JP6538266B2 - ヒストン脱アセチル化酵素６阻害剤としての１，３，４−オキサジアゾールスルファミド誘導体化合物及びこれを含有する薬剤学的組成物（１，３，４−Ｏｘａｄｉａｚｏｌｅ Ｓｕｌｆａｍｉｄｅ Ｄｅｒｉｖａｔｉｖｅ Ｃｏｍｐｏｕｎｄｓ ａｓ Ｈｉｓｔｏｎｅ Ｄｅａｃｅｔｙｌａｓｅ ６ Ｉｎｈｉｂｉｔｏｒ， ａｎｄ ｔｈｅ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏｍｐｏｓｉｔｉｏｎ Ｃｏｍｐｒｉｓｉｎｇ ｔｈｅ ｓａｍｅ） - Google Patents
ヒストン脱アセチル化酵素６阻害剤としての１，３，４−オキサジアゾールスルファミド誘導体化合物及びこれを含有する薬剤学的組成物（１，３，４−Ｏｘａｄｉａｚｏｌｅ Ｓｕｌｆａｍｉｄｅ Ｄｅｒｉｖａｔｉｖｅ Ｃｏｍｐｏｕｎｄｓ ａｓ Ｈｉｓｔｏｎｅ Ｄｅａｃｅｔｙｌａｓｅ ６ Ｉｎｈｉｂｉｔｏｒ， ａｎｄ ｔｈｅ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏｍｐｏｓｉｔｉｏｎ Ｃｏｍｐｒｉｓｉｎｇ ｔｈｅ ｓａｍｅ） Download PDFInfo
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- JP6538266B2 JP6538266B2 JP2018504096A JP2018504096A JP6538266B2 JP 6538266 B2 JP6538266 B2 JP 6538266B2 JP 2018504096 A JP2018504096 A JP 2018504096A JP 2018504096 A JP2018504096 A JP 2018504096A JP 6538266 B2 JP6538266 B2 JP 6538266B2
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- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 36
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 36
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- 235000019270 ammonium chloride Nutrition 0.000 description 28
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- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 26
- 238000000034 method Methods 0.000 description 26
- 235000001968 nicotinic acid Nutrition 0.000 description 26
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- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 25
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 21
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 21
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- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 17
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- ZYZHCWURMLIAJF-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-N-phenylpiperazine-1-sulfonamide Chemical compound FC(F)C1=NN=C(O1)C1=CC=C(CN(C2=CC=CC=C2)S(=O)(=O)N2CCNCC2)C(F)=C1 ZYZHCWURMLIAJF-UHFFFAOYSA-N 0.000 description 7
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- IRQSKJQDKUAART-UHFFFAOYSA-N methyl 6-(bromomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CBr)N=C1 IRQSKJQDKUAART-UHFFFAOYSA-N 0.000 description 7
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- WNPFDMGMNSMOMD-UHFFFAOYSA-M 1-imidazol-1-ylsulfonyl-3-methylimidazol-3-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=[N+](C)C=CN1S(=O)(=O)N1C=NC=C1 WNPFDMGMNSMOMD-UHFFFAOYSA-M 0.000 description 6
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- UVVZJWAYADASDN-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-4-cyclobutylpiperazine Chemical compound ClC=1C=C(C=CC=1F)N1CCN(CC1)C1CCC1 UVVZJWAYADASDN-UHFFFAOYSA-N 0.000 description 4
- MALBGOTVCYKCHP-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-4-propan-2-ylpiperazine Chemical compound ClC=1C=C(C=CC=1F)N1CCN(CC1)C(C)C MALBGOTVCYKCHP-UHFFFAOYSA-N 0.000 description 4
- XVJGMMIQHDGDBM-TXEJJXNPSA-N 1-[(2R,6S)-2,6-dimethyl-4-phenylpiperazin-1-yl]ethanone Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)C1=CC=CC=C1)C XVJGMMIQHDGDBM-TXEJJXNPSA-N 0.000 description 4
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
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- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 4
- 150000004682 monohydrates Chemical class 0.000 description 4
- KNBZBXCCUDRUIK-UHFFFAOYSA-N pyridine-3-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C1=CC=CN=C1 KNBZBXCCUDRUIK-UHFFFAOYSA-N 0.000 description 4
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
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- GRBUTWWFTFQSMF-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-methylpiperazine Chemical compound C1CNC(C)CN1C1=CC=CC(Cl)=C1 GRBUTWWFTFQSMF-UHFFFAOYSA-N 0.000 description 3
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- CXKADMFVIMIQMK-UHFFFAOYSA-N 3-methyl-1-(3-methylphenyl)piperazine Chemical compound C1CNC(C)CN1C1=CC=CC(C)=C1 CXKADMFVIMIQMK-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
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Classifications
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- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| AU2016303891B2 (en) | 2015-08-04 | 2019-08-01 | Chong Kun Dang Pharmaceutical Corp. | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| HUE061967T2 (hu) | 2015-10-12 | 2023-09-28 | Chong Kun Dang Pharmaceutical Corp | Hiszton deacetiláz-6 inhibitor oxadiazol-amin származékok és az azokat tartalmazó gyógyászati készítmény |
| WO2018165520A1 (en) | 2017-03-10 | 2018-09-13 | Vps-3, Inc. | Metalloenzyme inhibitor compounds |
| WO2019027054A1 (en) | 2017-07-31 | 2019-02-07 | Takeda Pharmaceutical Company Limited | HETEROCYCLIC COMPOUND |
| KR102059027B1 (ko) * | 2018-01-12 | 2019-12-24 | 주식회사 비엔에이치리서치 | Hdac6 억제제를 유효성분으로 포함하는 가려움증 예방 또는 치료용 약제학적 조성물 |
| KR102316234B1 (ko) | 2018-07-26 | 2021-10-22 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| US12084436B2 (en) | 2019-01-30 | 2024-09-10 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| JP7593647B2 (ja) * | 2019-04-17 | 2024-12-03 | キマトリクス、エセ．エレ． | ヒストン脱アセチル化酵素阻害剤としての１，３，４－オキサジアゾール誘導体 |
| PH12021552905A1 (en) | 2019-05-31 | 2022-04-04 | Chong Kun Dang Pharmaceutical Corp | 1,3,4-oxadiazole homophthalimide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| US12485174B2 (en) | 2019-06-27 | 2025-12-02 | The George Washington University, A Congressionally Chartered Not-For-Profit Corporation | HDAC6-activated macrophages, compositions, and uses thereof |
| CN114846012B (zh) | 2019-09-27 | 2024-01-26 | 武田药品工业株式会社 | 可用作hdac6抑制剂的2-异吲哚-1,3,4-噁二唑衍生物 |
| BR112022011917A2 (pt) | 2019-12-20 | 2022-09-06 | Tenaya Therapeutics Inc | Fluoroalquil-oxadiazois e seus usos |
| KR102537616B1 (ko) * | 2020-02-25 | 2023-05-26 | 주식회사 종근당 | 히스톤 탈아세틸화 효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| KR102504830B1 (ko) * | 2020-07-14 | 2023-03-02 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 새로운 구조의 화합물 및 이를 포함하는 약제학적 조성물 |
| CA3189738A1 (en) | 2020-08-07 | 2022-02-10 | Italfarmaco S.P.A. | Novel oxadiazole-based selective hdac6 inhibitors |
| US20240208956A1 (en) * | 2021-04-08 | 2024-06-27 | Chong Kun Dang Pharmaceutical Corp. | 1,3,4-oxadiazole thiocarbonyl compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same |
| EP4326263A1 (en) | 2021-04-23 | 2024-02-28 | Tenaya Therapeutics, Inc. | Hdac6 inhibitors for use in the treatment of dilated cardiomyopathy |
| MX2023012875A (es) | 2021-05-04 | 2024-01-12 | Tenaya Therapeutics Inc | Inhibidores 2-fluoro alquil-l,3,4-oxadiazol-5-il-tiazol de hdac6 para su uso en el tratamiento de enfermedades metabólicas y hfpef. |
| TW202412772A (zh) | 2022-07-19 | 2024-04-01 | 義大利商義大利藥品股份有限公司 | 作為選擇性組蛋白去乙醯酶６抑制劑之１，３，４－㗁二唑衍生物 |
| AU2023322448A1 (en) | 2022-08-08 | 2025-02-13 | Italfarmaco S.P.A. | Difluoro- and trifluoro-acetyl hydrazides as selective hdac6 inhibitors |
| KR20240035172A (ko) * | 2022-09-08 | 2024-03-15 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이의 용도 |
| WO2024079682A1 (en) * | 2022-10-14 | 2024-04-18 | Chong Kun Dang Pharmaceutical Corp. | Sulfoximine compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same |
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| US7868204B2 (en) | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| US6897220B2 (en) | 2001-09-14 | 2005-05-24 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| JP2005509606A (ja) | 2001-10-03 | 2005-04-14 | ファルマシア・コーポレーション | 凝血カスケードを選択的に阻害するのに有用な置換された多環式化合物のプロドラッグ |
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