CN112969689A - 一种含磺酰氟的对parp受体具有高亲和力的化合物及其制备和用途 - Google Patents
一种含磺酰氟的对parp受体具有高亲和力的化合物及其制备和用途 Download PDFInfo
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- CN112969689A CN112969689A CN201880099237.6A CN201880099237A CN112969689A CN 112969689 A CN112969689 A CN 112969689A CN 201880099237 A CN201880099237 A CN 201880099237A CN 112969689 A CN112969689 A CN 112969689A
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- A—HUMAN NECESSITIES
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- 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
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及有机化学领域,特别是涉及一种含磺酰氟的对PARP受体具有高亲和力的化合物或其药学上可接受的盐、异构体、前药或溶剂化物。本发明提供一种化合物或其药学上可接受的盐、异构体、前药或溶剂化物,所述化合物的结构式如式I所示。本发明所提供的化合物是一种更安全、高效的新型PARP抑制剂药物及以PARP为生物标志物的正电子断层显像剂,具有巨大的社会价值和经济价值。
Description
PCT国内申请,说明书已公开。
Claims (10)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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PCT/CN2018/114371 WO2020093272A1 (zh) | 2018-11-07 | 2018-11-07 | 一种含磺酰氟的对parp受体具有高亲和力的化合物及其制备和用途 |
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CN112969689A true CN112969689A (zh) | 2021-06-15 |
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CN201880099237.6A Pending CN112969689A (zh) | 2018-11-07 | 2018-11-07 | 一种含磺酰氟的对parp受体具有高亲和力的化合物及其制备和用途 |
Country Status (2)
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CN (1) | CN112969689A (zh) |
WO (1) | WO2020093272A1 (zh) |
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WO2022000946A1 (zh) * | 2020-06-29 | 2022-01-06 | 中国药科大学 | 含有酞嗪-1(2h)-酮结构的parp抑制剂、其制法及医药用途 |
CN112375070B (zh) * | 2020-06-29 | 2023-03-28 | 中国药科大学 | 含有酞嗪-1(2h)-酮结构的parp抑制剂、其制法及医药用途 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016033293A1 (en) * | 2014-08-27 | 2016-03-03 | Memorial Sloan Kettering Cancer Center | Radiohalide-labeled targeted diagnostics and therapeutics |
CN112480082A (zh) * | 2020-12-17 | 2021-03-12 | 天津市肿瘤医院 | 一种化合物、制备方法及其在制备治疗小细胞肺癌药物中的应用 |
CN112739856A (zh) * | 2018-07-18 | 2021-04-30 | 上海科技大学 | 有机化合物功能性独立的标记 |
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2018
- 2018-11-07 WO PCT/CN2018/114371 patent/WO2020093272A1/zh active Application Filing
- 2018-11-07 CN CN201880099237.6A patent/CN112969689A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016033293A1 (en) * | 2014-08-27 | 2016-03-03 | Memorial Sloan Kettering Cancer Center | Radiohalide-labeled targeted diagnostics and therapeutics |
CN112739856A (zh) * | 2018-07-18 | 2021-04-30 | 上海科技大学 | 有机化合物功能性独立的标记 |
CN112480082A (zh) * | 2020-12-17 | 2021-03-12 | 天津市肿瘤医院 | 一种化合物、制备方法及其在制备治疗小细胞肺癌药物中的应用 |
Non-Patent Citations (5)
Title |
---|
FILIP ZMUDA ET AL.: "An 18F‑Labeled Poly(ADP-ribose) Polymerase Positron Emission Tomography Imaging Agent" * |
PEIXIANG MA ET AL.: "Discovery, mechanism and metabolism studies of 2,3-difluorophenyl -containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy Products" * |
QINHENG ZHENG ET AL.: "Sulfur [18F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis" * |
WENHUA CHEN ET AL.: "Discovery, mechanism and metabolism studies of 2,3-difluorophenyl -containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy" * |
YIYUAN ZHANG ET AL.: "Palladium-catalyzed one-pot phosphorylation of phenols mediated by sulfuryl fluoride" * |
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