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
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- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (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) | PH12015500689B1 (enExample) |
| SG (1) | SG11201502301YA (enExample) |
| TW (1) | TWI663165B (enExample) |
| WO (1) | WO2014052699A1 (enExample) |
| ZA (1) | ZA201502783B (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ706857A (en) * | 2012-09-28 | 2018-05-25 | Ignyta Inc | Azaquinazoline inhibitors of atypical protein kinase c |
| EP2938608B1 (en) | 2012-12-20 | 2021-08-04 | Sanford-Burnham Medical Research Institute | Small molecule agonists of neurotensin receptor 1 |
| DK2970283T3 (da) | 2013-03-14 | 2021-01-25 | Boehringer Ingelheim Int | Substituerede 2-aza-bicyclo[2.2.1]heptan-3-carboxylsyre-(benzyl-cyano-methyl)-amider som inhibitorer af cathepsin-c |
| AU2014308616B2 (en) | 2013-08-23 | 2018-12-06 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| 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 |
| JP6599908B2 (ja) | 2014-06-25 | 2019-10-30 | サンフォード−バーンハム メディカル リサーチ インスティテュート | ニューロテンシン受容体１の小分子アゴニスト |
| WO2016004305A2 (en) | 2014-07-02 | 2016-01-07 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| US10759792B2 (en) * | 2014-09-05 | 2020-09-01 | The Johns Hopkins University | CaMKII inhibitors and uses thereof |
| KR102510588B1 (ko) | 2014-09-12 | 2023-03-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 카텝신 c의 스피로사이클릭 억제제 |
| MX2017005346A (es) * | 2014-10-29 | 2017-08-02 | Dong A St Co Ltd | Nuevos compuestos de piridopirimidinona para modular la actividad catalitica de histona lisina desmetilasas (kdm). |
| CN105288512A (zh) * | 2015-12-08 | 2016-02-03 | 李野林 | 一种治疗肥胖症的中药组合物 |
| CA3026226A1 (en) | 2016-06-13 | 2017-12-21 | Glaxosmithkline Intellectual Property Development Limited | Substituted pyridines as inhibitors of dnmt1 |
| EP4006035B1 (en) * | 2016-08-15 | 2023-11-22 | Neupharma, Inc. | Quinazoline derivatives as tyrosine kinase inhibitors for the treatment of cancer |
| JP6954994B2 (ja) * | 2016-08-16 | 2021-10-27 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | 可逆性ｂｔｋ阻害剤としてのオキソ−イミダゾピリジン及びその使用 |
| CA3037456A1 (en) | 2016-09-19 | 2018-03-22 | Novartis Ag | Therapeutic combinations comprising a raf inhibitor and a erk inhibitor |
| JOP20190257A1 (ar) * | 2017-04-28 | 2019-10-28 | Novartis Ag | مركبات أريل غير متجانسة ثنائية الحلقة مندمجة 6-6 واستخدامها كمثبطات lats |
| IL270224B1 (en) | 2017-05-02 | 2024-04-01 | Novartis Ag | Combination therapy employing trametinib and a defined raf inhibitor |
| 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 |
| EP3421465B1 (en) | 2017-06-30 | 2022-10-26 | Beijing Tide Pharmaceutical Co., Ltd. | Rho-associated protein kinase inhibitor, pharmaceutical composition comprising the same, as well as preparation method and use thereof |
| 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 |
| ES2929227T3 (es) * | 2018-07-25 | 2022-11-25 | Faes Farma Sa | Piridopirimidinas como inhibidores del receptor de histamina H4 |
| US20210347785A1 (en) * | 2018-08-01 | 2021-11-11 | Shanghai Ennovabio Pharmaceuticals Co., Ltd. | Preparation and application of aromatic compound having immunoregulatory 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 |
| KR20220002930A (ko) * | 2019-03-28 | 2022-01-07 | 캔써 리서치 테크놀로지 리미티드 | 비정형 단백질 키나제 c의 억제제 및 헷지호그 경로 의존성 암의 치료에서 이의 용도 |
| 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 |
| 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 |
| CN117088898A (zh) * | 2022-05-13 | 2023-11-21 | 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 |
| IL321456A (en) * | 2022-12-13 | 2025-08-01 | 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 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| AU2001296871A1 (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 |
| CA2520323C (en) * | 2003-04-09 | 2013-07-09 | Exelixis, Inc. | Tie-2 modulators and methods of use |
| 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 |
| KR20070113252A (ko) * | 2005-02-25 | 2007-11-28 | 쿠도스 파마슈티칼스 리미티드 | 2,4-디아미노-피리도피리미딘 유도체 및 이의 ｍＴＯＲ억제제로서의 용도 |
| AU2007287430B2 (en) * | 2006-08-23 | 2011-07-21 | Kudos Pharmaceuticals Limited | 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors |
| AU2007297286A1 (en) * | 2006-09-08 | 2008-03-20 | Pfizer Products Inc. | Synthesis of 2-(pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones |
| CA2773131C (en) * | 2009-09-04 | 2015-07-14 | The Regents Of The University Of Michigan | Compositions and methods for treatment of leukemia |
| NZ706857A (en) * | 2012-09-28 | 2018-05-25 | Ignyta Inc | Azaquinazoline inhibitors of atypical protein kinase c |
| BR112015022602A2 (pt) * | 2013-03-13 | 2017-07-18 | Univ Michigan Regents | composições compreendendo compostos de tienopirimidina e tienopiridina e métodos de uso dos mesmos |
| US10246464B2 (en) * | 2014-09-09 | 2019-04-02 | The Regents Of The University Of Michigan | Thienopyrimidine and thienopyridine compounds and methods of use thereof |
| RU2018126774A (ru) * | 2015-12-22 | 2020-01-23 | Витэ Фармасьютикалз, Инк. | Ингибиторы менин-mll взаимодействия |
-
2013
- 2013-09-27 NZ NZ706857A patent/NZ706857A/en unknown
- 2013-09-27 EA EA201590661A patent/EA030253B1/ru not_active IP Right Cessation
- 2013-09-27 US US14/038,915 patent/US9914730B2/en active Active
- 2013-09-27 MX MX2015004016A patent/MX372736B/es active IP Right Grant
- 2013-09-27 JP JP2015534689A patent/JP6535430B2/ja active Active
- 2013-09-27 AU AU2013323360A patent/AU2013323360B2/en active Active
- 2013-09-27 CN CN201380062263.9A patent/CN105102456B/zh active 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 WO PCT/US2013/062085 patent/WO2014052699A1/en not_active Ceased
- 2013-09-27 SG SG11201502301YA patent/SG11201502301YA/en unknown
- 2013-09-27 TW TW102134928A patent/TWI663165B/zh active
- 2013-09-27 EP EP13774578.2A patent/EP2900666B1/en active Active
- 2013-09-27 CA CA2886495A patent/CA2886495C/en active Active
-
2015
- 2015-03-24 IL IL237918A patent/IL237918B/en active IP Right Grant
- 2015-03-26 PH PH12015500689A patent/PH12015500689B1/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 * |
Also Published As
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