JPS6040420B2 - ３−アミノ−２−（５−フルオル−及び５−メトキシ−１ｈ−インド−ル−３−イル）プロパン酸誘導体類、その製法及び利用 - Google Patents
３−アミノ−２−（５−フルオル−及び５−メトキシ−１ｈ−インド−ル−３−イル）プロパン酸誘導体類、その製法及び利用Info
- Publication number
- JPS6040420B2 JPS6040420B2 JP54074082A JP7408279A JPS6040420B2 JP S6040420 B2 JPS6040420 B2 JP S6040420B2 JP 54074082 A JP54074082 A JP 54074082A JP 7408279 A JP7408279 A JP 7408279A JP S6040420 B2 JPS6040420 B2 JP S6040420B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- methoxy
- tables
- group
- 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.)
- Expired
Links
- -1 5-methoxy-1H-indol-3-yl Chemical group 0.000 title claims description 6
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical class COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- PZMDNDUCUWFSRP-UHFFFAOYSA-N 3-amino-2-(5-methoxy-1h-indol-3-yl)propanoic acid Chemical compound COC1=CC=C2NC=C(C(CN)C(O)=O)C2=C1 PZMDNDUCUWFSRP-UHFFFAOYSA-N 0.000 claims description 4
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 claims description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 239000007868 Raney catalyst Substances 0.000 claims description 4
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- KLGSBANGKXGRTA-UHFFFAOYSA-N methyl 3-amino-2-(5-methoxy-1h-indol-3-yl)propanoate;hydrochloride Chemical compound Cl.C1=C(OC)C=C2C(C(CN)C(=O)OC)=CNC2=C1 KLGSBANGKXGRTA-UHFFFAOYSA-N 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003377 acid catalyst Substances 0.000 claims description 3
- 239000011260 aqueous acid Substances 0.000 claims description 3
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 2
- 239000012346 acetyl chloride Substances 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- PIZLBWGMERQCOC-UHFFFAOYSA-N dibenzyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OCC1=CC=CC=C1 PIZLBWGMERQCOC-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 claims description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 8
- 239000004480 active ingredient Substances 0.000 claims 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims 1
- 230000000911 decarboxylating effect Effects 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims 1
- 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 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 239000006188 syrup Substances 0.000 description 6
- 235000020357 syrup Nutrition 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 230000001631 hypertensive effect Effects 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 229940000681 5-hydroxytryptophan Drugs 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 229940125890 compound Ia Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- VVWQFHKMIZUZJP-UHFFFAOYSA-N ethyl 3-(3-acetamido-1-ethoxy-1-oxopropan-2-yl)-5-methoxyindole-1-carboxylate Chemical compound C1=C(OC)C=C2C(C(CNC(C)=O)C(=O)OCC)=CN(C(=O)OCC)C2=C1 VVWQFHKMIZUZJP-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QNCNSISRJMCGPK-UHFFFAOYSA-N 1-(5-fluoro-1h-indol-3-yl)-n,n-dimethylmethanamine Chemical compound C1=C(F)C=C2C(CN(C)C)=CNC2=C1 QNCNSISRJMCGPK-UHFFFAOYSA-N 0.000 description 1
- HHMIZCBOTYJRQU-UHFFFAOYSA-N 2-(5-fluoro-1h-indol-3-yl)acetonitrile Chemical compound FC1=CC=C2NC=C(CC#N)C2=C1 HHMIZCBOTYJRQU-UHFFFAOYSA-N 0.000 description 1
- ZBQCXEREMRGOCO-UHFFFAOYSA-N 2-(5-methoxy-1h-indol-3-yl)acetonitrile Chemical compound COC1=CC=C2NC=C(CC#N)C2=C1 ZBQCXEREMRGOCO-UHFFFAOYSA-N 0.000 description 1
- OZPSGURLNSOOAG-UHFFFAOYSA-N 2-(5-methoxy-1h-indol-3-yl)propanoic acid Chemical compound COC1=CC=C2NC=C(C(C)C(O)=O)C2=C1 OZPSGURLNSOOAG-UHFFFAOYSA-N 0.000 description 1
- PVOLUMDYFNYXNK-UHFFFAOYSA-N 3-amino-2-(5-fluoro-1h-indol-3-yl)propanoic acid Chemical compound C1=C(F)C=C2C(C(C(O)=O)CN)=CNC2=C1 PVOLUMDYFNYXNK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- INPQIVHQSQUEAJ-UHFFFAOYSA-N 5-fluorotryptophan Chemical compound C1=C(F)C=C2C(CC(N)C(O)=O)=CNC2=C1 INPQIVHQSQUEAJ-UHFFFAOYSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- 206010005746 Blood pressure fluctuation Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- HIHZWVKQSWRKCO-NSHDSACASA-N ethyl (2s)-2-amino-3-(5-hydroxy-1h-indol-3-yl)propanoate Chemical compound C1=C(O)C=C2C(C[C@H](N)C(=O)OCC)=CNC2=C1 HIHZWVKQSWRKCO-NSHDSACASA-N 0.000 description 1
- MXWKMIHKEJZLHA-UHFFFAOYSA-N ethyl 3-(1-cyano-2-ethoxy-2-oxoethyl)-5-fluoroindole-1-carboxylate Chemical compound C1=C(F)C=C2C(C(C#N)C(=O)OCC)=CN(C(=O)OCC)C2=C1 MXWKMIHKEJZLHA-UHFFFAOYSA-N 0.000 description 1
- VTQVMZZRZMSXIX-UHFFFAOYSA-N ethyl 3-(1-cyano-2-ethoxy-2-oxoethyl)-5-methoxyindole-1-carboxylate Chemical compound C1=C(OC)C=C2C(C(C#N)C(=O)OCC)=CN(C(=O)OCC)C2=C1 VTQVMZZRZMSXIX-UHFFFAOYSA-N 0.000 description 1
- ALIUXDQXTXWQEV-UHFFFAOYSA-N ethyl 3-(3-acetamido-1-ethoxy-1-oxopropan-2-yl)-5-fluoroindole-1-carboxylate Chemical compound C1=C(F)C=C2C(C(CNC(C)=O)C(=O)OCC)=CN(C(=O)OCC)C2=C1 ALIUXDQXTXWQEV-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91573578A | 1978-06-15 | 1978-06-15 | |
| US915735 | 2001-07-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55397A JPS55397A (en) | 1980-01-05 |
| JPS6040420B2 true JPS6040420B2 (ja) | 1985-09-11 |
Family
ID=25436194
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP54074082A Expired JPS6040420B2 (ja) | 1978-06-15 | 1979-06-14 | ３−アミノ−２−（５−フルオル−及び５−メトキシ−１ｈ−インド−ル−３−イル）プロパン酸誘導体類、その製法及び利用 |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS6040420B2 (enrdf_load_stackoverflow) |
| CA (1) | CA1098910A (enrdf_load_stackoverflow) |
| DE (1) | DE2921978A1 (enrdf_load_stackoverflow) |
| FR (1) | FR2428630A1 (enrdf_load_stackoverflow) |
| GB (1) | GB2023590B (enrdf_load_stackoverflow) |
| IL (1) | IL57367A0 (enrdf_load_stackoverflow) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0514111U (ja) * | 1991-08-12 | 1993-02-23 | エステー化学株式会社 | 作業用腕カバー |
| JPH0519308U (ja) * | 1991-08-23 | 1993-03-09 | 由美子 松本 | 日焼防止ブラウス |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1648867T3 (da) * | 2003-07-17 | 2013-12-16 | Plexxikon Inc | Ppar-aktive forbindelser |
| JP6434968B2 (ja) | 2013-07-02 | 2018-12-05 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｒｏｃｋ阻害剤としての三環式ピリド−カルボキサミド誘導体 |
| JP6522602B2 (ja) | 2013-07-02 | 2019-05-29 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｒｏｃｋ阻害剤としての三環式ピリド−カルボキサミド誘導体 |
-
1979
- 1979-05-08 CA CA327,140A patent/CA1098910A/en not_active Expired
- 1979-05-22 IL IL57367A patent/IL57367A0/xx not_active IP Right Cessation
- 1979-05-30 DE DE19792921978 patent/DE2921978A1/de active Granted
- 1979-06-04 GB GB7919449A patent/GB2023590B/en not_active Expired
- 1979-06-14 JP JP54074082A patent/JPS6040420B2/ja not_active Expired
- 1979-06-14 FR FR7915278A patent/FR2428630A1/fr active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0514111U (ja) * | 1991-08-12 | 1993-02-23 | エステー化学株式会社 | 作業用腕カバー |
| JPH0519308U (ja) * | 1991-08-23 | 1993-03-09 | 由美子 松本 | 日焼防止ブラウス |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2921978C2 (enrdf_load_stackoverflow) | 1988-09-01 |
| DE2921978A1 (de) | 1979-12-20 |
| GB2023590A (en) | 1980-01-03 |
| FR2428630B1 (enrdf_load_stackoverflow) | 1983-04-15 |
| JPS55397A (en) | 1980-01-05 |
| IL57367A0 (en) | 1979-09-30 |
| FR2428630A1 (fr) | 1980-01-11 |
| GB2023590B (en) | 1982-11-17 |
| CA1098910A (en) | 1981-04-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3072530A (en) | Therapeutic indoles for psychic stimulation and relief of mental depression | |
| EP0000167A1 (en) | 1,2,3,6-Tetrahydroisonicotinic acid and derivatives thereof, methods and starting products for their preparation, and pharmaceutical compositions containing them. | |
| HK82089A (en) | 4-aminoalkyl-2(3h)-indolones | |
| JPH0587504B2 (enrdf_load_stackoverflow) | ||
| DE3631824A1 (de) | Cycloalkano(1.2-b)indol-sulfonamide | |
| JPS59118766A (ja) | シス，エンド−２−アザビシクロ〔５．３．０〕デカン−３−カルボン酸の誘導体およびその製法 | |
| SU1195903A3 (ru) | Способ получени 1-фенил- 2-аминокарбонилиндольных соединений или их солей присоединени кислот | |
| US4134991A (en) | Derivatives of 2-(3-phenyl-2-aminopropionyloxy)-acetic acid | |
| JPS6040420B2 (ja) | ３−アミノ−２−（５−フルオル−及び５−メトキシ−１ｈ−インド−ル−３−イル）プロパン酸誘導体類、その製法及び利用 | |
| EP0083222B1 (en) | New quinolylacetic acid compounds and pharmaceutical compositions containing them | |
| Cragoe Jr et al. | The synthesis of 3-hydroxycinchoninic acid and certain of its derivatives | |
| US4283410A (en) | 3-Amino or amido-2-(1H-indol-3-yl) propanoic acid derivatives | |
| US3637804A (en) | Phenylalanine derivatives and preparation thereof | |
| JPS63310866A (ja) | 新規ポリヒドロベンズ［ｃ，ｄ］インドールスルホンアミド、その製造方法及び薬物におけるその使用 | |
| DE3300522A1 (de) | 3,3-dialkyl- und 3,3-alkylen-indolinderivate, verfahren zu ihrer herstellung und pharmazeutische praeparate sie enthaltend | |
| US4446151A (en) | Decarboxylase-inhibiting fluorinated pentane diamine derivatives | |
| FR2543952A1 (fr) | Composes hydrocarbones heterocycliques appartenant aux series indoliques et leur application pharmacologique | |
| DK150541B (da) | Analogifremgangsmaade til fremstilling af 1-(3-bromisoxazol-5-yl)-2-tert.-butyl-aminoethanol eller farmaceutisk acceptable syreadditionssalte heraf | |
| NO881899L (no) | Nye 2-aminoalkyl-4-benzyl-1-(2h)-ftalazino-derivater. | |
| US4283336A (en) | Process for the preparation of 3-amino-2-(5-fluoro and 5-methoxy-1H-indol-3-yl)propanoic acid derivatives | |
| GB2204579A (en) | Optically active oxo-isoindolinyl derivatives | |
| CH620678A5 (en) | Process for the preparation of a derivative of piperidine | |
| FR2653999A1 (fr) | Nouveaux derives de la morpholine, leur procede de preparation et les compositions pharmaceutiques les renfermant. | |
| WO1990001483A1 (en) | Tetrahydropyridine derivatives | |
| JPH0550499B2 (enrdf_load_stackoverflow) |