CN113302185A - 苯并呋喃-6-甲酰胺衍生物、其制备方法和药学上的应用 - Google Patents
苯并呋喃-6-甲酰胺衍生物、其制备方法和药学上的应用 Download PDFInfo
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- CN113302185A CN113302185A CN201980088575.4A CN201980088575A CN113302185A CN 113302185 A CN113302185 A CN 113302185A CN 201980088575 A CN201980088575 A CN 201980088575A CN 113302185 A CN113302185 A CN 113302185A
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- radical
- deuterium
- substituted
- membered
- cycloalkyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- VVHLRXBWCJUTGG-UHFFFAOYSA-N 1-benzofuran-6-carboxamide Chemical class NC(=O)C1=CC=C2C=COC2=C1 VVHLRXBWCJUTGG-UHFFFAOYSA-N 0.000 title abstract description 5
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- 239000003814 drug Substances 0.000 claims abstract description 12
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- 238000000034 method Methods 0.000 claims abstract description 5
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- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 344
- 229910052805 deuterium Inorganic materials 0.000 claims description 344
- -1 C2-10Alkenyl radical Chemical class 0.000 claims description 330
- 150000003254 radicals Chemical class 0.000 claims description 289
- 229910052736 halogen Inorganic materials 0.000 claims description 210
- 150000002367 halogens Chemical class 0.000 claims description 210
- 125000000623 heterocyclic group Chemical group 0.000 claims description 189
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 166
- 125000001072 heteroaryl group Chemical group 0.000 claims description 156
- 125000001424 substituent group Chemical group 0.000 claims description 136
- 229910052739 hydrogen Inorganic materials 0.000 claims description 134
- 239000001257 hydrogen Substances 0.000 claims description 134
- 150000002431 hydrogen Chemical class 0.000 claims description 128
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 92
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 92
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 79
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 67
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 65
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 65
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 62
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- 239000000651 prodrug Substances 0.000 claims description 39
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
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- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
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- 125000005418 aryl aryl group Chemical group 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
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- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 239000000556 agonist Substances 0.000 abstract description 6
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 140
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 25
- 125000000217 alkyl group Chemical group 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 238000004809 thin layer chromatography Methods 0.000 description 19
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- 239000003208 petroleum Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
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- 238000001914 filtration Methods 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 238000001035 drying Methods 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
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- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Health & Medical Sciences (AREA)
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Abstract
一种具有式(I)结构的苯并呋喃‑6‑甲酰胺衍生物、其制备方法和药学上的应用，各取代基的定义如说明书和权利要求书所述。本发明系列化合物可广泛应用于制备治疗一种或多种肿瘤、癌症、代谢性疾病、自身免疫性疾病或紊乱的药物，有望开发成新一代RORγt激动剂药物。
Description
PCT国内申请，说明书已公开。
Claims (19)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910356174 | 2019-04-29 | ||
| CN2019103561744 | 2019-04-29 | ||
| PCT/CN2019/105994 WO2020220562A1 (zh) | 2019-04-29 | 2019-09-16 | 苯并呋喃-6-甲酰胺衍生物、其制备方法和药学上的应用 |
Publications (2)
| Publication Number | Publication Date |
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| CN113302185A true CN113302185A (zh) | 2021-08-24 |
| CN113302185B CN113302185B (zh) | 2024-04-09 |
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| CN201980088575.4A Active CN113302185B (zh) | 2019-04-29 | 2019-09-16 | 苯并呋喃-6-甲酰胺衍生物、其制备方法和药学上的应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN113302185B (zh) |
| WO (1) | WO2020220562A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016057931A1 (en) | 2014-10-10 | 2016-04-14 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104853757A (zh) * | 2012-08-15 | 2015-08-19 | 默沙东公司 | 作为RORγT抑制剂的4-杂芳基取代的苯甲酸化合物及其用途 |
| CN106132422A (zh) * | 2014-02-27 | 2016-11-16 | 莱斯拉公司 | 使用视黄酸受体相关孤儿受体γ的激动剂的过继细胞疗法＆相关治疗方法 |
| CN106995416A (zh) * | 2016-01-26 | 2017-08-01 | 上海翰森生物医药科技有限公司 | Fxr激动剂及其制备方法和应用 |
| CN107428742A (zh) * | 2015-11-19 | 2017-12-01 | 江苏恒瑞医药股份有限公司 | 苯并呋喃类衍生物、其制备方法及其在医药上的应用 |
| WO2018137655A1 (zh) * | 2017-01-25 | 2018-08-02 | 江苏豪森药业集团有限公司 | 吡咯并吡啶类n-氧化衍生物及其制备方法和应用 |
| WO2018233553A1 (zh) * | 2017-06-19 | 2018-12-27 | 广东东阳光药业有限公司 | 稠合双环类化合物及其在药物中的应用 |
| WO2019062848A1 (zh) * | 2017-09-29 | 2019-04-04 | 浙江海正药业股份有限公司 | N-(取代磺酰基)苯甲酰胺类衍生物及其制备方法和医药用途 |
-
2019
- 2019-09-16 CN CN201980088575.4A patent/CN113302185B/zh active Active
- 2019-09-16 WO PCT/CN2019/105994 patent/WO2020220562A1/zh active Application Filing
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104853757A (zh) * | 2012-08-15 | 2015-08-19 | 默沙东公司 | 作为RORγT抑制剂的4-杂芳基取代的苯甲酸化合物及其用途 |
| CN106132422A (zh) * | 2014-02-27 | 2016-11-16 | 莱斯拉公司 | 使用视黄酸受体相关孤儿受体γ的激动剂的过继细胞疗法＆相关治疗方法 |
| CN107428742A (zh) * | 2015-11-19 | 2017-12-01 | 江苏恒瑞医药股份有限公司 | 苯并呋喃类衍生物、其制备方法及其在医药上的应用 |
| CN106995416A (zh) * | 2016-01-26 | 2017-08-01 | 上海翰森生物医药科技有限公司 | Fxr激动剂及其制备方法和应用 |
| CN109071470A (zh) * | 2016-01-26 | 2018-12-21 | 江苏豪森药业集团有限公司 | Fxr激动剂及其制备方法和应用 |
| WO2018137655A1 (zh) * | 2017-01-25 | 2018-08-02 | 江苏豪森药业集团有限公司 | 吡咯并吡啶类n-氧化衍生物及其制备方法和应用 |
| WO2018233553A1 (zh) * | 2017-06-19 | 2018-12-27 | 广东东阳光药业有限公司 | 稠合双环类化合物及其在药物中的应用 |
| WO2019062848A1 (zh) * | 2017-09-29 | 2019-04-04 | 浙江海正药业股份有限公司 | N-(取代磺酰基)苯甲酰胺类衍生物及其制备方法和医药用途 |
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