CN103739553B - 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 - Google Patents
含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 Download PDFInfo
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- CN103739553B CN103739553B CN201310716377.2A CN201310716377A CN103739553B CN 103739553 B CN103739553 B CN 103739553B CN 201310716377 A CN201310716377 A CN 201310716377A CN 103739553 B CN103739553 B CN 103739553B
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- substituted imidazole
- etomidate
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 95
- -1 N-substituted imidazole carboxylate Chemical class 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 125000001033 ether group Chemical group 0.000 title claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 24
- 241001465754 Metazoa Species 0.000 claims abstract description 21
- 230000003444 anaesthetic effect Effects 0.000 claims abstract description 10
- 241000282414 Homo sapiens Species 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 5
- 230000002557 soporific effect Effects 0.000 claims description 5
- 230000002936 tranquilizing effect Effects 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 210000003462 vein Anatomy 0.000 claims description 4
- 238000013459 approach Methods 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000003880 polar aprotic solvent Substances 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 abstract description 43
- 229960001690 etomidate Drugs 0.000 abstract description 41
- 230000000694 effects Effects 0.000 abstract description 12
- 230000005764 inhibitory process Effects 0.000 abstract description 11
- 150000003839 salts Chemical class 0.000 abstract description 9
- 239000003470 adrenal cortex hormone Substances 0.000 abstract description 5
- 238000002695 general anesthesia Methods 0.000 abstract description 5
- 238000001990 intravenous administration Methods 0.000 abstract description 4
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 3
- 238000011084 recovery Methods 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 239000003193 general anesthetic agent Substances 0.000 abstract description 2
- 125000002883 imidazolyl group Chemical group 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 230000002441 reversible effect Effects 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 230000004799 sedative–hypnotic effect Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 20
- 102400000739 Corticotropin Human genes 0.000 description 12
- 101800000414 Corticotropin Proteins 0.000 description 12
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 12
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 12
- 229960000258 corticotropin Drugs 0.000 description 12
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000003287 optical effect Effects 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 206010002091 Anaesthesia Diseases 0.000 description 7
- 230000037005 anaesthesia Effects 0.000 description 7
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- 241000282472 Canis lupus familiaris Species 0.000 description 6
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- 230000005311 nuclear magnetism Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 108010049356 Steroid 11-beta-Hydroxylase Proteins 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229960001866 silicon dioxide Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- RGYCCBLTSWHXIS-SECBINFHSA-N 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid Chemical compound C1([C@@H](C)N2C(=CN=C2)C(O)=O)=CC=CC=C1 RGYCCBLTSWHXIS-SECBINFHSA-N 0.000 description 2
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102400000336 Thyrotropin-releasing hormone Human genes 0.000 description 2
- 101800004623 Thyrotropin-releasing hormone Proteins 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 210000004404 adrenal cortex Anatomy 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
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- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000979 retarding effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- RGYCCBLTSWHXIS-UHFFFAOYSA-N 3-(1-phenylethyl)imidazole-4-carboxylic acid Chemical compound C1=NC=C(C(O)=O)N1C(C)C1=CC=CC=C1 RGYCCBLTSWHXIS-UHFFFAOYSA-N 0.000 description 1
- RGYCCBLTSWHXIS-VIFPVBQESA-N 3-[(1s)-1-phenylethyl]imidazole-4-carboxylic acid Chemical compound C1([C@H](C)N2C(=CN=C2)C(O)=O)=CC=CC=C1 RGYCCBLTSWHXIS-VIFPVBQESA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Anesthesiology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
化合物 | 皮质醇提高倍数 | 皮质酮提高倍数 |
DMSO | 40.25±33.02 | 33.79±12.4 |
依托咪酯 | 2.12±0.56 | 2.53±0.65 |
化合物(Ⅰ) | 19.88±19.8 | 11.46±4.30 |
化合物(Ⅳ) | 3.32±2.36 | 1.19±0.87 |
化合物(Ⅴ) | 5.17±2.28 | 3.18±1.15 |
化合物 | 皮质醇提高倍数 | 皮质酮提高倍数 |
DMSO | 41.26±28.64 | 30.24±10.38 |
依托咪酯 | 2.46±0.87 | 2.80±0.76 |
化合物(Ⅰ)的盐酸盐 | 25.36±14.77 | 18.14±5.66 |
化合物(Ⅰ)的氢溴酸盐 | 29.14±11.86 | 12.36±6.65 |
化合物(Ⅰ)的三氟醋酸盐 | 26.14±13.89 | 13.64±4.22 |
Claims (9)
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310716377.2A CN103739553B (zh) | 2013-12-23 | 2013-12-23 | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 |
SG11201605055SA SG11201605055SA (en) | 2013-12-23 | 2014-10-30 | N-substituted imidazole carboxylic ester chiral compound containing ether side chain, preparation method and application |
CA2933098A CA2933098A1 (en) | 2013-12-23 | 2014-10-30 | N-substituted imidazole carboxylic ester chiral compound containing an ether side chain, its preparation and application |
US15/107,415 US9969695B2 (en) | 2013-12-23 | 2014-10-30 | N-substituted imidazole carboxylic ester chiral compound containing an ether side chain, its preparation and application |
AU2014373186A AU2014373186B2 (en) | 2013-12-23 | 2014-10-30 | N-substituted imidazole carboxylic ester chiral compound containing ether side chain, preparation method and application |
RU2016123144A RU2659784C2 (ru) | 2013-12-23 | 2014-10-30 | Сложноэфирное хиральное соединение (n-замещенный имидазол)-карбоновой кислоты, содержащее простую эфирную боковую цепь, его получение и применение |
PCT/CN2014/089898 WO2015096551A1 (zh) | 2013-12-23 | 2014-10-30 | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 |
EP14873468.4A EP3088394B1 (en) | 2013-12-23 | 2014-10-30 | Chiral methoxyethyl etomidate compound, its prepartion and application as anesthesia |
KR1020167017220A KR20160089516A (ko) | 2013-12-23 | 2014-10-30 | 에테르 측쇄를 함유한 n-치환 이미다졸 카르복실산 에스테르 키랄 화합물, 제조 방법 및 용도 |
JP2016539968A JP2016540795A (ja) | 2013-12-23 | 2014-10-30 | エーテル側鎖を有するキラルなn−置換イミダゾールカルボキシルエステル化合物、その製造方法及び用途 |
PH12016501246A PH12016501246A1 (en) | 2013-12-23 | 2016-06-23 | N-substituted imidazole carboxylic ester chiral compound containing an ether side chain, its preparation and application |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310716377.2A CN103739553B (zh) | 2013-12-23 | 2013-12-23 | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103739553A CN103739553A (zh) | 2014-04-23 |
CN103739553B true CN103739553B (zh) | 2014-11-12 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN201310716377.2A Active CN103739553B (zh) | 2013-12-23 | 2013-12-23 | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 |
Country Status (11)
Country | Link |
---|---|
US (1) | US9969695B2 (zh) |
EP (1) | EP3088394B1 (zh) |
JP (1) | JP2016540795A (zh) |
KR (1) | KR20160089516A (zh) |
CN (1) | CN103739553B (zh) |
AU (1) | AU2014373186B2 (zh) |
CA (1) | CA2933098A1 (zh) |
PH (1) | PH12016501246A1 (zh) |
RU (1) | RU2659784C2 (zh) |
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CN103739553B (zh) * | 2013-12-23 | 2014-11-12 | 四川大学华西医院 | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 |
PL3360863T3 (pl) * | 2015-10-10 | 2022-08-08 | Jiangsu Nhwaluokang Pharmaceutical Research And Development Co., Ltd. | Pochodna i związek pośredni etomidatu, sposób przygotowania i zastosowanie |
CN107382870A (zh) * | 2016-05-17 | 2017-11-24 | 四川海思科制药有限公司 | N‑取代咪唑羧酸酯类化合物及其制备方法和在医药上的用途 |
CN107445898A (zh) * | 2016-05-30 | 2017-12-08 | 四川海思科制药有限公司 | N‑取代咪唑羧酸酯类化合物及其制备方法和在医药上的用途 |
CN107522662A (zh) * | 2016-06-16 | 2017-12-29 | 四川海思科制药有限公司 | N‑取代咪唑羧酸酯类化合物及其制备方法和在医药上的用途 |
CN107641105A (zh) * | 2016-07-22 | 2018-01-30 | 四川海思科制药有限公司 | N‑取代咪唑羧酸酯类化合物及其制备方法和在医药上的用途 |
CN109776512A (zh) * | 2018-01-30 | 2019-05-21 | 成都安诺晨创医药科技有限公司 | 一种n-取代咪唑甲酸酯类衍生物及其用途 |
CN112174890B (zh) * | 2020-10-09 | 2022-05-27 | 成都麻沸散医药科技有限公司 | 酮取代杂环化合物及其麻醉作用 |
CN110922361B (zh) * | 2019-11-21 | 2021-01-08 | 武汉大安制药有限公司 | 一种依托咪酯氧化杂质及其制备方法 |
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US3354173A (en) * | 1964-04-16 | 1967-11-21 | Janssen Pharmaceutica Nv | Imidazole carboxylates |
US4770689A (en) * | 1986-03-10 | 1988-09-13 | Janssen Pharmaceutica N.V. | Herbicidal imidazole-5-carboxylic acid derivatives |
JP5580287B2 (ja) * | 2008-03-31 | 2014-08-27 | ザ ジェネラル ホスピタル コーポレイション | 改善された薬物速度論的および薬力学的特性を有するエトミデート類似体 |
CN103588757B (zh) * | 2013-01-04 | 2014-11-12 | 四川大学华西医院 | 超短效麻醉效应的n-取代咪唑羧酸酯类化合物、制备方法和用途 |
CN103739553B (zh) * | 2013-12-23 | 2014-11-12 | 四川大学华西医院 | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 |
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RU2016123144A (ru) | 2018-01-30 |
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PH12016501246A1 (en) | 2016-08-15 |
KR20160089516A (ko) | 2016-07-27 |
EP3088394A4 (en) | 2017-05-10 |
CN103739553A (zh) | 2014-04-23 |
EP3088394A1 (en) | 2016-11-02 |
AU2014373186B2 (en) | 2017-11-23 |
WO2015096551A1 (zh) | 2015-07-02 |
SG11201605055SA (en) | 2016-09-29 |
AU2014373186A1 (en) | 2016-07-14 |
US9969695B2 (en) | 2018-05-15 |
CA2933098A1 (en) | 2015-07-02 |
RU2659784C2 (ru) | 2018-07-04 |
RU2016123144A3 (zh) | 2018-04-27 |
JP2016540795A (ja) | 2016-12-28 |
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