JP2020514252A5 - - Google Patents
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- JP2020514252A5 JP2020514252A5 JP2019530811A JP2019530811A JP2020514252A5 JP 2020514252 A5 JP2020514252 A5 JP 2020514252A5 JP 2019530811 A JP2019530811 A JP 2019530811A JP 2019530811 A JP2019530811 A JP 2019530811A JP 2020514252 A5 JP2020514252 A5 JP 2020514252A5
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- 150000001875 compounds Chemical class 0.000 claims description 61
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 claims description 40
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 claims description 40
- 102000013698 Cyclin-Dependent Kinase 6 Human genes 0.000 claims description 38
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 claims description 38
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 239000003446 ligand Substances 0.000 claims description 14
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 13
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 230000015556 catabolic process Effects 0.000 claims description 10
- 238000006731 degradation reaction Methods 0.000 claims description 10
- 230000006378 damage Effects 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
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- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
- SGJLSPUSUBJWHO-UHFFFAOYSA-N 6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperidin-4-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(N=C1)=CC=C1C1CCNCC1 SGJLSPUSUBJWHO-UHFFFAOYSA-N 0.000 description 2
- RHXHGRAEPCAFML-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 RHXHGRAEPCAFML-UHFFFAOYSA-N 0.000 description 2
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- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 2
- UZWDCWONPYILKI-UHFFFAOYSA-N n-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine Chemical compound C1CN(CC)CCN1CC(C=N1)=CC=C1NC1=NC=C(F)C(C=2C=C3N(C(C)C)C(C)=NC3=C(F)C=2)=N1 UZWDCWONPYILKI-UHFFFAOYSA-N 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- 229960004390 palbociclib Drugs 0.000 description 2
- AHJRHEGDXFFMBM-UHFFFAOYSA-N palbociclib Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 AHJRHEGDXFFMBM-UHFFFAOYSA-N 0.000 description 2
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- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 description 2
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- UFPFGVNKHCLJJO-SSKFGXFMSA-N (2s)-n-[(1s)-1-cyclohexyl-2-[(2s)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1([C@H](NC(=O)[C@H](C)NC)C(=O)N2[C@@H](CCC2)C=2SC=C(N=2)C(=O)C=2C=CC(F)=CC=2)CCCCC1 UFPFGVNKHCLJJO-SSKFGXFMSA-N 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- DRLCSJFKKILATL-YWCVFVGNSA-N 2-[(3r,5r,6s)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(2s)-3-methyl-1-propan-2-ylsulfonylbutan-2-yl]-2-oxopiperidin-3-yl]acetic acid Chemical compound C1([C@@H]2[C@H](N(C([C@@](C)(CC(O)=O)C2)=O)[C@H](CS(=O)(=O)C(C)C)C(C)C)C=2C=CC(Cl)=CC=2)=CC=CC(Cl)=C1 DRLCSJFKKILATL-YWCVFVGNSA-N 0.000 description 1
- BDUHCSBCVGXTJM-WUFINQPMSA-N 4-[[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazol-1-yl]-oxomethyl]-2-piperazinone Chemical compound CC(C)OC1=CC(OC)=CC=C1C1=N[C@@H](C=2C=CC(Cl)=CC=2)[C@@H](C=2C=CC(Cl)=CC=2)N1C(=O)N1CC(=O)NCC1 BDUHCSBCVGXTJM-WUFINQPMSA-N 0.000 description 1
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- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
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- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- YJCZPJQGFSSFOL-MNZPCBJKSA-N CCN1[C@H]([C@H](C2=CC=CC(Cl)=C2F)[C@]2(C(=O)NC3=CC(Cl)=CC=C23)C11CCCCC1)C(=O)NC12CCC(CC1)(CC2)C(O)=O Chemical compound CCN1[C@H]([C@H](C2=CC=CC(Cl)=C2F)[C@]2(C(=O)NC3=CC(Cl)=CC=C23)C11CCCCC1)C(=O)NC12CCC(CC1)(CC2)C(O)=O YJCZPJQGFSSFOL-MNZPCBJKSA-N 0.000 description 1
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- QBGKPEROWUKSBK-QPPIDDCLSA-N [(4s,5r)-2-(4-tert-butyl-2-ethoxyphenyl)-4,5-bis(4-chlorophenyl)-4,5-dimethylimidazol-1-yl]-[4-(3-methylsulfonylpropyl)piperazin-1-yl]methanone Chemical compound CCOC1=CC(C(C)(C)C)=CC=C1C(N([C@]1(C)C=2C=CC(Cl)=CC=2)C(=O)N2CCN(CCCS(C)(=O)=O)CC2)=N[C@@]1(C)C1=CC=C(Cl)C=C1 QBGKPEROWUKSBK-QPPIDDCLSA-N 0.000 description 1
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- UUPZYAHONNHULX-CJBSCAABSA-N methyl 1-{(2S)-2-cyclohexyl-2-[(N-methyl-L-alanyl)amino]acetyl}-L-prolyl-beta-phenyl-L-phenylalaninate Chemical compound C1([C@H](NC(=O)[C@H](C)NC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(=O)OC)CCCCC1 UUPZYAHONNHULX-CJBSCAABSA-N 0.000 description 1
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662431806P | 2016-12-08 | 2016-12-08 | |
| US62/431,806 | 2016-12-08 | ||
| PCT/US2017/065027 WO2018106870A1 (en) | 2016-12-08 | 2017-12-07 | Compositions and methods for treating cdk4/6-mediated cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020514252A JP2020514252A (ja) | 2020-05-21 |
| JP2020514252A5 true JP2020514252A5 (enExample) | 2021-01-28 |
Family
ID=62491322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019530811A Pending JP2020514252A (ja) | 2016-12-08 | 2017-12-07 | Ｃｄｋ４／６媒介性がんを治療するための組成物および方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US11541051B2 (enExample) |
| EP (1) | EP3551185A4 (enExample) |
| JP (1) | JP2020514252A (enExample) |
| CN (1) | CN110267659A (enExample) |
| AU (1) | AU2017370694A1 (enExample) |
| CA (1) | CA3045037A1 (enExample) |
| WO (1) | WO2018106870A1 (enExample) |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6430483B2 (ja) | 2013-03-15 | 2018-11-28 | ジー１、セラピューティクス、インコーポレイテッドＧ１ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 化学療法の間の正常細胞の一時的な保護 |
| WO2018005863A1 (en) * | 2016-07-01 | 2018-01-04 | G1 Therapeutics, Inc. | Pyrimidine-based compounds for the treatment of cancer |
| CN109789143A (zh) | 2016-07-01 | 2019-05-21 | G1治疗公司 | 基于嘧啶的抗增殖剂 |
| MX2019004950A (es) | 2016-10-28 | 2019-09-26 | Icahn School Med Mount Sinai | Composiciones y metodos para tratar el cancer mediado por el potenciador del homologo zeste 2. |
| CA3045037A1 (en) | 2016-12-08 | 2018-06-14 | Icahn School Of Medicine At Mount Sinai | Compositions and methods for treating cdk4/6-mediated cancer |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| JP7258009B2 (ja) | 2017-07-10 | 2023-04-14 | セルジーン コーポレイション | 抗増殖化合物及びその使用方法 |
| CN109516989B (zh) * | 2017-09-17 | 2021-12-31 | 上海美志医药科技有限公司 | 一类抑制并降解cdk的化合物 |
| WO2019126731A1 (en) | 2017-12-22 | 2019-06-27 | Petra Pharma Corporation | Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors |
| JP2021515013A (ja) | 2018-03-06 | 2021-06-17 | アイカーン スクール オブ メディスン アット マウント シナイ | セリンスレオニンキナーゼ（ａｋｔ）分解／破壊化合物および使用方法 |
| US12539292B2 (en) | 2018-04-01 | 2026-02-03 | Arvinas Operations, Inc. | BRM targeting compounds and associated methods of use |
| CN118344338A (zh) | 2018-04-23 | 2024-07-16 | 细胞基因公司 | 取代的4-氨基异吲哚啉-1,3-二酮化合物以及它们用于治疗淋巴瘤的用途 |
| WO2019242625A1 (zh) * | 2018-06-20 | 2019-12-26 | 上海科技大学 | 制备来那度胺衍生物的方法 |
| JP2021527666A (ja) * | 2018-06-21 | 2021-10-14 | アイカーン スクール オブ メディスン アット マウント シナイ | Ｗｄ４０反復ドメインタンパク質５（ｗｄｒ５）分解／破壊化合物および使用の方法 |
| WO2020010204A1 (en) | 2018-07-05 | 2020-01-09 | Icahn School Of Medicine At Mount Sinai | Protein tyrosine kinase 6 (ptk6) degradation / disruption compounds and methods of use |
| US11091522B2 (en) | 2018-07-23 | 2021-08-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN108948136A (zh) * | 2018-08-06 | 2018-12-07 | 浙江华海药业股份有限公司 | 一种赖诺普利杂质及其制备方法 |
| CN110835345A (zh) * | 2018-08-17 | 2020-02-25 | 中国科学院上海药物研究所 | 一类细胞周期依赖性激酶的降解剂、其制备方法、药物组合物及其用途 |
| US11707452B2 (en) | 2018-08-20 | 2023-07-25 | Arvinas Operations, Inc. | Modulators of alpha-synuclein proteolysis and associated methods of use |
| BR112021006647A2 (pt) * | 2018-10-08 | 2021-07-13 | The Regents Of The University Of Michigan | degradores de proteína mdm2 de pequenas moléculas |
| EP3867242A1 (en) * | 2018-10-15 | 2021-08-25 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading btk via ubiquitin proteosome pathway |
| WO2020092662A1 (en) * | 2018-11-02 | 2020-05-07 | The Wistar Institute Of Anatomy And Biology | Proteolysis-targeting chimeras |
| WO2020103878A1 (zh) * | 2018-11-21 | 2020-05-28 | 上海科技大学 | Er蛋白调节剂及其应用 |
| WO2020163823A2 (en) * | 2019-02-08 | 2020-08-13 | University Of Florida Research Foundation, Incorporated | Therapeutic agents and methods of treatment |
| EP3924350A1 (en) | 2019-02-13 | 2021-12-22 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading btk via ubiquitin proteosome pathway |
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2021
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