KR101717872B1 - 소아 간질 및 간질-관련 증후군의 예방 또는 치료용 페닐카바메이트 화합물 - Google Patents
소아 간질 및 간질-관련 증후군의 예방 또는 치료용 페닐카바메이트 화합물 Download PDFInfo
- Publication number
- KR101717872B1 KR101717872B1 KR1020157026389A KR20157026389A KR101717872B1 KR 101717872 B1 KR101717872 B1 KR 101717872B1 KR 1020157026389 A KR1020157026389 A KR 1020157026389A KR 20157026389 A KR20157026389 A KR 20157026389A KR 101717872 B1 KR101717872 B1 KR 101717872B1
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- KR
- South Korea
- Prior art keywords
- chlorophenyl
- hydroxypropyl
- carbamate
- dichlorophenyl
- nmr
- 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.)
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- 208000011580 syndromic disease Diseases 0.000 title claims abstract description 47
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- 206010015037 epilepsy Diseases 0.000 claims abstract description 115
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
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- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 203
- 238000000034 method Methods 0.000 claims description 175
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- 150000003839 salts Chemical class 0.000 claims description 25
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
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- 208000037158 Partial Epilepsies Diseases 0.000 claims description 13
- 201000007186 focal epilepsy Diseases 0.000 claims description 13
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 11
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- 125000000217 alkyl group Chemical group 0.000 claims description 11
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
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- 150000002367 halogens Chemical group 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
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- 229910052794 bromium Chemical group 0.000 claims description 4
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 206010016284 febrile convulsion Diseases 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 210000004227 basal ganglia Anatomy 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- ZUHQRBOAKRLOGM-UHFFFAOYSA-N heptylcarbamic acid Chemical compound CCCCCCCNC(O)=O ZUHQRBOAKRLOGM-UHFFFAOYSA-N 0.000 claims description 2
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- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 claims 1
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- 238000003786 synthesis reaction Methods 0.000 description 167
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical group C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 112
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 102
- 239000001294 propane Substances 0.000 description 65
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 37
- 238000010898 silica gel chromatography Methods 0.000 description 29
- VMBILFRHBQVTOS-IMTBSYHQSA-N (1s,2s)-1-(2-chlorophenyl)propane-1,2-diol Chemical compound C[C@H](O)[C@@H](O)C1=CC=CC=C1Cl VMBILFRHBQVTOS-IMTBSYHQSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 27
- 239000001273 butane Substances 0.000 description 26
- 238000012360 testing method Methods 0.000 description 25
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 22
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- 241000700159 Rattus Species 0.000 description 20
- RZZFOJKGQIYSBE-UHFFFAOYSA-N cyclopropyl carbamate Chemical compound NC(=O)OC1CC1 RZZFOJKGQIYSBE-UHFFFAOYSA-N 0.000 description 20
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- OVPLZYJGTGDFNB-UHFFFAOYSA-N propan-2-yl carbamate Chemical compound CC(C)OC(N)=O OVPLZYJGTGDFNB-UHFFFAOYSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 15
- 229940083957 1,2-butanediol Drugs 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 14
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 13
- 208000013257 developmental and epileptic encephalopathy Diseases 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 11
- 229940015975 1,2-hexanediol Drugs 0.000 description 10
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 10
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- IGKJZZNHGRQLAI-GORDUTHDSA-N 1-chloro-2-[(e)-prop-1-enyl]benzene Chemical compound C\C=C\C1=CC=CC=C1Cl IGKJZZNHGRQLAI-GORDUTHDSA-N 0.000 description 7
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- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 7
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
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- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361776926P | 2013-03-12 | 2013-03-12 | |
| US61/776,926 | 2013-03-12 | ||
| PCT/KR2014/001903 WO2014142477A1 (en) | 2013-03-12 | 2014-03-07 | Phenyl carbamate compounds for use in preventing or treating pediatric epilesy and epilesy-related syndromes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20150120520A KR20150120520A (ko) | 2015-10-27 |
| KR101717872B1 true KR101717872B1 (ko) | 2017-03-17 |
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| KR1020157026389A Active KR101717872B1 (ko) | 2013-03-12 | 2014-03-07 | 소아 간질 및 간질-관련 증후군의 예방 또는 치료용 페닐카바메이트 화합물 |
| KR1020177013680A Active KR101992035B1 (ko) | 2013-03-12 | 2014-03-11 | 운동장애의 예방 또는 치료용 페닐카바메이트 화합물 |
| KR1020157026369A Active KR101739676B1 (ko) | 2013-03-12 | 2014-03-11 | 간질 또는 간질-관련 증후군의 예방 또는 치료용 페닐 알킬 카바메이트 화합물 |
| KR1020157026378A Ceased KR20150120518A (ko) | 2013-03-12 | 2014-03-11 | 운동장애의 예방 또는 치료용 페닐카바메이트 화합물 |
| KR1020157026390A Active KR101717873B1 (ko) | 2013-03-12 | 2014-03-11 | 간질 또는 간질-관련 증후군의 예방 또는 치료용 페닐카바메이트 화합물 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020177013680A Active KR101992035B1 (ko) | 2013-03-12 | 2014-03-11 | 운동장애의 예방 또는 치료용 페닐카바메이트 화합물 |
| KR1020157026369A Active KR101739676B1 (ko) | 2013-03-12 | 2014-03-11 | 간질 또는 간질-관련 증후군의 예방 또는 치료용 페닐 알킬 카바메이트 화합물 |
| KR1020157026378A Ceased KR20150120518A (ko) | 2013-03-12 | 2014-03-11 | 운동장애의 예방 또는 치료용 페닐카바메이트 화합물 |
| KR1020157026390A Active KR101717873B1 (ko) | 2013-03-12 | 2014-03-11 | 간질 또는 간질-관련 증후군의 예방 또는 치료용 페닐카바메이트 화합물 |
Country Status (7)
| Country | Link |
|---|---|
| US (5) | US9504668B2 (https=) |
| EP (4) | EP2968210B1 (https=) |
| JP (5) | JP6062077B2 (https=) |
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| US9566261B2 (en) | 2013-03-12 | 2017-02-14 | Bio-Pharm Solutions Co., Ltd. | Phenyl carbamate compound and a composition for preventing or treating a memory loss-related disease comprising the same |
| EP2968210B1 (en) * | 2013-03-12 | 2024-09-11 | Bio-Pharm Solutions Co., Ltd. | Phenyl carbamate compounds for use in preventing or treating pediatric epilesy |
| ES3059582T3 (en) * | 2016-02-29 | 2026-03-23 | Bio Pharm Solutions Co Ltd | Sulfamate derivative compounds, processes for preparing them and their uses |
| MX391363B (es) * | 2016-12-14 | 2025-03-21 | Sk Biopharmaceuticals Co Ltd | Uso de compuesto de carbamato para prevenir, aliviar o tratar temblores o el sindrome de temblor. |
| CN109920550A (zh) * | 2018-12-25 | 2019-06-21 | 天津大学 | 一种基于dMRI研究青少年肌阵挛性癫痫的方法 |
| JP2023539291A (ja) * | 2020-08-31 | 2023-09-13 | バイオ－ファーム ソリューションズ カンパニー リミテッド | 神経変性疾患の予防又は治療用フェニルアルキルカルバメート化合物 |
| KR20230051206A (ko) | 2020-09-10 | 2023-04-17 | (주)바이오팜솔루션즈 | 정신질환 치료 또는 완화용 설파메이트 유도체 화합물 |
| US12054449B2 (en) | 2021-08-05 | 2024-08-06 | Bio-Pharm Solutions Co., Ltd. | Phenylcarbamate crystalline form and method for manufacturing the same |
| CN119552104B (zh) * | 2024-12-03 | 2025-07-15 | 西安瑞谱源生物技术有限公司 | 一种氘代维生素a的制备方法 |
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