CN109134432B - 氘代抗抑郁药物 - Google Patents
氘代抗抑郁药物 Download PDFInfo
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- CN109134432B CN109134432B CN201710450966.9A CN201710450966A CN109134432B CN 109134432 B CN109134432 B CN 109134432B CN 201710450966 A CN201710450966 A CN 201710450966A CN 109134432 B CN109134432 B CN 109134432B
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- 239000000935 antidepressant agent Substances 0.000 title description 8
- 230000001430 anti-depressive effect Effects 0.000 title description 7
- 229940005513 antidepressants Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 11
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 11
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 6
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 229940073608 benzyl chloride Drugs 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- -1 N- [ (N-benzyl-4-hydroxypiperidin-4-YL) -methyl ] -pyridine Chemical compound 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- KJKHFQBTYMJFNP-UHFFFAOYSA-N 6-benzyl-1-oxa-6-azaspiro[2.5]octane Chemical compound C=1C=CC=CC=1CN(CC1)CCC21CO2 KJKHFQBTYMJFNP-UHFFFAOYSA-N 0.000 description 2
- 241000581650 Ivesia Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000011505 plaster Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- MSOZDGCODQNTAR-UHFFFAOYSA-N 1-benzyl-4-hydroxypiperidin-2-one Chemical compound O=C1CC(O)CCN1CC1=CC=CC=C1 MSOZDGCODQNTAR-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201710450966.9A CN109134432B (zh) | 2017-06-15 | 2017-06-15 | 氘代抗抑郁药物 |
Applications Claiming Priority (1)
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CN201710450966.9A CN109134432B (zh) | 2017-06-15 | 2017-06-15 | 氘代抗抑郁药物 |
Publications (2)
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CN109134432A CN109134432A (zh) | 2019-01-04 |
CN109134432B true CN109134432B (zh) | 2021-06-11 |
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CN201710450966.9A Active CN109134432B (zh) | 2017-06-15 | 2017-06-15 | 氘代抗抑郁药物 |
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CN (1) | CN109134432B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111747926B (zh) * | 2020-06-23 | 2024-01-30 | 浙江华海药业股份有限公司 | 一种羟哌吡酮游离碱的合成工艺改进方法 |
CN112521357B (zh) * | 2020-08-31 | 2021-10-08 | 深圳瑞健生物科技有限公司 | 一种长效低成瘾性hnk衍生物及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5075337A (en) * | 1989-07-26 | 1991-12-24 | G. D. Searle & Co. | Alpha-deuterated 2-alkylaminoacetamide derivatives having reduced toxicity for treatment of CNS disorders |
CN101273024A (zh) * | 2005-07-29 | 2008-09-24 | 康瑟特制药公司 | 新颖苯并[d][1,3]-二氧杂环戊烯衍生物 |
CN101360742A (zh) * | 2005-11-14 | 2009-02-04 | 奥斯拜客斯制药有限公司 | 具有血清素源性活性和增强的治疗特性的取代苯基哌啶 |
CN106554318A (zh) * | 2015-09-25 | 2017-04-05 | 正大天晴药业集团股份有限公司 | 氘代二苯基氨基嘧啶化合物 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090076161A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched bupropion |
US20090075994A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched radafaxine |
-
2017
- 2017-06-15 CN CN201710450966.9A patent/CN109134432B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5075337A (en) * | 1989-07-26 | 1991-12-24 | G. D. Searle & Co. | Alpha-deuterated 2-alkylaminoacetamide derivatives having reduced toxicity for treatment of CNS disorders |
CN101273024A (zh) * | 2005-07-29 | 2008-09-24 | 康瑟特制药公司 | 新颖苯并[d][1,3]-二氧杂环戊烯衍生物 |
CN101360742A (zh) * | 2005-11-14 | 2009-02-04 | 奥斯拜客斯制药有限公司 | 具有血清素源性活性和增强的治疗特性的取代苯基哌啶 |
CN106554318A (zh) * | 2015-09-25 | 2017-04-05 | 正大天晴药业集团股份有限公司 | 氘代二苯基氨基嘧啶化合物 |
Non-Patent Citations (2)
Title |
---|
氘代药物研发的过去、现在与未来;张寅生;《药学进展》;20171231;第41卷(第12期);第902-918页 * |
氚标记盐酸羟哌吡酮的制备;陈宝军 等;《中国原子能科学研究院年报》;20150731;第2014卷(第00期);第221页 * |
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Publication number | Publication date |
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CN109134432A (zh) | 2019-01-04 |
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PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20210415 Address after: 100070 room 1208, building 3, yard 8, Haiying Road, Fengtai District, Beijing Applicant after: Beijing Junke Huayuan Pharmaceutical Technology Co.,Ltd. Address before: 225312 Room 707, Building D, Phase II, New Drug Creation Base, No. 1 Yaocheng Avenue, Taizhou City, Taizhou City, Jiangsu Province Applicant before: TAIZHOU HUAYUAN MEDICINAL TECH Co.,Ltd. |
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TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Deuterinated antidepressants Effective date of registration: 20231221 Granted publication date: 20210611 Pledgee: Beijing Zhongguancun bank Limited by Share Ltd. Pledgor: Beijing Junke Huayuan Pharmaceutical Technology Co.,Ltd. Registration number: Y2023990000634 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |