JPWO2020160295A5 - - Google Patents
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- JPWO2020160295A5 JPWO2020160295A5 JP2021544763A JP2021544763A JPWO2020160295A5 JP WO2020160295 A5 JPWO2020160295 A5 JP WO2020160295A5 JP 2021544763 A JP2021544763 A JP 2021544763A JP 2021544763 A JP2021544763 A JP 2021544763A JP WO2020160295 A5 JPWO2020160295 A5 JP WO2020160295A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- optionally substituted
- halo
- substituted
- difluoro
- 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.)
- Granted
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- 125000000217 alkyl group Chemical group 0.000 claims description 135
- 125000005843 halogen group Chemical group 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- -1 NR L3 Inorganic materials 0.000 claims description 6
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 claims description 6
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000005647 linker group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- PQQRHWFRZHFGFM-UHFFFAOYSA-N 1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC=N1 PQQRHWFRZHFGFM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001334 alicyclic compounds Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 125000004001 thioalkyl group Chemical group 0.000 claims description 4
- FAFSBLFSHCGHSG-IADFLZFBSA-N (2S,4R)-1-[(2S)-2-[8-[2,3-difluoro-6-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]octanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide Chemical compound FC1=C(OCCCCCCCC(=O)N[C@H](C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N[C@@H](C)C2=CC=C(C=C2)C2=C(N=CS2)C)C(C)(C)C)C(=CC=C1F)C=1N=C(SC=1)N1CCOCC1 FAFSBLFSHCGHSG-IADFLZFBSA-N 0.000 claims description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- JQJMKXVVRNUAOH-UHFFFAOYSA-N 2-[2,3-difluoro-6-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]-N-[10-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]decyl]acetamide Chemical compound FC1=C(OCC(=O)NCCCCCCCCCCNC2=C3C(N(C(C3=CC=C2)=O)C2C(NC(CC2)=O)=O)=O)C(=CC=C1F)C=1N=C(SC=1)N1CCOCC1 JQJMKXVVRNUAOH-UHFFFAOYSA-N 0.000 claims description 2
- IJKSBYRAJCSENF-UHFFFAOYSA-N 2-[2,3-difluoro-6-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]-N-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexyl]acetamide Chemical compound FC1=C(OCC(=O)NCCCCCCNC2=C3C(N(C(C3=CC=C2)=O)C2C(NC(CC2)=O)=O)=O)C(=CC=C1F)C=1N=C(SC=1)N1CCOCC1 IJKSBYRAJCSENF-UHFFFAOYSA-N 0.000 claims description 2
- BBQUPKKQVQXRBQ-UHFFFAOYSA-N 4-(10-aminodecylamino)-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride Chemical compound Cl.NCCCCCCCCCCNC1=C2C(N(C(C2=CC=C1)=O)C1C(NC(CC1)=O)=O)=O BBQUPKKQVQXRBQ-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 102000003960 Ligases Human genes 0.000 claims description 2
- 108090000364 Ligases Proteins 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical class C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical class *C#N 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 108020001756 ligand binding domains Proteins 0.000 claims description 2
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 230000004952 protein activity Effects 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 3
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962798554P | 2019-01-30 | 2019-01-30 | |
| US62/798,554 | 2019-01-30 | ||
| PCT/US2020/015922 WO2020160295A1 (en) | 2019-01-30 | 2020-01-30 | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2022523916A JP2022523916A (ja) | 2022-04-27 |
| JP2022523916A5 JP2022523916A5 (https=) | 2023-02-06 |
| JPWO2020160295A5 true JPWO2020160295A5 (https=) | 2023-02-06 |
| JP7555938B2 JP7555938B2 (ja) | 2024-09-25 |
Family
ID=71733785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021544763A Active JP7555938B2 (ja) | 2019-01-30 | 2020-01-30 | アンドロゲン受容体を標的とするユビキチン化のための二官能性化合物および方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (3) | US11098025B2 (https=) |
| EP (1) | EP3917916A4 (https=) |
| JP (1) | JP7555938B2 (https=) |
| CN (1) | CN113677668B (https=) |
| WO (1) | WO2020160295A1 (https=) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7555938B2 (ja) | 2019-01-30 | 2024-09-25 | モンテリノ・セラピューティクス・インコーポレイテッド | アンドロゲン受容体を標的とするユビキチン化のための二官能性化合物および方法 |
| CA3165168A1 (en) | 2019-12-19 | 2021-06-24 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| CN115996918A (zh) | 2020-05-09 | 2023-04-21 | 阿尔维纳斯运营股份有限公司 | 制造双官能团化合物的方法、双官能团化合物的超纯形式以及包括所述双官能团化合物的剂型 |
| WO2021236695A1 (en) * | 2020-05-18 | 2021-11-25 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| CN114262319B (zh) * | 2020-12-01 | 2023-05-05 | 南昌奥瑞药业有限公司 | 一类双功能分子、其制备方法及其应用 |
| JP2024508841A (ja) * | 2021-02-25 | 2024-02-28 | メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ | プログラム可能なタンパク質分解のための化合物及び疾患処置のための使用方法 |
| WO2023039601A1 (en) * | 2021-09-13 | 2023-03-16 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| US11981672B2 (en) | 2021-09-13 | 2024-05-14 | Montelino Therapeutics Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| US20240376118A1 (en) * | 2021-09-13 | 2024-11-14 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| WO2023039603A2 (en) * | 2021-09-13 | 2023-03-16 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| US20240382603A1 (en) * | 2021-09-13 | 2024-11-21 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| EP4426286A4 (en) * | 2021-11-03 | 2025-12-24 | Relay Therapeutics Inc | Bifunctional PI3K-Alpha Inhibitors and Their Uses |
| AU2022424178A1 (en) | 2021-12-30 | 2024-07-11 | Beone Medicines I Gmbh | Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use |
| CN119301111A (zh) | 2022-03-24 | 2025-01-10 | 葛兰素史密斯克莱知识产权发展有限公司 | 作为protac中的降解决定子的2,4-二氧代四氢嘧啶基衍生物 |
| CN114890989B (zh) * | 2022-05-25 | 2024-03-22 | 广东晨康生物科技有限公司 | 一种含氮衍生物为Linker的HDAC8降解剂其制备方法和应用 |
| US20240207415A1 (en) * | 2022-11-08 | 2024-06-27 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| KR20250047848A (ko) * | 2023-09-27 | 2025-04-07 | 강원대학교산학협력단 | Kras의 g12v 돌연변이체 단백질의 특이적 분해 방법 및 그 조성물 |
| US12496301B2 (en) | 2023-12-08 | 2025-12-16 | Arvinas Operations, Inc. | Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9817224D0 (en) | 1998-08-08 | 1998-10-07 | Univ Nottingham | Ocular surface infection |
| US6306663B1 (en) | 1999-02-12 | 2001-10-23 | Proteinex, Inc. | Controlling protein levels in eucaryotic organisms |
| EP1087334B1 (fr) | 1999-09-15 | 2007-12-19 | European Community | Scellé multi-usage électronique à transpondeur passif |
| CN102186836A (zh) | 2008-10-17 | 2011-09-14 | 雅培制药有限公司 | Trpv1拮抗剂 |
| EP2519664A4 (en) | 2009-12-30 | 2014-03-12 | Avila Therapeutics Inc | LIGAND-RELATED COVALENTS MODIFYING A PROTEIN |
| WO2011098904A1 (en) | 2010-02-12 | 2011-08-18 | Aegera Therapeutics, Inc. | Iap bir domain binding compounds |
| JP5934986B2 (ja) * | 2011-09-07 | 2016-06-15 | 公益財団法人ヒューマンサイエンス振興財団 | アポトーシス阻害タンパク質リガンド−エストロゲン受容体リガンドハイブリッド化合物並びにそれを利用したエストロゲン受容体分解誘導剤及び乳癌、子宮頚癌又は卵巣癌の予防及び治療剤 |
| CA2861066C (en) | 2012-01-12 | 2024-01-02 | Yale University | Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase |
| US20150284422A1 (en) | 2012-08-10 | 2015-10-08 | Epizyme, Inc. | Inhibitors of protein methyltransferase dot1l and methods of use thereof |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| BR112016018691A2 (pt) | 2014-02-14 | 2017-08-08 | Univ British Columbia | Compostos do domínio de ligação ao dna (dbd) de receptor de andrógeno humano como terapêuticos e métodos para seu uso |
| AU2015247817C1 (en) * | 2014-04-14 | 2022-02-10 | Arvinas Operations, Inc. | Imide-based modulators of proteolysis and associated methods of use |
| JP6815318B2 (ja) | 2014-12-23 | 2021-01-20 | ダナ−ファーバー キャンサー インスティテュート，インコーポレイテッド | 二官能性分子によって標的化タンパク質分解を誘導する方法 |
| US9694084B2 (en) | 2014-12-23 | 2017-07-04 | Dana-Farber Cancer Institute, Inc. | Methods to induce targeted protein degradation through bifunctional molecules |
| US12312316B2 (en) | 2015-01-20 | 2025-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| JP6817962B2 (ja) | 2015-01-20 | 2021-01-20 | アルビナス・オペレーションズ・インコーポレイテッドＡｒｖｉｎａｓ Ｏｐｅｒａｔｉｏｎｓ， Ｉｎｃ． | ターゲティングされたアンドロゲン受容体分解のための化合物および方法 |
| GB201506871D0 (en) | 2015-04-22 | 2015-06-03 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201506872D0 (en) | 2015-04-22 | 2015-06-03 | Ge Oil & Gas Uk Ltd | Novel compounds |
| WO2017007612A1 (en) | 2015-07-07 | 2017-01-12 | Dana-Farber Cancer Institute, Inc. | Methods to induce targeted protein degradation through bifunctional molecules |
| WO2017011371A1 (en) * | 2015-07-10 | 2017-01-19 | Arvinas, Inc | Mdm2-based modulators of proteolysis and associated methods of use |
| CA2988436A1 (en) * | 2015-07-13 | 2017-01-19 | Arvinas, Inc. | Alanine-based modulators of proteolysis and associated methods of use |
| AU2017246452C1 (en) | 2016-04-06 | 2021-06-03 | The Regents Of The University Of Michigan | MDM2 protein degraders |
| WO2017197056A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Bromodomain targeting degronimers for target protein degradation |
| WO2018071606A1 (en) | 2016-10-11 | 2018-04-19 | Arvinas, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| EP3555091A1 (en) * | 2016-12-19 | 2019-10-23 | H. Hoffnabb-La Roche Ag | Ar-v7 inhibitors |
| BR112019015484A2 (pt) * | 2017-01-31 | 2020-04-28 | Arvinas Operations Inc | ligantes de cereblon e compostos bifuncionais compreendendo os mesmos |
| US20200172927A1 (en) | 2017-05-15 | 2020-06-04 | The Trustees Of Columbia University In The City Of New York | Reprogramming metabolism by inhibiting vhl for treatment of neurodegeneration |
| IL315310A (en) | 2017-12-26 | 2024-10-01 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| US20220356185A1 (en) * | 2018-07-06 | 2022-11-10 | Kymera Therapeutics, Inc. | Mertk degraders and uses thereof |
| KR102596354B1 (ko) | 2018-11-05 | 2023-10-31 | 삼성디스플레이 주식회사 | 액정 표시 장치 및 그 제조 방법 |
| WO2020102575A1 (en) | 2018-11-16 | 2020-05-22 | Inception Ibd, Inc. | Heterocyclic aminothiazoles and uses thereof |
| US11547759B2 (en) | 2019-01-30 | 2023-01-10 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
| JP7555938B2 (ja) | 2019-01-30 | 2024-09-25 | モンテリノ・セラピューティクス・インコーポレイテッド | アンドロゲン受容体を標的とするユビキチン化のための二官能性化合物および方法 |
| JP2022549222A (ja) | 2019-09-23 | 2022-11-24 | アキュター バイオテクノロジー インコーポレイテッド | アンドロゲン受容体分解活性を有する新規尿素およびその使用 |
| US11820781B2 (en) | 2019-12-04 | 2023-11-21 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading BTK via ubiquitin proteosome pathway |
| WO2021236695A1 (en) | 2020-05-18 | 2021-11-25 | Montelino Therapeutics, Inc. | Bi-functional compounds and methods for targeted ubiquitination of androgen receptor |
-
2020
- 2020-01-30 JP JP2021544763A patent/JP7555938B2/ja active Active
- 2020-01-30 EP EP20748314.0A patent/EP3917916A4/en not_active Withdrawn
- 2020-01-30 CN CN202080026615.5A patent/CN113677668B/zh not_active Expired - Fee Related
- 2020-01-30 WO PCT/US2020/015922 patent/WO2020160295A1/en not_active Ceased
- 2020-01-30 US US16/777,294 patent/US11098025B2/en active Active
-
2021
- 2021-05-27 US US17/331,940 patent/US11787778B2/en active Active
-
2023
- 2023-09-01 US US18/459,944 patent/US20240002360A1/en not_active Abandoned
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