JP2018536649A - イミダゾ［４，５−ｃ］キノリン−２−オン化合物及び癌の治療におけるその使用 - Google Patents
イミダゾ［４，５−ｃ］キノリン−２−オン化合物及び癌の治療におけるその使用 Download PDFInfo
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- JP2018536649A JP2018536649A JP2018522026A JP2018522026A JP2018536649A JP 2018536649 A JP2018536649 A JP 2018536649A JP 2018522026 A JP2018522026 A JP 2018522026A JP 2018522026 A JP2018522026 A JP 2018522026A JP 2018536649 A JP2018536649 A JP 2018536649A
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- Prior art keywords
- methyl
- imidazo
- quinolin
- phenyl
- dimethylamino
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 90
- 201000011510 cancer Diseases 0.000 title claims abstract description 84
- NSHFLKZNBPJNPA-UHFFFAOYSA-N imidazo[4,5-c]quinolin-2-one Chemical class C1=CC=C2C3=NC(=O)N=C3C=NC2=C1 NSHFLKZNBPJNPA-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 238000011282 treatment Methods 0.000 title claims description 88
- 150000003839 salts Chemical class 0.000 claims abstract description 226
- 150000001875 compounds Chemical class 0.000 claims abstract description 220
- 239000000126 substance Substances 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 29
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- -1 3-methoxycyclobut-1-yl Chemical group 0.000 claims description 121
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 241001465754 Metazoa Species 0.000 claims description 38
- 238000001959 radiotherapy Methods 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 230000000259 anti-tumor effect Effects 0.000 claims description 32
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- 125000002393 azetidinyl group Chemical group 0.000 claims description 16
- 125000003386 piperidinyl group Chemical group 0.000 claims description 16
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 238000002560 therapeutic procedure Methods 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- VICUFCKPAORKNQ-FYYLOGMGSA-N 8-[4-[3-(dimethylamino)propoxy]phenyl]-1-[(1R,3R)-3-methoxycyclopentyl]-3-methylimidazo[4,5-c]quinolin-2-one Chemical compound CN(CCCOC1=CC=C(C=C1)C1=CC=2C3=C(C=NC=2C=C1)N(C(N3[C@H]1C[C@@H](CC1)OC)=O)C)C VICUFCKPAORKNQ-FYYLOGMGSA-N 0.000 claims description 7
- VICUFCKPAORKNQ-GMAHTHKFSA-N 8-[4-[3-(dimethylamino)propoxy]phenyl]-1-[(1S,3S)-3-methoxycyclopentyl]-3-methylimidazo[4,5-c]quinolin-2-one Chemical compound CN(CCCOC1=CC=C(C=C1)C1=CC=2C3=C(C=NC=2C=C1)N(C(N3[C@@H]1C[C@H](CC1)OC)=O)C)C VICUFCKPAORKNQ-GMAHTHKFSA-N 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- PBQDFTZTPPULAN-AZGAKELHSA-N 1-[(1S,3R)-3-methoxycyclohexyl]-3-methyl-8-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]imidazo[4,5-c]quinolin-2-one Chemical compound CO[C@@H]1CCC[C@@H](C1)n1c2c(cnc3ccc(cc23)-c2ccc(OCCCN3CCCC3)cc2)n(C)c1=O PBQDFTZTPPULAN-AZGAKELHSA-N 0.000 claims description 6
- GLIDQHAUAKRTCP-FQEVSTJZSA-N 8-[4-[2-(dimethylamino)ethoxy]phenyl]-3-methyl-1-[(3S)-oxan-3-yl]imidazo[4,5-c]quinolin-2-one Chemical compound CN(CCOC1=CC=C(C=C1)C1=CC=2C3=C(C=NC=2C=C1)N(C(N3[C@@H]1COCCC1)=O)C)C GLIDQHAUAKRTCP-FQEVSTJZSA-N 0.000 claims description 6
- BWFJHLCIUJECFJ-UPVQGACJSA-N 8-[4-[3-(dimethylamino)propoxy]phenyl]-1-[(1S,3S)-3-methoxycyclohexyl]-3-methylimidazo[4,5-c]quinolin-2-one Chemical compound CN(CCCOC1=CC=C(C=C1)C1=CC=2C3=C(C=NC=2C=C1)N(C(N3[C@@H]1C[C@H](CCC1)OC)=O)C)C BWFJHLCIUJECFJ-UPVQGACJSA-N 0.000 claims description 6
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- BWFJHLCIUJECFJ-LADGPHEKSA-N 8-[4-[3-(dimethylamino)propoxy]phenyl]-1-[(1S,3R)-3-methoxycyclohexyl]-3-methylimidazo[4,5-c]quinolin-2-one Chemical compound CN(CCCOC1=CC=C(C=C1)C1=CC=2C3=C(C=NC=2C=C1)N(C(N3[C@@H]1C[C@@H](CCC1)OC)=O)C)C BWFJHLCIUJECFJ-LADGPHEKSA-N 0.000 claims description 5
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- CTSQGUOQTINESS-PZJWPPBQSA-N 8-[4-[3-(dimethylamino)propoxy]phenyl]-7-fluoro-1-[(1S,3R)-3-methoxycyclopentyl]-3-methylimidazo[4,5-c]quinolin-2-one Chemical compound CO[C@@H]1CC[C@@H](C1)n1c2c(cnc3cc(F)c(cc23)-c2ccc(OCCCN(C)C)cc2)n(C)c1=O CTSQGUOQTINESS-PZJWPPBQSA-N 0.000 claims description 4
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- OHUHVTCQTUDPIJ-JYCIKRDWSA-N ceralasertib Chemical compound C[C@@H]1COCCN1C1=CC(C2(CC2)[S@](C)(=N)=O)=NC(C=2C=3C=CNC=3N=CC=2)=N1 OHUHVTCQTUDPIJ-JYCIKRDWSA-N 0.000 claims description 4
- 229950009791 durvalumab Drugs 0.000 claims description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- QWLLFXDZPBLPOP-AHWVRZQESA-N 1-[(1S,3S)-3-methoxycyclopentyl]-3-methyl-8-[4-(3-piperidin-1-ylpropoxy)phenyl]imidazo[4,5-c]quinolin-2-one Chemical compound CO[C@H]1CC[C@@H](C1)N1C(=O)N(C)C2=C1C1=CC(=CC=C1N=C2)C1=CC=C(OCCCN2CCCCC2)C=C1 QWLLFXDZPBLPOP-AHWVRZQESA-N 0.000 claims description 3
- VPQISSQURVSVEH-UHFFFAOYSA-N 1-cyclobutyl-8-[4-[2-(dimethylamino)ethoxy]phenyl]-3-methylimidazo[4,5-c]quinolin-2-one Chemical compound C1(CCC1)N1C(N(C=2C=NC=3C=CC(=CC=3C=21)C1=CC=C(C=C1)OCCN(C)C)C)=O VPQISSQURVSVEH-UHFFFAOYSA-N 0.000 claims description 3
- HNGQMAWSKLQFDG-UHFFFAOYSA-N 3-methyl-1-(oxan-4-yl)-8-[4-(3-piperidin-1-ylpropoxy)phenyl]imidazo[4,5-c]quinolin-2-one Chemical compound CN1C(N(C2=C1C=NC=1C=CC(=CC2=1)C1=CC=C(C=C1)OCCCN1CCCCC1)C1CCOCC1)=O HNGQMAWSKLQFDG-UHFFFAOYSA-N 0.000 claims description 3
- FASVMHFSMHRYNN-HSZRJFAPSA-N 3-methyl-1-[(3R)-oxan-3-yl]-8-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]imidazo[4,5-c]quinolin-2-one Chemical compound CN1C(N(C2=C1C=NC=1C=CC(=CC2=1)C1=CC=C(C=C1)OCCCN1CCCC1)[C@H]1COCCC1)=O FASVMHFSMHRYNN-HSZRJFAPSA-N 0.000 claims description 3
- FASVMHFSMHRYNN-QHCPKHFHSA-N 3-methyl-1-[(3S)-oxan-3-yl]-8-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]imidazo[4,5-c]quinolin-2-one Chemical compound CN1C(N(C2=C1C=NC=1C=CC(=CC2=1)C1=CC=C(C=C1)OCCCN1CCCC1)[C@@H]1COCCC1)=O FASVMHFSMHRYNN-QHCPKHFHSA-N 0.000 claims description 3
- IGOJVOACVMDYGE-QHCPKHFHSA-N 3-methyl-1-[(3S)-oxolan-3-yl]-8-[4-(3-piperidin-1-ylpropoxy)phenyl]imidazo[4,5-c]quinolin-2-one Chemical compound CN1C(N(C2=C1C=NC=1C=CC(=CC2=1)C1=CC=C(C=C1)OCCCN1CCCCC1)[C@@H]1COCC1)=O IGOJVOACVMDYGE-QHCPKHFHSA-N 0.000 claims description 3
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- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- A61K31/28—Compounds containing heavy metals
- A61K31/282—Platinum compounds
-
- 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
- A61K31/407—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 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GB1519406.1 | 2015-11-03 | ||
| GBGB1519406.1A GB201519406D0 (en) | 2015-11-03 | 2015-11-03 | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| PCT/EP2016/076412 WO2017076895A1 (en) | 2015-11-03 | 2016-11-02 | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
Publications (2)
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| JP2018536649A true JP2018536649A (ja) | 2018-12-13 |
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| EP (1) | EP3371183A1 (enExample) |
| JP (1) | JP2018536649A (enExample) |
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| SV (1) | SV2018005663A (enExample) |
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Families Citing this family (19)
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| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| WO2019057757A1 (en) | 2017-09-20 | 2019-03-28 | Astrazeneca Ab | 1,3-DIHYDROIMIDAZO [4,5-C] CINNOLIN-2-ONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER |
| WO2019201283A1 (en) * | 2018-04-20 | 2019-10-24 | Xrad Therapeutics, Inc. | Dual atm and dna-pk inhibitors for use in anti-tumor therapy |
| CN110386932A (zh) | 2018-04-20 | 2019-10-29 | 艾科思莱德制药公司 | 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂 |
| US12226414B2 (en) | 2018-09-14 | 2025-02-18 | Suzhou Zanrong Pharma Limited | 1-isopropyl-3-methyl-8-(pyridin-3-yl)-1,3-dihydro-2H-imidazo[4,5-c] cinnolin-2-one as selective modulators of ataxia telangiectasia mutated (ATM) kinase and uses thereof |
| KR102345208B1 (ko) | 2018-09-30 | 2021-12-30 | 메드샤인 디스커버리 아이엔씨. | 퀴놀리노-피롤리딘-2-온 유도체 및 이의 응용 |
| CR20210504A (es) * | 2019-03-05 | 2022-02-08 | Astrazeneca Ab | Compuestos tricíclicos condensados útiles como agentes anticancerígenos |
| CN114746421A (zh) * | 2019-11-19 | 2022-07-12 | 南京明德新药研发有限公司 | 作为atm抑制剂的有取代的喹啉吡咯酮类合物及其应用 |
| WO2021139814A1 (zh) * | 2020-01-09 | 2021-07-15 | 南京明德新药研发有限公司 | 喹啉并咪唑类化合物及其应用 |
| CN115380031A (zh) * | 2020-03-30 | 2022-11-22 | 南京明德新药研发有限公司 | 作为atm抑制剂的喹啉并吡咯烷-2-酮类化合物的晶型及其应用 |
| EP4171651A1 (en) | 2020-06-24 | 2023-05-03 | AstraZeneca UK Limited | Combination of antibody-drug conjugate and atm inhibitor |
| JP7669473B2 (ja) * | 2020-09-21 | 2025-04-28 | ウェイ ジョン | 血液脳関門透過能力を有する置換１－（３，３－ジフルオロピペリジン－４－イル）－イミダゾ［４，５－ｃ］キノリン－２－オン化合物 |
| EP3992191A1 (en) | 2020-11-03 | 2022-05-04 | Deutsches Krebsforschungszentrum | Imidazo[4,5-c]quinoline compounds and their use as atm kinase inhibitors |
| WO2022128833A1 (en) | 2020-12-15 | 2022-06-23 | Merck Patent Gmbh | Solid transition metal-ligand complexes |
| WO2022193166A1 (en) | 2021-03-17 | 2022-09-22 | Suzhou Zanrong Pharma Limited | Selective modulators of ataxia telangiectasia mutated (atm) kinase and uses thereof |
| KR20240138097A (ko) * | 2022-01-26 | 2024-09-20 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | 히드라진기 함유 화합물 |
| WO2023200427A1 (en) * | 2022-04-11 | 2023-10-19 | Wei Zhong | Substituted 1-(3,3-difluoropiperidin-4-yl)-imidazo[4,5-c] quinolin-2-one derivative crystal form, salt crystal form, preparation method and application |
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| CN102803259A (zh) * | 2009-06-04 | 2012-11-28 | 诺瓦提斯公司 | 用于治疗增殖性疾病的1H-咪唑并[4,5-c]喹啉酮化合物 |
| CN102372711B (zh) * | 2010-08-18 | 2014-09-17 | 山东轩竹医药科技有限公司 | 咪唑并喹啉类PI3K和mTOR双重抑制剂 |
| CN102399218A (zh) * | 2010-09-16 | 2012-04-04 | 和记黄埔医药（上海）有限公司 | 一类并合三杂环及其作为pi3k抑制剂的用途 |
| NO2714752T3 (enExample) * | 2014-05-08 | 2018-04-21 | ||
| DK3277681T3 (da) * | 2015-04-02 | 2019-07-29 | Merck Patent Gmbh | Imidazolonylquinoliner og deres anvendelse som atm-kinaseinhibitorer |
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2015
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2016
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- 2016-11-02 CN CN201680063688.5A patent/CN108349971A/zh active Pending
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- 2016-11-02 JP JP2018522026A patent/JP2018536649A/ja not_active Withdrawn
- 2016-11-02 BR BR112018007772A patent/BR112018007772A2/pt not_active Application Discontinuation
- 2016-11-02 KR KR1020187015448A patent/KR20180070703A/ko not_active Withdrawn
- 2016-11-02 US US15/772,118 patent/US20180318287A1/en not_active Abandoned
- 2016-11-02 PE PE2018000612A patent/PE20181345A1/es unknown
- 2016-11-02 CR CR20180307A patent/CR20180307A/es unknown
- 2016-11-02 HK HK18114727.1A patent/HK1255598A1/zh unknown
- 2016-11-02 WO PCT/EP2016/076412 patent/WO2017076895A1/en not_active Ceased
- 2016-11-02 RU RU2018120318A patent/RU2018120318A/ru not_active Application Discontinuation
- 2016-11-02 MX MX2018005445A patent/MX2018005445A/es unknown
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2018
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Also Published As
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| IL258818A (en) | 2018-06-28 |
| AU2016348546A1 (en) | 2018-06-14 |
| AU2016348546B2 (en) | 2019-05-02 |
| CN108349971A (zh) | 2018-07-31 |
| RU2018120318A3 (enExample) | 2019-12-24 |
| KR20180070703A (ko) | 2018-06-26 |
| CO2018003969A2 (es) | 2018-07-10 |
| CR20180307A (es) | 2018-10-05 |
| RU2018120318A (ru) | 2019-12-05 |
| US20180318287A1 (en) | 2018-11-08 |
| PE20181345A1 (es) | 2018-08-22 |
| HK1257678A1 (zh) | 2019-10-25 |
| EP3371183A1 (en) | 2018-09-12 |
| CA3002608A1 (en) | 2017-05-11 |
| BR112018007772A2 (pt) | 2018-10-30 |
| SV2018005663A (es) | 2018-07-20 |
| PH12018500958A1 (en) | 2018-11-19 |
| CL2018001146A1 (es) | 2018-09-04 |
| GB201519406D0 (en) | 2015-12-16 |
| WO2017076895A1 (en) | 2017-05-11 |
| MX2018005445A (es) | 2018-08-14 |
| HK1255598A1 (zh) | 2019-08-23 |
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