CN102548963A - 新颖的作为MDM2-p53相互作用抑制剂的N经取代的吡咯烷类化合物 - Google Patents
新颖的作为MDM2-p53相互作用抑制剂的N经取代的吡咯烷类化合物 Download PDFInfo
- Publication number
- CN102548963A CN102548963A CN2010800461741A CN201080046174A CN102548963A CN 102548963 A CN102548963 A CN 102548963A CN 2010800461741 A CN2010800461741 A CN 2010800461741A CN 201080046174 A CN201080046174 A CN 201080046174A CN 102548963 A CN102548963 A CN 102548963A
- Authority
- CN
- China
- Prior art keywords
- chloro
- phenyl
- fluoro
- dimethyl
- tetramethyleneimine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 C[C@@]([C@@](*)(c1cccc(I)*1*)N(*)C1)([C@@]1(CC(*)(*)*)I)c1ccc(*)cc1*=C Chemical compound C[C@@]([C@@](*)(c1cccc(I)*1*)N(*)C1)([C@@]1(CC(*)(*)*)I)c1ccc(*)cc1*=C 0.000 description 2
- LEOQGWFKCSHZTE-UXBLZVDNSA-N CC(C)(C)C/C=C(/c(c(F)c1)ccc1Cl)\C#N Chemical compound CC(C)(C)C/C=C(/c(c(F)c1)ccc1Cl)\C#N LEOQGWFKCSHZTE-UXBLZVDNSA-N 0.000 description 1
- KMWJIUUVZAGJHS-UJMBSWQDSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cc(Cl)ccc2)C(NCC[C@@H](CO)O)=O)C1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cc(Cl)ccc2)C(NCC[C@@H](CO)O)=O)C1(c(c(F)c1)ccc1Cl)C#N KMWJIUUVZAGJHS-UJMBSWQDSA-N 0.000 description 1
- PIOJBQYSLLLCKB-OSDUOIJGSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(N2CCC(CC(O)=O)CC2)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(N2CCC(CC(O)=O)CC2)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N PIOJBQYSLLLCKB-OSDUOIJGSA-N 0.000 description 1
- ZNAOPVRHWFKFNJ-KBWZXQCUSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCCC(N)=O)=O)C1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCCC(N)=O)=O)C1(c(c(F)c1)ccc1Cl)C#N ZNAOPVRHWFKFNJ-KBWZXQCUSA-N 0.000 description 1
- JLHRMQAWWQYEFV-ZSRPKCNMSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCCCC(NC)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCCCC(NC)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N JLHRMQAWWQYEFV-ZSRPKCNMSA-N 0.000 description 1
- GLAVWTBVMORNAA-SNMFSRKCSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCc(cc2)cc(F)c2C(O)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCc(cc2)cc(F)c2C(O)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N GLAVWTBVMORNAA-SNMFSRKCSA-N 0.000 description 1
- NRYDHRPCHWVEDU-KFTYYEIZSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCc(cc2)cc(OC)c2C(O)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(NCc(cc2)cc(OC)c2C(O)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N NRYDHRPCHWVEDU-KFTYYEIZSA-N 0.000 description 1
- LCFIRQPPGMRTRF-UXRLXBOWSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(Nc(cc2)cc(OC)c2C(O)=[IH])=O)[C@@]1(c(ccc(Cl)c1)c1F)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(Nc(cc2)cc(OC)c2C(O)=[IH])=O)[C@@]1(c(ccc(Cl)c1)c1F)C#N LCFIRQPPGMRTRF-UXRLXBOWSA-N 0.000 description 1
- SHNLZFBEQAPIJR-JJZKUNFFSA-N CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(Nc(cc2)ccc2C(O)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N Chemical compound CC(C)(C)C[C@H](CN([C@@H]1c2cccc(Cl)c2F)C(Nc(cc2)ccc2C(O)=O)=O)[C@@]1(c(c(F)c1)ccc1Cl)C#N SHNLZFBEQAPIJR-JJZKUNFFSA-N 0.000 description 1
- YBYAUYKHQWYPSD-LURJTMIESA-N CC1(C)O[C@@H](CCN)CO1 Chemical compound CC1(C)O[C@@H](CCN)CO1 YBYAUYKHQWYPSD-LURJTMIESA-N 0.000 description 1
- VSFAAGWKSYWSIX-UHFFFAOYSA-N CN(C)Cc(cccc1Cl)c1Cl Chemical compound CN(C)Cc(cccc1Cl)c1Cl VSFAAGWKSYWSIX-UHFFFAOYSA-N 0.000 description 1
- PVHMYONDAPXJSB-QPJJXVBHSA-N COC(c1ccc(/C=C/C(O)=O)cc1)=O Chemical compound COC(c1ccc(/C=C/C(O)=O)cc1)=O PVHMYONDAPXJSB-QPJJXVBHSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25141309P | 2009-10-14 | 2009-10-14 | |
| US61/251,413 | 2009-10-14 | ||
| US34562610P | 2010-05-18 | 2010-05-18 | |
| US61/345,626 | 2010-05-18 | ||
| PCT/EP2010/065159 WO2011045257A1 (en) | 2009-10-14 | 2010-10-11 | Novel n-substituted-pyrrolidines as inhibitors of mdm2-p-53 interactions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102548963A true CN102548963A (zh) | 2012-07-04 |
Family
ID=43567698
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010800461741A Pending CN102548963A (zh) | 2009-10-14 | 2010-10-11 | 新颖的作为MDM2-p53相互作用抑制剂的N经取代的吡咯烷类化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8017607B2 (2) |
| EP (1) | EP2488491A1 (2) |
| JP (1) | JP2013507416A (2) |
| KR (1) | KR20120081210A (2) |
| CN (1) | CN102548963A (2) |
| AU (1) | AU2010305914A1 (2) |
| BR (1) | BR112012008485A2 (2) |
| CA (1) | CA2774512A1 (2) |
| IL (1) | IL218018A0 (2) |
| IN (1) | IN2012DN02487A (2) |
| MX (1) | MX2012003982A (2) |
| WO (1) | WO2011045257A1 (2) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2952522B1 (en) | 2007-01-31 | 2019-10-30 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| AU2008232709C1 (en) | 2007-03-28 | 2015-01-15 | President And Fellows Of Harvard College | Stitched polypeptides |
| US8354444B2 (en) * | 2008-09-18 | 2013-01-15 | Hoffmann-La Roche Inc. | Substituted pyrrolidine-2-carboxamides |
| US20110118283A1 (en) * | 2009-11-17 | 2011-05-19 | Qingjie Ding | Substituted Pyrrolidine-2-Carboxamides |
| KR20170058446A (ko) | 2010-08-13 | 2017-05-26 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| WO2012076513A1 (en) * | 2010-12-09 | 2012-06-14 | F. Hoffmann-La Roche Ag | 3-cyano-1-hydroxymethyl-2-phenylpyrrolidine derivatives as inhibitors of mdm2-p53 interactions useful for the treatment of cancer |
| AU2012226890B2 (en) | 2011-03-10 | 2016-10-06 | Daiichi Sankyo Company, Limited | Dispiropyrrolidine derivative |
| AR088392A1 (es) | 2011-10-18 | 2014-05-28 | Aileron Therapeutics Inc | Macrociclos peptidomimeticos |
| CA2862038C (en) | 2012-02-15 | 2021-05-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| TWI586668B (zh) | 2012-09-06 | 2017-06-11 | 第一三共股份有限公司 | 二螺吡咯啶衍生物之結晶 |
| BR112015009470A2 (pt) | 2012-11-01 | 2019-12-17 | Aileron Therapeutics Inc | aminoácidos dissubstituídos e seus métodos de preparação e uso |
| TW201429969A (zh) | 2012-12-20 | 2014-08-01 | Merck Sharp & Dohme | 作爲ｈｄｍ２抑制劑之經取代咪唑吡啶 |
| WO2016049359A1 (en) | 2014-09-24 | 2016-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| SG11201702175YA (en) | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and formulations thereof |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| JP2018528217A (ja) | 2015-09-10 | 2018-09-27 | エルロン・セラピューティクス・インコーポレイテッドＡｉｌｅｒｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | Ｍｃｌ−１のモジュレーターとしてのペプチド模倣大環状分子 |
| EP3458101B1 (en) | 2016-05-20 | 2020-12-30 | H. Hoffnabb-La Roche Ag | Protac antibody conjugates and methods of use |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0947511A1 (en) | 1998-03-30 | 1999-10-06 | F. Hoffmann-La Roche Ag | Derivatives of phenoxy acetic acid and of phenoxymethyl tetrazole having antitumor activity |
| NZ516452A (en) | 1999-07-21 | 2004-06-25 | Astrazeneca Ab | Spirooxindole Derivatives |
| WO2005099687A2 (en) | 2004-04-09 | 2005-10-27 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| US7423051B2 (en) | 2004-07-15 | 2008-09-09 | Hoffmann-La Roche Inc. | 2,6-diaminopyridine derivatives |
| KR100944301B1 (ko) | 2005-02-22 | 2010-02-24 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Ｍｄｍ２의 소분자 억제제 및 이의 용도 |
| BRPI0710477A2 (pt) | 2006-01-18 | 2011-08-16 | Hoffmann La Roche | cis-4, 5- biarila - 2- imidazolinas heterocìclicas como inibidores da mdm2 |
| CN101595107A (zh) | 2006-06-30 | 2009-12-02 | 先灵公司 | 能提高p53活性的有取代哌啶及其用途 |
| AU2009294673B2 (en) | 2008-09-18 | 2014-08-14 | F. Hoffmann-La Roche Ag | Substituted pyrrolidine-2-carboxamides |
-
2010
- 2010-10-06 US US12/898,974 patent/US8017607B2/en not_active Expired - Fee Related
- 2010-10-11 EP EP10768450A patent/EP2488491A1/en not_active Withdrawn
- 2010-10-11 AU AU2010305914A patent/AU2010305914A1/en not_active Abandoned
- 2010-10-11 BR BR112012008485A patent/BR112012008485A2/pt not_active IP Right Cessation
- 2010-10-11 MX MX2012003982A patent/MX2012003982A/es not_active Application Discontinuation
- 2010-10-11 CA CA2774512A patent/CA2774512A1/en not_active Abandoned
- 2010-10-11 JP JP2012533592A patent/JP2013507416A/ja active Pending
- 2010-10-11 IN IN2487DEN2012 patent/IN2012DN02487A/en unknown
- 2010-10-11 KR KR1020127012100A patent/KR20120081210A/ko not_active Ceased
- 2010-10-11 WO PCT/EP2010/065159 patent/WO2011045257A1/en not_active Ceased
- 2010-10-11 CN CN2010800461741A patent/CN102548963A/zh active Pending
-
2012
- 2012-02-09 IL IL218018A patent/IL218018A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2012003982A (es) | 2012-05-08 |
| KR20120081210A (ko) | 2012-07-18 |
| US20110086854A1 (en) | 2011-04-14 |
| IN2012DN02487A (2) | 2015-08-28 |
| WO2011045257A1 (en) | 2011-04-21 |
| JP2013507416A (ja) | 2013-03-04 |
| IL218018A0 (en) | 2012-04-30 |
| CA2774512A1 (en) | 2011-04-21 |
| US8017607B2 (en) | 2011-09-13 |
| BR112012008485A2 (pt) | 2019-09-24 |
| AU2010305914A1 (en) | 2012-03-08 |
| EP2488491A1 (en) | 2012-08-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120704 |