JP7035027B2 - Betタンパク質分解物質としての縮合1,4-ジアゼピン - Google Patents
Betタンパク質分解物質としての縮合1,4-ジアゼピン Download PDFInfo
- Publication number
- JP7035027B2 JP7035027B2 JP2019513958A JP2019513958A JP7035027B2 JP 7035027 B2 JP7035027 B2 JP 7035027B2 JP 2019513958 A JP2019513958 A JP 2019513958A JP 2019513958 A JP2019513958 A JP 2019513958A JP 7035027 B2 JP7035027 B2 JP 7035027B2
- Authority
- JP
- Japan
- Prior art keywords
- diazepine
- chlorophenyl
- ethynyl
- thieno
- triazolo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 0 *C1=**=C2*1c([n]c(C#*)c1*)c1C(c1ccccc1)=*C2 Chemical compound *C1=**=C2*1c([n]c(C#*)c1*)c1C(c1ccccc1)=*C2 0.000 description 16
- VNOIIAHVJYKWCF-UHFFFAOYSA-N C#Cc1c[n](CCCC#Cc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)nn1 Chemical compound C#Cc1c[n](CCCC#Cc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)nn1 VNOIIAHVJYKWCF-UHFFFAOYSA-N 0.000 description 2
- RXYPXQSKLGGKOL-UHFFFAOYSA-N CN1CCN(C)CC1 Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- BXMPTABHXKPFHQ-VIFPVBQESA-N C[C@@H](c1nnc(C)[n]1-c([s]1)c2c(C)c1I)N=C2c(cc1)ccc1Cl Chemical compound C[C@@H](c1nnc(C)[n]1-c([s]1)c2c(C)c1I)N=C2c(cc1)ccc1Cl BXMPTABHXKPFHQ-VIFPVBQESA-N 0.000 description 2
- PGMQRYZQVRHFSE-UHFFFAOYSA-N Cc(c(C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]1-1)c-1[s]1)c1I Chemical compound Cc(c(C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]1-1)c-1[s]1)c1I PGMQRYZQVRHFSE-UHFFFAOYSA-N 0.000 description 2
- NKCRVSLFDGZZEX-UHFFFAOYSA-N OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O Chemical compound OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O NKCRVSLFDGZZEX-UHFFFAOYSA-N 0.000 description 2
- BJXDBXQZKWQSBV-UHFFFAOYSA-N C#Cc1c[nH]cn1 Chemical compound C#Cc1c[nH]cn1 BJXDBXQZKWQSBV-UHFFFAOYSA-N 0.000 description 1
- ZBQYZDNVOUABIJ-UHFFFAOYSA-N C#Cc1ncc(CCCCNc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 Chemical compound C#Cc1ncc(CCCCNc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 ZBQYZDNVOUABIJ-UHFFFAOYSA-N 0.000 description 1
- RFMGNXYYTBOQAV-UHFFFAOYSA-N C#Cc1ncc(COCCCCc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 Chemical compound C#Cc1ncc(COCCCCc2cccc3c2CN(C(CCC(N2)=O)C2=O)C3=O)cc1 RFMGNXYYTBOQAV-UHFFFAOYSA-N 0.000 description 1
- QPRHXGPAGFNADJ-KRXBUXKQSA-N C/C=C(\C#Cc1c[nH]cn1)/S Chemical compound C/C=C(\C#Cc1c[nH]cn1)/S QPRHXGPAGFNADJ-KRXBUXKQSA-N 0.000 description 1
- ONPIRZWOLVCPGQ-UHFFFAOYSA-N CC(C(C=C1)C2=NCc3nnc(C)[n]3-c3c2c(C)c(C#Cc2c[n](CCCC#Cc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cn2)[s]3)C=C1Cl Chemical compound CC(C(C=C1)C2=NCc3nnc(C)[n]3-c3c2c(C)c(C#Cc2c[n](CCCC#Cc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cn2)[s]3)C=C1Cl ONPIRZWOLVCPGQ-UHFFFAOYSA-N 0.000 description 1
- IAJMOILSUIJSMI-UHFFFAOYSA-N CS(OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O)(=O)=O Chemical compound CS(OCCCC#Cc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O)(=O)=O IAJMOILSUIJSMI-UHFFFAOYSA-N 0.000 description 1
- ZAHJDBKKACFOQC-UHFFFAOYSA-N CS(OCCCCCc1c(CN(C(CCC(N2)=O)C2=O)C2=O)c2ccc1)(=O)=O Chemical compound CS(OCCCCCc1c(CN(C(CCC(N2)=O)C2=O)C2=O)c2ccc1)(=O)=O ZAHJDBKKACFOQC-UHFFFAOYSA-N 0.000 description 1
- YWNIISHGJPELBA-RUBXLXHKSA-N C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3c[n](CCCCCc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)nc3)[s]1)N=C2c(cc1)ccc1Cl Chemical compound C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3c[n](CCCCCc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)nc3)[s]1)N=C2c(cc1)ccc1Cl YWNIISHGJPELBA-RUBXLXHKSA-N 0.000 description 1
- MZJOVBREDPNNKF-PPVAYSNCSA-N C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3cnc(CCCCNc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cc3)[s]1)N=C2c(cc1)ccc1Cl Chemical compound C[C@@H](c1nnc(C)[n]1-c1c2c(C)c(C#Cc3cnc(CCCCNc4cccc5c4CN(C(CCC(N4)=O)C4=O)C5=O)cc3)[s]1)N=C2c(cc1)ccc1Cl MZJOVBREDPNNKF-PPVAYSNCSA-N 0.000 description 1
- FCOCTISPZQFCLQ-GWJDSUCGSA-N C[C@@H](c1nnc(C)[n]11)N=C(c(cc2)ccc2Cl)C(/C(/C)=C(\C)/C#Cc2c[n](CCCC#Cc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)=C1S Chemical compound C[C@@H](c1nnc(C)[n]11)N=C(c(cc2)ccc2Cl)C(/C(/C)=C(\C)/C#Cc2c[n](CCCC#Cc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)=C1S FCOCTISPZQFCLQ-GWJDSUCGSA-N 0.000 description 1
- PGYUBRMQDYIZFD-UHFFFAOYSA-N Cc1c(C#Cc2c[n](CCCC#C)cn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 Chemical compound Cc1c(C#Cc2c[n](CCCC#C)cn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 PGYUBRMQDYIZFD-UHFFFAOYSA-N 0.000 description 1
- FTOKUERYAJMQJF-UHFFFAOYSA-N Cc1c(C#Cc2c[n](CCCCCc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 Chemical compound Cc1c(C#Cc2c[n](CCCCCc3cccc4c3CN(C(CCC(N3)=O)C3=O)C4=O)nn2)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 FTOKUERYAJMQJF-UHFFFAOYSA-N 0.000 description 1
- GFUYCZDCAQCDGA-UHFFFAOYSA-N Cc1c(C#Cc2cnc[n]2CCCC#C)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 Chemical compound Cc1c(C#Cc2cnc[n]2CCCC#C)[s]c-2c1C(c(cc1)ccc1Cl)=NCc1nnc(C)[n]-21 GFUYCZDCAQCDGA-UHFFFAOYSA-N 0.000 description 1
- PAZUSKGTBLWJAI-UHFFFAOYSA-N Cc1c[n](CCCCN)[n]c1 Chemical compound Cc1c[n](CCCCN)[n]c1 PAZUSKGTBLWJAI-UHFFFAOYSA-N 0.000 description 1
- MYGYXFCDNNRSJM-UHFFFAOYSA-N Cc1c[s]c(N)c1C(c1ccc(C)cc1)=O Chemical compound Cc1c[s]c(N)c1C(c1ccc(C)cc1)=O MYGYXFCDNNRSJM-UHFFFAOYSA-N 0.000 description 1
- URLKBWYHVLBVBO-UHFFFAOYSA-N Cc1ccc(C)cc1 Chemical compound Cc1ccc(C)cc1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 1
- RHOOLJLEYYXKTK-UHFFFAOYSA-N Cc1cnc(C)nc1 Chemical compound Cc1cnc(C)nc1 RHOOLJLEYYXKTK-UHFFFAOYSA-N 0.000 description 1
- LHMZYMGVGMFPFJ-UHFFFAOYSA-N Cc1nnc(CNC)[nH]1 Chemical compound Cc1nnc(CNC)[nH]1 LHMZYMGVGMFPFJ-UHFFFAOYSA-N 0.000 description 1
- UNJJNIWGIYMKDN-UHFFFAOYSA-N NC(C=CC1)=C(CN2C(CCC(N3)=O)C3=O)C1C2=O Chemical compound NC(C=CC1)=C(CN2C(CCC(N3)=O)C3=O)C1C2=O UNJJNIWGIYMKDN-UHFFFAOYSA-N 0.000 description 1
- SCZFMUWTABGOGF-UHFFFAOYSA-N O=C(c1c(C2)c(Br)ccc1)N2C(CCC(N1)=O)C1=O Chemical compound O=C(c1c(C2)c(Br)ccc1)N2C(CCC(N1)=O)C1=O SCZFMUWTABGOGF-UHFFFAOYSA-N 0.000 description 1
- VROGWIJGMISOHP-UHFFFAOYSA-N OCCCCCc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O Chemical compound OCCCCCc1cccc2c1CN(C(CCC(N1)=O)C1=O)C2=O VROGWIJGMISOHP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D495/12—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 three hetero rings
- C07D495/14—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662393923P | 2016-09-13 | 2016-09-13 | |
| US62/393,923 | 2016-09-13 | ||
| PCT/US2017/051286 WO2018052949A1 (en) | 2016-09-13 | 2017-09-13 | Fused 1,4-diazepines as bet protein degraders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019526616A JP2019526616A (ja) | 2019-09-19 |
| JP2019526616A5 JP2019526616A5 (enExample) | 2020-10-22 |
| JP7035027B2 true JP7035027B2 (ja) | 2022-03-14 |
Family
ID=60002003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019513958A Expired - Fee Related JP7035027B2 (ja) | 2016-09-13 | 2017-09-13 | Betタンパク質分解物質としての縮合1,4-ジアゼピン |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US10975093B2 (enExample) |
| EP (2) | EP3512853B1 (enExample) |
| JP (1) | JP7035027B2 (enExample) |
| CN (1) | CN110072866A (enExample) |
| AU (1) | AU2017326175B2 (enExample) |
| CA (1) | CA3036841A1 (enExample) |
| ES (1) | ES2857743T3 (enExample) |
| WO (1) | WO2018052949A1 (enExample) |
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|---|---|---|---|---|
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| CN109562107A (zh) | 2016-05-10 | 2019-04-02 | C4医药公司 | 用于靶蛋白降解的杂环降解决定子体 |
| CN109562113A (zh) | 2016-05-10 | 2019-04-02 | C4医药公司 | 用于靶蛋白降解的螺环降解决定子体 |
| CN121974842A (zh) | 2016-05-10 | 2026-05-05 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| WO2017197046A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| EP3577120A1 (en) * | 2017-02-03 | 2019-12-11 | The Regents of The University of Michigan | Fused 1,4-diazepines as bet bromodomain inhibitors |
| EP4717317A3 (en) | 2017-06-20 | 2026-06-03 | C4 Therapeutics, Inc. | N/o-linked degrons and degronimers for protein degradation |
| WO2019043208A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROQUINOLINONES |
| CN118108706A (zh) | 2017-09-04 | 2024-05-31 | C4医药公司 | 戊二酰亚胺 |
| WO2019043217A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROBENZIMIDAZOLONES |
| EP3710002A4 (en) | 2017-11-16 | 2021-07-07 | C4 Therapeutics, Inc. | DEGRADER AND DEGRONE FOR TARGETED PROTEIN DEGRADATION |
| CN111902141A (zh) | 2018-03-26 | 2020-11-06 | C4医药公司 | 用于ikaros降解的羟脑苷脂结合剂 |
| US12539292B2 (en) | 2018-04-01 | 2026-02-03 | Arvinas Operations, Inc. | BRM targeting compounds and associated methods of use |
| EP3778590A4 (en) | 2018-04-09 | 2021-12-22 | ShanghaiTech University | ANTI PROTEIN DEGRADATION COMPOUND, ANTITUMOR APPLICATION, INTERMEDIATE THEREOF, AND INTERMEDIATE USE |
| CA3095912A1 (en) * | 2018-04-13 | 2019-10-17 | Arvinas Operations, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| WO2019204354A1 (en) | 2018-04-16 | 2019-10-24 | C4 Therapeutics, Inc. | Spirocyclic compounds |
| WO2019213005A1 (en) * | 2018-04-30 | 2019-11-07 | Dana-Farber Cancer Institute, Inc. | Small molecule degraders of polybromo-1 (pbrm1) |
| EP3578561A1 (en) | 2018-06-04 | 2019-12-11 | F. Hoffmann-La Roche AG | Spiro compounds |
| US11542273B2 (en) | 2018-07-04 | 2023-01-03 | Mitsubishi Tanabe Pharma Corporation | Amide compound having bet proteolysis-inducing action and medicinal application thereof |
| CN110407854B (zh) * | 2018-08-17 | 2020-09-15 | 北京加科思新药研发有限公司 | 新的四环化合物 |
| US11707452B2 (en) | 2018-08-20 | 2023-07-25 | Arvinas Operations, Inc. | Modulators of alpha-synuclein proteolysis and associated methods of use |
| MX2021001957A (es) | 2018-08-22 | 2021-07-15 | Cullgen Shanghai Inc | Compuestos de degradacion y metodos de uso del receptor de tropomiosina quinasa (trk). |
| US11969472B2 (en) | 2018-08-22 | 2024-04-30 | Cullgen (Shanghai), Inc. | Tropomyosin receptor kinase (TRK) degradation compounds and methods of use |
| JP2022507267A (ja) * | 2018-11-13 | 2022-01-18 | バイオセリックス, インコーポレイテッド | 置換イソインドリノン |
| EP3897631A4 (en) | 2018-12-20 | 2022-11-23 | C4 Therapeutics, Inc. | TARGETED PROTEIN BREAKDOWN |
| EP3932922A4 (en) | 2019-02-25 | 2022-05-11 | ShanghaiTech University | SULPHUR-CONTAINING COMPOUND BASED ON A GLUTARIMIDE FRAMEWORK AND ITS USE |
| ES2995214T3 (en) | 2019-03-06 | 2025-02-07 | C4 Therapeutics Inc | Heterocyclic compounds for medical treatment |
| EP3999182A1 (en) | 2019-07-17 | 2022-05-25 | Arvinas Operations, Inc. | Tau-protein targeting compounds and associated methods of use |
| WO2021023233A1 (zh) | 2019-08-05 | 2021-02-11 | 上海科技大学 | Egfr蛋白降解剂及其抗肿瘤应用 |
| MX2022004526A (es) | 2019-10-17 | 2022-07-21 | Arvinas Operations Inc | Moléculas bifuncionales que contienen una porción de unión a la ligasa de ubiquitina e3 unida a una porción de direccionamiento a bcl6. |
| US20230099031A1 (en) * | 2019-12-17 | 2023-03-30 | Orionis Biosciences, Inc. | Bifunctional agents for protein recruitment and/or degradation |
| BR112022016901A2 (pt) | 2020-02-26 | 2022-12-06 | Cullgen Shanghai Inc | Compostos de degradação do receptor de tropomiosina quinase (trk) e métodos de uso |
| CN119823124A (zh) | 2020-03-05 | 2025-04-15 | C4医药公司 | 用于brd9的靶向降解的化合物 |
| WO2022047145A1 (en) | 2020-08-28 | 2022-03-03 | Arvinas Operations, Inc. | Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use |
| CN117242060B (zh) | 2021-01-13 | 2026-07-17 | 蒙特罗莎治疗股份有限公司 | 异吲哚啉酮化合物 |
| CN116802180B (zh) * | 2021-01-22 | 2024-05-28 | 泰比棣医药科技(石家庄)有限公司 | 一种降解脱氧核糖核酸(dna)聚合酶的化合物及其用途 |
| CN118388454A (zh) | 2021-04-16 | 2024-07-26 | 阿尔维纳斯运营股份有限公司 | Bcl6蛋白水解的调节剂和其相关使用方法 |
| TW202317546A (zh) | 2021-07-09 | 2023-05-01 | 美商普萊克斯姆公司 | 調節ikzf2之芳基化合物及醫藥組合物 |
| CN115611881B (zh) * | 2021-07-13 | 2024-09-20 | 复旦大学 | 一种合成新型vhl配体4-f-vh032的方法 |
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| CN116585322B (zh) * | 2023-01-16 | 2023-10-13 | 中山大学中山眼科中心 | Bet蛋白降解剂在预防和治疗视网膜退行性改变相关疾病中的应用 |
| WO2024243441A1 (en) | 2023-05-24 | 2024-11-28 | Kumquat Biosciences Inc. | Heterocyclic compounds and uses thereof |
| EP4735451A1 (en) | 2023-06-30 | 2026-05-06 | Kumquat Biosciences Inc. | Substituted condensed tricyclic amine compounds and uses thereof as ras inhibitors |
| WO2025011624A1 (en) * | 2023-07-11 | 2025-01-16 | Etern Biopharma (Shanghai) Co., Ltd. | Bifunctional compounds for androgen receptor degradation and methods of use |
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- 2017-09-13 JP JP2019513958A patent/JP7035027B2/ja not_active Expired - Fee Related
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| US10975093B2 (en) | 2021-04-13 |
| JP2019526616A (ja) | 2019-09-19 |
| ES2857743T3 (es) | 2021-09-29 |
| AU2017326175B2 (en) | 2022-01-27 |
| US20190263827A1 (en) | 2019-08-29 |
| EP3858837A1 (en) | 2021-08-04 |
| US20220356192A1 (en) | 2022-11-10 |
| WO2018052949A1 (en) | 2018-03-22 |
| CA3036841A1 (en) | 2018-03-22 |
| EP3512853A1 (en) | 2019-07-24 |
| CN110072866A (zh) | 2019-07-30 |
| EP3512853B1 (en) | 2020-12-23 |
| AU2017326175A1 (en) | 2019-04-04 |
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