PE20220131A1 - Protacs que degradan el receptor de estrogeno - Google Patents
Protacs que degradan el receptor de estrogenoInfo
- Publication number
- PE20220131A1 PE20220131A1 PE2021001583A PE2021001583A PE20220131A1 PE 20220131 A1 PE20220131 A1 PE 20220131A1 PE 2021001583 A PE2021001583 A PE 2021001583A PE 2021001583 A PE2021001583 A PE 2021001583A PE 20220131 A1 PE20220131 A1 PE 20220131A1
- Authority
- PE
- Peru
- Prior art keywords
- methyl
- 6alkylene
- het2
- piperidyl
- ome
- Prior art date
Links
- 102000015694 estrogen receptors Human genes 0.000 title 1
- 108010038795 estrogen receptors Proteins 0.000 title 1
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- 229910052799 carbon Inorganic materials 0.000 abstract 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- IJEJPRVUJLKGAE-PBHRBXGSSA-N FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C=1C=NC(=NC=1)N1CCC(CC1)CCN1CCN(CC1)C=1C=C2CN(C(C2=CC=1)=O)C1C(NC(CC1)=O)=O)(C)C Chemical compound FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C=1C=NC(=NC=1)N1CCC(CC1)CCN1CCN(CC1)C=1C=C2CN(C(C2=CC=1)=O)C1C(NC(CC1)=O)=O)(C)C IJEJPRVUJLKGAE-PBHRBXGSSA-N 0.000 abstract 1
- XPYPSMVKJINFTA-STDKDGGTSA-N FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C=1C=NC(=NC=1)N1CCC(CC1)CN1CCN(CC1)C=1C=C2CN(C(C2=CC=1)=O)C1C(NC(CC1)=O)=O)(C)C Chemical compound FC(CN1[C@@H](C=2NC3=CC=CC=C3C=2C[C@H]1C)C=1C=NC(=NC=1)N1CCC(CC1)CN1CCN(CC1)C=1C=C2CN(C(C2=CC=1)=O)C1C(NC(CC1)=O)=O)(C)C XPYPSMVKJINFTA-STDKDGGTSA-N 0.000 abstract 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 abstract 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 abstract 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 150000001721 carbon Chemical group 0.000 abstract 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 abstract 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 abstract 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 abstract 1
- 125000005647 linker group Chemical group 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 abstract 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 abstract 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
Classifications
-
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-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
- A61K31/495—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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D471/02—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 two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Referida a un compuesto de formula (I) o una sal farmaceuticamente aceptable del mismo, en donde: A y G son independientemente CR5 o N; D y E son independientemente CH o N; R1 es H; R2 es H; o R1 y R2 junto con el carbono al que estan unidos forman carbonilo; R3 es H o OMe; R4 es H o OMe; R5 se selecciona independientemente de H, F, Cl, CN, Me o OMe; R6 es H, Me o F; R7 es H, Me o F; o R6 y R7 tomados junto con el atomo de carbono al que estan unidos forman un anillo de ciclopropilo o un anillo de oxetanilo; R8 es H, Me, F, CH2F, CHF2, CF3, CN, CH2CN, CH2OMe, CH2OH, C(O)OH, C(O)OMe o SO2Me; el enlazador es un resto de formula -X-[W]p-Het1 -, en el que: X se selecciona del grupo que consiste en -Het2 -alquileno C1-6-, -C(O)-Het2 -alquileno C1- 6-, -Het2 -C(O)-alquileno C1-6-, -alquileno C1-6-, -O-Het2 -alquileno C1-6-, -alquileno C1-6- y -O-Cicalquileno C1-6, en el que una o dos unidades de -CH2- en la cadena de alquileno se reemplazan independientemente con -O-, -NH- o -NMe-; W se selecciona de -Het3 -alquileno C1-6-; Het1 es un grupo heterocicloalquilo monociclico o biciclico que contiene nitrogeno; Het2 es un grupo heterocicloalquilo monociclico o biciclico que contiene nitrogeno; Het3 es un grupo heterocicloalquilo monociclico o biciclico que contiene nitrogeno; Cic es cicloalquilo C3-6; p es 0 o 1; en el que el heterocicloalquilo se sustituye opcionalmente con 1 o 2 sustituyentes oxo. Son compuestos preferidos: 3-[5-[4-[[1-[5-[(1R,3R)-2-(2-Fluoro-2-metil-propil)-3-metil-1,3,4,9-tetrahidropirido[3,4- b]indol-1-il]pirimidin-2-il]-4-piperidil]metil]piperazin-1-il]-1-oxo-isoindolin-2-il]piperidin-2,6-diona; 3-[5-[4-[2-[1-[5-[(1R,3R)-2-(2-Fluoro-2-metil-propil)-3-metil-1,3,4,9-tetrahidropirido[3,4- b]indol-1-il]pirimidin-2-il]-4-piperidil]etil]piperazin-1-il]-1-oxo-isoindolin-2-il]piperidin-2,6-diona; Formiato de 2-[2,6-dioxo3-piperidil]-5-[4-[[1-[5-[(1R,3R)-2-(2-fluoro-2-metil-propil)-3- metil-1,3,4,9-tetrahidropirido[3,4-b]indol-1-il]pirimidin-2-il]-4-piperidil]metil]piperazin-1- il]isoindolin-1,3-diona; entre otros. Dichos compuestos son utiles en el tratamiento del cancer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962825924P | 2019-03-29 | 2019-03-29 | |
| PCT/EP2020/058702 WO2020201080A1 (en) | 2019-03-29 | 2020-03-27 | Estrogen receptor degrading protacs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20220131A1 true PE20220131A1 (es) | 2022-01-27 |
Family
ID=70050126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2021001583A PE20220131A1 (es) | 2019-03-29 | 2020-03-27 | Protacs que degradan el receptor de estrogeno |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US20220169643A1 (es) |
| EP (1) | EP3947376A1 (es) |
| JP (1) | JP2022526370A (es) |
| KR (1) | KR20210146984A (es) |
| CN (1) | CN113646306A (es) |
| AR (1) | AR118515A1 (es) |
| AU (1) | AU2020252116B2 (es) |
| BR (1) | BR112021019007A2 (es) |
| CA (1) | CA3133763A1 (es) |
| CL (1) | CL2021002489A1 (es) |
| CO (1) | CO2021013927A2 (es) |
| CR (1) | CR20210532A (es) |
| DO (1) | DOP2021000198A (es) |
| EA (1) | EA202192553A1 (es) |
| EC (1) | ECSP21077887A (es) |
| IL (1) | IL286461A (es) |
| JO (1) | JOP20210259A1 (es) |
| MA (1) | MA55495A (es) |
| MX (1) | MX2021011811A (es) |
| PE (1) | PE20220131A1 (es) |
| PH (1) | PH12021552362A1 (es) |
| SG (1) | SG11202110527RA (es) |
| TW (1) | TW202102497A (es) |
| UY (1) | UY38625A (es) |
| WO (1) | WO2020201080A1 (es) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20220348595A1 (en) * | 2021-04-09 | 2022-11-03 | Endotarget Inc. | Compounds and methods for the targeted degradation of estrogen receptors |
| WO2023016518A1 (zh) | 2021-08-11 | 2023-02-16 | 四川海思科制药有限公司 | 一种杂环衍生物及其组合物和药学上的应用 |
| EP4455133A4 (en) * | 2021-12-24 | 2026-04-15 | Suzhou Kintor Pharmaceuticals Inc | MULTI-PROTEIN DEGRADING AGENT WITH AN IMIDE SKELETON |
| CA3240051A1 (en) | 2021-12-30 | 2023-07-06 | Beigene Switzerland Gmbh | Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use |
| WO2023212599A2 (en) * | 2022-04-26 | 2023-11-02 | Endotarget Inc. | Compounds and methods for targeted degradation of estrogen receptors |
| CN114853751B (zh) * | 2022-05-13 | 2024-01-16 | 郑州大学第一附属医院 | 一组吩噻嗪类衍生物及其应用 |
| KR20250020448A (ko) | 2022-06-02 | 2025-02-11 | 시젱 하이스코 파마수티칼 씨오., 엘티디. | Bcl6을 억제하거나 분해하는 화합물 및 의약학에서의 응용 |
| WO2024015406A1 (en) * | 2022-07-12 | 2024-01-18 | Regents Of The University Of Michigan | Indole derivatives as estrogen receptor degraders |
| WO2024141052A1 (zh) * | 2022-12-30 | 2024-07-04 | 江苏威凯尔医药科技有限公司 | 雌激素受体调节剂及其用途 |
| WO2025090847A1 (en) | 2023-10-25 | 2025-05-01 | Bpgbio, Inc. | Estrogen receptor degraders and their use in the treatment of cancer |
| WO2025117682A1 (en) | 2023-12-01 | 2025-06-05 | Blueprint Medicines Corporation | Cyclin-dependent kinase 2 degraders |
| WO2025114875A1 (en) | 2023-12-01 | 2025-06-05 | Astrazeneca Ab | Er degraders and uses thereof |
| CN118027003B (zh) * | 2024-02-03 | 2024-10-29 | 山东大学 | 一种protac化合物及其制备方法和作为雌激素受体降解剂的用途 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008152394A1 (en) * | 2007-06-12 | 2008-12-18 | F.Hoffmann-La Roche Ag | Pharmaceutical compounds |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| NO2714752T3 (es) * | 2014-05-08 | 2018-04-21 | ||
| US10149839B2 (en) * | 2016-07-25 | 2018-12-11 | Astrazeneca Ab | Chemical compounds |
| SI3526202T1 (sl) | 2016-10-11 | 2025-04-30 | Arvinas Operations, Inc. | Spojine in postopki za ciljno razgradnjo androgenskih receptorjev |
| IL266842B (en) | 2016-12-01 | 2022-09-01 | Arvinas Operations Inc | History of tetrahydronaphthalene and tetrahydroisoquinoline as estrogen receptor antagonists |
| IL300417A (en) | 2017-01-26 | 2023-04-01 | Arvinas Operations Inc | Bifunctional benzothiophene compounds, preparations containing them and their use in therapy |
-
2020
- 2020-03-18 TW TW109109065A patent/TW202102497A/zh unknown
- 2020-03-27 EA EA202192553A patent/EA202192553A1/ru unknown
- 2020-03-27 CN CN202080026741.0A patent/CN113646306A/zh active Pending
- 2020-03-27 BR BR112021019007A patent/BR112021019007A2/pt not_active Application Discontinuation
- 2020-03-27 EP EP20715055.8A patent/EP3947376A1/en active Pending
- 2020-03-27 CR CR20210532A patent/CR20210532A/es unknown
- 2020-03-27 JP JP2021557786A patent/JP2022526370A/ja active Pending
- 2020-03-27 PE PE2021001583A patent/PE20220131A1/es unknown
- 2020-03-27 AU AU2020252116A patent/AU2020252116B2/en active Active
- 2020-03-27 KR KR1020217035041A patent/KR20210146984A/ko not_active Ceased
- 2020-03-27 AR ARP200100864A patent/AR118515A1/es not_active Application Discontinuation
- 2020-03-27 SG SG11202110527RA patent/SG11202110527RA/en unknown
- 2020-03-27 US US17/442,329 patent/US20220169643A1/en not_active Abandoned
- 2020-03-27 MX MX2021011811A patent/MX2021011811A/es unknown
- 2020-03-27 WO PCT/EP2020/058702 patent/WO2020201080A1/en not_active Ceased
- 2020-03-27 UY UY0001038625A patent/UY38625A/es not_active Application Discontinuation
- 2020-03-27 MA MA055495A patent/MA55495A/fr unknown
- 2020-03-27 PH PH1/2021/552362A patent/PH12021552362A1/en unknown
- 2020-03-27 CA CA3133763A patent/CA3133763A1/en active Pending
-
2021
- 2021-09-19 IL IL286461A patent/IL286461A/en unknown
- 2021-09-23 JO JOP/2021/0259A patent/JOP20210259A1/ar unknown
- 2021-09-23 DO DO2021000198A patent/DOP2021000198A/es unknown
- 2021-09-24 CL CL2021002489A patent/CL2021002489A1/es unknown
- 2021-10-15 CO CONC2021/0013927A patent/CO2021013927A2/es unknown
- 2021-10-21 EC ECSENADI202177887A patent/ECSP21077887A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW202102497A (zh) | 2021-01-16 |
| CA3133763A1 (en) | 2020-10-08 |
| AU2020252116A1 (en) | 2021-11-11 |
| BR112021019007A2 (pt) | 2021-11-30 |
| ECSP21077887A (es) | 2021-11-30 |
| MA55495A (fr) | 2022-02-09 |
| EA202192553A1 (ru) | 2022-02-21 |
| SG11202110527RA (en) | 2021-10-28 |
| IL286461A (en) | 2021-10-31 |
| AU2020252116B2 (en) | 2023-04-27 |
| WO2020201080A1 (en) | 2020-10-08 |
| CL2021002489A1 (es) | 2022-06-03 |
| MX2021011811A (es) | 2021-10-22 |
| DOP2021000198A (es) | 2021-10-31 |
| UY38625A (es) | 2020-10-30 |
| JP2022526370A (ja) | 2022-05-24 |
| US20220169643A1 (en) | 2022-06-02 |
| CO2021013927A2 (es) | 2021-10-29 |
| EP3947376A1 (en) | 2022-02-09 |
| AR118515A1 (es) | 2021-10-20 |
| CN113646306A (zh) | 2021-11-12 |
| CR20210532A (es) | 2022-02-10 |
| JOP20210259A1 (ar) | 2023-01-30 |
| PH12021552362A1 (en) | 2022-09-05 |
| KR20210146984A (ko) | 2021-12-06 |
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