JP2018520195A5 - - Google Patents
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- JP2018520195A5 JP2018520195A5 JP2018502355A JP2018502355A JP2018520195A5 JP 2018520195 A5 JP2018520195 A5 JP 2018520195A5 JP 2018502355 A JP2018502355 A JP 2018502355A JP 2018502355 A JP2018502355 A JP 2018502355A JP 2018520195 A5 JP2018520195 A5 JP 2018520195A5
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- compound
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- haloalkyl
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- 150000001875 compounds Chemical class 0.000 claims description 144
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
- -1 cyano, amino Chemical group 0.000 claims description 37
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 30
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 28
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 28
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 28
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 28
- 125000002837 carbocyclic group Chemical group 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 102200124918 NRAS G12C Human genes 0.000 claims description 16
- 230000035772 mutation Effects 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 102100009283 HRAS Human genes 0.000 claims description 14
- 101710033925 HRAS Proteins 0.000 claims description 14
- 102100009279 KRAS Human genes 0.000 claims description 14
- 101710033922 KRAS Proteins 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
- 239000000203 mixture Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 102200006538 KRAS G12C Human genes 0.000 claims description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
- 235000018102 proteins Nutrition 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 102200006614 HRAS G12C Human genes 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims description 4
- 201000011231 colorectal cancer Diseases 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 230000001404 mediated Effects 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 230000035755 proliferation Effects 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- 235000002407 Jessenia polycarpa Nutrition 0.000 claims description 2
- 244000232488 Jessenia polycarpa Species 0.000 claims description 2
- 206010027476 Metastasis Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N OBO Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 125000005418 aryl aryl group Chemical group 0.000 claims description 2
- 230000003833 cell viability Effects 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 2
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 230000000051 modifying Effects 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrugs Drugs 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 102100001119 NRAS Human genes 0.000 claims 2
- 101710033916 NRAS Proteins 0.000 claims 2
- 230000002489 hematologic Effects 0.000 claims 2
- 206010056981 Adenomatous polyposis coli Diseases 0.000 claims 1
- 0 CC(C(C)=*)C(C(*)=N[C@@]1C=C(C)*)=C(**)[C@]1C=IC=CC Chemical compound CC(C(C)=*)C(C(*)=N[C@@]1C=C(C)*)=C(**)[C@]1C=IC=CC 0.000 description 6
- 201000005787 hematologic cancer Diseases 0.000 description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N Amino radical Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562195636P | 2015-07-22 | 2015-07-22 | |
US62/195,636 | 2015-07-22 | ||
US201662342078P | 2016-05-26 | 2016-05-26 | |
US62/342,078 | 2016-05-26 | ||
JOP/2016/0150A JOP20160150B1 (ar) | 2015-07-22 | 2016-07-21 | مركبات كينازولين مستبدلة وطرق استعمالها |
GCGC-2016-31750 | 2016-07-21 | ||
JO150/2016 | 2016-07-21 | ||
GC201631750 | 2016-07-21 | ||
PCT/US2016/043568 WO2017015562A1 (en) | 2015-07-22 | 2016-07-22 | Substituted quinazoline compounds and their use as inhibitors of g12c mutant kras, hras and/or nras proteins |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018520195A JP2018520195A (ja) | 2018-07-26 |
JP2018520195A5 true JP2018520195A5 (uk) | 2019-08-15 |
JP6869947B2 JP6869947B2 (ja) | 2021-05-12 |
Family
ID=57821530
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018502355A Active JP6869947B2 (ja) | 2015-07-22 | 2016-07-22 | 置換キナゾリン化合物ならびにそのg12c変異kras、hrasおよび/またはnrasタンパク質の阻害剤としての使用 |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP3325447A1 (uk) |
JP (1) | JP6869947B2 (uk) |
CA (1) | CA2993013A1 (uk) |
MX (1) | MX2018000777A (uk) |
WO (1) | WO2017015562A1 (uk) |
Families Citing this family (81)
Publication number | Priority date | Publication date | Assignee | Title |
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US9227978B2 (en) | 2013-03-15 | 2016-01-05 | Araxes Pharma Llc | Covalent inhibitors of Kras G12C |
JO3805B1 (ar) | 2013-10-10 | 2021-01-31 | Araxes Pharma Llc | مثبطات كراس جي12سي |
JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
ES2826443T3 (es) | 2014-09-25 | 2021-05-18 | Araxes Pharma Llc | Inhibidores de proteínas mutantes KRAS G12C |
US10011600B2 (en) | 2014-09-25 | 2018-07-03 | Araxes Pharma Llc | Methods and compositions for inhibition of Ras |
KR20180005178A (ko) | 2015-04-10 | 2018-01-15 | 아락세스 파마 엘엘씨 | 치환된 퀴나졸린 화합물 및 이의 사용방법 |
JP6789239B2 (ja) | 2015-04-15 | 2020-11-25 | アラクセス ファーマ エルエルシー | Krasの縮合三環系インヒビターおよびその使用の方法 |
US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
US10858343B2 (en) | 2015-09-28 | 2020-12-08 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
US10875842B2 (en) | 2015-09-28 | 2020-12-29 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
EP3356349A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
EP3356351A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
US10882847B2 (en) | 2015-09-28 | 2021-01-05 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
EP3356339A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
EP3356354A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
WO2017070256A2 (en) | 2015-10-19 | 2017-04-27 | Araxes Pharma Llc | Method for screening inhibitors of ras |
EA038635B9 (ru) | 2015-11-16 | 2021-10-26 | Араксис Фарма Ллк | 2-замещенные соединения хиназолина, содержащие замещенную гетероциклическую группу, и способы их применения |
WO2017100546A1 (en) | 2015-12-09 | 2017-06-15 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
CN109311868B (zh) | 2015-12-22 | 2022-04-01 | 尚医治疗有限责任公司 | 用于治疗癌症和炎性疾病的化合物 |
US10822312B2 (en) | 2016-03-30 | 2020-11-03 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use |
US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
JP2019529484A (ja) | 2016-09-29 | 2019-10-17 | アラクセス ファーマ エルエルシー | Kras g12c変異体タンパク質の阻害剤 |
CN110312711A (zh) | 2016-10-07 | 2019-10-08 | 亚瑞克西斯制药公司 | 作为ras抑制剂的杂环化合物及其使用方法 |
RS62456B1 (sr) | 2016-12-22 | 2021-11-30 | Amgen Inc | Derivati benzizotiazola, izotiazolo[3,4-b]piridina, hinazolina, ftalazina, pirido[2,3-d]piridazina i pirido[2,3-d]pirimidina kao kras g12c inhibitori za tretman raka pluća, pankreasa ili debelog creva |
JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
BR112019024674A2 (pt) | 2017-05-25 | 2020-06-16 | Araxes Pharma Llc | Inibidores covalentes da kras |
JP2020521741A (ja) * | 2017-05-25 | 2020-07-27 | アラクセス ファーマ エルエルシー | がんの処置のための化合物およびその使用の方法 |
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US11306132B2 (en) * | 2017-09-20 | 2022-04-19 | The United States Of America, As Represented By The Secretary Department Of Health And Human Services | HLA class II-restricted T cell receptors against mutated RAS |
TW201938561A (zh) | 2017-12-08 | 2019-10-01 | 瑞典商阿斯特捷利康公司 | 化學化合物 |
TW201942115A (zh) * | 2018-02-01 | 2019-11-01 | 美商輝瑞股份有限公司 | 作為抗癌藥之經取代的喹唑啉和吡啶並嘧啶衍生物 |
MA52501A (fr) | 2018-05-04 | 2021-03-10 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
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MX2020014116A (es) * | 2018-06-27 | 2021-06-15 | Reborna Biosciences Inc | Agente profilactico o terapeutico para atrofia muscular espinal. |
SG11202102679QA (en) | 2018-09-18 | 2021-04-29 | Nikang Therapeutics Inc | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
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JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Kras g12c阻害剤化合物の重要な中間体の改良合成法 |
JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのkrasg12c阻害剤及び1種以上の薬学的に活性な追加の薬剤を含む併用療法 |
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EP3924053A1 (en) | 2019-02-12 | 2021-12-22 | Novartis AG | Pharmaceutical combination comprising tno155 and a krasg12c inhibitor |
JP7426398B2 (ja) | 2019-02-26 | 2024-02-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ras阻害剤としての新規イソインドリノン置換インドールおよび誘導体 |
EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
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TW202132316A (zh) | 2019-11-04 | 2021-09-01 | 美商銳新醫藥公司 | Ras抑制劑 |
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WO2023240024A1 (en) | 2022-06-08 | 2023-12-14 | Nikang Therapeutics, Inc. | Sulfamide derivatives as cyclin-dependent kinase 2 inhibitors |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
GB202212641D0 (en) | 2022-08-31 | 2022-10-12 | Jazz Pharmaceuticals Ireland Ltd | Novel compounds |
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WO2024102849A1 (en) | 2022-11-11 | 2024-05-16 | Nikang Therapeutics, Inc. | Bifunctional compounds containing 2,5-substituted pyrimidine derivatives for degrading cyclin-dependent kinase 2 via ubiquitin proteasome pathway |
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Publication number | Priority date | Publication date | Assignee | Title |
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TWI271406B (en) * | 1999-12-13 | 2007-01-21 | Eisai Co Ltd | Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same |
JP2002371078A (ja) * | 2001-06-12 | 2002-12-26 | Sankyo Co Ltd | キノリン誘導体及びキノロン誘導体 |
AU2002352444A1 (en) * | 2001-12-20 | 2003-07-09 | Celltech R And D Limited | Quinazolinedione derivatives |
US7368445B2 (en) * | 2004-03-01 | 2008-05-06 | Eli Lilly And Company | Fused pyrazole derivatives as TGF-β signal transduction inhibitors for the treatment of fibrosis and neoplasms |
TW200643015A (en) * | 2005-03-11 | 2006-12-16 | Akzo Nobel Nv | 2-(4-oxo-4H-quinazolin-3-yl)acetamide derivatives |
SG10201505951VA (en) * | 2010-07-30 | 2015-08-28 | Oncotherapy Science Inc | Quinoline derivatives and melk inhibitors containing the same |
CN105407894A (zh) * | 2013-03-14 | 2016-03-16 | 康威基内有限公司 | 用于抑制含布罗莫结构域的蛋白质的方法和组合物 |
EP3055290B1 (en) * | 2013-10-10 | 2019-10-02 | Araxes Pharma LLC | Inhibitors of kras g12c |
EP3124482B1 (en) * | 2014-03-24 | 2019-09-11 | Guangdong Zhongsheng Pharmaceutical Co., Ltd | Quinoline derivatives as smo inhibitors |
-
2016
- 2016-07-22 EP EP16747678.7A patent/EP3325447A1/en not_active Withdrawn
- 2016-07-22 WO PCT/US2016/043568 patent/WO2017015562A1/en active Application Filing
- 2016-07-22 CA CA2993013A patent/CA2993013A1/en not_active Abandoned
- 2016-07-22 JP JP2018502355A patent/JP6869947B2/ja active Active
- 2016-07-22 MX MX2018000777A patent/MX2018000777A/es unknown
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