JP2010517998A - 化合物 - Google Patents
化合物 Download PDFInfo
- Publication number
- JP2010517998A JP2010517998A JP2009548187A JP2009548187A JP2010517998A JP 2010517998 A JP2010517998 A JP 2010517998A JP 2009548187 A JP2009548187 A JP 2009548187A JP 2009548187 A JP2009548187 A JP 2009548187A JP 2010517998 A JP2010517998 A JP 2010517998A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- treating
- thiocyanate
- 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.)
- Pending
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- 150000001875 compounds Chemical class 0.000 title claims description 90
- 239000003814 drug Substances 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 22
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims description 12
- -1 alkali metal thiocyanate Chemical class 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 229960002748 norepinephrine Drugs 0.000 claims description 12
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims description 9
- 229940116357 potassium thiocyanate Drugs 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- 206010019280 Heart failures Diseases 0.000 claims description 8
- 238000010511 deprotection reaction Methods 0.000 claims description 8
- 229960003638 dopamine Drugs 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 7
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 claims description 7
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 7
- ARXKVVRQIIOZGF-UHFFFAOYSA-N 1,2,4-butanetriol Chemical compound OCCC(O)CO ARXKVVRQIIOZGF-UHFFFAOYSA-N 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 230000006793 arrhythmia Effects 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 208000012322 Raynaud phenomenon Diseases 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 claims description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 238000005341 cation exchange Methods 0.000 claims description 3
- 229920001429 chelating resin Polymers 0.000 claims description 3
- 238000006477 desulfuration reaction Methods 0.000 claims description 3
- 230000023556 desulfurization Effects 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 230000033444 hydroxylation Effects 0.000 claims description 3
- 238000005805 hydroxylation reaction Methods 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- AGOSGCWATIJZHQ-UHFFFAOYSA-N tert-butyl [(2-methylpropan-2-yl)oxycarbonylamino] carbonate Chemical compound CC(C)(C)OC(=O)NOC(=O)OC(C)(C)C AGOSGCWATIJZHQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 230000009286 beneficial effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims 10
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims 7
- 230000000397 acetylating effect Effects 0.000 claims 3
- 239000012442 inert solvent Substances 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 claims 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims 1
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical group C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000006884 silylation reaction Methods 0.000 claims 1
- VTYSDDGFTAOBOD-UHFFFAOYSA-N 3-(6,8-difluoro-3,4-dihydro-2h-chromen-3-yl)-1h-imidazole-2-thione Chemical compound C1C2=CC(F)=CC(F)=C2OCC1N1C=CNC1=S VTYSDDGFTAOBOD-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 239000003208 petroleum Substances 0.000 description 25
- 230000002829 reductive effect Effects 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 230000002889 sympathetic effect Effects 0.000 description 5
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 4
- IJNWXEVIDGBHHT-SNVBAGLBSA-N 2-[3-[(3r)-6,8-difluoro-3,4-dihydro-2h-chromen-3-yl]-2-sulfanylidene-1h-imidazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CNC(=S)N1[C@@H]1CC2=CC(F)=CC(F)=C2OC1 IJNWXEVIDGBHHT-SNVBAGLBSA-N 0.000 description 4
- WRANTHLMINRHTR-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-2-amine Chemical compound C1=CC=C2OC(N)CCC2=C1 WRANTHLMINRHTR-UHFFFAOYSA-N 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- NDBQJIBNNUJNHA-DFWYDOINSA-N methyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CO NDBQJIBNNUJNHA-DFWYDOINSA-N 0.000 description 4
- YZZVIKDAOTXDEB-JTQLQIEISA-N nepicastat Chemical compound NCC1=CNC(=S)N1[C@@H]1CC2=CC(F)=CC(F)=C2CC1 YZZVIKDAOTXDEB-JTQLQIEISA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- HRRVVFJKAQVKFM-UHFFFAOYSA-N tert-butyl [3,4-dihydroxybutyl-[(2-methylpropan-2-yl)oxycarbonyl]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON(C(=O)OC(C)(C)C)CCC(O)CO HRRVVFJKAQVKFM-UHFFFAOYSA-N 0.000 description 4
- XPKQHJJKXONCHR-UHFFFAOYSA-N 2-amino-3,4-dihydrochromen-2-ol Chemical compound C1=CC=C2OC(N)(O)CCC2=C1 XPKQHJJKXONCHR-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 238000010917 Friedel-Crafts cyclization Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
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- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- ZYMJCPDCUHPWRB-CYBMUJFWSA-N n-[2-[3-[(3r)-6,8-difluoro-3,4-dihydro-2h-chromen-3-yl]-2-sulfanylidene-1h-imidazol-4-yl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CNC(=S)N1[C@@H]1CC2=CC(F)=CC(F)=C2OC1 ZYMJCPDCUHPWRB-CYBMUJFWSA-N 0.000 description 3
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- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- YCZHKAKURRYGEJ-UHFFFAOYSA-N tert-butyl [[4-[tert-butyl(dimethyl)silyl]oxy-3-hydroxybutyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON(C(=O)OC(C)(C)C)CCC(O)CO[Si](C)(C)C(C)(C)C YCZHKAKURRYGEJ-UHFFFAOYSA-N 0.000 description 3
- DGEPEPIBCYEBBX-UHFFFAOYSA-N tert-butyl [[4-[tert-butyl(dimethyl)silyl]oxy-3-oxobutyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON(C(=O)OC(C)(C)C)CCC(=O)CO[Si](C)(C)C(C)(C)C DGEPEPIBCYEBBX-UHFFFAOYSA-N 0.000 description 3
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- CWWWTTYMUOYSQA-LLVKDONJSA-N 4-(2-aminoethyl)-3-[(3r)-6,8-difluoro-3,4-dihydro-2h-chromen-3-yl]-1h-imidazole-2-thione Chemical compound NCCC1=CNC(=S)N1[C@@H]1CC2=CC(F)=CC(F)=C2OC1 CWWWTTYMUOYSQA-LLVKDONJSA-N 0.000 description 2
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
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- 230000000747 cardiac effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 150000003943 catecholamines Chemical class 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 150000002009 diols Chemical group 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- FWARNCMTCYKUBS-UHFFFAOYSA-N ethyl n-(ethoxycarbonylcarbamoyl)carbamate Chemical compound CCOC(=O)NC(=O)NC(=O)OCC FWARNCMTCYKUBS-UHFFFAOYSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
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- 229910052763 palladium Inorganic materials 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0701969A GB0701969D0 (en) | 2007-02-01 | 2007-02-01 | Compounds |
| GB0701968A GB0701968D0 (en) | 2007-02-01 | 2007-02-01 | Compounds |
| PCT/PT2008/000004 WO2008094054A2 (en) | 2007-02-01 | 2008-01-31 | 6, 8-dichlorchroman-3-yl-l, 3-dihydroimidazole-2-thione derivatives and their use for the treatment of cardiovascular disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010517998A true JP2010517998A (ja) | 2010-05-27 |
| JP2010517998A5 JP2010517998A5 (enExample) | 2011-03-24 |
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| JP2009548187A Pending JP2010517998A (ja) | 2007-02-01 | 2008-01-31 | 化合物 |
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|---|---|
| US (1) | US20100093817A1 (enExample) |
| EP (1) | EP2121668A2 (enExample) |
| JP (1) | JP2010517998A (enExample) |
| AR (1) | AR065107A1 (enExample) |
| WO (1) | WO2008094054A2 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016525145A (ja) * | 2013-07-25 | 2016-08-22 | サイノファーム タイワン，リミティド | フォンダパリヌクスナトリウムを製造するための方法 |
| WO2018070543A1 (ja) * | 2016-10-14 | 2018-04-19 | 株式会社ボナック | 新規な配糖体化合物及びその製造方法 |
| US10072039B2 (en) | 2013-07-25 | 2018-09-11 | Scinopharm Taiwan, Ltd. | Process for the production of Fondaparinux sodium |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0701965D0 (en) * | 2007-02-01 | 2007-03-14 | Portela & Ca Sa | Process |
| CN111333528B (zh) * | 2020-04-10 | 2022-10-21 | 苏州爱玛特生物科技有限公司 | 一种多构型o-苯基-丝氨酸类化合物的合成方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006507261A (ja) * | 2002-10-11 | 2006-03-02 | ポルテラ・アンド・シーエー・エスエー | ドーパミン−ベータ−ヒドロキシラーゼの末梢選択的阻害剤としてのイミダゾール誘導体、及びこれらの用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0757677B1 (en) * | 1994-04-26 | 2003-06-18 | Syntex (U.S.A.) LLC | Benzocyclohexylimidazolethione derivatives |
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2008
- 2008-01-31 WO PCT/PT2008/000004 patent/WO2008094054A2/en not_active Ceased
- 2008-01-31 EP EP08705174A patent/EP2121668A2/en not_active Withdrawn
- 2008-01-31 AR ARP080100395A patent/AR065107A1/es unknown
- 2008-01-31 US US12/524,940 patent/US20100093817A1/en not_active Abandoned
- 2008-01-31 JP JP2009548187A patent/JP2010517998A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006507261A (ja) * | 2002-10-11 | 2006-03-02 | ポルテラ・アンド・シーエー・エスエー | ドーパミン−ベータ−ヒドロキシラーゼの末梢選択的阻害剤としてのイミダゾール誘導体、及びこれらの用途 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016525145A (ja) * | 2013-07-25 | 2016-08-22 | サイノファーム タイワン，リミティド | フォンダパリヌクスナトリウムを製造するための方法 |
| US10072039B2 (en) | 2013-07-25 | 2018-09-11 | Scinopharm Taiwan, Ltd. | Process for the production of Fondaparinux sodium |
| WO2018070543A1 (ja) * | 2016-10-14 | 2018-04-19 | 株式会社ボナック | 新規な配糖体化合物及びその製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008094054A2 (en) | 2008-08-07 |
| WO2008094054A3 (en) | 2008-09-18 |
| EP2121668A2 (en) | 2009-11-25 |
| US20100093817A1 (en) | 2010-04-15 |
| AR065107A1 (es) | 2009-05-13 |
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