CA2931064C - Withanolides useful for the treatment of neurodegenerative diseases - Google Patents
Withanolides useful for the treatment of neurodegenerative diseases Download PDFInfo
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- CA2931064C CA2931064C CA2931064A CA2931064A CA2931064C CA 2931064 C CA2931064 C CA 2931064C CA 2931064 A CA2931064 A CA 2931064A CA 2931064 A CA2931064 A CA 2931064A CA 2931064 C CA2931064 C CA 2931064C
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- 230000004770 neurodegeneration Effects 0.000 title abstract description 29
- 208000015122 neurodegenerative disease Diseases 0.000 title abstract description 26
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- PQZVBIJEPVKNOZ-PCLZMVHQSA-N (2R)-2-[(1S)-1-hydroxy-1-[(5R,6R,8R,9S,10R,13S,14R,17S)-5,6,14,17-tetrahydroxy-10,13-dimethyl-1-oxo-6,7,8,9,11,12,15,16-octahydro-4H-cyclopenta[a]phenanthren-17-yl]ethyl]-4,5-dimethyl-2,3-dihydropyran-6-one Chemical class C1C(C)=C(C)C(=O)O[C@H]1[C@](C)(O)[C@@]1(O)[C@@]2(C)CC[C@@H]3[C@@]4(C)C(=O)C=CC[C@]4(O)[C@H](O)C[C@H]3[C@]2(O)CC1 PQZVBIJEPVKNOZ-PCLZMVHQSA-N 0.000 title description 17
- 150000001875 compounds Chemical class 0.000 claims description 117
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229930182877 withaferin Natural products 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361908455P | 2013-11-25 | 2013-11-25 | |
| US61/908,455 | 2013-11-25 | ||
| PCT/US2014/067436 WO2015077780A1 (en) | 2013-11-25 | 2014-11-25 | Withanolides useful for the treatment of neurodegenerative diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2931064A1 CA2931064A1 (en) | 2015-05-28 |
| CA2931064C true CA2931064C (en) | 2022-10-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2931064A Active CA2931064C (en) | 2013-11-25 | 2014-11-25 | Withanolides useful for the treatment of neurodegenerative diseases |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US10351590B2 (enExample) |
| EP (1) | EP3074414B1 (enExample) |
| JP (1) | JP6517833B2 (enExample) |
| KR (1) | KR20160137945A (enExample) |
| CN (1) | CN105940010B (enExample) |
| AU (1) | AU2014352629B2 (enExample) |
| BR (1) | BR112016012002A2 (enExample) |
| CA (1) | CA2931064C (enExample) |
| ES (1) | ES2728870T3 (enExample) |
| MX (1) | MX364528B (enExample) |
| PL (1) | PL3074414T3 (enExample) |
| TR (1) | TR201905218T4 (enExample) |
| WO (1) | WO2015077780A1 (enExample) |
| ZA (1) | ZA201603117B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210087222A1 (en) * | 2017-12-11 | 2021-03-25 | Ethnodyne | Compounds for treating neurodegenerative disorders |
| EP3724170B1 (en) | 2017-12-11 | 2022-04-27 | Ethnodyne | Compounds for treating neurodegenerative disorders |
| EP3724207A1 (en) * | 2017-12-11 | 2020-10-21 | Ethnodyne | Compounds for treating neurodegenerative disorders |
| CN111377994A (zh) * | 2018-12-28 | 2020-07-07 | 南开大学 | 七种来源于灯笼果的醉茄内酯类化合物及其制备方法和用途 |
| CN116063373B (zh) * | 2023-02-14 | 2025-04-15 | 广西医科大学 | 天然产物27-Deoxywithaferin A的制备方法 |
| TW202521103A (zh) * | 2023-10-03 | 2025-06-01 | 美商恩維達醫療公司 | 醉茄素a（withaferin a）類似物及使用彼之治療方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010030395A2 (en) | 2008-09-15 | 2010-03-18 | Whitehead Institute For Biomedical Research | Withaferin a analogs and uses thereof |
| WO2010053655A2 (en) * | 2008-11-07 | 2010-05-14 | University Of Kansas | Therapeutic methods with withaferin a and analogs |
| WO2012106393A2 (en) * | 2011-02-01 | 2012-08-09 | University Of Kansas | Withanolide isolated from physalis longifolia and analogs and methods of use thereof |
| EP2723866B1 (en) | 2011-06-22 | 2018-03-28 | Universite Laval | Methods for the prognostic and/or diagnostic of neurodegenerative disease, methods to identify candidate compounds and compounds for treating neurodegenerative disease |
-
2014
- 2014-11-25 AU AU2014352629A patent/AU2014352629B2/en not_active Ceased
- 2014-11-25 US US15/038,927 patent/US10351590B2/en active Active
- 2014-11-25 EP EP14812105.6A patent/EP3074414B1/en active Active
- 2014-11-25 WO PCT/US2014/067436 patent/WO2015077780A1/en not_active Ceased
- 2014-11-25 ES ES14812105T patent/ES2728870T3/es active Active
- 2014-11-25 TR TR2019/05218T patent/TR201905218T4/tr unknown
- 2014-11-25 KR KR1020167015115A patent/KR20160137945A/ko not_active Ceased
- 2014-11-25 JP JP2016554830A patent/JP6517833B2/ja active Active
- 2014-11-25 CA CA2931064A patent/CA2931064C/en active Active
- 2014-11-25 PL PL14812105T patent/PL3074414T3/pl unknown
- 2014-11-25 BR BR112016012002A patent/BR112016012002A2/pt not_active IP Right Cessation
- 2014-11-25 CN CN201480064227.0A patent/CN105940010B/zh not_active Expired - Fee Related
- 2014-11-25 MX MX2016006544A patent/MX364528B/es active IP Right Grant
-
2016
- 2016-05-10 ZA ZA2016/03117A patent/ZA201603117B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2728870T3 (es) | 2019-10-29 |
| JP2016537432A (ja) | 2016-12-01 |
| BR112016012002A2 (pt) | 2017-09-19 |
| CN105940010A (zh) | 2016-09-14 |
| AU2014352629A1 (en) | 2016-05-26 |
| CA2931064A1 (en) | 2015-05-28 |
| MX364528B (es) | 2019-04-30 |
| EP3074414B1 (en) | 2019-01-09 |
| MX2016006544A (es) | 2016-12-12 |
| WO2015077780A1 (en) | 2015-05-28 |
| CN105940010B (zh) | 2018-03-30 |
| US10351590B2 (en) | 2019-07-16 |
| ZA201603117B (en) | 2020-05-27 |
| EP3074414A1 (en) | 2016-10-05 |
| PL3074414T3 (pl) | 2019-12-31 |
| AU2014352629B2 (en) | 2019-03-28 |
| JP6517833B2 (ja) | 2019-05-22 |
| US20170022247A1 (en) | 2017-01-26 |
| KR20160137945A (ko) | 2016-12-02 |
| TR201905218T4 (tr) | 2019-05-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20191121 |
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| EEER | Examination request |
Effective date: 20191121 |