KR910003362B1 - 중추 신경계 활성을 갖는 피롤리디논의 제조방법 - Google Patents
중추 신경계 활성을 갖는 피롤리디논의 제조방법 Download PDFInfo
- Publication number
- KR910003362B1 KR910003362B1 KR1019840004083A KR840004083A KR910003362B1 KR 910003362 B1 KR910003362 B1 KR 910003362B1 KR 1019840004083 A KR1019840004083 A KR 1019840004083A KR 840004083 A KR840004083 A KR 840004083A KR 910003362 B1 KR910003362 B1 KR 910003362B1
- Authority
- KR
- South Korea
- Prior art keywords
- group
- general formula
- product
- alkyl group
- pyrrolidinone
- 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
- 238000000034 method Methods 0.000 title claims description 21
- 230000000694 effects Effects 0.000 title description 9
- 210000003169 central nervous system Anatomy 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 6
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
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- 241001465754 Metazoa Species 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- -1 succinic acid diester Chemical class 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 0 CC1*CCC1 Chemical compound CC1*CCC1 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 208000005392 Spasm Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000001773 anti-convulsant effect Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000033001 locomotion Effects 0.000 description 4
- 229960001412 pentobarbital Drugs 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- NCELJWJKTASLQV-UHFFFAOYSA-N 3-ethyl-5-[(2-fluorophenyl)methyl]-3-methylpyrrolidin-2-one Chemical compound N1C(=O)C(CC)(C)CC1CC1=CC=CC=C1F NCELJWJKTASLQV-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000007101 Muscle Cramp Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 230000000147 hypnotic effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 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 description 2
- LNJMWLKRWRKEKT-UHFFFAOYSA-N 2-ethyl-5-(2-fluorophenyl)-2-methyl-4-oxopentanoic acid Chemical compound CCC(C)(C(O)=O)CC(=O)CC1=CC=CC=C1F LNJMWLKRWRKEKT-UHFFFAOYSA-N 0.000 description 2
- MJEMKGDDJMSUTD-UHFFFAOYSA-N 2-ethyl-5-(2-fluorophenyl)-4-hydroxyimino-2-methylpentanoic acid Chemical compound CCC(C)(C(O)=O)CC(=NO)CC1=CC=CC=C1F MJEMKGDDJMSUTD-UHFFFAOYSA-N 0.000 description 2
- WXUAQHNMJWJLTG-UHFFFAOYSA-N 2-methylbutanedioic acid Chemical compound OC(=O)C(C)CC(O)=O WXUAQHNMJWJLTG-UHFFFAOYSA-N 0.000 description 2
- PIAOLBVUVDXHHL-UHFFFAOYSA-N 2-nitroethenylbenzene Chemical compound [O-][N+](=O)C=CC1=CC=CC=C1 PIAOLBVUVDXHHL-UHFFFAOYSA-N 0.000 description 2
- LCCFHKXRTCVOCD-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-3,3-dimethylpyrrolidin-2-one Chemical compound N1C(=O)C(C)(C)CC1CC1=CC=C(F)C=C1 LCCFHKXRTCVOCD-UHFFFAOYSA-N 0.000 description 2
- SJGPJZBAWVAGLX-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-3-methylpyrrolidin-2-one Chemical compound N1C(=O)C(C)CC1CC1=CC=C(F)C=C1 SJGPJZBAWVAGLX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 229930194542 Keto Natural products 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
- QVDYYQXUNAQSNI-UHFFFAOYSA-N ethyl acetate;pentane Chemical compound CCCCC.CCOC(C)=O QVDYYQXUNAQSNI-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-N sodium;hydron;carbonate Chemical compound [Na+].OC(O)=O UIIMBOGNXHQVGW-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- LUBVCBITQHEVCJ-UHFFFAOYSA-N 1-trimethylsilylpyrrolidin-2-one Chemical compound C[Si](C)(C)N1CCCC1=O LUBVCBITQHEVCJ-UHFFFAOYSA-N 0.000 description 1
- UTPOWFFIBWOQRK-ONEGZZNKSA-N 2-[(e)-2-nitroethenyl]thiophene Chemical compound [O-][N+](=O)\C=C\C1=CC=CS1 UTPOWFFIBWOQRK-ONEGZZNKSA-N 0.000 description 1
- FDYJJKHDNNVUDR-UHFFFAOYSA-N 2-ethyl-2-methylbutanedioic acid Chemical compound CCC(C)(C(O)=O)CC(O)=O FDYJJKHDNNVUDR-UHFFFAOYSA-N 0.000 description 1
- CQJDQMOEHSCRHT-UHFFFAOYSA-N 2-methyl-4-nitro-5-thiophen-2-ylpentanoic acid Chemical compound OC(=O)C(C)CC([N+]([O-])=O)CC1=CC=CS1 CQJDQMOEHSCRHT-UHFFFAOYSA-N 0.000 description 1
- RLIOIYLGOJYLSA-UHFFFAOYSA-N 3,3-dibutyl-5-(3-methoxyphenyl)pyrrolidin-2-one Chemical compound N1C(=O)C(CCCC)(CCCC)CC1C1=CC=CC(OC)=C1 RLIOIYLGOJYLSA-UHFFFAOYSA-N 0.000 description 1
- VVHDUFWEIJOYHW-UHFFFAOYSA-N 3-butyl-5-(3-methoxyphenyl)pyrrolidin-2-one Chemical compound N1C(=O)C(CCCC)CC1C1=CC=CC(OC)=C1 VVHDUFWEIJOYHW-UHFFFAOYSA-N 0.000 description 1
- WMFWNCRXGCDGSS-UHFFFAOYSA-N 3-methyl-5-(thiophen-2-ylmethyl)pyrrolidin-2-one Chemical compound N1C(=O)C(C)CC1CC1=CC=CS1 WMFWNCRXGCDGSS-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- FUHNWQLJIATIMD-UHFFFAOYSA-N 5-(3-methoxyphenyl)-1-trimethylsilylpyrrolidin-2-one Chemical compound COC1=CC=CC(C2N(C(=O)CC2)[Si](C)(C)C)=C1 FUHNWQLJIATIMD-UHFFFAOYSA-N 0.000 description 1
- NEYOREJSKMMSRI-UHFFFAOYSA-N 5-[(3-methoxyphenyl)methyl]pyrrolidin-2-one Chemical compound COC1=CC=CC(CC2NC(=O)CC2)=C1 NEYOREJSKMMSRI-UHFFFAOYSA-N 0.000 description 1
- UJTLWBQZNAXBAQ-UHFFFAOYSA-N 5-benzylpyrrolidin-2-one Chemical compound N1C(=O)CCC1CC1=CC=CC=C1 UJTLWBQZNAXBAQ-UHFFFAOYSA-N 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- RDYWJXLOEJKHFH-UHFFFAOYSA-N CBC(C)N1CC1 Chemical compound CBC(C)N1CC1 RDYWJXLOEJKHFH-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
- 206010022998 Irritability Diseases 0.000 description 1
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- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 244000223014 Syzygium aromaticum Species 0.000 description 1
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
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- 150000001450 anions Chemical class 0.000 description 1
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- 230000003542 behavioural effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
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- 238000011156 evaluation Methods 0.000 description 1
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- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 150000004721 gamma keto acids Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical class N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000021542 voluntary musculoskeletal movement Effects 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/50—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
- C07C205/51—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/6533—Six-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8311636A FR2549053B1 (fr) | 1983-07-12 | 1983-07-12 | Nouveaux derives de la pyrrolidine actifs sur le systeme nerveux central, leur procede de preparation, les medicaments en contenant |
| FR8311636 | 1983-07-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR850001165A KR850001165A (ko) | 1985-03-16 |
| KR910003362B1 true KR910003362B1 (ko) | 1991-05-28 |
Family
ID=9290775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019840004083A Expired KR910003362B1 (ko) | 1983-07-12 | 1984-07-12 | 중추 신경계 활성을 갖는 피롤리디논의 제조방법 |
Country Status (23)
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3336024A1 (de) * | 1983-10-04 | 1985-04-18 | Boehringer Ingelheim KG, 6507 Ingelheim | 4-amino-l-benzyl-pyrrolidinone und ihre saeureadditionssalze, verfahren zu ihrer herstellung und arzneimittel |
| CA1336333C (en) * | 1988-05-20 | 1995-07-18 | Davide Della Bella | Pyrrolidone-2 compounds and their use for central analgesic activity |
| GB9307431D0 (en) * | 1993-04-08 | 1993-06-02 | Oxford Asymmetry Ltd | Improvements in or relating to chiral auxiliaries |
| CN106977415B (zh) * | 2016-01-15 | 2021-03-26 | 广东东阳光药业有限公司 | 一种沙库必曲的中间体及其制备方法 |
| EP3424899B1 (en) * | 2016-02-29 | 2022-05-11 | Sunshine Lake Pharma Co., Ltd. | Sacubitril intermediate and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3272842A (en) * | 1965-06-25 | 1966-09-13 | Lilly Co Eli | Novel pyrrolinones |
| AU518986B2 (en) * | 1977-10-11 | 1981-10-29 | Takeda Chemical Industries Ltd. | Lactams |
| FR2436779A1 (fr) * | 1978-09-22 | 1980-04-18 | Pharmindustrie | Derives de pyrrolidine-2 methanol utilisables comme medicaments |
-
1983
- 1983-07-12 FR FR8311636A patent/FR2549053B1/fr not_active Expired
-
1984
- 1984-07-03 AU AU30216/84A patent/AU560725B2/en not_active Ceased
- 1984-07-04 EP EP84401419A patent/EP0135406B1/fr not_active Expired
- 1984-07-04 AT AT84401419T patent/ATE30150T1/de not_active IP Right Cessation
- 1984-07-04 DE DE8484401419T patent/DE3466686D1/de not_active Expired
- 1984-07-04 CA CA000458049A patent/CA1249593A/en not_active Expired
- 1984-07-05 US US06/628,211 patent/US4604383A/en not_active Expired - Fee Related
- 1984-07-06 IL IL72324A patent/IL72324A/xx unknown
- 1984-07-09 GR GR75247A patent/GR81502B/el unknown
- 1984-07-10 PT PT78874A patent/PT78874B/pt not_active IP Right Cessation
- 1984-07-11 AR AR297160A patent/AR240451A1/es active
- 1984-07-11 SU SU843764652A patent/SU1391497A3/ru active
- 1984-07-11 FI FI842795A patent/FI77848C/fi not_active IP Right Cessation
- 1984-07-11 ES ES534221A patent/ES534221A0/es active Granted
- 1984-07-11 YU YU01213/84A patent/YU121384A/xx unknown
- 1984-07-11 NZ NZ208865A patent/NZ208865A/en unknown
- 1984-07-11 DD DD84276870A patent/DD229121A5/de not_active IP Right Cessation
- 1984-07-11 DD DD84265162A patent/DD227962A5/de not_active IP Right Cessation
- 1984-07-11 NO NO842821A patent/NO163617C/no unknown
- 1984-07-11 HU HU842710A patent/HU192564B/hu not_active IP Right Cessation
- 1984-07-12 JP JP59143423A patent/JPS6084265A/ja active Pending
- 1984-07-12 ZA ZA845397A patent/ZA845397B/xx unknown
- 1984-07-12 DK DK343784A patent/DK343784A/da not_active Application Discontinuation
- 1984-07-12 KR KR1019840004083A patent/KR910003362B1/ko not_active Expired
-
1986
- 1986-05-16 YU YU00810/86A patent/YU81086A/xx unknown
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| Date | Code | Title | Description |
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