JPWO2019178590A5 - - Google Patents
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- JPWO2019178590A5 JPWO2019178590A5 JP2020548995A JP2020548995A JPWO2019178590A5 JP WO2019178590 A5 JPWO2019178590 A5 JP WO2019178590A5 JP 2020548995 A JP2020548995 A JP 2020548995A JP 2020548995 A JP2020548995 A JP 2020548995A JP WO2019178590 A5 JPWO2019178590 A5 JP WO2019178590A5
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- alkyl
- heterocycloalkyl
- cycloalkyl
- groups
- 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.)
- Granted
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- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 23
- 125000000217 alkyl group Chemical group 0.000 claims 21
- 150000001875 compounds Chemical class 0.000 claims 14
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 14
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 10
- 206010028980 Neoplasm Diseases 0.000 claims 8
- 201000011510 cancer Diseases 0.000 claims 8
- -1 cyano, hydroxy Chemical group 0.000 claims 7
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 150000002367 halogens Chemical class 0.000 claims 7
- 125000004043 oxo group Chemical group O=* 0.000 claims 7
- 239000008194 pharmaceutical composition Substances 0.000 claims 7
- 125000003118 aryl group Chemical group 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 125000001188 haloalkyl group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 4
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical group C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000004429 atom Chemical group 0.000 claims 4
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 239000011593 sulfur Substances 0.000 claims 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 3
- 108091000080 Phosphotransferase Proteins 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 102000020233 phosphotransferase Human genes 0.000 claims 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- HFTVJMFWJUFBNO-UHFFFAOYSA-N 5h-pyrrolo[2,3-b]pyrazine Chemical group C1=CN=C2NC=CC2=N1 HFTVJMFWJUFBNO-UHFFFAOYSA-N 0.000 claims 2
- 101000581289 Homo sapiens Microcephalin Proteins 0.000 claims 2
- 102100027632 Microcephalin Human genes 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 230000033590 base-excision repair Effects 0.000 claims 2
- 230000007547 defect Effects 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 201000010536 head and neck cancer Diseases 0.000 claims 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 208000016691 refractory malignant neoplasm Diseases 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- ZKAMEFMDQNTDFK-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyrazine Chemical group C1=CN=C2NC=NC2=N1 ZKAMEFMDQNTDFK-UHFFFAOYSA-N 0.000 claims 1
- DDZGQYREBDXECY-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyrazine Chemical group C1=CN=C2C=NNC2=N1 DDZGQYREBDXECY-UHFFFAOYSA-N 0.000 claims 1
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical group C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims 1
- NMEPLWZDUIIAAC-UHFFFAOYSA-N 1h-pyrazolo[4,3-c]pyridazine Chemical group C1=NN=C2C=NNC2=C1 NMEPLWZDUIIAAC-UHFFFAOYSA-N 0.000 claims 1
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical group C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 claims 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical group C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical group C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 claims 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims 1
- BXOVRVJPVVRHKP-UHFFFAOYSA-N 7h-pyrrolo[2,3-c]pyridazine Chemical group C1=NN=C2NC=CC2=C1 BXOVRVJPVVRHKP-UHFFFAOYSA-N 0.000 claims 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical group N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims 1
- 206010004593 Bile duct cancer Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 230000005778 DNA damage Effects 0.000 claims 1
- 231100000277 DNA damage Toxicity 0.000 claims 1
- 239000012623 DNA damaging agent Substances 0.000 claims 1
- 102100039524 DNA endonuclease RBBP8 Human genes 0.000 claims 1
- 102100039116 DNA repair protein RAD50 Human genes 0.000 claims 1
- 102100033996 Double-strand break repair protein MRE11 Human genes 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 102100034533 Histone H2AX Human genes 0.000 claims 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 claims 1
- 101000743929 Homo sapiens DNA repair protein RAD50 Proteins 0.000 claims 1
- 101000591400 Homo sapiens Double-strand break repair protein MRE11 Proteins 0.000 claims 1
- 101001067891 Homo sapiens Histone H2AX Proteins 0.000 claims 1
- 101000581326 Homo sapiens Mediator of DNA damage checkpoint protein 1 Proteins 0.000 claims 1
- 101001128138 Homo sapiens NACHT, LRR and PYD domains-containing protein 2 Proteins 0.000 claims 1
- 101000981336 Homo sapiens Nibrin Proteins 0.000 claims 1
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 claims 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 102100027643 Mediator of DNA damage checkpoint protein 1 Human genes 0.000 claims 1
- 102100024403 Nibrin Human genes 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 101150097169 RBBP8 gene Proteins 0.000 claims 1
- 206010039491 Sarcoma Diseases 0.000 claims 1
- 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 102100029538 Structural maintenance of chromosomes protein 1A Human genes 0.000 claims 1
- 102000000504 Tumor Suppressor p53-Binding Protein 1 Human genes 0.000 claims 1
- 108010041385 Tumor Suppressor p53-Binding Protein 1 Proteins 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 230000001668 ameliorated effect Effects 0.000 claims 1
- 208000026900 bile duct neoplasm Diseases 0.000 claims 1
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical group C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 208000006990 cholangiocarcinoma Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 230000002950 deficient Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 201000008968 osteosarcoma Diseases 0.000 claims 1
- 150000003216 pyrazines Chemical class 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 230000001235 sensitizing effect Effects 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 108010004731 structural maintenance of chromosome protein 1 Proteins 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862644189P | 2018-03-16 | 2018-03-16 | |
| US62/644,189 | 2018-03-16 | ||
| PCT/US2019/022727 WO2019178590A1 (en) | 2018-03-16 | 2019-03-18 | Heterocyclic inhibitors of atr kinase |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021518344A JP2021518344A (ja) | 2021-08-02 |
| JPWO2019178590A5 true JPWO2019178590A5 (https=) | 2022-03-22 |
| JP2021518344A5 JP2021518344A5 (https=) | 2022-03-22 |
| JP7341156B2 JP7341156B2 (ja) | 2023-09-08 |
Family
ID=67904811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020548995A Active JP7341156B2 (ja) | 2018-03-16 | 2019-03-18 | Ａｔｒキナーゼの複素環式阻害剤 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US10894052B2 (https=) |
| EP (1) | EP3765008B1 (https=) |
| JP (1) | JP7341156B2 (https=) |
| CN (1) | CN112218631B (https=) |
| WO (1) | WO2019178590A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018218197A2 (en) | 2017-05-26 | 2018-11-29 | Board Of Regents, The University Of Texas System | Tetrahydropyrido[4,3-d]pyrimidine inhibitors of atr kinase |
| HUE066043T2 (hu) | 2017-07-13 | 2024-07-28 | Univ Texas | A TR kináz beterociklusos inhibitorai |
| JP7290627B2 (ja) | 2017-08-17 | 2023-06-13 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | Ａｔｒキナーゼの複素環式阻害剤 |
| JP7341156B2 (ja) | 2018-03-16 | 2023-09-08 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | Ａｔｒキナーゼの複素環式阻害剤 |
| WO2022094218A1 (en) * | 2020-10-29 | 2022-05-05 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Process for the preparation of heteroaryl-substituted sulfur(vi) compounds |
| IL308409A (en) * | 2021-05-12 | 2024-01-01 | Chia Tai Tianqing Pharmaceutical Group Co Ltd | Sulfoximine-containing atr inhibitor compound |
| KR20220156468A (ko) * | 2021-05-18 | 2022-11-25 | 온코닉 테라퓨틱스 주식회사 | Parp 저해제 저항성 암 치료제 |
| WO2023131234A1 (en) * | 2022-01-06 | 2023-07-13 | Shanghai Antengene Corporation Limited | Crystalline forms of an atr inhibitor |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009523161A (ja) | 2006-01-11 | 2009-06-18 | アストラゼネカ アクチボラグ | モルホリノピリミジン誘導体と療法におけるその使用 |
| MX2009002046A (es) | 2006-08-24 | 2009-03-06 | Astrazeneca Ab | Derivados de morfolino pirimidina utiles en el tratamiento de trastornos proliferativos. |
| WO2008032072A1 (en) | 2006-09-14 | 2008-03-20 | Astrazeneca Ab | 2-benzimidaz0lyl-6-m0rph0lin0-4-piperidin-4-ylpyrimidine derivatives as pi3k and mtor inhibitors for the treatment of proliferative disorders |
| WO2008125833A1 (en) | 2007-04-12 | 2008-10-23 | Piramed Limited | Pharmaceutical compounds |
| US20080292588A1 (en) | 2007-05-17 | 2008-11-27 | Anadys Pharmaceuticals, Inc. | 1-methyl-benzo[1,2,4]thiadiazine 1-oxide derivatives |
| CA2692945A1 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Compounds - 945 |
| CN101809002B (zh) | 2007-07-09 | 2013-03-27 | 阿斯利康(瑞典)有限公司 | 用于与mtor激酶和/或pi3k相关的疾病中的吗啉代嘧啶衍生物 |
| WO2009007751A2 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| US20110015181A1 (en) | 2008-03-06 | 2011-01-20 | Makoto Ando | Alkylaminopyridine derivative |
| CN102143746A (zh) | 2008-07-03 | 2011-08-03 | 埃克塞利希斯股份有限公司 | Cdk 调节剂 |
| US20110053923A1 (en) | 2008-12-22 | 2011-03-03 | Astrazeneca | Chemical compounds 610 |
| WO2010120996A1 (en) | 2009-04-17 | 2010-10-21 | Wyeth Llc | 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
| JP2013032290A (ja) | 2009-11-20 | 2013-02-14 | Dainippon Sumitomo Pharma Co Ltd | 新規縮合ピリミジン誘導体 |
| WO2011106276A1 (en) | 2010-02-25 | 2011-09-01 | Merck Sharp & Dohme Corp. | Task channel antagonists |
| WO2011103715A1 (en) | 2010-02-25 | 2011-09-01 | Merck Sharp & Dohme Corp. | Task channel antagonists |
| US9249129B2 (en) | 2010-03-04 | 2016-02-02 | Cellzome Limited | Morpholino substituted urea derivatives as mTOR inhibitors |
| JP2013526539A (ja) | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用なピラジン |
| SA111320519B1 (ar) | 2010-06-11 | 2014-07-02 | Astrazeneca Ab | مركبات بيريميدينيل للاستخدام كمثبطات atr |
| UA112517C2 (uk) | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| WO2012147890A1 (ja) | 2011-04-27 | 2012-11-01 | 持田製薬株式会社 | 新規アゾール誘導体 |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| DK3077397T3 (da) | 2013-12-06 | 2019-12-16 | Vertex Pharma | 2-amino-6-fluor-n-[5-fluor-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamidforbindelse anvendelig som atr-kinase-inhibitor, dens fremstilling, forskellige faste former og radiomarkerede derivater deraf |
| JP6487921B2 (ja) | 2013-12-17 | 2019-03-20 | ファイザー・インク | ＬＲＲＫ２阻害薬としての新規の３，４−二置換−１Ｈ−ピロロ［２，３−ｂ］ピリジンおよび４，５−二置換−７Ｈ−ピロロ［２，３−ｃ］ピリダジン |
| PL3152212T3 (pl) | 2014-06-05 | 2020-06-15 | Vertex Pharmaceuticals Inc. | Radioznakowane pochodne związku 2-amino-6-fluoro-n-[5-fluoro-piridyn-3-ylo]-pirazolo[1,5-a]pirymidino-3-karboksamidu przydatne jako inhibitor kinazy atr, wytwarzanie tego związku i jego różnych postaci stałych |
| TWI700283B (zh) * | 2014-08-04 | 2020-08-01 | 德商拜耳製藥公司 | ２-(嗎啉-４-基)-１,７-萘啶 |
| KR102569226B1 (ko) | 2014-10-13 | 2023-08-22 | 아트린 파마슈티컬스 엘엘씨 | 운동실조 모세혈관확장증 및 Rad3-관련 (ATR) 단백질 키나제 억제제 |
| JP6873145B2 (ja) | 2016-01-14 | 2021-05-19 | バイエル・ファルマ・アクティエンゲゼルシャフト | ５−置換２−（モルホリン−４−イル）−１，７−ナフチリジン |
| AU2017275657B2 (en) | 2016-06-02 | 2021-08-19 | Novartis Ag | Potassium channel modulators |
| WO2018218197A2 (en) | 2017-05-26 | 2018-11-29 | Board Of Regents, The University Of Texas System | Tetrahydropyrido[4,3-d]pyrimidine inhibitors of atr kinase |
| HUE066043T2 (hu) | 2017-07-13 | 2024-07-28 | Univ Texas | A TR kináz beterociklusos inhibitorai |
| JP7290627B2 (ja) | 2017-08-17 | 2023-06-13 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | Ａｔｒキナーゼの複素環式阻害剤 |
| JP7341156B2 (ja) | 2018-03-16 | 2023-09-08 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | Ａｔｒキナーゼの複素環式阻害剤 |
-
2019
- 2019-03-18 JP JP2020548995A patent/JP7341156B2/ja active Active
- 2019-03-18 US US16/356,450 patent/US10894052B2/en active Active
- 2019-03-18 CN CN201980019299.6A patent/CN112218631B/zh active Active
- 2019-03-18 EP EP19767169.6A patent/EP3765008B1/en active Active
- 2019-03-18 WO PCT/US2019/022727 patent/WO2019178590A1/en not_active Ceased
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