PE20230847A1 - Analogos de n-(2-(2,6-dioxopiperidin-3-il)-1,3-dioxoisoindolin-5-il)arilsufonamida sustituidos como modulares de la proteina cereblon - Google Patents
Analogos de n-(2-(2,6-dioxopiperidin-3-il)-1,3-dioxoisoindolin-5-il)arilsufonamida sustituidos como modulares de la proteina cereblonInfo
- Publication number
- PE20230847A1 PE20230847A1 PE2023001201A PE2023001201A PE20230847A1 PE 20230847 A1 PE20230847 A1 PE 20230847A1 PE 2023001201 A PE2023001201 A PE 2023001201A PE 2023001201 A PE2023001201 A PE 2023001201A PE 20230847 A1 PE20230847 A1 PE 20230847A1
- Authority
- PE
- Peru
- Prior art keywords
- compounds
- gspt1
- substituted
- dioxoisoindolin
- analogues
- Prior art date
Links
- 101000941994 Homo sapiens Protein cereblon Proteins 0.000 title abstract 2
- 102100032783 Protein cereblon Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 5
- 102100036816 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A Human genes 0.000 abstract 4
- 101000851788 Homo sapiens Eukaryotic peptide chain release factor GTP-binding subunit ERF3A Proteins 0.000 abstract 4
- 230000015556 catabolic process Effects 0.000 abstract 2
- 238000006731 degradation reaction Methods 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 230000004064 dysfunction Effects 0.000 abstract 2
- 102000015367 CRBN Human genes 0.000 abstract 1
- 102100037799 DNA-binding protein Ikaros Human genes 0.000 abstract 1
- 101000599038 Homo sapiens DNA-binding protein Ikaros Proteins 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000004421 aryl sulphonamide group Chemical group 0.000 abstract 1
- 230000007177 brain activity Effects 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 230000004663 cell proliferation Effects 0.000 abstract 1
- 230000002490 cerebral effect Effects 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 239000001064 degrader Substances 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 230000017854 proteolysis Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
-
- 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
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Steroid Compounds (AREA)
- Pyridine Compounds (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Esta referido a compuestos de la formula general descrita a continuacion, en donde: A1 y A2 son -(C=O)- o -CH2; R1 es un arilo o heteroarilo de 5 a 10 miembros, o un cicloalquilo de 5 a 10 miembros, cualquiera de ellos opcionalmente sustituido; y, n es 0, 1, 2. Estos compuestos son analogos de N-(2-(2,6-dioxopiperidinil-3-il)- 1,3-dioxoisoindolin-5-il)arilsulfonamida sustituidos que son utiles como moduladores de la actividad de cereblon (CRBN), y se emplean para tratar diversos trastornos como por ejemplo, un trastorno de proliferacion celular descontrolada, tal como un cancer, que puede estar asociado con una disfuncion de la proteina cereblon y/o una disfuncion de GSPT1. Estos compuestos pueden modular selectivamente la degradacion de la proteina GSPT1, es decir, los compuestos divulgados pueden actuar como degradadores de GSPT1. Ademas, estos compuestos muestran selectivamente la degradacion de GSPT1 sobre la degradacion de IKZF1 en por lo menos 5 veces.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063082365P | 2020-09-23 | 2020-09-23 | |
| PCT/US2021/051648 WO2022066835A1 (en) | 2020-09-23 | 2021-09-23 | Substituted n-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide analogs as modulators of cereblon protein |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20230847A1 true PE20230847A1 (es) | 2023-05-23 |
Family
ID=80845797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2023001201A PE20230847A1 (es) | 2020-09-23 | 2021-09-23 | Analogos de n-(2-(2,6-dioxopiperidin-3-il)-1,3-dioxoisoindolin-5-il)arilsufonamida sustituidos como modulares de la proteina cereblon |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20220274948A1 (es) |
| EP (1) | EP4217352A4 (es) |
| JP (1) | JP2023542930A (es) |
| KR (1) | KR102499522B1 (es) |
| CN (1) | CN116209439A (es) |
| AU (1) | AU2021347238A1 (es) |
| BR (1) | BR112023005344A2 (es) |
| CA (1) | CA3196278A1 (es) |
| CL (1) | CL2023000394A1 (es) |
| IL (1) | IL301588A (es) |
| MX (1) | MX2023003114A (es) |
| PE (1) | PE20230847A1 (es) |
| WO (1) | WO2022066835A1 (es) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024015855A1 (en) | 2022-07-13 | 2024-01-18 | Monte Rosa Therapeutics, Inc. | COMBINATION THERAPY COMPRISING GSPT1-DIRECTED MOLECULAR GLUE DEGRADERS AND PI3K/AKT/mTOR PATHWAY INHIBITORS |
| WO2024015618A2 (en) * | 2022-07-15 | 2024-01-18 | St. Jude Children's Research Hospital, Inc. | Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione/2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione analogs as modulators of cereblon protein |
| US20240158370A1 (en) | 2022-09-09 | 2024-05-16 | Innovo Therapeutics, Inc. | CK1 alpha AND DUAL CK1 alpha / GSPT1 DEGRADING COMPOUNDS |
| WO2024073871A1 (en) * | 2022-10-04 | 2024-04-11 | Biofront Ltd | Gspt1 degraders, compositions comprising the degrader, and methods of using the same |
| WO2024109918A1 (zh) * | 2022-11-24 | 2024-05-30 | 西藏海思科制药有限公司 | 一种gspt1降解剂及其在医药上的应用 |
| KR102570883B1 (ko) * | 2023-04-13 | 2023-08-29 | (주) 사이러스테라퓨틱스 | 신규한 gspt1 분해제 및 이의 용도 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT946166E (pt) * | 1996-12-17 | 2004-06-30 | Warner Lambert Co | Utilizacao de inibidores das metaloproteinases da matriz para tratar disturbios neurologicos e promover a cicatrizacao de feridas |
| US7091353B2 (en) * | 2000-12-27 | 2006-08-15 | Celgene Corporation | Isoindole-imide compounds, compositions, and uses thereof |
| EP1474399A1 (en) * | 2002-02-13 | 2004-11-10 | Glaxo Group Limited | Benzenesulfonamide derivatives as antipsychotic agents |
| ES2426350T3 (es) * | 2006-08-30 | 2013-10-22 | Celgene Corporation | Compuestos de isoindolina sustituidos en 5 |
| WO2016191178A1 (en) * | 2015-05-22 | 2016-12-01 | Biotheryx, Inc. | Compounds targeting proteins, compositions, methods, and uses thereof |
| WO2017120446A1 (en) * | 2016-01-08 | 2017-07-13 | Celgene Corporation | Methods for treating cancer and the use of biomarkers as a predictor of clinical sensitivity to therapies |
| EP3463358A4 (en) * | 2016-06-06 | 2020-07-22 | Celgene Corporation | TREATMENT OF HEMATOLOGICAL MALIGNANT TUMOR WITH 2- (4-CHLOROPHENYL) -N - ((2- (2,6-DIOXOPIPERIDIN-3-YL) -1-OXOISOINDOLIN-5-YL) METHYL) -2,2- DIFLUOROACETAMIDE |
| WO2019078522A1 (ko) * | 2017-10-20 | 2019-04-25 | 한국화학연구원 | 세레브론 단백질의 분해 유도 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 |
| US20230045737A1 (en) * | 2018-12-05 | 2023-02-09 | Vividion Therapeutics, Inc. | Substituted isoindolinones as modulators of cereblon-mediated neo-substrate recruitment |
-
2021
- 2021-09-23 EP EP21873389.7A patent/EP4217352A4/en active Pending
- 2021-09-23 PE PE2023001201A patent/PE20230847A1/es unknown
- 2021-09-23 JP JP2023518170A patent/JP2023542930A/ja active Pending
- 2021-09-23 KR KR1020227017575A patent/KR102499522B1/ko active IP Right Grant
- 2021-09-23 BR BR112023005344A patent/BR112023005344A2/pt unknown
- 2021-09-23 WO PCT/US2021/051648 patent/WO2022066835A1/en active Application Filing
- 2021-09-23 IL IL301588A patent/IL301588A/en unknown
- 2021-09-23 AU AU2021347238A patent/AU2021347238A1/en active Pending
- 2021-09-23 MX MX2023003114A patent/MX2023003114A/es unknown
- 2021-09-23 CA CA3196278A patent/CA3196278A1/en active Pending
- 2021-09-23 CN CN202180065415.5A patent/CN116209439A/zh active Pending
-
2022
- 2022-05-09 US US17/740,148 patent/US20220274948A1/en active Pending
-
2023
- 2023-02-07 CL CL2023000394A patent/CL2023000394A1/es unknown
- 2023-09-14 US US18/368,497 patent/US20240132463A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR112023005344A2 (pt) | 2023-05-09 |
| MX2023003114A (es) | 2023-03-23 |
| CA3196278A1 (en) | 2022-03-31 |
| EP4217352A4 (en) | 2024-04-10 |
| CL2023000394A1 (es) | 2023-08-18 |
| KR20220080003A (ko) | 2022-06-14 |
| WO2022066835A1 (en) | 2022-03-31 |
| IL301588A (en) | 2023-05-01 |
| CN116209439A (zh) | 2023-06-02 |
| EP4217352A1 (en) | 2023-08-02 |
| KR102499522B1 (ko) | 2023-02-13 |
| US20240132463A1 (en) | 2024-04-25 |
| JP2023542930A (ja) | 2023-10-12 |
| AU2021347238A1 (en) | 2023-06-01 |
| US20220274948A1 (en) | 2022-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PE20230847A1 (es) | Analogos de n-(2-(2,6-dioxopiperidin-3-il)-1,3-dioxoisoindolin-5-il)arilsufonamida sustituidos como modulares de la proteina cereblon | |
| BR112021007222A8 (pt) | Moduladores de receptor de androgênio e métodos para seu uso | |
| CL2017003436A1 (es) | Compuestos de benzoxacepina oxazolidinona y métodos de uso | |
| PE20180462A1 (es) | Moduladores cot y metodos de uso de los mismos | |
| PE20161035A1 (es) | Compuestos y usos de estos para la modulacion de la hemoglobina | |
| BR112018006259A2 (pt) | "adjunto compressível com estruturas de suporte intermediárias" | |
| PE20180160A1 (es) | Sulfonilureas y compuestos relacionados y uso de estos | |
| NI201900075A (es) | Compuesto moduladores del receptor de hidrocarburos de arilo (ahr) | |
| UY37656A (es) | Compuestos que inhiben la proteína mcl-1 | |
| PE20221457A1 (es) | Degradadores de moleculas pequenas de helios y procedimientos de uso | |
| DOP2018000187A (es) | Derivados de pirazolo[1,5-a]pirazin-4-ilo | |
| CR20190124A (es) | Inhibidores de ssao de aminopirimidina | |
| CR20190392A (es) | Compuestos moduladores del receptor de hidrocarburos de arilo (ahr) | |
| GT200600253A (es) | Aminopirimidinas como moduladores de quinasas | |
| CL2019002671A1 (es) | Compuestos de pirimidinil-pyridiloxi-naftil y métodos para tratar enfermedades y trastornos relacionados con ire1. | |
| NO20081975L (no) | Diarylamin-inneholdende forbindelser og sammensetninger, og deres anvendelse som modulatorer av C-kit-reseptorer | |
| SV2007002526A (es) | Diarilsulfona sulfonamidas y el uso de las mismas ref. p1018 | |
| CY1110555T1 (el) | 4-((φαινοξυαλκυλ)θειο)-φαινοξυοξεικα οξεα και αναλογα | |
| BR112015028613A2 (pt) | análogos de uréia com ligações por pontes substituída como moduladores de sirtuína | |
| AR119010A1 (es) | Compuestos, composiciones y métodos de uso | |
| CL2021001537A1 (es) | Formas cristalinas y formas de sal de un inhibidor de cinasa | |
| ECSP077991A (es) | Aminopirimidinas como moduladores de cinasa | |
| CO2021004141A2 (es) | Moduladores de la expresión de pnpla3 | |
| RU2015141592A (ru) | АРИЛ-СУЛЬФАМИДЫ И СУЛЬФАМАТЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ RORc | |
| CL2021000196A1 (es) | Método de tratamiento de la epilepsia |