CN105102456B - 非典型蛋白激酶c的氮杂喹唑啉抑制剂 - Google Patents
非典型蛋白激酶c的氮杂喹唑啉抑制剂 Download PDFInfo
- Publication number
- CN105102456B CN105102456B CN201380062263.9A CN201380062263A CN105102456B CN 105102456 B CN105102456 B CN 105102456B CN 201380062263 A CN201380062263 A CN 201380062263A CN 105102456 B CN105102456 B CN 105102456B
- Authority
- CN
- China
- Prior art keywords
- bases
- pyrimidine
- pyrido
- base
- pyridine
- 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.)
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Links
- 0 *c1nc(-c2ccncc2)nc2c1ccnc2 Chemical compound *c1nc(-c2ccncc2)nc2c1ccnc2 0.000 description 7
- IDADDVVQRWZAJB-HUUCEWRRSA-N CC(C)(C)OC(N[C@H](COC(OCC=C)=O)[C@@H](c1ccccc1)O)=O Chemical compound CC(C)(C)OC(N[C@H](COC(OCC=C)=O)[C@@H](c1ccccc1)O)=O IDADDVVQRWZAJB-HUUCEWRRSA-N 0.000 description 1
- DCCUPMKSUWAUOE-HPAIREQNSA-N CC(C)(C)[U]C(N/C(/COC(/[O]=C/C=C)=O)=C(\c1ccccc1)/F)=O Chemical compound CC(C)(C)[U]C(N/C(/COC(/[O]=C/C=C)=O)=C(\c1ccccc1)/F)=O DCCUPMKSUWAUOE-HPAIREQNSA-N 0.000 description 1
- DWQKEJJBJKXYOT-UHFFFAOYSA-N CN1C#CCOCC1 Chemical compound CN1C#CCOCC1 DWQKEJJBJKXYOT-UHFFFAOYSA-N 0.000 description 1
- XMHOTRLGMLLWPQ-UHFFFAOYSA-N COC1=C2C(O)=NC(c3ccncc3)=NC2=CNC1 Chemical compound COC1=C2C(O)=NC(c3ccncc3)=NC2=CNC1 XMHOTRLGMLLWPQ-UHFFFAOYSA-N 0.000 description 1
- XUXBZYUJCJQGPF-UHFFFAOYSA-N COc1cncc2c1c(NC1CNCC1)nc(-c1cc(NC3=CCC=CC=C3)ncc1)n2 Chemical compound COc1cncc2c1c(NC1CNCC1)nc(-c1cc(NC3=CCC=CC=C3)ncc1)n2 XUXBZYUJCJQGPF-UHFFFAOYSA-N 0.000 description 1
- BRUGROWMBBPCHL-UHFFFAOYSA-N COc1cncc2c1c(O)nc(S)n2 Chemical compound COc1cncc2c1c(O)nc(S)n2 BRUGROWMBBPCHL-UHFFFAOYSA-N 0.000 description 1
- HSCHIYCNYGYHGZ-UHFFFAOYSA-N Oc1nc(-c2ccncc2)nc2c1c(Br)cnc2 Chemical compound Oc1nc(-c2ccncc2)nc2c1c(Br)cnc2 HSCHIYCNYGYHGZ-UHFFFAOYSA-N 0.000 description 1
- OZYKDPPLEHEFGR-UHFFFAOYSA-N Oc1nc(N2CCOCC2)nc2c1ccnc2Cl Chemical compound Oc1nc(N2CCOCC2)nc2c1ccnc2Cl OZYKDPPLEHEFGR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-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
- A61K31/495—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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged 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
- C07D498/02—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 two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261707340P | 2012-09-28 | 2012-09-28 | |
| US61/707,340 | 2012-09-28 | ||
| US201361781364P | 2013-03-14 | 2013-03-14 | |
| US61/781,364 | 2013-03-14 | ||
| PCT/US2013/062085 WO2014052699A1 (en) | 2012-09-28 | 2013-09-27 | Azaquinazoline inhibitors of atypical protein kinase c |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105102456A CN105102456A (zh) | 2015-11-25 |
| CN105102456B true CN105102456B (zh) | 2017-11-14 |
Family
ID=49326872
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380062263.9A Active CN105102456B (zh) | 2012-09-28 | 2013-09-27 | 非典型蛋白激酶c的氮杂喹唑啉抑制剂 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US9914730B2 (enExample) |
| EP (1) | EP2900666B1 (enExample) |
| JP (1) | JP6535430B2 (enExample) |
| KR (1) | KR102215272B1 (enExample) |
| CN (1) | CN105102456B (enExample) |
| AU (1) | AU2013323360B2 (enExample) |
| BR (1) | BR112015007061B1 (enExample) |
| CA (1) | CA2886495C (enExample) |
| CL (1) | CL2015000781A1 (enExample) |
| EA (1) | EA030253B1 (enExample) |
| IL (1) | IL237918B (enExample) |
| MX (1) | MX372736B (enExample) |
| NZ (1) | NZ706857A (enExample) |
| PH (1) | PH12015500689A1 (enExample) |
| SG (1) | SG11201502301YA (enExample) |
| TW (1) | TWI663165B (enExample) |
| WO (1) | WO2014052699A1 (enExample) |
| ZA (1) | ZA201502783B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6535430B2 (ja) * | 2012-09-28 | 2019-06-26 | イグニタ、インク． | 非定型プロテインキナーゼｃのアザキナゾリン阻害薬 |
| WO2014100501A1 (en) | 2012-12-20 | 2014-06-26 | Sanford-Burnham Medical Research Institute | Small molecule agonists of neurotensin receptor 1 |
| EA029052B1 (ru) | 2013-03-14 | 2018-02-28 | Бёрингер Ингельхайм Интернациональ Гмбх | Замещенные (бензилцианометил)амиды 2-азабицикло[2.2.1]гептан-3-карбоновых кислот в качестве ингибиторов катепсина с |
| ES3069593T3 (en) | 2013-08-23 | 2026-06-09 | Neupharma Inc | Quinazolin-8-yl derivatives for use in methods of treating melanoma, non-small cell lung cancer, thyroid cancer, ovarian cancer, or colon cancer |
| WO2015143376A1 (en) * | 2014-03-21 | 2015-09-24 | Nivalis Therapeutics, Inc. | Novel compounds for the treatment of cystic fibrosis |
| TWI675836B (zh) | 2014-03-25 | 2019-11-01 | 美商伊格尼塔公司 | 非典型蛋白質激酶ｃ之氮雜喹唑啉抑制劑 |
| WO2015200534A2 (en) * | 2014-06-25 | 2015-12-30 | Sanford-Burnham Medical Research Institute | Small molecule agonists of neurotensin receptor 1 |
| WO2016004305A2 (en) | 2014-07-02 | 2016-01-07 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| CA2960101C (en) * | 2014-09-05 | 2024-05-21 | Allosteros Therapeutics, Inc. | Substituted carboline derivative and compositions thereof useful as camkii inhibitors |
| HUE047208T2 (hu) | 2014-09-12 | 2020-04-28 | Boehringer Ingelheim Int | A katepszin-C spirociklikus inhibitorai |
| CN107001358A (zh) * | 2014-10-29 | 2017-08-01 | 东亚St株式会社 | 调节组蛋白赖氨酸脱甲基酶(kdm)催化活性的新型吡啶并嘧啶酮化合物 |
| CN105288512A (zh) * | 2015-12-08 | 2016-02-03 | 李野林 | 一种治疗肥胖症的中药组合物 |
| SG11201809559UA (en) | 2016-06-13 | 2018-12-28 | Glaxosmithkline Ip Dev Ltd | Substituted pyridines as inhibitors of dnmt1 |
| CN109843858B (zh) * | 2016-08-15 | 2023-05-05 | 润新生物公司 | 某些化学实体、组合物及方法 |
| AU2017312970B2 (en) * | 2016-08-16 | 2021-08-12 | Merck Patent Gmbh | 2-oxo-imidazopyridines as reversible BTK inhibitors and uses thereof |
| CN109715163B (zh) | 2016-09-19 | 2022-11-22 | 诺华股份有限公司 | 包含raf抑制剂和erk抑制剂的治疗组合 |
| JOP20190257A1 (ar) * | 2017-04-28 | 2019-10-28 | Novartis Ag | مركبات أريل غير متجانسة ثنائية الحلقة مندمجة 6-6 واستخدامها كمثبطات lats |
| WO2018203219A1 (en) | 2017-05-02 | 2018-11-08 | Novartis Ag | Combination therapy |
| WO2019000683A1 (zh) | 2017-06-30 | 2019-01-03 | 北京泰德制药股份有限公司 | Rho相关蛋白激酶抑制剂、包含其的药物组合物及其制备方法和用途 |
| JP7311228B2 (ja) | 2017-06-30 | 2023-07-19 | ベイジン タイド ファーマシューティカル カンパニー リミテッド | Ｒｈｏ－関連プロテインキナーゼ阻害剤、それを含む医薬組成物並びにその調製方法及び使用 |
| US10329282B2 (en) | 2017-06-30 | 2019-06-25 | Beijing Tide Pharmaceutical Co., Ltd. | Rho-associated protein kinase inhibitor, pharmaceutical composition comprising the same, as well as preparation method and use thereof |
| DK3827005T3 (da) * | 2018-07-25 | 2022-09-19 | Faes Farma Sa | Pyridopyrimidiner som histamin H4-receptorhæmmere |
| EP3831823A4 (en) * | 2018-08-01 | 2022-04-27 | Shanghai Ennovabio Pharmaceuticals Co., Ltd. | PREPARATION AND USE OF AN AROMATIC COMPOUND WITH IMMUNEGULATORY FUNCTION |
| CN111100063B (zh) * | 2018-10-25 | 2022-05-17 | 南京药石科技股份有限公司 | 一种合成2-氟甲基取代的吡咯烷、哌啶以及哌嗪衍生物的制备方法 |
| US20220143028A1 (en) * | 2019-03-28 | 2022-05-12 | Cancer Research Technology Ltd | Inhibitors of atypical protein kinase c and their use in treating hedgehog pathway-dependent cancers |
| EP4563150A3 (en) | 2019-05-13 | 2025-07-23 | Novartis AG | New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl) isonicotinamide as raf inhibitors for the treatment of cancer |
| JP7688690B2 (ja) | 2020-07-28 | 2025-06-04 | スーチュアン・コールン－バイオテック・バイオファーマシューティカル・カンパニー・リミテッド | ピリミジン系化合物の塩、結晶形およびその調製方法 |
| CN116120243B (zh) * | 2021-11-15 | 2025-07-29 | 都创(上海)医药科技股份有限公司 | aPKC抑制剂化合物中间体片段及其制备方法和应用 |
| CN114349711B (zh) * | 2022-02-28 | 2023-08-15 | 四川依维欣医药科技有限公司 | 一种（R）-1-Boc-3-羟甲基哌嗪的合成方法 |
| CN117088898B (zh) * | 2022-05-13 | 2026-02-06 | 中国药科大学 | 稠环嘧啶类化合物及其制备方法、药物组合物和应用 |
| US20260209221A1 (en) * | 2022-12-13 | 2026-07-23 | Windtree Therapeutics, Inc. | Solid forms of {5-cyclopropyl-2-[2-(3,6-difluoro¬pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl }-( (s)-3,3-dimethyl-piperidin-4-yl)-amine |
| CN117343005A (zh) * | 2023-10-08 | 2024-01-05 | 上海泰坦科技股份有限公司 | 一种异烟酸衍生物的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS4936700A (enExample) | 1972-08-16 | 1974-04-05 | ||
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| JP2002080423A (ja) * | 2000-09-06 | 2002-03-19 | Daikin Ind Ltd | トリフルオロ酢酸エチルの合成方法 |
| AU2001290912A1 (en) * | 2000-09-15 | 2002-03-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| FR2846657B1 (fr) | 2002-11-05 | 2004-12-24 | Servier Lab | Nouveaux composes pyridopyrimidinone, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP4895806B2 (ja) * | 2003-04-09 | 2012-03-14 | エクセリクシス， インク． | Ｔｉｅ−２モジュレータと使用方法 |
| US20050038047A1 (en) * | 2003-08-14 | 2005-02-17 | Edwards Paul John | Azaquinazoline derivatives |
| US7582631B2 (en) * | 2004-01-14 | 2009-09-01 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| MX2007010401A (es) * | 2005-02-25 | 2008-02-19 | Kudos Pharm Ltd | Derivados de 2,4-diamino-piridopirimidina y su uso como inhbidores de mtor. |
| JP5227321B2 (ja) * | 2006-08-23 | 2013-07-03 | クドス ファーマシューティカルズ リミテッド | Ｍｔｏｒ阻害剤としての２−メチルモルホリンピリド−、ピラゾ−及びピリミド−ピリミジン誘導体 |
| KR20090052385A (ko) * | 2006-09-08 | 2009-05-25 | 화이자 프로덕츠 인크. | 2-（피리딘-2-일아미노）-피리도［2,3-ｄ］피리미딘-7-온의합성 |
| AU2010289321A1 (en) * | 2009-09-04 | 2012-04-05 | The Regents Of The University Of Michigan | Compositions and methods for treatment of leukemia |
| JP6535430B2 (ja) * | 2012-09-28 | 2019-06-26 | イグニタ、インク． | 非定型プロテインキナーゼｃのアザキナゾリン阻害薬 |
| AU2014249233A1 (en) * | 2013-03-13 | 2015-09-24 | The Regents Of The University Of Michigan | Compositions comprising thienopyrimidine and thienopyridine compounds and methods of use thereof |
| USRE49687E1 (en) * | 2014-09-09 | 2023-10-10 | The Regents Of The University Of Michigan | Thienopyrimidine and thienopyridine compounds and methods of use thereof |
| BR112018012707A2 (pt) * | 2015-12-22 | 2019-01-29 | Vitae Pharmaceuticals Inc | inibidores da interação de menin-mll |
-
2013
- 2013-09-27 JP JP2015534689A patent/JP6535430B2/ja active Active
- 2013-09-27 TW TW102134928A patent/TWI663165B/zh active
- 2013-09-27 KR KR1020157010868A patent/KR102215272B1/ko active Active
- 2013-09-27 BR BR112015007061-2A patent/BR112015007061B1/pt active IP Right Grant
- 2013-09-27 EA EA201590661A patent/EA030253B1/ru not_active IP Right Cessation
- 2013-09-27 CA CA2886495A patent/CA2886495C/en active Active
- 2013-09-27 AU AU2013323360A patent/AU2013323360B2/en not_active Ceased
- 2013-09-27 NZ NZ706857A patent/NZ706857A/en unknown
- 2013-09-27 MX MX2015004016A patent/MX372736B/es active IP Right Grant
- 2013-09-27 EP EP13774578.2A patent/EP2900666B1/en active Active
- 2013-09-27 WO PCT/US2013/062085 patent/WO2014052699A1/en not_active Ceased
- 2013-09-27 US US14/038,915 patent/US9914730B2/en active Active - Reinstated
- 2013-09-27 CN CN201380062263.9A patent/CN105102456B/zh active Active
- 2013-09-27 SG SG11201502301YA patent/SG11201502301YA/en unknown
-
2015
- 2015-03-24 IL IL237918A patent/IL237918B/en active IP Right Grant
- 2015-03-26 PH PH12015500689A patent/PH12015500689A1/en unknown
- 2015-03-27 CL CL2015000781A patent/CL2015000781A1/es unknown
- 2015-04-23 ZA ZA2015/02783A patent/ZA201502783B/en unknown
- 2015-12-18 US US14/975,605 patent/US9896446B2/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 《2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes》;Maurice J. van Eis et al.;《Bioorganic & Medicinal Chemistry Letters》;20111021;第21卷(第24期);第7367–7372页 * |
| 《Structure-Activity Relationships of the Diuretic Activity if Triaza- and Tetraaza-naphthalene compounds》;Kohei nishikawa et al.;《CHEMICAL AND PHARMACEUTICAL BULLETIN 》;19760101;第24卷(第9期);第2057-2077页 * |
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