KR20170042779A - Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 - Google Patents
Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 Download PDFInfo
- Publication number
- KR20170042779A KR20170042779A KR1020177007523A KR20177007523A KR20170042779A KR 20170042779 A KR20170042779 A KR 20170042779A KR 1020177007523 A KR1020177007523 A KR 1020177007523A KR 20177007523 A KR20177007523 A KR 20177007523A KR 20170042779 A KR20170042779 A KR 20170042779A
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- South Korea
- Prior art keywords
- alkyl
- independently
- cycloalkyl
- alkenyl
- compound
- Prior art date
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- Abandoned
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- 0 *C(*)(CCN)O Chemical compound *C(*)(CCN)O 0.000 description 3
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N C(C1)C2CNC1CC2 Chemical compound C(C1)C2CNC1CC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 description 1
- IUFRXYVUJWLFFS-UHFFFAOYSA-N C(C1)C2CNCC1NC2 Chemical compound C(C1)C2CNCC1NC2 IUFRXYVUJWLFFS-UHFFFAOYSA-N 0.000 description 1
- LKDJYZBKCVSODK-UHFFFAOYSA-N C(C1)C2NC1CNC2 Chemical compound C(C1)C2NC1CNC2 LKDJYZBKCVSODK-UHFFFAOYSA-N 0.000 description 1
- MNILDQSRDHCFJG-UHFFFAOYSA-N C(C1)C2NC1COC2 Chemical compound C(C1)C2NC1COC2 MNILDQSRDHCFJG-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N C(C1)N2CCN1CC2 Chemical compound C(C1)N2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- UKHJNJFJCGBKSF-UHFFFAOYSA-N C1C2NCC1NC2 Chemical compound C1C2NCC1NC2 UKHJNJFJCGBKSF-UHFFFAOYSA-N 0.000 description 1
- DIQOUXNTSMWQSA-UHFFFAOYSA-N C1C2OCC1NC2 Chemical compound C1C2OCC1NC2 DIQOUXNTSMWQSA-UHFFFAOYSA-N 0.000 description 1
- LBUJPTNKIBCYBY-UHFFFAOYSA-N C1CNc2ccccc2C1 Chemical compound C1CNc2ccccc2C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 1
- UWYZHKAOTLEWKK-UHFFFAOYSA-N C1c2ccccc2CNC1 Chemical compound C1c2ccccc2CNC1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 1
- FVNZGNCAFDFMHZ-UHFFFAOYSA-N CC1(C(CCO)=CC=C1)Cl Chemical compound CC1(C(CCO)=CC=C1)Cl FVNZGNCAFDFMHZ-UHFFFAOYSA-N 0.000 description 1
- WIBDULCBRAOYRF-UHFFFAOYSA-N CS(C)(C)(CCC1)(c2c1cccc2)O Chemical compound CS(C)(C)(CCC1)(c2c1cccc2)O WIBDULCBRAOYRF-UHFFFAOYSA-N 0.000 description 1
- RVXLBLSGEPQBIO-UHFFFAOYSA-N O=C(c(c(N1)c2)ccc2Cl)C1=O Chemical compound O=C(c(c(N1)c2)ccc2Cl)C1=O RVXLBLSGEPQBIO-UHFFFAOYSA-N 0.000 description 1
- OYCCXFOJXYCRID-UHFFFAOYSA-N O=C(c(cc1)c(N2)nc1Cl)C2=O Chemical compound O=C(c(cc1)c(N2)nc1Cl)C2=O OYCCXFOJXYCRID-UHFFFAOYSA-N 0.000 description 1
- OAYDJYXDTFGOFW-UHFFFAOYSA-N O=C1Nc2nc(Cl)ccc2C1(Br)Br Chemical compound O=C1Nc2nc(Cl)ccc2C1(Br)Br OAYDJYXDTFGOFW-UHFFFAOYSA-N 0.000 description 1
- CJZFOZAQGBLEFL-UHFFFAOYSA-N O=S(CCC1)c2c1cccc2 Chemical compound O=S(CCC1)c2c1cccc2 CJZFOZAQGBLEFL-UHFFFAOYSA-N 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N O=S1(CCCC1)=O Chemical compound O=S1(CCCC1)=O HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- HEAHLTGDUHXTTO-UHFFFAOYSA-N O=S1(CNCC1)=O Chemical compound O=S1(CNCC1)=O HEAHLTGDUHXTTO-UHFFFAOYSA-N 0.000 description 1
- ISXOBTBCNRIIQO-UHFFFAOYSA-N O=S1CCCC1 Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 description 1
- KZPUZEPLLNUDDZ-UHFFFAOYSA-N O=S1CNCC1 Chemical compound O=S1CNCC1 KZPUZEPLLNUDDZ-UHFFFAOYSA-N 0.000 description 1
- OOLPPEOLSCAABY-UHFFFAOYSA-N OCC/N=C(/c(c(N1)c2)ccc2Cl)\C1=O Chemical compound OCC/N=C(/c(c(N1)c2)ccc2Cl)\C1=O OOLPPEOLSCAABY-UHFFFAOYSA-N 0.000 description 1
- DNRHQDUNEHMQQR-AJAPIDPKSA-N OC[C@@H](C[C@@H]1c(cccc2Cl)c2F)N[C@@]1(c(ccc(Cl)c1)c1N1)C1=O Chemical compound OC[C@@H](C[C@@H]1c(cccc2Cl)c2F)N[C@@]1(c(ccc(Cl)c1)c1N1)C1=O DNRHQDUNEHMQQR-AJAPIDPKSA-N 0.000 description 1
- BSMXUUQWSKXVJY-SNAWJCMRSA-N [O-][N+](/C=C/c1cccc(Cl)c1F)=O Chemical compound [O-][N+](/C=C/c1cccc(Cl)c1F)=O BSMXUUQWSKXVJY-SNAWJCMRSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/20—Spiro-condensed systems
-
- 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
- A61K31/435—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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/20—Spiro-condensed systems
-
- 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
- C07D471/22—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 systems contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Polymers & Plastics (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020237020952A KR102627097B1 (ko) | 2014-08-21 | 2015-08-20 | Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14181746 | 2014-08-21 | ||
| EP14181746.0 | 2014-08-21 | ||
| PCT/EP2015/069174 WO2016026937A1 (en) | 2014-08-21 | 2015-08-20 | New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237020952A Division KR102627097B1 (ko) | 2014-08-21 | 2015-08-20 | Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20170042779A true KR20170042779A (ko) | 2017-04-19 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237020952A Active KR102627097B1 (ko) | 2014-08-21 | 2015-08-20 | Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 |
| KR1020177007523A Abandoned KR20170042779A (ko) | 2014-08-21 | 2015-08-20 | Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237020952A Active KR102627097B1 (ko) | 2014-08-21 | 2015-08-20 | Mdm2-p53 억제제로서의 신규 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체 |
Country Status (26)
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015155332A1 (en) | 2014-04-11 | 2015-10-15 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors |
| WO2016001376A1 (en) | 2014-07-03 | 2016-01-07 | Boehringer Ingelheim International Gmbh | New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| EP3183254B1 (en) | 2014-08-21 | 2019-05-22 | Boehringer Ingelheim International GmbH | New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| NO2721710T3 (cg-RX-API-DMAC7.html) | 2014-08-21 | 2018-03-31 | ||
| CN108137590B (zh) | 2015-10-09 | 2021-04-09 | 勃林格殷格翰国际有限公司 | 作为mdm2-p53抑制剂的新的螺(3h-吲哚-3,2′-吡咯烷)-2(1h)-酮化合物及其衍生物 |
| RU2743432C2 (ru) | 2016-04-06 | 2021-02-18 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Деструкторы белка mdm2 |
| JP2019522633A (ja) | 2016-05-20 | 2019-08-15 | ジェネンテック， インコーポレイテッド | Ｐｒｏｔａｃ抗体コンジュゲート及び使用方法 |
| WO2018185135A1 (en) * | 2017-04-05 | 2018-10-11 | Boehringer Ingelheim International Gmbh | Anticancer combination therapy |
| CN107290543A (zh) * | 2017-05-02 | 2017-10-24 | 南方医科大学 | 一种检测细胞内与p53转录激活域相互作用蛋白的方法 |
| EP3511334A1 (en) * | 2018-01-16 | 2019-07-17 | Adamed sp. z o.o. | 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53 |
| JP2020193181A (ja) * | 2019-05-30 | 2020-12-03 | 東ソー株式会社 | 芳香族ニトリル化合物の製造方法 |
| KR20220035038A (ko) * | 2019-07-17 | 2022-03-21 | 녹소팜 리미티드 | 이소플라본 화합물을 사용하는 면역종양학 요법 |
| EP4157837B1 (en) | 2020-06-02 | 2024-12-18 | Boehringer Ingelheim International GmbH | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| CN116583275A (zh) * | 2020-09-21 | 2023-08-11 | 诺华股份有限公司 | 用于治疗或预防造血细胞移植后血液肿瘤复发的mdm2抑制剂 |
| CN112375086A (zh) * | 2020-12-11 | 2021-02-19 | 浙江工业大学 | 一种手性螺[呋喃-3,3′-假吲哚]-2-酮类化合物的制备方法 |
| RU2770902C1 (ru) * | 2021-05-24 | 2022-04-25 | Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) | 3-Арил-6H-спиро[бензо[b]фуро[3',4':2,3]пирроло[1,2-d][1,4]оксазин 5,3'-индолин]-1,2,2',6-тетраоны, обладающие противовоспалительной активностью, и способ их получения |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| US20250129096A1 (en) | 2021-12-01 | 2025-04-24 | Boehringer Ingelheim Int'l GmbH Corp. | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| TW202337432A (zh) | 2021-12-01 | 2023-10-01 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物 |
| US20250313553A1 (en) | 2021-12-01 | 2025-10-09 | Boehringer Ingelheim Int'l GmbH Corp. | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| IL312905A (en) | 2021-12-01 | 2024-07-01 | Boehringer Ingelheim Int | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| WO2023099620A1 (en) | 2021-12-01 | 2023-06-08 | Boehringer Ingelheim International Gmbh | Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes |
| CN114831991B (zh) * | 2022-06-10 | 2024-02-06 | 陕西科技大学 | Gsk2334470用于制备抗真菌药物及其增效剂的应用 |
| US11944604B1 (en) | 2023-03-10 | 2024-04-02 | King Saud University | Nanoformulation of spriooxindole and methods for treating hepatocellular carcinoma |
| WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
| TW202511268A (zh) | 2023-05-30 | 2025-03-16 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療癌症之螺環狀2-胺基-3-氰基噻吩及衍生物 |
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| BR112018007161B1 (pt) | 2015-10-09 | 2024-01-16 | Galapagos Nv | COMPOSTOS PIRAZOLO[3,4-b]PIRIDIN-6-CARBOXAMIDA N-SULFONILADA, COMPOSIÇÃO FARMACÊUTICA CONTENDO OS DITOS COMPOSTOS E USOS DOS MESMOS PARA TRATAR FIBROSE CÍSTICA |
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