PE20121282A1 - Antagonistas de espiro-oxindol de mdm2 - Google Patents
Antagonistas de espiro-oxindol de mdm2Info
- Publication number
- PE20121282A1 PE20121282A1 PE2012000616A PE2012000616A PE20121282A1 PE 20121282 A1 PE20121282 A1 PE 20121282A1 PE 2012000616 A PE2012000616 A PE 2012000616A PE 2012000616 A PE2012000616 A PE 2012000616A PE 20121282 A1 PE20121282 A1 PE 20121282A1
- Authority
- PE
- Peru
- Prior art keywords
- alkyl
- cycloalkyl
- oxindol
- mdm2
- spiro
- Prior art date
Links
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 title abstract 2
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 title abstract 2
- 239000005557 antagonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 4
- -1 HYDROXY, AMINO Chemical class 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 230000003993 interaction Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 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)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
SE REFIERE A COMPUESTOS DERIVADOS DE ESPIRO-OXINDOL DE FORMULA (I) DONDE R1a, R1b, R1c Y R1d SON CADA UNO H, HALOGENO, HIDROXI, AMINO, NITRO, CN, ENTRE OTROS; R2 ES ARILO O HETEROARILO OPCIONALMENTE SUSTITUIDOS; R3 ES ALQULO, (CICLOALQUIL)ALQUILO, CICLOALQUILO OPCIONALMENTE SUSTITUIDOS, ENTRE OTROS; R4 ES H O ALQUILO(C1-C6) OPCIONALMENTE SUSTITUIDO; R5 ES EL COMPUESTO DE FORMULA (R5-1), ENTRE OTROS, EN DONDE R6a Y R6b SON CADA UNO H O ALQUILO(C1-C6); R7 ES H, ALQUILO(C1-C6) O CICLOALQUILO; R8a Y R8b SON CADA UNO H, ALQUILO(C1-C6), CICLOALQUILO, ENTRE OTROS; W1 ES -OR9a, ENTRE OTROS; W2 ES -OR10, ENTRE OTROS, EN DONDE R9a Y R10 SON CADA UNO H; X ES O, S O NR'; Y ES O, S O NR'', DONDE R' Y R'' SON CADA UNO H, ALQUILO, ARALQUILO O CICLOALQUILO OPCIONALMENTE SUSTITUIDOS. SON COMPUESTOS PREFERIDOS LOS DE FORMULA (i), (ii), ENTRE OTROS. TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS INHIBEN LA INTERACCION ENTRE p53 Y MDM2 SIENDO UTILES EN EL TRATAMIENTO DEL CANCER
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26068509P | 2009-11-12 | 2009-11-12 | |
| US26366209P | 2009-11-23 | 2009-11-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20121282A1 true PE20121282A1 (es) | 2012-10-12 |
Family
ID=43974649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2012000616A PE20121282A1 (es) | 2009-11-12 | 2010-11-10 | Antagonistas de espiro-oxindol de mdm2 |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US8518984B2 (es) |
| EP (1) | EP2499145B1 (es) |
| JP (1) | JP2013510860A (es) |
| KR (1) | KR20120099462A (es) |
| CN (2) | CN104876938A (es) |
| AR (1) | AR079026A1 (es) |
| AU (1) | AU2010319595B2 (es) |
| BR (1) | BR112012011317A2 (es) |
| CA (1) | CA2780547C (es) |
| CL (1) | CL2012001250A1 (es) |
| CO (1) | CO6501131A2 (es) |
| CR (1) | CR20120313A (es) |
| DO (1) | DOP2012000131A (es) |
| EC (1) | ECSP12011943A (es) |
| GT (1) | GT201200147A (es) |
| IL (1) | IL219706A (es) |
| MA (1) | MA33815B1 (es) |
| MX (1) | MX2012005507A (es) |
| NI (1) | NI201200083A (es) |
| NZ (1) | NZ600430A (es) |
| PE (1) | PE20121282A1 (es) |
| PH (1) | PH12012500870A1 (es) |
| RU (1) | RU2553269C2 (es) |
| TN (1) | TN2012000161A1 (es) |
| TW (1) | TWI508967B (es) |
| UA (1) | UA107814C2 (es) |
| UY (1) | UY33029A (es) |
| WO (1) | WO2011060049A2 (es) |
| ZA (1) | ZA201203323B (es) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2118123T3 (pl) | 2007-01-31 | 2016-06-30 | Dana Farber Cancer Inst Inc | Stabilizowane peptydy p53 i ich zastosowania |
| JP5631201B2 (ja) | 2007-03-28 | 2014-11-26 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ステッチングされたポリペプチド |
| JP2013510860A (ja) | 2009-11-12 | 2013-03-28 | 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 |
| US8088815B2 (en) * | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
| CA2800519A1 (en) * | 2010-04-09 | 2011-10-13 | The Regents Of The University Of Michigan | Biomarkers for mdm2 inhibitors for use in treating disease |
| KR102104762B1 (ko) | 2010-08-13 | 2020-04-24 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| CA2817585A1 (en) | 2010-11-12 | 2012-05-18 | The Regents Of The University Of Michigan | Spiro-oxindole mdm2 antagonists |
| DK2684880T3 (en) | 2011-03-10 | 2018-05-22 | Daiichi Sankyo Co Ltd | DISPIROPYRROLIDINE DERIVATIVES |
| ES2624808T3 (es) * | 2011-05-11 | 2017-07-17 | The Regents Of The University Of Michigan | Antagonistas de MDM2 espirooxindólicos |
| EP2768518A4 (en) | 2011-10-18 | 2015-05-27 | Aileron Therapeutics Inc | PEPTIDOMIMETIC MACROCYCLES |
| CA2858565A1 (en) | 2011-12-07 | 2013-07-04 | Duke University | Methods of identifying and using mdm2 inhibitors |
| RU2642299C2 (ru) | 2012-02-15 | 2018-01-24 | Эйлерон Терапьютикс, Инк. | P53 пептидомиметические макроциклы |
| CA2864120A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked 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 |
| BR112015009470A2 (pt) | 2012-11-01 | 2019-12-17 | Aileron Therapeutics Inc | aminoácidos dissubstituídos e seus métodos de preparação e uso |
| EP2935263B1 (en) | 2012-12-20 | 2018-12-05 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
| 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 |
| EP3131544B1 (en) * | 2014-04-17 | 2018-12-12 | The Regents of the University of Michigan | Mdm2 inhibitors and therapeutic methods using the same |
| 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 |
| ES2959097T3 (es) * | 2014-08-18 | 2024-02-20 | Hudson Biopharma Inc | Espiropirrolidinas como inhibidores de MDM2 |
| ES2739697T3 (es) | 2014-08-21 | 2020-02-03 | Boehringer Ingelheim Int | Nuevos compuestos y derivados de espiro[3H-indol-3,2-pirrolidin]-2(1H)-ona como inhibidores de MDM2-p53 |
| 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 |
| 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 |
| CN107106642B (zh) | 2014-09-24 | 2021-02-26 | 艾瑞朗医疗公司 | 拟肽大环化合物及其制剂 |
| EP3197478A4 (en) | 2014-09-24 | 2018-05-30 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2016147205A1 (en) * | 2015-03-13 | 2016-09-22 | Council Of Scientific & Industrial Research | Novel substituted 3-spirophosphoryl pyrazole-2-oxindoles as anti-infectives and process for the synthesis thereof |
| 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 (en) | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 |
| US9962380B2 (en) | 2015-09-23 | 2018-05-08 | Wisconsin Alumni Research Foundation | Methods for treating cognitive deficits associated with fragile X syndrome |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| HRP20210960T1 (hr) * | 2015-10-09 | 2021-09-03 | Boehringer Ingelheim International Gmbh | Spojevi i derivati spiro[3h-indol-3,2’-pirolidin]-2(1h)-ona kao inhibitori mdm2-p53 |
| JP7037500B2 (ja) * | 2016-04-06 | 2022-03-16 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Mdm2タンパク質分解剤 |
| AU2017246453A1 (en) | 2016-04-06 | 2018-11-08 | The Regents Of The University Of Michigan | Monofunctional intermediates for ligand-dependent target protein degradation |
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