CN114728938A - 作为prmt5抑制剂的四氢异喹啉螺环化合物 - Google Patents
作为prmt5抑制剂的四氢异喹啉螺环化合物 Download PDFInfo
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- CN114728938A CN114728938A CN202080077343.1A CN202080077343A CN114728938A CN 114728938 A CN114728938 A CN 114728938A CN 202080077343 A CN202080077343 A CN 202080077343A CN 114728938 A CN114728938 A CN 114728938A
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- Prior art keywords
- compound
- carbonyl
- hydroxy
- azaspiro
- dimethyl
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- 101710084427 Protein arginine N-methyltransferase 5 Proteins 0.000 title claims abstract description 35
- 239000003112 inhibitor Substances 0.000 title abstract description 5
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 13
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- 238000012360 testing method Methods 0.000 description 18
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
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- RHQBJRGRDIJKGP-UHFFFAOYSA-N tert-butyl 2-cyano-7-azaspiro[3.5]nonane-7-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11CC(C#N)C1 RHQBJRGRDIJKGP-UHFFFAOYSA-N 0.000 description 12
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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Abstract
本申请公开了式(I)所示作为PRMT5抑制剂的四氢异喹啉螺环化合物、其制备方法、含有该化合物的药物组合物、以及其在治疗PRMT5介导的疾病中的用途，其中，A为任选被R6取代的5‑14元螺环基。
Description
PCT国内申请，说明书已公开。
Claims (27)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019110811265 | 2019-11-07 | ||
| CN201911081126 | 2019-11-07 | ||
| CN202010555158 | 2020-06-17 | ||
| CN2020105551580 | 2020-06-17 | ||
| PCT/CN2020/127166 WO2021088992A1 (zh) | 2019-11-07 | 2020-11-06 | 作为prmt5抑制剂的四氢异喹啉螺环化合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114728938A true CN114728938A (zh) | 2022-07-08 |
| CN114728938B CN114728938B (zh) | 2024-05-24 |
Family
ID=75848273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080077343.1A Active CN114728938B (zh) | 2019-11-07 | 2020-11-06 | 作为prmt5抑制剂的四氢异喹啉螺环化合物 |
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| WO (1) | WO2021088992A1 (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014100764A2 (en) * | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Methods of inhibiting prmt5 |
| WO2014100695A1 (en) * | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
| WO2017153515A1 (en) * | 2016-03-09 | 2017-09-14 | Ctxt Pty Limited | Tetrahydroisoquinolines as prmt5-inhibitors |
| CN108570059A (zh) * | 2017-03-09 | 2018-09-25 | 中国科学院上海药物研究所 | 一种具有prmt5抑制活性的化合物及其制备和应用 |
| WO2019094312A1 (en) * | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
-
2020
- 2020-11-06 CN CN202080077343.1A patent/CN114728938B/zh active Active
- 2020-11-06 WO PCT/CN2020/127166 patent/WO2021088992A1/zh active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014100764A2 (en) * | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Methods of inhibiting prmt5 |
| WO2014100695A1 (en) * | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
| WO2017153515A1 (en) * | 2016-03-09 | 2017-09-14 | Ctxt Pty Limited | Tetrahydroisoquinolines as prmt5-inhibitors |
| CN108570059A (zh) * | 2017-03-09 | 2018-09-25 | 中国科学院上海药物研究所 | 一种具有prmt5抑制活性的化合物及其制备和应用 |
| WO2019094312A1 (en) * | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
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| CN114728938B (zh) | 2024-05-24 |
| WO2021088992A1 (zh) | 2021-05-14 |
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