CN115697967A - 磺酰苯甲酰胺类衍生物及其偶联物、其制备方法及其应用 - Google Patents
磺酰苯甲酰胺类衍生物及其偶联物、其制备方法及其应用 Download PDFInfo
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- CN115697967A CN115697967A CN202180037849.4A CN202180037849A CN115697967A CN 115697967 A CN115697967 A CN 115697967A CN 202180037849 A CN202180037849 A CN 202180037849A CN 115697967 A CN115697967 A CN 115697967A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
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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
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
提供一种磺酰苯甲酰胺类衍生物及其偶联物、其制备方法及其应用。具体而言,提供了一种具有式(D)所示结构的磺酰苯甲酰胺类衍生物及其偶联物,其制备方法,含有其的药物组合物,及其通过受体调节在制备治疗癌症的药物中的用途。其中通式(D)中的各取代基与说明书中的定义相同。
Description
PCT国内申请,说明书已公开。
Claims (35)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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CN2020106631258 | 2020-07-10 | ||
CN202010663125 | 2020-07-10 | ||
PCT/CN2021/105436 WO2022007940A1 (zh) | 2020-07-10 | 2021-07-09 | 磺酰苯甲酰胺类衍生物及其偶联物、其制备方法及其应用 |
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CN115697967A true CN115697967A (zh) | 2023-02-03 |
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CN202180037849.4A Pending CN115697967A (zh) | 2020-07-10 | 2021-07-09 | 磺酰苯甲酰胺类衍生物及其偶联物、其制备方法及其应用 |
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US (1) | US20230250077A1 (zh) |
EP (1) | EP4180422A4 (zh) |
JP (1) | JP2023533735A (zh) |
KR (1) | KR20230038231A (zh) |
CN (1) | CN115697967A (zh) |
AU (1) | AU2021306781A1 (zh) |
BR (1) | BR112023000320A2 (zh) |
CA (1) | CA3184959A1 (zh) |
MX (1) | MX2023000346A (zh) |
TW (1) | TW202214565A (zh) |
WO (1) | WO2022007940A1 (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005049593A2 (en) * | 2003-11-13 | 2005-06-02 | Abbott Laboratories | N-acylsulfonamide apoptosis promoters |
WO2012017251A1 (en) * | 2010-08-06 | 2012-02-09 | Astrazeneca Ab | N-acylsulfonamide apoptosis promoters |
CN110312531A (zh) * | 2017-02-22 | 2019-10-08 | 阿斯利康(瑞典)有限公司 | 治疗性树枝状体 |
CN110483501A (zh) * | 2016-08-05 | 2019-11-22 | 密歇根大学董事会 | 作为bcl-2抑制剂的n-(苯基磺酰基)苯甲酰胺及相关化合物 |
US20200216442A1 (en) * | 2017-06-26 | 2020-07-09 | Shenzhen Targetrx, Inc. | Benzenesulfonylbenazamide compound for inhibiting bcl-2 protein and composition and use thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US7223879B2 (en) | 1998-07-10 | 2007-05-29 | Massachusetts Institute Of Technology | Ligands for metals and improved metal-catalyzed processes based thereon |
BR122018071968B8 (pt) | 2003-11-06 | 2021-07-27 | Seattle Genetics Inc | conjugado de anticorpo-droga, composição farmacêutica, artigo de manufatura e uso de um conjugado de anticorpo-droga |
-
2021
- 2021-07-09 BR BR112023000320A patent/BR112023000320A2/pt unknown
- 2021-07-09 CN CN202180037849.4A patent/CN115697967A/zh active Pending
- 2021-07-09 WO PCT/CN2021/105436 patent/WO2022007940A1/zh unknown
- 2021-07-09 US US18/004,532 patent/US20230250077A1/en active Pending
- 2021-07-09 CA CA3184959A patent/CA3184959A1/en active Pending
- 2021-07-09 TW TW110125329A patent/TW202214565A/zh unknown
- 2021-07-09 EP EP21837191.2A patent/EP4180422A4/en active Pending
- 2021-07-09 JP JP2023501236A patent/JP2023533735A/ja active Pending
- 2021-07-09 KR KR1020237004479A patent/KR20230038231A/ko unknown
- 2021-07-09 MX MX2023000346A patent/MX2023000346A/es unknown
- 2021-07-09 AU AU2021306781A patent/AU2021306781A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005049593A2 (en) * | 2003-11-13 | 2005-06-02 | Abbott Laboratories | N-acylsulfonamide apoptosis promoters |
WO2012017251A1 (en) * | 2010-08-06 | 2012-02-09 | Astrazeneca Ab | N-acylsulfonamide apoptosis promoters |
CN110483501A (zh) * | 2016-08-05 | 2019-11-22 | 密歇根大学董事会 | 作为bcl-2抑制剂的n-(苯基磺酰基)苯甲酰胺及相关化合物 |
CN110312531A (zh) * | 2017-02-22 | 2019-10-08 | 阿斯利康(瑞典)有限公司 | 治疗性树枝状体 |
US20200216442A1 (en) * | 2017-06-26 | 2020-07-09 | Shenzhen Targetrx, Inc. | Benzenesulfonylbenazamide compound for inhibiting bcl-2 protein and composition and use thereof |
Non-Patent Citations (1)
Title |
---|
郭翠翠 等: "新型邻苯磺酰氨基苯甲酰胺类化合物的合成与抗肿瘤活性", 《天津医科大学学报》, vol. 19, no. 4, pages 275 - 278 * |
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AU2021306781A1 (en) | 2023-03-02 |
TW202214565A (zh) | 2022-04-16 |
JP2023533735A (ja) | 2023-08-04 |
CA3184959A1 (en) | 2022-01-13 |
EP4180422A1 (en) | 2023-05-17 |
US20230250077A1 (en) | 2023-08-10 |
KR20230038231A (ko) | 2023-03-17 |
EP4180422A4 (en) | 2024-01-24 |
MX2023000346A (es) | 2023-02-13 |
BR112023000320A2 (pt) | 2023-01-31 |
WO2022007940A1 (zh) | 2022-01-13 |
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