CN118512442A - 降低血清胆固醇和pcsk9的组合物和方法 - Google Patents
降低血清胆固醇和pcsk9的组合物和方法 Download PDFInfo
- Publication number
- CN118512442A CN118512442A CN202410548659.4A CN202410548659A CN118512442A CN 118512442 A CN118512442 A CN 118512442A CN 202410548659 A CN202410548659 A CN 202410548659A CN 118512442 A CN118512442 A CN 118512442A
- Authority
- CN
- China
- Prior art keywords
- inhibitor
- cholesterol
- ldl
- serum
- akr1a1
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 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 title claims abstract 13
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 title claims abstract 4
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 title claims abstract 4
- 239000000203 mixture Substances 0.000 title 1
- 239000003112 inhibitor Substances 0.000 claims abstract 20
- 235000012000 cholesterol Nutrition 0.000 claims abstract 4
- 102100026448 Aldo-keto reductase family 1 member A1 Human genes 0.000 claims 15
- 101000718007 Homo sapiens Aldo-keto reductase family 1 member A1 Proteins 0.000 claims 15
- 210000002966 serum Anatomy 0.000 claims 8
- 102100027265 Aldo-keto reductase family 1 member B1 Human genes 0.000 claims 6
- 101000836540 Homo sapiens Aldo-keto reductase family 1 member B1 Proteins 0.000 claims 6
- 108010028554 LDL Cholesterol Proteins 0.000 claims 5
- 238000008214 LDL Cholesterol Methods 0.000 claims 5
- 108010023302 HDL Cholesterol Proteins 0.000 claims 4
- 150000003626 triacylglycerols Chemical class 0.000 claims 4
- 108010069201 VLDL Cholesterol Proteins 0.000 claims 3
- 230000007423 decrease Effects 0.000 claims 3
- QCCHBHSAIQIQGO-UHFFFAOYSA-N 2,7-difluorospiro[fluorene-9,5'-imidazolidine]-2',4'-dione Chemical group C12=CC(F)=CC=C2C2=CC=C(F)C=C2C21NC(=O)NC2=O QCCHBHSAIQIQGO-UHFFFAOYSA-N 0.000 claims 2
- 101150005096 AKR1 gene Proteins 0.000 claims 2
- 108010027006 Apolipoproteins B Proteins 0.000 claims 2
- 102000018616 Apolipoproteins B Human genes 0.000 claims 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims 2
- 108010010234 HDL Lipoproteins Proteins 0.000 claims 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 2
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 2
- 101100215778 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ptr-1 gene Proteins 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 208000029078 coronary artery disease Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000002440 hepatic effect Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 2
- 150000003904 phospholipids Chemical class 0.000 claims 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 101150102415 Apob gene Proteins 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010019708 Hepatic steatosis Diseases 0.000 claims 1
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 238000009825 accumulation Methods 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 1
- 230000003234 polygenic effect Effects 0.000 claims 1
- 230000002028 premature Effects 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
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
- A61K31/33—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
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- 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
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- 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
- A61K31/41—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
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- 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
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/4245—Oxadiazoles
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Landscapes
- Health & Medical Sciences (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)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (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)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762562784P | 2017-09-25 | 2017-09-25 | |
| US62/562,784 | 2017-09-25 | ||
| PCT/US2018/052214 WO2019060720A1 (en) | 2017-09-25 | 2018-09-21 | COMPOSITIONS AND METHODS FOR REDUCING SERUM CHOLESTEROL AND PCSK9 |
| CN201880074862.5A CN111356764B (zh) | 2017-09-25 | 2018-09-21 | 降低血清胆固醇和pcsk9的组合物和方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880074862.5A Division CN111356764B (zh) | 2017-09-25 | 2018-09-21 | 降低血清胆固醇和pcsk9的组合物和方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118512442A true CN118512442A (zh) | 2024-08-20 |
Family
ID=65810650
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880074862.5A Active CN111356764B (zh) | 2017-09-25 | 2018-09-21 | 降低血清胆固醇和pcsk9的组合物和方法 |
| CN202410548659.4A Pending CN118512442A (zh) | 2017-09-25 | 2018-09-21 | 降低血清胆固醇和pcsk9的组合物和方法 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880074862.5A Active CN111356764B (zh) | 2017-09-25 | 2018-09-21 | 降低血清胆固醇和pcsk9的组合物和方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US11576900B2 (enExample) |
| EP (1) | EP3688163A4 (enExample) |
| JP (2) | JP7414712B2 (enExample) |
| CN (2) | CN111356764B (enExample) |
| CA (1) | CA3076889A1 (enExample) |
| WO (1) | WO2019060720A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3076889A1 (en) * | 2017-09-25 | 2019-03-28 | Case Western Reserve University | Compositions and methods of reducing serum cholesterol and pcsk9 |
| AU2019344066B2 (en) * | 2018-09-21 | 2025-05-29 | Case Western Reserve University | Aldoketo reductase inhibitors and uses thereof |
| CN113648427B (zh) * | 2021-08-20 | 2023-07-28 | 山东大学 | 透明质酸-es2-af肽偶联物及其制备方法和应用 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2683718A (en) | 1952-01-11 | 1954-07-13 | Searle & Co | Spiro-[xanthene-9, 4'-imidazolidine]-2, 5-dione |
| JPS58140020A (ja) | 1982-02-13 | 1983-08-19 | Nippon Zoki Pharmaceut Co Ltd | 脂質代謝改善剤 |
| US4436745A (en) | 1982-04-15 | 1984-03-13 | Alcon Laboratories, Inc. | Method of inhibiting aldose reductase activity |
| US5153211A (en) * | 1983-09-14 | 1992-10-06 | Alcon Laboratories, Inc. | Spiro-tricyclicaromatic succinimide derivatives as inhibitors of aldose reductase |
| AU2002239748A1 (en) | 2000-12-15 | 2002-06-24 | Galileo Laboratories, Inc. | Use of tocopherol, metabolites or derivatives thereof or flavonoid metabolites or derivatives thereof in the manufacture of a medicament for the treatment of tissue ischemia |
| US20020198201A1 (en) * | 2001-06-07 | 2002-12-26 | Wyeth | Combination of a PTPase inhibitor and an aldose reductase inhibitor |
| EP1431399A1 (en) | 2002-12-20 | 2004-06-23 | Clinigenetics | Methods and composition for identifying therapeutic agents of atherosclerotic plaque lesions |
| JP4544503B2 (ja) | 2003-04-15 | 2010-09-15 | 株式会社アミノアップ化学 | 雲南苦丁茶成分を含有する組成物 |
| MXPA05013054A (es) | 2003-06-04 | 2006-08-23 | Univ Duke | Composiciones y metodos para modular s-nitrosoglutationa reductasa. |
| JP2007015924A (ja) | 2003-06-12 | 2007-01-25 | Sanwa Kagaku Kenkyusho Co Ltd | 抗癌剤耐性を克服する薬剤及びそのスクリーニング方法 |
| US20100292178A1 (en) | 2003-07-21 | 2010-11-18 | Jeffrey Young | Method of treating non-insulin dependent diabetes mellitus and related complications |
| US9308206B2 (en) | 2004-08-23 | 2016-04-12 | The Board Of Regents Of The University Of Texas System | Compositions and methods for treating colon cancer |
| US20110092566A1 (en) | 2004-11-19 | 2011-04-21 | Srivastava Satish K | Treatment of cancer with aldose reductase inhibitors |
| FR2885904B1 (fr) | 2005-05-19 | 2007-07-06 | Aventis Pharma Sa | Nouveaux derives du fluorene, compositions les contenant et utilisation |
| EP1961420B1 (en) | 2005-12-16 | 2012-07-25 | Sanwa Kagaku Kenkyusho Co., Ltd | Agent for prevention and treatment of acute renal failure |
| AU2007218709A1 (en) | 2006-02-20 | 2007-08-30 | Sanwa Kagaku Kenkyusho Co., Ltd. | Prophylactic or therapeutic agent for cerebral ischemia or cerebral ischemic reperfusion injury in stroke |
| US8680270B2 (en) | 2006-11-21 | 2014-03-25 | Viamet Pharmaceuticals, Inc. | Metallo-oxidoreductase inhibitors using metal binding moieties in combination with targeting moieties |
| US8440617B2 (en) | 2007-03-22 | 2013-05-14 | The Trustees Of The University Of Pennsylvania | Hyperbaric treatment in wound healing |
| EP2405755A4 (en) | 2009-03-11 | 2012-11-28 | Xintria Pharmaceutical Corp Inc | METHOD AND COMPOSITIONS FOR TREATING METABOLISM AND CARDIOVASCULAR DISEASES |
| EP2295593A1 (en) | 2009-09-15 | 2011-03-16 | Philippe Marliere | Method for the enymatic production of 3-hydroxy-3-methylbutyric acid from acetone and acetyl-CoA |
| WO2012040641A2 (en) | 2010-09-24 | 2012-03-29 | Array Biopharma Inc. | Compounds for treating neurodegenerative diseases |
| US20150335615A1 (en) * | 2013-01-04 | 2015-11-26 | Toshihisa Kawai | Cholesterol-lowering compounds in combination with lipid metabolism-altering compounds of non-absorbable sugars, compounds that convert nh3 to nh4+, or hydrogen-generating compounds for the treatment of high cholesterol and inflammation |
| EP3179995B1 (en) | 2014-08-12 | 2018-11-07 | University of Pécs (Pécsi Tudományegyetem) | Methods and materials for reducing ischemia-reperfusion injury |
| AU2015357489A1 (en) | 2014-12-05 | 2017-07-06 | Case Western Reserve University | Compositions and methods of modulating S-nitrosylation |
| US10537557B2 (en) | 2016-01-27 | 2020-01-21 | Case Western Reserve University | Methods of treating respiratory disorders |
| CA3076889A1 (en) * | 2017-09-25 | 2019-03-28 | Case Western Reserve University | Compositions and methods of reducing serum cholesterol and pcsk9 |
| AU2019344066B2 (en) * | 2018-09-21 | 2025-05-29 | Case Western Reserve University | Aldoketo reductase inhibitors and uses thereof |
-
2018
- 2018-09-21 CA CA3076889A patent/CA3076889A1/en active Pending
- 2018-09-21 CN CN201880074862.5A patent/CN111356764B/zh active Active
- 2018-09-21 WO PCT/US2018/052214 patent/WO2019060720A1/en not_active Ceased
- 2018-09-21 EP EP18858000.5A patent/EP3688163A4/en active Pending
- 2018-09-21 US US16/648,737 patent/US11576900B2/en active Active
- 2018-09-21 JP JP2020516839A patent/JP7414712B2/ja active Active
- 2018-09-21 CN CN202410548659.4A patent/CN118512442A/zh active Pending
-
2023
- 2023-02-14 US US18/109,406 patent/US20230190710A1/en active Pending
- 2023-10-04 JP JP2023173195A patent/JP2024001162A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA3076889A1 (en) | 2019-03-28 |
| EP3688163A1 (en) | 2020-08-05 |
| JP7414712B2 (ja) | 2024-01-16 |
| US11576900B2 (en) | 2023-02-14 |
| WO2019060720A1 (en) | 2019-03-28 |
| CN111356764A (zh) | 2020-06-30 |
| JP2020535142A (ja) | 2020-12-03 |
| US20200268717A1 (en) | 2020-08-27 |
| JP2024001162A (ja) | 2024-01-09 |
| EP3688163A4 (en) | 2022-12-14 |
| CN111356764B (zh) | 2024-05-24 |
| US20230190710A1 (en) | 2023-06-22 |
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