JP2019530724A5 - - Google Patents
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- JP2019530724A5 JP2019530724A5 JP2019520406A JP2019520406A JP2019530724A5 JP 2019530724 A5 JP2019530724 A5 JP 2019530724A5 JP 2019520406 A JP2019520406 A JP 2019520406A JP 2019520406 A JP2019520406 A JP 2019520406A JP 2019530724 A5 JP2019530724 A5 JP 2019530724A5
- Authority
- JP
- Japan
- Prior art keywords
- optionally substituted
- alkyl
- hydrogen
- aryl
- heterocyclic
- 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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- 150000001875 compounds Chemical class 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims 64
- 229910052739 hydrogen Inorganic materials 0.000 claims 54
- 239000001257 hydrogen Substances 0.000 claims 50
- 125000000623 heterocyclic group Chemical group 0.000 claims 48
- 125000003118 aryl group Chemical group 0.000 claims 47
- 125000000547 substituted alkyl group Chemical group 0.000 claims 39
- 125000001072 heteroaryl group Chemical group 0.000 claims 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 34
- 125000002837 carbocyclic group Chemical group 0.000 claims 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims 26
- 239000008194 pharmaceutical composition Substances 0.000 claims 26
- 125000003342 alkenyl group Chemical group 0.000 claims 24
- 150000002148 esters Chemical class 0.000 claims 20
- 239000000651 prodrug Substances 0.000 claims 20
- 229940002612 prodrug Drugs 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 20
- 150000002431 hydrogen Chemical class 0.000 claims 16
- -1 pyrrolidino, phenyl Chemical group 0.000 claims 16
- 125000001424 substituent group Chemical group 0.000 claims 16
- 229910052717 sulfur Inorganic materials 0.000 claims 13
- 229910052757 nitrogen Inorganic materials 0.000 claims 12
- 125000003545 alkoxy group Chemical group 0.000 claims 11
- 125000005843 halogen group Chemical group 0.000 claims 11
- 229910052760 oxygen Inorganic materials 0.000 claims 11
- 125000000304 alkynyl group Chemical group 0.000 claims 10
- 125000005842 heteroatom Chemical group 0.000 claims 10
- 125000004429 atom Chemical group 0.000 claims 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 9
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 8
- 201000010099 disease Diseases 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 208000010706 fatty liver disease Diseases 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 125000004076 pyridyl group Chemical group 0.000 claims 6
- 101000885387 Homo sapiens Serine/threonine-protein kinase DCLK2 Proteins 0.000 claims 5
- 102100039775 Serine/threonine-protein kinase DCLK2 Human genes 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000004122 cyclic group Chemical group 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 230000005764 inhibitory process Effects 0.000 claims 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims 4
- 125000001544 thienyl group Chemical group 0.000 claims 4
- 108091000080 Phosphotransferase Proteins 0.000 claims 3
- 230000004663 cell proliferation Effects 0.000 claims 3
- 230000001419 dependent effect Effects 0.000 claims 3
- 230000001404 mediated effect Effects 0.000 claims 3
- 102000020233 phosphotransferase Human genes 0.000 claims 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 2
- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims 1
- 101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 claims 1
- 208000023514 Barrett esophagus Diseases 0.000 claims 1
- 208000023665 Barrett oesophagus Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000004930 Fatty Liver Diseases 0.000 claims 1
- 206010019708 Hepatic steatosis Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 1
- 208000026589 Wolman disease Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 230000002394 glycogenic effect Effects 0.000 claims 1
- 231100000283 hepatitis Toxicity 0.000 claims 1
- 208000006454 hepatitis Diseases 0.000 claims 1
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
- 208000019423 liver disease Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical group CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 230000035935 pregnancy Effects 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 210000003079 salivary gland Anatomy 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 231100000240 steatosis hepatitis Toxicity 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662409457P | 2016-10-18 | 2016-10-18 | |
| US62/409,457 | 2016-10-18 | ||
| PCT/US2017/057126 WO2018075608A1 (en) | 2016-10-18 | 2017-10-18 | Pyrimido-diazepinone kinase scaffold compounds and methods of treating dclk1/2-mediated disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019530724A JP2019530724A (ja) | 2019-10-24 |
| JP2019530724A5 true JP2019530724A5 (https=) | 2020-11-26 |
| JP7086948B2 JP7086948B2 (ja) | 2022-06-20 |
Family
ID=62018969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019520406A Active JP7086948B2 (ja) | 2016-10-18 | 2017-10-18 | ピリミド－ジアゼピノンキナーゼ骨格化合物およびｄｃｌｋ１／２媒介性障害の治療方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US11028089B2 (https=) |
| EP (1) | EP3528814B1 (https=) |
| JP (1) | JP7086948B2 (https=) |
| AU (1) | AU2017346845B2 (https=) |
| CA (1) | CA3040173A1 (https=) |
| WO (1) | WO2018075608A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11155556B2 (en) * | 2016-04-07 | 2021-10-26 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone kinase scaffold compounds and methods for treating PI3K-mediated disorders |
| AU2018392805A1 (en) * | 2017-12-22 | 2020-05-07 | Dana-Farber Cancer Institute, Inc. | NEK inhibitors and methods of use |
| WO2020206608A1 (en) | 2019-04-09 | 2020-10-15 | Ranok Therapeutics (Hangzhou) Co., Ltd. | Methods and compositions for targeted protein degradation |
| US20220280530A1 (en) * | 2019-08-08 | 2022-09-08 | Anhui Newstar Pharmaceutical Development Co., Ltd. | Prevention or treatment of diseases and disorders associated with tissue damage |
| CN115515589A (zh) * | 2020-02-14 | 2022-12-23 | 萨克生物研究学院 | Ulk1/2抑制剂及其使用方法 |
| KR20220153582A (ko) | 2020-02-14 | 2022-11-18 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 마크로시클릭 ulk1/2 억제제 |
| CA3195448A1 (en) * | 2020-10-14 | 2022-04-21 | Weiwen Ying | Methods and compositions for targeted protein degradation |
| US20240254138A1 (en) * | 2021-03-09 | 2024-08-01 | Janssen Pharmaceutica Nv | Tricyclic pyrimidines as cyclin-dependent kinase 7 (cdk7) inhibitors |
| CN115707469B (zh) * | 2021-08-19 | 2024-07-02 | 首都医科大学附属北京朝阳医院 | Dclk1抑制剂和tki在制备肺腺癌药物中的应用 |
| CN114478539B (zh) * | 2022-02-09 | 2024-02-02 | 中国人民解放军海军军医大学 | 一种新型dclk1抑制剂及其制备方法和应用 |
| CN115969978A (zh) * | 2022-10-27 | 2023-04-18 | 首都医科大学附属北京朝阳医院 | Dclk1及il6/stat3通路抑制剂在治疗三阴性乳腺癌中的应用 |
| CN115814094B (zh) * | 2023-01-04 | 2024-04-02 | 暨南大学附属第一医院（广州华侨医院） | Dclk抑制剂在制备治疗脊髓损伤的药物中的应用 |
| CN116375713B (zh) * | 2023-03-07 | 2024-11-19 | 中国人民解放军海军军医大学 | 一种dclk1蛋白降解靶向嵌合体及其应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2379559B1 (en) * | 2009-01-06 | 2017-10-25 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders |
| JP6110787B2 (ja) * | 2011-05-10 | 2017-04-05 | 協和発酵キリン株式会社 | ピリミドジアゼピノン化合物 |
| WO2014160430A1 (en) * | 2013-03-13 | 2014-10-02 | Georgetown University | Small molecule lrrk2 and erk5 inhibitors |
| WO2014145909A2 (en) * | 2013-03-15 | 2014-09-18 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone compounds and methods of treating disorders |
| WO2015117087A1 (en) * | 2014-01-31 | 2015-08-06 | Dana-Farber Cancer Institute, Inc. | Uses of diazepane derivatives |
| BR112016017045A2 (pt) * | 2014-01-31 | 2017-08-08 | Dana Farber Cancer Inst Inc | Derivados de diazepano e usos dos mesmos |
| CN106715437A (zh) * | 2014-08-08 | 2017-05-24 | 达纳-法伯癌症研究所股份有限公司 | 二氮杂环庚烷衍生物及其用途 |
| JP6815318B2 (ja) * | 2014-12-23 | 2021-01-20 | ダナ−ファーバー キャンサー インスティテュート，インコーポレイテッド | 二官能性分子によって標的化タンパク質分解を誘導する方法 |
| US9694084B2 (en) * | 2014-12-23 | 2017-07-04 | Dana-Farber Cancer Institute, Inc. | Methods to induce targeted protein degradation through bifunctional molecules |
| RU2748696C2 (ru) * | 2016-03-04 | 2021-05-28 | Аньхой Нью Стар Фармасьютикал Дивелопмент Ко., Лтд | Пиридиновые соединения, содержащие семь атомов в кольце, способ их получения, фармацевтическая композиция, содержащая указанные соединения, и их применение |
-
2017
- 2017-10-18 EP EP17862888.9A patent/EP3528814B1/en active Active
- 2017-10-18 WO PCT/US2017/057126 patent/WO2018075608A1/en not_active Ceased
- 2017-10-18 CA CA3040173A patent/CA3040173A1/en active Pending
- 2017-10-18 JP JP2019520406A patent/JP7086948B2/ja active Active
- 2017-10-18 US US16/343,102 patent/US11028089B2/en active Active
- 2017-10-18 AU AU2017346845A patent/AU2017346845B2/en active Active