JP2020516679A5 - - Google Patents
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- Publication number
- JP2020516679A5 JP2020516679A5 JP2020504290A JP2020504290A JP2020516679A5 JP 2020516679 A5 JP2020516679 A5 JP 2020516679A5 JP 2020504290 A JP2020504290 A JP 2020504290A JP 2020504290 A JP2020504290 A JP 2020504290A JP 2020516679 A5 JP2020516679 A5 JP 2020516679A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- cycloalkyl
- heteroaryl
- heterocycloalkyl
- 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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- 125000000217 alkyl group Chemical group 0.000 claims description 194
- 125000003118 aryl group Chemical group 0.000 claims description 128
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims description 120
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 108
- 125000001072 heteroaryl group Chemical group 0.000 claims description 108
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 102
- 229910052799 carbon Inorganic materials 0.000 claims description 77
- -1 pentafluorophenoxy, tetrafluorophenoxy Chemical group 0.000 claims description 72
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
- 150000001875 compounds Chemical class 0.000 claims description 49
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 48
- 125000005843 halogen group Chemical group 0.000 claims description 46
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 44
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 38
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 38
- 125000000304 alkynyl group Chemical group 0.000 claims description 36
- 125000004429 atom Chemical group 0.000 claims description 36
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 34
- 125000002252 acyl group Chemical group 0.000 claims description 34
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 32
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 26
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 239000012453 solvate Substances 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 16
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 16
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 16
- 229910004013 NO 2 Inorganic materials 0.000 claims description 16
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 16
- 125000003435 aroyl group Chemical group 0.000 claims description 16
- 125000002619 bicyclic group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 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 description 16
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 16
- 101150079125 DCN1 gene Proteins 0.000 claims description 13
- 102100026982 DCN1-like protein 1 Human genes 0.000 claims description 13
- 101100330861 Homo sapiens DCUN1D1 gene Proteins 0.000 claims description 13
- 125000002723 alicyclic group Chemical group 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 claims description 9
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- AZNMFVGFAFVVDA-UHFFFAOYSA-N 4-methyl-5-phenyl-1,3-oxazole Chemical compound N1=COC(C=2C=CC=CC=2)=C1C AZNMFVGFAFVVDA-UHFFFAOYSA-N 0.000 claims description 8
- DNHKSCAYDWTXHD-UHFFFAOYSA-N 4-methyl-5-phenyl-1,3-thiazole Chemical compound N1=CSC(C=2C=CC=CC=2)=C1C DNHKSCAYDWTXHD-UHFFFAOYSA-N 0.000 claims description 8
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 8
- 239000005977 Ethylene Substances 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000005549 heteroarylene group Chemical group 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 235000017788 Cydonia oblonga Nutrition 0.000 claims description 6
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000005282 allenyl group Chemical group 0.000 claims description 4
- 125000000732 arylene group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 150000007857 hydrazones Chemical class 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 4
- 150000002923 oximes Chemical class 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 101000644669 Homo sapiens NEDD8-conjugating enzyme Ubc12 Proteins 0.000 claims description 2
- 206010067125 Liver injury Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 102100020710 NEDD8-conjugating enzyme Ubc12 Human genes 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 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 description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 231100000753 hepatic injury Toxicity 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 230000036542 oxidative stress Effects 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
- 229960005489 paracetamol Drugs 0.000 claims description 2
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 230000000451 tissue damage Effects 0.000 claims description 2
- 231100000827 tissue damage Toxicity 0.000 claims description 2
- 208000037816 tissue injury Diseases 0.000 claims description 2
- 239000003981 vehicle Substances 0.000 claims description 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 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
- 0 C*N(**)*1CC(C)N*(C)*C1 Chemical compound C*N(**)*1CC(C)N*(C)*C1 0.000 description 11
- 239000000758 substrate Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZZGOFEVGYOFEQO-UHFFFAOYSA-N CCC[N](C)(C)CC Chemical compound CCC[N](C)(C)CC ZZGOFEVGYOFEQO-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762483640P | 2017-04-10 | 2017-04-10 | |
| US62/483,640 | 2017-04-10 | ||
| PCT/US2018/026789 WO2018191199A1 (en) | 2017-04-10 | 2018-04-10 | Covalent small molecule dcn1 inhibitors and therapeutic methods using the same |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020516679A JP2020516679A (ja) | 2020-06-11 |
| JP2020516679A5 true JP2020516679A5 (https=) | 2021-04-15 |
| JP7086171B2 JP7086171B2 (ja) | 2022-06-17 |
Family
ID=62067873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020504290A Active JP7086171B2 (ja) | 2017-04-10 | 2018-04-10 | 共有結合性小分子ｄｃｎ１阻害物質およびそれを使用する治療方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US10500194B2 (https=) |
| EP (1) | EP3609876B1 (https=) |
| JP (1) | JP7086171B2 (https=) |
| CN (1) | CN110740996B (https=) |
| AU (1) | AU2018251687B2 (https=) |
| CA (1) | CA3059256C (https=) |
| ES (1) | ES2916449T3 (https=) |
| WO (1) | WO2018191199A1 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109641874A (zh) | 2016-05-10 | 2019-04-16 | C4医药公司 | 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体 |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| ES2990061T3 (es) | 2016-05-10 | 2024-11-28 | C4 Therapeutics Inc | Degronímeros espirocíclicos para la degradación de proteínas diana |
| EP3454856B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| CN110769822A (zh) | 2017-06-20 | 2020-02-07 | C4医药公司 | 用于蛋白降解的n/o-连接的降解决定子和降解决定子体 |
| WO2019043217A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROBENZIMIDAZOLONES |
| WO2019043208A1 (en) | 2017-09-04 | 2019-03-07 | F. Hoffmann-La Roche Ag | DIHYDROQUINOLINONES |
| CN118108706A (zh) | 2017-09-04 | 2024-05-31 | C4医药公司 | 戊二酰亚胺 |
| CN111372585A (zh) | 2017-11-16 | 2020-07-03 | C4医药公司 | 用于靶蛋白降解的降解剂和降解决定子 |
| EP3773576A4 (en) | 2018-03-26 | 2021-12-29 | C4 Therapeutics, Inc. | Cereblon binders for the degradation of ikaros |
| EP3781156A4 (en) | 2018-04-16 | 2022-05-18 | C4 Therapeutics, Inc. | SPIROCYCLIC COMPOUNDS |
| WO2020106876A2 (en) * | 2018-11-20 | 2020-05-28 | Fulcrum Therapeutics, Inc. | Compositions and methods for increasing fetal hemoglobin and treating sickle cell disease |
| CN120698983A (zh) | 2018-12-20 | 2025-09-26 | C4医药公司 | 靶向蛋白降解 |
| ES2995214T3 (en) | 2019-03-06 | 2025-02-07 | C4 Therapeutics Inc | Heterocyclic compounds for medical treatment |
| WO2020190754A1 (en) | 2019-03-15 | 2020-09-24 | Fulcrum Therapeutics, Inc. | Macrocyclic azolopyridine derivatives as eed and prc2 modulators |
| CN116685319A (zh) * | 2020-12-10 | 2023-09-01 | 阿德格罗生物制药控股有限公司 | 用于治疗皮肤转移性癌的方法 |
| CN112830957B (zh) * | 2021-01-07 | 2022-07-22 | 江西师范大学 | 一种制备卡非佐米的方法 |
| WO2023059582A1 (en) * | 2021-10-04 | 2023-04-13 | Halda Therapeutics Opco, Inc. | Heterobifunctional compounds and their use in treating disease |
| WO2023059605A1 (en) * | 2021-10-04 | 2023-04-13 | Halda Therapeutics Opco, Inc. | Heterobifunctional compounds and their use in treating disease |
| CA3249074A1 (en) | 2022-06-06 | 2023-12-14 | C4 Therapeutics, Inc. | BICYCLIC SUBSTITUTION GLUTARIMIDE CEREBLON BINDERS |
| CN116987062A (zh) * | 2023-08-03 | 2023-11-03 | 中国热带农业科学院分析测试中心 | 一种氨基酸键联槟榔碱衍生物的制备方法 |
| US12473285B2 (en) | 2023-11-03 | 2025-11-18 | Cellarity, Inc. | DCN-1 modulating compounds and methods of use thereof |
| WO2025096981A1 (en) | 2023-11-03 | 2025-05-08 | Cellarity, Inc. | Modulators of dcn-1 and methods of use thereof |
| TW202543650A (zh) | 2024-03-08 | 2025-11-16 | 美商海爾達醫療運營公司 | 異雙官能化合物及其在治療疾病中之用途 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ234264A (en) * | 1989-06-29 | 1993-05-26 | Warner Lambert Co | N-substituted cycloalkyl and polycycloalkyl alpha-substituted trp-phe- and phenethylamine derivatives, and pharmaceutical compositions |
| CA2998753A1 (en) | 2015-09-18 | 2017-03-23 | St. Jude Children's Research Hospital | Methods and compositions of inhibiting dcn1-ubc12 interaction |
-
2018
- 2018-04-10 JP JP2020504290A patent/JP7086171B2/ja active Active
- 2018-04-10 EP EP18720910.1A patent/EP3609876B1/en active Active
- 2018-04-10 CN CN201880038225.2A patent/CN110740996B/zh active Active
- 2018-04-10 US US15/949,799 patent/US10500194B2/en active Active
- 2018-04-10 WO PCT/US2018/026789 patent/WO2018191199A1/en not_active Ceased
- 2018-04-10 AU AU2018251687A patent/AU2018251687B2/en active Active
- 2018-04-10 CA CA3059256A patent/CA3059256C/en active Active
- 2018-04-10 ES ES18720910T patent/ES2916449T3/es active Active
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