JP2020537645A5 - - Google Patents
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- JP2020537645A5 JP2020537645A5 JP2020520323A JP2020520323A JP2020537645A5 JP 2020537645 A5 JP2020537645 A5 JP 2020537645A5 JP 2020520323 A JP2020520323 A JP 2020520323A JP 2020520323 A JP2020520323 A JP 2020520323A JP 2020537645 A5 JP2020537645 A5 JP 2020537645A5
- Authority
- JP
- Japan
- Prior art keywords
- compound according
- halo
- alkyl
- cyano
- optionally substituted
- 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 419
- 125000005843 halogen group Chemical group 0.000 claims description 240
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 125
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 110
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 98
- 229910052799 carbon Inorganic materials 0.000 claims description 68
- 125000005842 heteroatom Chemical group 0.000 claims description 59
- 229910052760 oxygen Inorganic materials 0.000 claims description 59
- 229910052717 sulfur Inorganic materials 0.000 claims description 59
- -1 cyano, hydroxyl Chemical group 0.000 claims description 58
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 44
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- 125000004043 oxo group Chemical group O=* 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 19
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 17
- 150000001721 carbon Chemical group 0.000 claims description 13
- 208000019838 Blood disease Diseases 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 208000014951 hematologic disease Diseases 0.000 claims description 12
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 12
- 125000005647 linker group Chemical group 0.000 claims description 12
- 102100035043 Histone-lysine N-methyltransferase EHMT1 Human genes 0.000 claims description 10
- 102100035042 Histone-lysine N-methyltransferase EHMT2 Human genes 0.000 claims description 10
- 101000877314 Homo sapiens Histone-lysine N-methyltransferase EHMT1 Proteins 0.000 claims description 10
- 101000877312 Homo sapiens Histone-lysine N-methyltransferase EHMT2 Proteins 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 108091000080 Phosphotransferase Proteins 0.000 claims description 7
- 102000020233 phosphotransferase Human genes 0.000 claims description 7
- 206010011703 Cyanosis Diseases 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 201000005787 hematologic cancer Diseases 0.000 claims description 5
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
- 229940124639 Selective inhibitor Drugs 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 3
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 claims description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- 108010055196 EphA2 Receptor Proteins 0.000 claims description 2
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 claims description 2
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims description 2
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims description 2
- 101000977771 Homo sapiens Interleukin-1 receptor-associated kinase 4 Proteins 0.000 claims description 2
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims description 2
- 101001059443 Homo sapiens Serine/threonine-protein kinase MARK1 Proteins 0.000 claims description 2
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 2
- 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 claims description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 2
- 101150028321 Lck gene Proteins 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 102100033610 MAP kinase-interacting serine/threonine-protein kinase 2 Human genes 0.000 claims description 2
- 101710138999 MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims description 2
- 102100028921 Serine/threonine-protein kinase MARK1 Human genes 0.000 claims description 2
- 208000018020 Sickle cell-beta-thalassemia disease syndrome Diseases 0.000 claims description 2
- 206010043391 Thalassaemia beta Diseases 0.000 claims description 2
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 2
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 201000003444 follicular lymphoma Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 239000003112 inhibitor 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
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 208000007056 sickle cell anemia Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 24
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 11
- 125000003282 alkyl amino group Chemical group 0.000 claims 6
- 125000004429 atom Chemical group 0.000 claims 6
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- SWKAVEUTKGKHSR-UHFFFAOYSA-N 3-(benzylsulfamoyl)-4-bromo-n-(4-bromophenyl)benzamide Chemical compound C1=CC(Br)=CC=C1NC(=O)C1=CC=C(Br)C(S(=O)(=O)NCC=2C=CC=CC=2)=C1 SWKAVEUTKGKHSR-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims 1
- 125000006193 alkinyl group Chemical group 0.000 claims 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 description 38
- 150000001345 alkine derivatives Chemical class 0.000 description 18
- 238000000034 method Methods 0.000 description 16
- 125000002947 alkylene group Chemical group 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 0 CCC(C)=NC([*@](*)C1**1)=NC(*)=CN Chemical compound CCC(C)=NC([*@](*)C1**1)=NC(*)=CN 0.000 description 5
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 229940125532 enzyme inhibitor Drugs 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- NCQZOTZKSQUJRS-UHFFFAOYSA-N CC(C)NCc1c[n](C)nc1 Chemical compound CC(C)NCc1c[n](C)nc1 NCQZOTZKSQUJRS-UHFFFAOYSA-N 0.000 description 1
- JAGQVVHJEKXLBZ-UHFFFAOYSA-N CCCC[n]1nnc(CNC)c1 Chemical compound CCCC[n]1nnc(CNC)c1 JAGQVVHJEKXLBZ-UHFFFAOYSA-N 0.000 description 1
- WZQVOACVRDDEJS-UHFFFAOYSA-N CCN(CC1)CC1C(NC)=O Chemical compound CCN(CC1)CC1C(NC)=O WZQVOACVRDDEJS-UHFFFAOYSA-N 0.000 description 1
- IANNBWVHGOIPRN-UHFFFAOYSA-N CNOCc1ccccc1 Chemical compound CNOCc1ccccc1 IANNBWVHGOIPRN-UHFFFAOYSA-N 0.000 description 1
- ZVLSNSQXNJVHMG-UHFFFAOYSA-N NOCC1CCCCC1 Chemical compound NOCC1CCCCC1 ZVLSNSQXNJVHMG-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2024006712A JP2024038447A (ja) | 2017-10-17 | 2024-01-19 | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物及びその誘導体 |
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762573442P | 2017-10-17 | 2017-10-17 | |
| US62/573,442 | 2017-10-17 | ||
| US201862681804P | 2018-06-07 | 2018-06-07 | |
| US62/681,804 | 2018-06-07 | ||
| US201862746495P | 2018-10-16 | 2018-10-16 | |
| US201862746252P | 2018-10-16 | 2018-10-16 | |
| US62/746,252 | 2018-10-16 | ||
| US62/746,495 | 2018-10-16 | ||
| PCT/US2018/056333 WO2019079485A1 (en) | 2017-10-17 | 2018-10-17 | AMINO-SUBSTITUTED HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS AND DERIVATIVES THEREOF |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024006712A Division JP2024038447A (ja) | 2017-10-17 | 2024-01-19 | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物及びその誘導体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020537645A JP2020537645A (ja) | 2020-12-24 |
| JP2020537645A5 true JP2020537645A5 (https=) | 2021-10-07 |
| JP7425724B2 JP7425724B2 (ja) | 2024-01-31 |
Family
ID=66174630
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020520323A Active JP7425724B2 (ja) | 2017-10-17 | 2018-10-17 | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物及びその誘導体 |
| JP2024006712A Pending JP2024038447A (ja) | 2017-10-17 | 2024-01-19 | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物及びその誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024006712A Pending JP2024038447A (ja) | 2017-10-17 | 2024-01-19 | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物及びその誘導体 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20200317642A1 (https=) |
| EP (1) | EP3697419A4 (https=) |
| JP (2) | JP7425724B2 (https=) |
| CN (1) | CN111343988A (https=) |
| AU (2) | AU2018350989A1 (https=) |
| CA (1) | CA3079260A1 (https=) |
| WO (1) | WO2019079485A1 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110621316B (zh) | 2017-04-21 | 2024-01-26 | Epizyme股份有限公司 | 用ehmt2抑制剂进行的组合疗法 |
| AU2018353139A1 (en) * | 2017-10-18 | 2020-06-04 | Epizyme, Inc. | Methods of using EHMT2 inhibitors in immunotherapies |
| US12522583B2 (en) | 2018-11-07 | 2026-01-13 | Dana-Farber Cancer Institute, Inc. | Benzimidazole derivatives and aza-benzimidazole derivatives as Janus kinase 2 inhibitors and uses thereof |
| EP3877371A4 (en) | 2018-11-07 | 2022-07-27 | Dana-Farber Cancer Institute, Inc. | IMIDAZOPYRIDINE DERIVATIVES AND AZA-IMIDAZOPYRIDINE DERIVATIVES AS JANUS KINASE 2 INHIBITORS AND USES THEREOF |
| EP3876939A4 (en) | 2018-11-07 | 2022-08-10 | Dana-Farber Cancer Institute, Inc. | Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof |
| CA3156474A1 (en) * | 2019-11-08 | 2021-05-14 | Heptares Therapeutics Limited | GPR52 MODULATING COMPOUNDS |
| US11691963B2 (en) | 2020-05-06 | 2023-07-04 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors |
| US12492184B2 (en) | 2020-12-22 | 2025-12-09 | InventisBio Co., Ltd. | Heteroaryl compounds, preparation methods and uses thereof |
| US12043632B2 (en) | 2020-12-23 | 2024-07-23 | Ajax Therapeutics, Inc. | 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors |
| WO2023086319A1 (en) | 2021-11-09 | 2023-05-19 | Ajax Therapeutics, Inc. | 6-he tero aryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors |
| US12162881B2 (en) | 2021-11-09 | 2024-12-10 | Ajax Therapeutics, Inc. | Forms and compositions of inhibitors of JAK2 |
| JP2025503429A (ja) * | 2021-12-14 | 2025-02-04 | プレーザー セラピューティクス インコーポレイティド | ポリユビキチン化による標的タンパク質またはポリペプチドの分解用の新規化合物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2443305A (en) * | 1948-06-15 | Pyrimidine derivatives | ||
| US6596747B2 (en) * | 1998-10-29 | 2003-07-22 | Bristol-Myers Squibb Company | Compounds derived from an amine nucleus and pharmaceutical compositions comprising same |
| WO2003040141A1 (en) * | 2001-09-28 | 2003-05-15 | Bayer Pharmaceuticals Corporation | Oxazolyl-phenyl-2,4-diamino-pyrimidine compounds and methods for treating hyperproliferative disorders |
| US7419984B2 (en) * | 2002-10-17 | 2008-09-02 | Cell Therapeutics, Inc. | Pyrimidines and uses thereof |
| US20070105839A1 (en) * | 2003-09-18 | 2007-05-10 | Patricia Imbach | 2, 4-Di (phenylamino) pyrimidines useful in the treatment of proliferative disorders |
| JP5781943B2 (ja) * | 2009-01-21 | 2015-09-24 | ライジェル ファーマシューティカルズ， インコーポレイテッド | 炎症性疾患、自己免疫疾患または増殖性疾患の治療に有用なｎ２−（３−ピリジルまたはフェニル）−ｎ４−（４−ピペリジル）−２，４−ピリミジンジアミン誘導体 |
| BR112013005806B1 (pt) * | 2010-09-10 | 2022-05-10 | Epizyme, Inc | Métodos para detectar se um indivíduo é um candidato para o tratamento com ou responsivo a um inibidor de ezh2 e usos terapêuticos do dito inibidor de ezh2 |
| KR101682417B1 (ko) * | 2011-02-25 | 2016-12-06 | 주식회사유한양행 | 다이아미노피리미딘 유도체 및 그의 제조방법 |
| MX2015009952A (es) * | 2013-02-08 | 2015-10-05 | Celgene Avilomics Res Inc | Inhibidores de cinasas reguladas por señales extracelulares (erk) y sus usos. |
| PL3442947T3 (pl) * | 2016-04-15 | 2023-10-02 | Epizyme, Inc. | Związki arylowe lub heteroarylowe podstawione aminą jako inhibitory ehmt1 i ehmt2 |
| US20200039998A1 (en) * | 2016-12-19 | 2020-02-06 | Epizyme, Inc. | Amine-substituted heterocyclic compounds as ehmt2 inhibitors and methods of use thereof |
| US20200113901A1 (en) * | 2017-03-31 | 2020-04-16 | Epizyme, Inc. | Methods of using ehmt2 inhibitors |
| CN110621316B (zh) * | 2017-04-21 | 2024-01-26 | Epizyme股份有限公司 | 用ehmt2抑制剂进行的组合疗法 |
-
2018
- 2018-10-17 CA CA3079260A patent/CA3079260A1/en active Pending
- 2018-10-17 AU AU2018350989A patent/AU2018350989A1/en not_active Abandoned
- 2018-10-17 JP JP2020520323A patent/JP7425724B2/ja active Active
- 2018-10-17 US US16/756,292 patent/US20200317642A1/en not_active Abandoned
- 2018-10-17 CN CN201880072647.1A patent/CN111343988A/zh active Pending
- 2018-10-17 EP EP18869423.6A patent/EP3697419A4/en active Pending
- 2018-10-17 WO PCT/US2018/056333 patent/WO2019079485A1/en not_active Ceased
-
2023
- 2023-10-18 AU AU2023251449A patent/AU2023251449A1/en not_active Abandoned
-
2024
- 2024-01-19 JP JP2024006712A patent/JP2024038447A/ja active Pending