
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