PE20181205A1 - Nuevos compuestos de espiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53 - Google Patents
Nuevos compuestos de espiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53Info
- Publication number
- PE20181205A1 PE20181205A1 PE2018000507A PE2018000507A PE20181205A1 PE 20181205 A1 PE20181205 A1 PE 20181205A1 PE 2018000507 A PE2018000507 A PE 2018000507A PE 2018000507 A PE2018000507 A PE 2018000507A PE 20181205 A1 PE20181205 A1 PE 20181205A1
- Authority
- PE
- Peru
- Prior art keywords
- mdm2
- inhibitors
- indol
- pyrrolidin
- derivatives
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 150000003413 spiro compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 2
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 abstract 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000003993 interaction Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 230000000771 oncological effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002265 prevention 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
- C07D487/22—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 four or more hetero rings
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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
- A61K31/41—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
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- 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
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- 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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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
-
- 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
- C07D471/22—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 systems contains four or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Oncology (AREA)
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- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
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- Tropical Medicine & Parasitology (AREA)
- Hematology (AREA)
- Toxicology (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
La presente invencion abarca los compuestos de la Formula (I) en donde los grupos R1 a R4, R7, A, D, E, F, V, W, X, Y, n, r y q se definen en la reivindicacion 1, su uso como inhibidores de la interaccion entre MDM2 y p53, composiciones farmaceuticas que contienen compuestos de este tipo, su uso como medicamentos, especialmente, como agentes para el tratamiento y/o la prevencion de enfermedades oncologicas e intermediarios sinteticos.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15189210 | 2015-10-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20181205A1 true PE20181205A1 (es) | 2018-07-23 |
Family
ID=54292702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2018000507A PE20181205A1 (es) | 2015-10-09 | 2016-10-07 | Nuevos compuestos de espiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53 |
Country Status (32)
| Country | Link |
|---|---|
| US (4) | US10144739B2 (es) |
| EP (1) | EP3359542B1 (es) |
| JP (1) | JP6602470B2 (es) |
| KR (2) | KR102722493B1 (es) |
| CN (5) | CN119569739A (es) |
| AR (1) | AR106314A1 (es) |
| AU (1) | AU2016333721B2 (es) |
| BR (1) | BR112018007155B1 (es) |
| CA (1) | CA3000063A1 (es) |
| CL (1) | CL2018000666A1 (es) |
| CO (1) | CO2018003565A2 (es) |
| CY (1) | CY1124284T1 (es) |
| DK (1) | DK3359542T3 (es) |
| EA (1) | EA036013B1 (es) |
| ES (1) | ES2873895T3 (es) |
| HR (1) | HRP20210960T1 (es) |
| HU (1) | HUE054985T2 (es) |
| IL (1) | IL258073B (es) |
| LT (1) | LT3359542T (es) |
| MA (1) | MA50065B1 (es) |
| MX (1) | MX377009B (es) |
| MY (1) | MY199688A (es) |
| PE (1) | PE20181205A1 (es) |
| PH (1) | PH12018500763A1 (es) |
| PL (1) | PL3359542T3 (es) |
| PT (1) | PT3359542T (es) |
| RS (1) | RS61936B1 (es) |
| SA (1) | SA518391307B1 (es) |
| SI (1) | SI3359542T1 (es) |
| TW (1) | TWI737635B (es) |
| UA (1) | UA123905C2 (es) |
| WO (1) | WO2017060431A1 (es) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3129380B1 (en) | 2014-04-11 | 2018-11-28 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors |
| EP3164401B1 (en) | 2014-07-03 | 2018-12-26 | Boehringer Ingelheim International GmbH | New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| DK3183254T3 (da) | 2014-08-21 | 2019-08-19 | Boehringer Ingelheim Int | Nye spiro[3h-indol-3,2 ?-pyrrolidin]-2(1h)-one forbindelser og derivater som mdm2-p53 inhibitorer |
| WO2017060431A1 (en) | 2015-10-09 | 2017-04-13 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
| TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
| CN110505884B (zh) | 2017-04-05 | 2022-08-12 | 勃林格殷格翰国际有限公司 | 抗癌组合疗法 |
| CN112041320B (zh) * | 2017-12-29 | 2023-05-23 | 甘李药业股份有限公司 | 一种可用作肿瘤抑制剂的化合物及其制备方法与应用 |
| EP3511334A1 (en) * | 2018-01-16 | 2019-07-17 | Adamed sp. z o.o. | 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53 |
| WO2020018611A1 (en) * | 2018-07-18 | 2020-01-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of ewing sarcoma using tp53 dependency biomarkers and modulators |
| US10590147B1 (en) | 2019-09-10 | 2020-03-17 | King Saud University | Spirooxindole-pyrrolothiazole heterocyclic hybrids |
| US11285159B2 (en) * | 2019-11-05 | 2022-03-29 | Abbvie Inc. | Dosing regimens for use in treating myelofibrosis and MPN-related disorders with navitoclax |
| PE20240493A1 (es) | 2020-06-02 | 2024-03-15 | Boehringer Ingelheim Int | 2-amino-3-cianotiofenos anulados y derivados para el tratamiento del cancer |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
| CN112047951A (zh) * | 2020-10-16 | 2020-12-08 | 吉林大学 | 手性螺[吡咯-2，2’-呋喃]化合物及其制备方法 |
| TW202309022A (zh) | 2021-04-13 | 2023-03-01 | 美商努法倫特公司 | 用於治療具egfr突變之癌症之胺基取代雜環 |
| MX2024001832A (es) | 2021-08-09 | 2024-02-28 | Boehringer Ingelheim Int | Nueva composicion farmaceutica oral para terapias contra el cancer. |
| US20250313553A1 (en) | 2021-12-01 | 2025-10-09 | Boehringer Ingelheim Int'l GmbH Corp. | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| TW202340208A (zh) | 2021-12-01 | 2023-10-16 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物 |
| WO2023099624A1 (en) | 2021-12-01 | 2023-06-08 | Boehringer Ingelheim International Gmbh | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| WO2023099620A1 (en) | 2021-12-01 | 2023-06-08 | Boehringer Ingelheim International Gmbh | Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes |
| US20250129095A1 (en) | 2021-12-01 | 2025-04-24 | Boehringer Ingelheim Int'l GmbH Corp. | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| TW202440585A (zh) | 2022-12-22 | 2024-10-16 | 德商百靈佳殷格翰國際股份有限公司 | MDM2-p53抑制劑之晶型及醫藥組合物 |
| EP4638416A1 (en) | 2022-12-23 | 2025-10-29 | Boehringer Ingelheim International GmbH | New process for the manufacture of mdm2-p53 antagonists |
| WO2024238404A2 (en) * | 2023-05-12 | 2024-11-21 | Pmv Pharmaceuticals, Inc. | Combination therapy for treatment of cancer |
| AR132802A1 (es) | 2023-05-30 | 2025-07-30 | Boehringer Ingelheim Int | 2-amino-3-cianotiofenos con anillos espirocíclicos y derivados para el tratamiento del cáncer |
| WO2024246114A1 (en) | 2023-05-31 | 2024-12-05 | Boehringer Ingelheim International Gmbh | Survivin as a biomarker for predicting the responsiveness of cancer treatment |
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| US3361759A (en) | 1963-10-07 | 1968-01-02 | Upjohn Co | 3-(2-pyrrolidinyl)-indoles and method of preparation |
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| MX2007010272A (es) | 2005-02-22 | 2008-03-12 | Univ Michigan | Inhibidores de moleculas pequenas de mdm2 y usos de los mismos. |
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