NO840241L - Fremgangsmaate for fremstilling av terapeutisk aktive 2-((fenetyl)-5-((3,4-metylendioksy)-alfa-hydroksylbenzyl)pyrrolidiner - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive 2-((fenetyl)-5-((3,4-metylendioksy)-alfa-hydroksylbenzyl)pyrrolidinerInfo
- Publication number
- NO840241L NO840241L NO840241A NO840241A NO840241L NO 840241 L NO840241 L NO 840241L NO 840241 A NO840241 A NO 840241A NO 840241 A NO840241 A NO 840241A NO 840241 L NO840241 L NO 840241L
- Authority
- NO
- Norway
- Prior art keywords
- phenethyl
- methylenedioxy
- pyrrolidine
- hydroxybenzyl
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 39
- -1 PHENETHYL Chemical class 0.000 title claims description 67
- 150000003235 pyrrolidines Chemical class 0.000 title description 4
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims abstract description 17
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 73
- 239000000203 mixture Substances 0.000 claims description 54
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 49
- WOIBCZMSDVCMIN-UHFFFAOYSA-N 1,3-benzodioxol-5-yl-[5-(2-phenylethyl)pyrrolidin-2-yl]methanol Chemical compound C=1C=C2OCOC2=CC=1C(O)C(N1)CCC1CCC1=CC=CC=C1 WOIBCZMSDVCMIN-UHFFFAOYSA-N 0.000 claims description 43
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 30
- 101100514842 Xenopus laevis mtus1 gene Proteins 0.000 claims description 14
- 230000009467 reduction Effects 0.000 claims description 13
- 239000012458 free base Substances 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 2
- 229940030600 antihypertensive agent Drugs 0.000 abstract description 7
- 239000002220 antihypertensive agent Substances 0.000 abstract description 7
- 210000000748 cardiovascular system Anatomy 0.000 abstract description 6
- 230000003389 potentiating effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 22
- 235000019441 ethanol Nutrition 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 16
- 230000035488 systolic blood pressure Effects 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- STFMKWCNBOPACP-UHFFFAOYSA-N 2-phenyl-1-(1h-pyrrol-2-yl)ethanone Chemical compound C=1C=CNC=1C(=O)CC1=CC=CC=C1 STFMKWCNBOPACP-UHFFFAOYSA-N 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- MCWZVZDPXXEBEQ-UHFFFAOYSA-N FC(C(=O)O)(F)F.C(CC1=CC=CC=C1)C1NC(CC1)C(C1=CC2=C(C=C1)OCO2)O Chemical compound FC(C(=O)O)(F)F.C(CC1=CC=CC=C1)C1NC(CC1)C(C1=CC2=C(C=C1)OCO2)O MCWZVZDPXXEBEQ-UHFFFAOYSA-N 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- MRGVUWNMTRFDSW-UHFFFAOYSA-N 2-(2-phenylethyl)-1h-pyrrole Chemical compound C=1C=CNC=1CCC1=CC=CC=C1 MRGVUWNMTRFDSW-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 206010020772 Hypertension Diseases 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ZSPGIKSFFHUKEE-PMACEKPBSA-N tert-butyl (2s,5s)-2-(1,3-benzodioxole-5-carbonyl)-5-(2-phenylethyl)pyrrolidine-1-carboxylate Chemical compound C([C@@H]1N([C@@H](CC1)C(=O)C=1C=C2OCOC2=CC=1)C(=O)OC(C)(C)C)CC1=CC=CC=C1 ZSPGIKSFFHUKEE-PMACEKPBSA-N 0.000 description 7
- JDBLQRCNIIWXQJ-UHFFFAOYSA-N tert-butyl 2-[1,3-benzodioxol-5-yl(hydroxy)methyl]-5-(2-phenylethyl)pyrrolidine-1-carboxylate Chemical compound C1CC(C(O)C=2C=C3OCOC3=CC=2)N(C(=O)OC(C)(C)C)C1CCC1=CC=CC=C1 JDBLQRCNIIWXQJ-UHFFFAOYSA-N 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- KMWWEJJZOOMSFH-UHFFFAOYSA-N 1,3-benzodioxol-5-yl-[5-(2-phenylethyl)pyrrolidin-2-yl]methanone Chemical compound C=1C=C2OCOC2=CC=1C(=O)C(N1)CCC1CCC1=CC=CC=C1 KMWWEJJZOOMSFH-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- LDIZQBWAXBLCLV-UHFFFAOYSA-N 1,3-benzodioxol-5-yl-[5-(2-phenylethyl)-1h-pyrrol-2-yl]methanone Chemical compound C=1C=C2OCOC2=CC=1C(=O)C(N1)=CC=C1CCC1=CC=CC=C1 LDIZQBWAXBLCLV-UHFFFAOYSA-N 0.000 description 5
- POXCSSPOACDPHW-UHFFFAOYSA-N FC(C(=O)O)(F)F.C1(=CC=CC=C1)CCC1NC(CC1)C(C1=CC2=C(C=C1)OCO2)=O Chemical compound FC(C(=O)O)(F)F.C1(=CC=CC=C1)CCC1NC(CC1)C(C1=CC2=C(C=C1)OCO2)=O POXCSSPOACDPHW-UHFFFAOYSA-N 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 230000001077 hypotensive effect Effects 0.000 description 5
- 238000011835 investigation Methods 0.000 description 5
- QUQDCJQTFDWNQF-UHFFFAOYSA-N tert-butyl 2-(1,3-benzodioxole-5-carbonyl)-5-(2-phenylethyl)pyrrole-1-carboxylate Chemical compound C=1C=C(C(=O)C=2C=C3OCOC3=CC=2)N(C(=O)OC(C)(C)C)C=1CCC1=CC=CC=C1 QUQDCJQTFDWNQF-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000004531 blood pressure lowering effect Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229910000510 noble metal Inorganic materials 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
- VDVJGIYXDVPQLP-UHFFFAOYSA-N piperonylic acid Chemical compound OC(=O)C1=CC=C2OCOC2=C1 VDVJGIYXDVPQLP-UHFFFAOYSA-N 0.000 description 4
- 229910003446 platinum oxide Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- MHZPMAQMPFJRSL-UHFFFAOYSA-N 2-(4-phenylmethoxyphenyl)-1-(1h-pyrrol-2-yl)ethanone Chemical compound C=1C=CNC=1C(=O)CC(C=C1)=CC=C1OCC1=CC=CC=C1 MHZPMAQMPFJRSL-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- FUYKQXPDYJZWLB-UHFFFAOYSA-N 2-[2-(4-phenylmethoxyphenyl)ethyl]-1h-pyrrole Chemical compound C=1C=CNC=1CCC(C=C1)=CC=C1OCC1=CC=CC=C1 FUYKQXPDYJZWLB-UHFFFAOYSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
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- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000010531 catalytic reduction reaction Methods 0.000 description 3
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 3
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical group CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 3
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- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
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- 230000003000 nontoxic effect Effects 0.000 description 3
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- 238000007911 parenteral administration Methods 0.000 description 3
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000001144 postural effect Effects 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- LSESEWWPDBDCHQ-UHFFFAOYSA-N 1,3-benzodioxol-5-yl-[5-[2-(3,4-dimethoxyphenyl)ethyl]pyrrolidin-2-yl]methanol Chemical compound C1=C(OC)C(OC)=CC=C1CCC1NC(C(O)C=2C=C3OCOC3=CC=2)CC1 LSESEWWPDBDCHQ-UHFFFAOYSA-N 0.000 description 2
- RLQGPVPMWLWMIA-UHFFFAOYSA-N 4-[hydroxy-[5-(2-phenylethyl)pyrrolidin-2-yl]methyl]benzene-1,2-diol Chemical compound C=1C=C(O)C(O)=CC=1C(O)C(N1)CCC1CCC1=CC=CC=C1 RLQGPVPMWLWMIA-UHFFFAOYSA-N 0.000 description 2
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
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- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000009724 venous congestion Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/323—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—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
- 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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8300098 | 1983-01-24 | ||
US06/527,717 US4543361A (en) | 1983-08-29 | 1983-08-29 | ±2-[Phenethyl]-5-[(3,4-methylenedioxy)-α-hydroxybenzyl]pyrrolidine antihypertensives and use thereas |
Publications (1)
Publication Number | Publication Date |
---|---|
NO840241L true NO840241L (no) | 1984-07-25 |
Family
ID=26768103
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO840241A NO840241L (no) | 1983-01-24 | 1984-01-23 | Fremgangsmaate for fremstilling av terapeutisk aktive 2-((fenetyl)-5-((3,4-metylendioksy)-alfa-hydroksylbenzyl)pyrrolidiner |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP0115413A1 (fi) |
JP (2) | JPS59161381A (fi) |
AU (1) | AU2369984A (fi) |
DK (1) | DK30184A (fi) |
ES (3) | ES8600759A1 (fi) |
FI (1) | FI840255A (fi) |
IE (1) | IE840151L (fi) |
IL (1) | IL70753A0 (fi) |
NO (1) | NO840241L (fi) |
ZA (2) | ZA84508B (fi) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0562185A1 (en) * | 1992-03-17 | 1993-09-29 | Council of Scientific and Industrial Research | 3-(Arylmethyl)-1-(3'-diethylaminopropyl) pyrrolidines and process of preparation thereof |
JPH061371A (ja) * | 1992-06-17 | 1994-01-11 | Uintetsuku Kk | ストレッチフィルム包装の開披容易化法とその装置 |
US6015824A (en) * | 1998-02-10 | 2000-01-18 | Hoffmann-La Roche Ag | Pyrrolidine and piperidine derivatives and treatment of neurodegenerative disorders |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
LU78625A1 (de) * | 1977-12-02 | 1979-06-13 | Byk Gulden Lomberg Chem Fab | Substituierte 1-phenyl-2-pyrrolidin-2-yl-ethanole,verfahren zu ihrer herstellung,ihre verwendung und sie enthaltende arzneimittel |
FR2436779A1 (fr) * | 1978-09-22 | 1980-04-18 | Pharmindustrie | Derives de pyrrolidine-2 methanol utilisables comme medicaments |
FR2460929A1 (fr) * | 1979-07-06 | 1981-01-30 | Roussel Uclaf | Nouveaux derives de l'a-phenyl 2-pyrrolidinemethanol et leur sels, procede de preparation, application a titre de medicaments et compositions les renfermant |
US4342692A (en) * | 1980-10-20 | 1982-08-03 | Usv Pharmaceutical Corporation | Pyrrolidines |
KR840000486A (ko) * | 1981-07-22 | 1984-02-22 | 원본미기재 | 치환된 피롤리딘의 제조방법 |
-
1984
- 1984-01-23 NO NO840241A patent/NO840241L/no unknown
- 1984-01-23 AU AU23699/84A patent/AU2369984A/en not_active Abandoned
- 1984-01-23 IE IE840151A patent/IE840151L/xx unknown
- 1984-01-23 IL IL70753A patent/IL70753A0/xx unknown
- 1984-01-23 JP JP59008671A patent/JPS59161381A/ja active Pending
- 1984-01-23 ES ES529086A patent/ES8600759A1/es not_active Expired
- 1984-01-23 DK DK30184A patent/DK30184A/da not_active Application Discontinuation
- 1984-01-23 FI FI840255A patent/FI840255A/fi not_active Application Discontinuation
- 1984-01-23 EP EP84300386A patent/EP0115413A1/en not_active Withdrawn
- 1984-01-23 ZA ZA84508A patent/ZA84508B/xx unknown
- 1984-01-23 ZA ZA84507A patent/ZA84507B/xx unknown
- 1984-01-23 JP JP59008670A patent/JPS59161380A/ja active Pending
-
1985
- 1985-06-14 ES ES544201A patent/ES8604210A1/es not_active Expired
- 1985-06-14 ES ES544205A patent/ES8603871A1/es not_active Expired
Also Published As
Publication number | Publication date |
---|---|
ES544201A0 (es) | 1986-02-01 |
ES544205A0 (es) | 1986-01-16 |
IL70753A0 (en) | 1984-04-30 |
ES529086A0 (es) | 1985-11-01 |
ZA84508B (en) | 1985-09-25 |
FI840255A0 (fi) | 1984-01-23 |
AU2369984A (en) | 1984-07-26 |
FI840255A (fi) | 1984-07-25 |
JPS59161381A (ja) | 1984-09-12 |
ZA84507B (en) | 1985-09-25 |
IE840151L (en) | 1985-02-28 |
ES8603871A1 (es) | 1986-01-16 |
DK30184A (da) | 1984-07-25 |
ES8600759A1 (es) | 1985-11-01 |
JPS59161380A (ja) | 1984-09-12 |
ES8604210A1 (es) | 1986-02-01 |
EP0115413A1 (en) | 1984-08-08 |
DK30184D0 (da) | 1984-01-23 |
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