JP2020521730A5 - - Google Patents
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- JP2020521730A5 JP2020521730A5 JP2019561718A JP2019561718A JP2020521730A5 JP 2020521730 A5 JP2020521730 A5 JP 2020521730A5 JP 2019561718 A JP2019561718 A JP 2019561718A JP 2019561718 A JP2019561718 A JP 2019561718A JP 2020521730 A5 JP2020521730 A5 JP 2020521730A5
- Authority
- JP
- Japan
- Prior art keywords
- cyanopyrrolidine
- carbonitrile
- sulfonyl
- pyrrolidine
- benzenesulfonamide
- 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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- -1 cyano, hydroxy Chemical group 0.000 claims 28
- 150000001875 compounds Chemical class 0.000 claims 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 12
- 239000008194 pharmaceutical composition Substances 0.000 claims 11
- 125000000623 heterocyclic group Chemical group 0.000 claims 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 9
- 206010016654 Fibrosis Diseases 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 8
- 230000004761 fibrosis Effects 0.000 claims 7
- 229910052760 oxygen Inorganic materials 0.000 claims 7
- 229910052717 sulfur Inorganic materials 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 125000005842 heteroatom Chemical group 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000004076 pyridyl group Chemical group 0.000 claims 6
- 208000011580 syndromic disease Diseases 0.000 claims 6
- 230000007812 deficiency Effects 0.000 claims 5
- 230000003176 fibrotic effect Effects 0.000 claims 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 5
- 125000003386 piperidinyl group Chemical group 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 208000029523 Interstitial Lung disease Diseases 0.000 claims 4
- 208000035475 disorder Diseases 0.000 claims 4
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 3
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- 206010028980 Neoplasm Diseases 0.000 claims 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 230000035772 mutation Effects 0.000 claims 3
- 125000004193 piperazinyl group Chemical group 0.000 claims 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- 125000006413 ring segment Chemical group 0.000 claims 3
- 231100000241 scar Toxicity 0.000 claims 3
- 125000000335 thiazolyl group Chemical group 0.000 claims 3
- BEEMGCAOXBWJIO-ZIAGYGMSSA-N (4aR,7aR)-4-(4-methylphenyl)sulfonyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazine-6-carbonitrile Chemical compound C(#N)N1C[C@@H]2[C@H](N(S(=O)(=O)C3=CC=C(C=C3)C)CCO2)C1 BEEMGCAOXBWJIO-ZIAGYGMSSA-N 0.000 claims 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 2
- QDICTGLHTPMYLM-UHFFFAOYSA-N 1-cyano-N-(4-phenylphenyl)pyrrolidine-3-sulfonamide Chemical compound C1(=CC=C(C=C1)NS(=O)(=O)C1CN(CC1)C#N)C1=CC=CC=C1 QDICTGLHTPMYLM-UHFFFAOYSA-N 0.000 claims 2
- JIFYKOUMBCOVFM-UHFFFAOYSA-N 4-[(4-methylphenyl)methylsulfonyl]-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazine-6-carbonitrile Chemical compound CC1=CC=C(CS(=O)(=O)N2C3C(OCC2)CN(C3)C#N)C=C1 JIFYKOUMBCOVFM-UHFFFAOYSA-N 0.000 claims 2
- QTDYBTUZXLRWQJ-UHFFFAOYSA-N C(#N)N1CC(CC1)NS(=O)(=O)C1=CC=C(C=C1)C(C)C Chemical compound C(#N)N1CC(CC1)NS(=O)(=O)C1=CC=C(C=C1)C(C)C QTDYBTUZXLRWQJ-UHFFFAOYSA-N 0.000 claims 2
- SIJCHMWGIWVJAH-UHFFFAOYSA-N C(#N)N1CC(CC1)NS(=O)(=O)C1=NC=C(C=C1)C1=CC=CC=C1 Chemical compound C(#N)N1CC(CC1)NS(=O)(=O)C1=NC=C(C=C1)C1=CC=CC=C1 SIJCHMWGIWVJAH-UHFFFAOYSA-N 0.000 claims 2
- IGCJSGQUBIYSSD-UHFFFAOYSA-N C(#N)N1CC(CC1)NS(=O)(=O)C=1C=NC(=CC=1)OC1=CC=CC=C1 Chemical compound C(#N)N1CC(CC1)NS(=O)(=O)C=1C=NC(=CC=1)OC1=CC=CC=C1 IGCJSGQUBIYSSD-UHFFFAOYSA-N 0.000 claims 2
- HBAOUZBEZQZDDA-UHFFFAOYSA-N C(C1=CC=CC=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound C(C1=CC=CC=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N HBAOUZBEZQZDDA-UHFFFAOYSA-N 0.000 claims 2
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- GOUNALIZYDVKHO-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N GOUNALIZYDVKHO-UHFFFAOYSA-N 0.000 claims 2
- GOUNALIZYDVKHO-INIZCTEOSA-N ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@@H]1CN(CC1)C#N GOUNALIZYDVKHO-INIZCTEOSA-N 0.000 claims 2
- GOUNALIZYDVKHO-MRXNPFEDSA-N ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@H]1CN(CC1)C#N GOUNALIZYDVKHO-MRXNPFEDSA-N 0.000 claims 2
- WRCNLCVEVZQITB-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)C1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)C1CN(CC1)C#N WRCNLCVEVZQITB-UHFFFAOYSA-N 0.000 claims 2
- WRCNLCVEVZQITB-AWEZNQCLSA-N ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@@H]1CN(CC1)C#N WRCNLCVEVZQITB-AWEZNQCLSA-N 0.000 claims 2
- WRCNLCVEVZQITB-CQSZACIVSA-N ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@H]1CN(CC1)C#N WRCNLCVEVZQITB-CQSZACIVSA-N 0.000 claims 2
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims 2
- LWHZBVOWIRURSN-UHFFFAOYSA-N FC1=CC=C(C=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound FC1=CC=C(C=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N LWHZBVOWIRURSN-UHFFFAOYSA-N 0.000 claims 2
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- YCPRYUOSAYYWAH-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-2-phenylbenzenesulfonamide Chemical compound C(#N)N1CC(CC1)NS(=O)(=O)C=1C(=CC=CC=1)C1=CC=CC=C1 YCPRYUOSAYYWAH-UHFFFAOYSA-N 0.000 claims 2
- CWHZUYIHGGINNU-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-4-phenylbenzenesulfonamide Chemical compound C(#N)N1CC(CC1)NS(=O)(=O)C1=CC=C(C=C1)C1=CC=CC=C1 CWHZUYIHGGINNU-UHFFFAOYSA-N 0.000 claims 2
- CWHZUYIHGGINNU-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-phenylbenzenesulfonamide Chemical compound C(#N)N1C[C@@H](CC1)NS(=O)(=O)C1=CC=C(C=C1)C1=CC=CC=C1 CWHZUYIHGGINNU-MRXNPFEDSA-N 0.000 claims 2
- CWHZUYIHGGINNU-INIZCTEOSA-N N-[(3S)-1-cyanopyrrolidin-3-yl]-4-phenylbenzenesulfonamide Chemical compound C(#N)N1C[C@H](CC1)NS(=O)(=O)C1=CC=C(C=C1)C1=CC=CC=C1 CWHZUYIHGGINNU-INIZCTEOSA-N 0.000 claims 2
- TWONXSWEDQMNGI-UHFFFAOYSA-N N1=C(C=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound N1=C(C=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N TWONXSWEDQMNGI-UHFFFAOYSA-N 0.000 claims 2
- ZSDGNUMYZTWCOB-UHFFFAOYSA-N N1=C(N=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound N1=C(N=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N ZSDGNUMYZTWCOB-UHFFFAOYSA-N 0.000 claims 2
- TYDQESZKNCOCEH-AEFFLSMTSA-N N1=CC(=CC=C1)C1=CC=C(C=C1)S(=O)(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N Chemical compound N1=CC(=CC=C1)C1=CC=C(C=C1)S(=O)(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N TYDQESZKNCOCEH-AEFFLSMTSA-N 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 125000004450 alkenylene group Chemical group 0.000 claims 2
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- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 2
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- 125000004432 carbon atom Chemical group C* 0.000 claims 2
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- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
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- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims 2
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 2
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- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
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- 0 CB*C(C)(C)*IS(N(*)C(C*(C1)I)CN1C#N)(=O)=O Chemical compound CB*C(C)(C)*IS(N(*)C(C*(C1)I)CN1C#N)(=O)=O 0.000 description 1
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| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| JP7208931B2 (ja) | 2017-06-20 | 2023-01-19 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての活性をもつ置換シアノピロリジン類 |
| BR112020003725A2 (pt) | 2017-10-06 | 2020-11-03 | Forma Therapeutics, Inc. | inibição da peptidase 30 específica de ubiquitina |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス，インコーポレイテッド | ユビキチン特異的ペプチダーゼ３０（ｕｓｐ３０）阻害剤として有用な縮合二環化合物 |
| LT3860989T (lt) | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| EP3917508A4 (en) | 2019-01-28 | 2022-12-21 | Mitochondria Emotion, Inc. | EAAT2 ACTIVATORS AND METHODS OF USE THEREOF |
| CA3127453A1 (en) | 2019-01-28 | 2020-08-06 | Mitochondria Emotion, Inc. | Trans-4-hydroxycyclohexyl phenyl amide mitofusin activators and methods of use thereof |
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| WO2021204856A1 (en) | 2020-04-08 | 2021-10-14 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| IL298526A (en) | 2020-05-28 | 2023-01-01 | Mission Therapeutics Ltd | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction |
| BR112022019722A2 (pt) | 2020-06-04 | 2022-12-20 | Mission Therapeutics Ltd | N-cianopirrolidinas com atividade como inibidores de usp30 |
| DK4161929T3 (da) | 2020-06-08 | 2025-08-18 | Mission Therapeutics Ltd | 1-(5-(2-cyanopyridin-4-yl)oxazol-2-carbonyl)-4-methylhexahydropyrrolo[3,4-b]pyrrol-5(1h)-carbonitril som usp30-hæmmer til anvendelse i behandling af mitokondriedysfunktion, cancer og fibrose |
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| WO2022159566A1 (en) * | 2021-01-21 | 2022-07-28 | Icahn School Of Medicine At Mount Sinai | Benzenesulfonamide agonists of trap1 for treating organ fibrosis |
| US20250034122A1 (en) | 2021-12-01 | 2025-01-30 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
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| US6867221B2 (en) * | 2001-08-30 | 2005-03-15 | Kowa Co., Ltd. | Cyclic amine compounds and pharmaceutical composition containing the same |
| EP1948597A1 (en) | 2005-10-21 | 2008-07-30 | Vertex Pharmaceuticals Incorporated | Derivatives for modulation of ion channels |
| US8242271B2 (en) | 2007-06-04 | 2012-08-14 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
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| EP2565186A1 (en) | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| CN103183673B (zh) * | 2011-12-30 | 2016-09-14 | 浙江新和成股份有限公司 | (s,s)-2,8-二氮杂双环[4,3,0]壬烷的合成方法 |
| CA2918242C (en) | 2013-07-31 | 2022-06-21 | Merck Patent Gmbh | Pyridines, pyrimidines, and pyrazines, as btk inhibitors and uses thereof |
| US9963444B2 (en) | 2014-05-19 | 2018-05-08 | Northeastern University | N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof |
| WO2015183987A1 (en) | 2014-05-27 | 2015-12-03 | Pharmakea, Inc. | Compositions and methods of delivery of deubiquitinase inhibitors |
| WO2016019237A2 (en) | 2014-07-31 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| GB201416754D0 (en) * | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| MX373656B (es) * | 2015-03-30 | 2020-04-02 | Mission Therapeutics Ltd | Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér. |
| US10669234B2 (en) * | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
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| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
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| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| JP6959252B2 (ja) | 2016-03-24 | 2021-11-02 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての１−シアノピロリジン誘導体 |
| ES2850349T3 (es) | 2016-09-27 | 2021-08-27 | Mission Therapeutics Ltd | Derivados de cianopirrolidina con actividad como inhibidores de USP30 |
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| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| JP7208931B2 (ja) | 2017-06-20 | 2023-01-19 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての活性をもつ置換シアノピロリジン類 |
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