CN113966331A - 含脲结构的三芳环化合物及其应用 - Google Patents
含脲结构的三芳环化合物及其应用 Download PDFInfo
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- CN113966331A CN113966331A CN202180002962.9A CN202180002962A CN113966331A CN 113966331 A CN113966331 A CN 113966331A CN 202180002962 A CN202180002962 A CN 202180002962A CN 113966331 A CN113966331 A CN 113966331A
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- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract 27
- 150000001875 compounds Chemical class 0.000 title claims abstract 5
- 239000002207 metabolite Substances 0.000 claims abstract 22
- 229940002612 prodrug Drugs 0.000 claims abstract 22
- 239000000651 prodrug Substances 0.000 claims abstract 22
- 150000003839 salts Chemical class 0.000 claims abstract 22
- 239000012453 solvate Substances 0.000 claims abstract 22
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 claims abstract 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract 4
- 201000010099 disease Diseases 0.000 claims abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 3
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 claims abstract 2
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims abstract 2
- 208000032839 leukemia Diseases 0.000 claims abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 19
- 125000000217 alkyl group Chemical group 0.000 claims 18
- -1 amino, hydroxyl Chemical group 0.000 claims 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims 8
- 238000006467 substitution reaction Methods 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 150000002367 halogens Chemical class 0.000 claims 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 7
- 150000002148 esters Chemical class 0.000 claims 6
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 5
- 150000001408 amides Chemical class 0.000 claims 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
- 108091000080 Phosphotransferase Proteins 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 3
- 229910052794 bromium Inorganic materials 0.000 claims 3
- 229910052801 chlorine Inorganic materials 0.000 claims 3
- 239000000460 chlorine Substances 0.000 claims 3
- 229910052731 fluorine Inorganic materials 0.000 claims 3
- 239000011737 fluorine Substances 0.000 claims 3
- 102000020233 phosphotransferase Human genes 0.000 claims 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000004202 carbamide Substances 0.000 claims 2
- 239000007789 gas Substances 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 claims 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 125000004442 acylamino group Chemical group 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 210000002919 epithelial cell Anatomy 0.000 claims 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 229940043355 kinase inhibitor Drugs 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 201000006845 reticulosarcoma Diseases 0.000 claims 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 abstract 2
- 108060006633 protein kinase Proteins 0.000 abstract 2
- 230000004913 activation Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000037361 pathway Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了一种具有式(I)所示结构的含脲结构的三芳环化合物或其药学上可接受的盐或其立体异构体或其前药分子或其代谢产物或其溶剂化物,该类化合物可以有效地抑制激酶,尤其是FLT3和RET激酶,进而调节下游的多条通路的激活,可以用于制备防治RET激酶、FLT3激酶和/或Kit激酶相关的多种疾病的药物,比如白血病、肿瘤。
Description
PCT国内申请,说明书已公开。
Claims (24)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2020101661011 | 2020-03-11 | ||
CN202010166101 | 2020-03-11 | ||
PCT/CN2021/079354 WO2021180008A1 (zh) | 2020-03-11 | 2021-03-05 | 含脲结构的三芳环化合物及其应用 |
Publications (2)
Publication Number | Publication Date |
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CN113966331A true CN113966331A (zh) | 2022-01-21 |
CN113966331B CN113966331B (zh) | 2024-04-12 |
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CN202180002962.9A Active CN113966331B (zh) | 2020-03-11 | 2021-03-05 | 含脲结构的三芳环化合物及其应用 |
Country Status (2)
Country | Link |
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CN (1) | CN113966331B (zh) |
WO (1) | WO2021180008A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115772167A (zh) * | 2021-09-08 | 2023-03-10 | 暨南大学 | 含脲结构的化合物及其应用 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2025502748A (ja) | 2021-12-30 | 2025-01-28 | バイオメア フュージョン,インコーポレイテッド | Flt3の阻害剤としてのピラジン化合物 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1544420A (zh) * | 1997-12-22 | 2004-11-10 | 用取代杂环脲抑制raf激酶 | |
CN101448843A (zh) * | 2006-03-17 | 2009-06-03 | 埃姆比特生物科学公司 | 用于疾病治疗的咪唑并噻唑化合物 |
CN101835472A (zh) * | 2007-11-08 | 2010-09-15 | 埃姆比特生物科学公司 | N-(5-叔丁基-异噁唑-3-基)-N′-{4-[7-(2-吗啉-4-基-乙氧基)咪唑并[2,1-b][1,3]苯并噻唑-2-基]苯基}脲治疗增殖性疾病的给药方法 |
US20120225880A1 (en) * | 2011-03-04 | 2012-09-06 | National Health Research Institutes | Pyrazole compounds and thiazole compounds as protein kinases inhibitors |
CN107459521A (zh) * | 2016-06-03 | 2017-12-12 | 合肥中科普瑞昇生物医药科技有限公司 | Flt3激酶的新型抑制剂及其用途 |
CN110437220A (zh) * | 2018-07-13 | 2019-11-12 | 暨南大学 | 三氮唑类化合物及其应用 |
-
2021
- 2021-03-05 CN CN202180002962.9A patent/CN113966331B/zh active Active
- 2021-03-05 WO PCT/CN2021/079354 patent/WO2021180008A1/zh active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1544420A (zh) * | 1997-12-22 | 2004-11-10 | 用取代杂环脲抑制raf激酶 | |
CN101448843A (zh) * | 2006-03-17 | 2009-06-03 | 埃姆比特生物科学公司 | 用于疾病治疗的咪唑并噻唑化合物 |
CN101835472A (zh) * | 2007-11-08 | 2010-09-15 | 埃姆比特生物科学公司 | N-(5-叔丁基-异噁唑-3-基)-N′-{4-[7-(2-吗啉-4-基-乙氧基)咪唑并[2,1-b][1,3]苯并噻唑-2-基]苯基}脲治疗增殖性疾病的给药方法 |
US20120225880A1 (en) * | 2011-03-04 | 2012-09-06 | National Health Research Institutes | Pyrazole compounds and thiazole compounds as protein kinases inhibitors |
CN107459521A (zh) * | 2016-06-03 | 2017-12-12 | 合肥中科普瑞昇生物医药科技有限公司 | Flt3激酶的新型抑制剂及其用途 |
CN110437220A (zh) * | 2018-07-13 | 2019-11-12 | 暨南大学 | 三氮唑类化合物及其应用 |
Non-Patent Citations (1)
Title |
---|
KAIFU WU ET AL.: "Discovery of 3,5-diaryl-1H-pyrazol-based ureas as potent RET inhibitors", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》, vol. 251, pages 115237 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115772167A (zh) * | 2021-09-08 | 2023-03-10 | 暨南大学 | 含脲结构的化合物及其应用 |
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Publication number | Publication date |
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WO2021180008A1 (zh) | 2021-09-16 |
CN113966331B (zh) | 2024-04-12 |
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