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
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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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 System
- 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
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 (28)
Country | Link |
---|---|
US (3) | US8518984B2 (es) |
EP (1) | EP2499145B1 (es) |
JP (1) | JP2013510860A (es) |
KR (1) | KR20120099462A (es) |
CN (2) | CN102712650B (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) |
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) |
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PT2118123E (pt) | 2007-01-31 | 2016-02-10 | Harvard College | Péptidos de p53 estabilizados e suas utilizações |
EP2508531B1 (en) | 2007-03-28 | 2016-10-19 | President and Fellows of Harvard College | Stitched polypeptides |
UA107814C2 (uk) | 2009-11-12 | 2015-02-25 | Дзе Ріджентс Оф Дзе Юніверсіті Оф Мічіган | Спірооксіндольні антагоністи мdм2 |
US8088815B2 (en) * | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
RU2012147597A (ru) * | 2010-04-09 | 2014-05-20 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Биомаркеры для ингибиторов mdm2, использующиеся для лечения заболевания |
PT2603600T (pt) | 2010-08-13 | 2019-02-27 | Aileron Therapeutics Inc | Macrociclos peptidomiméticos |
EP2638046A4 (en) * | 2010-11-12 | 2014-06-25 | Univ Michigan | SPIRO-OXINDOLES ANTAGONISTS OF MDM2 |
JP5792279B2 (ja) | 2011-03-10 | 2015-10-07 | 第一三共株式会社 | ジスピロピロリジン誘導体 |
BR112013028983A2 (pt) | 2011-05-11 | 2017-02-07 | Sanofi Sa | antagonistas mdm2 espiro-oxindol |
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US9937178B2 (en) | 2011-12-07 | 2018-04-10 | Duke University | Methods of identifying and using MDM2 inhibitors |
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RU2017145921A (ru) | 2012-02-15 | 2019-02-21 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы |
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ES2712973T3 (es) * | 2014-04-17 | 2019-05-17 | Univ Michigan Regents | Inhibidores de MDM2 y métodos terapéuticos que usan los mismos |
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 |
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ES2959097T3 (es) * | 2014-08-18 | 2024-02-20 | Hudson Biopharma Inc | Espiropirrolidinas como inhibidores de MDM2 |
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 |
CN112972378A (zh) | 2014-09-24 | 2021-06-18 | 艾瑞朗医疗公司 | 拟肽大环化合物及其制剂 |
SG11201702223UA (en) | 2014-09-24 | 2017-04-27 | 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 |
BR112017019738A2 (pt) | 2015-03-20 | 2018-05-29 | Aileron Therapeutics Inc | macrociclos peptidomiméticos e usos dos mesmos |
WO2017044633A1 (en) | 2015-09-10 | 2017-03-16 | 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 |
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