MA33815B1 - Antagonistes, de type spiro-oxindole, de l'oncoprotéine mdm2 - Google Patents
Antagonistes, de type spiro-oxindole, de l'oncoprotéine mdm2Info
- Publication number
- MA33815B1 MA33815B1 MA34958A MA34958A MA33815B1 MA 33815 B1 MA33815 B1 MA 33815B1 MA 34958 A MA34958 A MA 34958A MA 34958 A MA34958 A MA 34958A MA 33815 B1 MA33815 B1 MA 33815B1
- Authority
- MA
- Morocco
- Prior art keywords
- antagonists
- spiro
- oxindole
- type
- compounds
- Prior art date
Links
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 title abstract 2
- 239000005557 antagonist Substances 0.000 title abstract 2
- 102100032257 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 239000000203 mixture Substances 0.000 abstract 2
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000003993 interaction Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
La présente invention concerne des composés, des compositions et des procédés appartenant au domaine de la chimie médicinale. Les composés et compositions de la présente invention incluent des spiro-oxindoles qui fonctionnent comme des antagonistes de l'interaction entre la protéine p53 et l'oncoprotéine MDM2. L'invention concerne leur utilisation comme composés thérapeutiques dans le cadre du traitement du cancer et d'autres maladies.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26068509P | 2009-11-12 | 2009-11-12 | |
| US26366209P | 2009-11-23 | 2009-11-23 | |
| PCT/US2010/056197 WO2011060049A2 (fr) | 2009-11-12 | 2010-11-10 | Antagonistes, de type spiro-oxindole, de l'oncoprotéine mdm2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MA33815B1 true MA33815B1 (fr) | 2012-12-03 |
Family
ID=43974649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MA34958A MA33815B1 (fr) | 2009-11-12 | 2012-06-11 | Antagonistes, de type spiro-oxindole, de l'oncoprotéine mdm2 |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US8518984B2 (fr) |
| EP (1) | EP2499145B1 (fr) |
| JP (1) | JP2013510860A (fr) |
| KR (1) | KR20120099462A (fr) |
| CN (2) | CN104876938A (fr) |
| AR (1) | AR079026A1 (fr) |
| AU (1) | AU2010319595B2 (fr) |
| BR (1) | BR112012011317A2 (fr) |
| CA (1) | CA2780547C (fr) |
| CL (1) | CL2012001250A1 (fr) |
| CO (1) | CO6501131A2 (fr) |
| CR (1) | CR20120313A (fr) |
| DO (1) | DOP2012000131A (fr) |
| EC (1) | ECSP12011943A (fr) |
| GT (1) | GT201200147A (fr) |
| IL (1) | IL219706A (fr) |
| MA (1) | MA33815B1 (fr) |
| MX (1) | MX2012005507A (fr) |
| NI (1) | NI201200083A (fr) |
| NZ (1) | NZ600430A (fr) |
| PE (1) | PE20121282A1 (fr) |
| PH (1) | PH12012500870A1 (fr) |
| RU (1) | RU2553269C2 (fr) |
| TN (1) | TN2012000161A1 (fr) |
| TW (1) | TWI508967B (fr) |
| UA (1) | UA107814C2 (fr) |
| UY (1) | UY33029A (fr) |
| WO (1) | WO2011060049A2 (fr) |
| ZA (1) | ZA201203323B (fr) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008095063A1 (fr) | 2007-01-31 | 2008-08-07 | Dana-Farber Cancer Institute, Inc. | Peptides p53 stabilisés et utilisations de ceux-ci |
| ES2430067T3 (es) | 2007-03-28 | 2013-11-18 | President And Fellows Of Harvard College | Polipéptidos cosidos |
| AU2010319595B2 (en) | 2009-11-12 | 2015-09-17 | The Regents Of The University Of Michigan | Spiro-oxindole MDM2 antagonists |
| US8088815B2 (en) * | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
| EP2563360A4 (fr) * | 2010-04-09 | 2015-12-16 | Univ Michigan | Biomarqueurs pour inhibiteurs de mdm2 destinés à être utilisés dans le traitement de maladies |
| DK2603600T3 (da) | 2010-08-13 | 2019-03-04 | Aileron Therapeutics Inc | Peptidomimetiske makrocyklusser |
| JP2014500870A (ja) * | 2010-11-12 | 2014-01-16 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン | スピロ−オキシインドールmdm2アンタゴニスト |
| CA2829188C (fr) * | 2011-03-10 | 2016-10-18 | Daiichi Sankyo Company, Limited | Derive de dispiropyrrolidine |
| ES2624808T3 (es) * | 2011-05-11 | 2017-07-17 | The Regents Of The University Of Michigan | Antagonistas de MDM2 espirooxindólicos |
| CA2852468A1 (fr) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Macrocycles peptidomimetiques |
| US9937178B2 (en) | 2011-12-07 | 2018-04-10 | Duke University | Methods of identifying and using MDM2 inhibitors |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| SG10201606775YA (en) | 2012-02-15 | 2016-10-28 | Aileron Therapeutics Inc | Peptidomimetic macrocycles |
| TWI586668B (zh) | 2012-09-06 | 2017-06-11 | 第一三共股份有限公司 | 二螺吡咯啶衍生物之結晶 |
| CA2887285A1 (fr) | 2012-11-01 | 2014-05-08 | Aileron Therapeutics, Inc. | Acides amines disubstitues et procedes de preparation et d'utilisation de ceux-ci |
| TW201429969A (zh) | 2012-12-20 | 2014-08-01 | Merck Sharp & Dohme | 作爲hdm2抑制劑之經取代咪唑吡啶 |
| CN103739566B (zh) * | 2014-01-24 | 2016-01-20 | 中国人民解放军第三军医大学 | 含有磺酰胺的手性五元并环骨架化合物及制备方法和用途 |
| WO2015161032A1 (fr) * | 2014-04-17 | 2015-10-22 | The Regents Of The University Of Michigan | Inhibiteurs de hdac et méthodes thérapeutiques les utilisant |
| CN103992334A (zh) * | 2014-05-29 | 2014-08-20 | 中国人民解放军第二军医大学 | 吲哚酮螺四氢硫代吡喃类抗肿瘤衍生物及其制备方法 |
| JP6503386B2 (ja) | 2014-07-03 | 2019-04-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | MDM2−p53阻害剤としての新しいスピロ[3H−インドール−3,2’−ピロリジン]−2(1H)−オン化合物および誘導体 |
| CN105829318B (zh) * | 2014-08-18 | 2018-10-02 | 哈德森生物医药有限公司 | 作为mdm2抑制剂的螺吡咯烷 |
| KR20170042779A (ko) | 2014-08-21 | 2017-04-19 | 베링거 인겔하임 인터내셔날 게엠베하 | Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 |
| JP6412753B2 (ja) * | 2014-09-19 | 2018-10-24 | 日本テルペン化学株式会社 | 抗菌活性を持つ化合物、およびその製造方法 |
| JP6408318B2 (ja) * | 2014-09-19 | 2018-10-17 | 日本テルペン化学株式会社 | 抗菌活性を持つ化合物、およびその製造方法 |
| JP2017533889A (ja) | 2014-09-24 | 2017-11-16 | エルロン・セラピューティクス・インコーポレイテッドAileron Therapeutics,Inc. | ペプチド模倣大環状分子およびその使用 |
| SG10201902598VA (en) | 2014-09-24 | 2019-04-29 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and formulations thereof |
| WO2016147205A1 (fr) * | 2015-03-13 | 2016-09-22 | Council Of Scientific & Industrial Research | Nouveaux 3-spirophosphoryl pyrazole-2-oxindoles substitués en tant qu'agents anti-infectieux et procédé de synthèse correspondant |
| JP2018516844A (ja) | 2015-03-20 | 2018-06-28 | エルロン・セラピューティクス・インコーポレイテッドAileron Therapeutics,Inc. | ペプチド模倣大環状分子およびその使用 |
| EP3347372A4 (fr) | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | Macrocycles peptidomimétiques en tant que modulateurs de mcl-1 |
| US9962380B2 (en) | 2015-09-23 | 2018-05-08 | Wisconsin Alumni Research Foundation | Methods for treating cognitive deficits associated with fragile X syndrome |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| PL3359542T3 (pl) | 2015-10-09 | 2021-09-20 | Boehringer Ingelheim International Gmbh | Związki i pochodne spiro[3h-indolo-3,2’-pirolidyno]-2(1h)-onowe jako inhibitory mdm2-p53 |
| US10759808B2 (en) | 2016-04-06 | 2020-09-01 | The Regents Of The University Of Michigan | Monofunctional intermediates for ligand-dependent target protein degradation |
| CN109415336B (zh) * | 2016-04-06 | 2023-08-29 | 密执安大学评议会 | Mdm2蛋白质降解剂 |
| JP2019522633A (ja) | 2016-05-20 | 2019-08-15 | ジェネンテック, インコーポレイテッド | Protac抗体コンジュゲート及び使用方法 |
| GB201704966D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201704965D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| US9822128B1 (en) | 2017-06-01 | 2017-11-21 | King Saud University | Substituted spirooxindoles |
| CN107312115B (zh) * | 2017-06-22 | 2020-06-12 | 北京理工大学 | 一种双吲哚稀土金属催化剂、制备方法及应用 |
| CN109988070B (zh) * | 2017-12-29 | 2022-07-26 | 南京富润凯德生物医药有限公司 | 反式-1-羟基-1-(三氟甲基)-3-氨基环丁烷盐酸盐的中间体及制备方法和应用 |
| KR101857408B1 (ko) | 2018-02-28 | 2018-05-14 | 경북대학교 산학협력단 | 탈모 예방 또는 치료용 조성물 |
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