HU202862B - Process for producing substituted pyrrolidinone derivatives and pharmaceutical compositions containing them - Google Patents
Process for producing substituted pyrrolidinone derivatives and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- HU202862B HU202862B HU87277A HU27787A HU202862B HU 202862 B HU202862 B HU 202862B HU 87277 A HU87277 A HU 87277A HU 27787 A HU27787 A HU 27787A HU 202862 B HU202862 B HU 202862B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- oxo
- preparation
- group
- pyrrolidin
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 31
- 239000008194 pharmaceutical composition Chemical class 0.000 title description 5
- 150000004040 pyrrolidinones Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 59
- 150000003839 salts Chemical group 0.000 claims description 53
- -1 monosubstituted phenyl Chemical group 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 25
- 239000007858 starting material Substances 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000001118 alkylidene group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical group C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- QPKMIYNBZGPJAR-UHFFFAOYSA-N cebaracetam Chemical compound C1=CC(Cl)=CC=C1C1CC(=O)N(CC(=O)N2CC(=O)NCC2)C1 QPKMIYNBZGPJAR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 230000001777 nootropic effect Effects 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- QTHVEJAKSLMWDZ-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-[2-oxo-2-[4-[2-(2-oxopyrrolidin-1-yl)acetyl]piperazin-1-yl]ethyl]pyrrolidin-2-one Chemical compound C1=CC(Cl)=CC=C1C1CC(=O)N(CC(=O)N2CCN(CC2)C(=O)CN2C(CCC2)=O)C1 QTHVEJAKSLMWDZ-UHFFFAOYSA-N 0.000 claims description 2
- NQTNCBLRWHMMHF-UHFFFAOYSA-N 4-[2-[4-(4-fluorophenyl)-2-oxopyrrolidin-1-yl]acetyl]piperazin-2-one Chemical compound C1=CC(F)=CC=C1C1CC(=O)N(CC(=O)N2CC(=O)NCC2)C1 NQTNCBLRWHMMHF-UHFFFAOYSA-N 0.000 claims description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 239000000829 suppository Substances 0.000 claims 2
- QVEIKLYABSFXAE-UHFFFAOYSA-N 1-(2-oxo-2-piperazin-1-ylethyl)-4-phenylpyrrolidin-2-one Chemical compound C1CNCCN1C(=O)CN(C(C1)=O)CC1C1=CC=CC=C1 QVEIKLYABSFXAE-UHFFFAOYSA-N 0.000 claims 1
- BPUDJKSPTPDPTF-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-(2-oxo-2-piperazin-1-ylethyl)pyrrolidin-2-one Chemical compound C1=CC(Cl)=CC=C1C1CC(=O)N(CC(=O)N2CCNCC2)C1 BPUDJKSPTPDPTF-UHFFFAOYSA-N 0.000 claims 1
- CUMNWCBDKVMSLS-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]pyrrolidin-2-one Chemical compound C1CN(C)CCN1C(=O)CN1C(=O)CC(C=2C=CC(Cl)=CC=2)C1 CUMNWCBDKVMSLS-UHFFFAOYSA-N 0.000 claims 1
- MKSMVMYOMKWVCN-UHFFFAOYSA-N 4-[2-[4-(4-chlorophenyl)-2-oxopyrrolidin-1-yl]acetyl]-1-methylpiperazin-2-one Chemical compound C1C(=O)N(C)CCN1C(=O)CN1C(=O)CC(C=2C=CC(Cl)=CC=2)C1 MKSMVMYOMKWVCN-UHFFFAOYSA-N 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical class C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- 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 5
- 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 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 229940099112 cornstarch Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 3
- LKCHYFKRGFDOAC-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-2-oxopyrrolidin-1-yl]acetic acid Chemical compound C1C(=O)N(CC(=O)O)CC1C1=CC=C(Cl)C=C1 LKCHYFKRGFDOAC-UHFFFAOYSA-N 0.000 description 3
- VRDFVCCNKXZPEI-UHFFFAOYSA-N 4-(4-chlorophenyl)pyrrolidin-2-one;sodium Chemical compound [Na].C1=CC(Cl)=CC=C1C1CC(=O)NC1 VRDFVCCNKXZPEI-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
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- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 150000007513 acids Chemical class 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
- 239000008116 calcium stearate Substances 0.000 description 3
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- 125000001309 chloro group Chemical group Cl* 0.000 description 3
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- 238000007912 intraperitoneal administration Methods 0.000 description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- VMOWKUTXPNPTEN-UHFFFAOYSA-N n,n-dimethylpropan-2-amine Chemical group CC(C)N(C)C VMOWKUTXPNPTEN-UHFFFAOYSA-N 0.000 description 1
- LSCYTCMNCWMCQE-UHFFFAOYSA-N n-methylpyridin-4-amine Chemical compound CNC1=CC=NC=C1 LSCYTCMNCWMCQE-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000011302 passive avoidance test Methods 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- SJRDNQOIQZOVQD-UHFFFAOYSA-M sodium;2,2-dimethylpropanoate Chemical compound [Na+].CC(C)(C)C([O-])=O SJRDNQOIQZOVQD-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 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 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH34686 | 1986-01-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT43058A HUT43058A (en) | 1987-09-28 |
| HU202862B true HU202862B (en) | 1991-04-29 |
Family
ID=4184917
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU87277A HU202862B (en) | 1986-01-30 | 1987-01-29 | Process for producing substituted pyrrolidinone derivatives and pharmaceutical compositions containing them |
Country Status (21)
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI95572C (fi) * | 1987-06-22 | 1996-02-26 | Eisai Co Ltd | Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi |
| CA2433090A1 (en) * | 2000-12-27 | 2002-07-04 | Kyowa Hakko Kogyo Co., Ltd. | Dipeptidyl peptidase iv inhibitor |
| EP4101561A1 (de) | 2021-06-08 | 2022-12-14 | Meusburger Georg GmbH & Co. KG | Zentriereinrichtung für ein formwerkzeug mit gleichzeitig tragenden wälzkörpereinheiten |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1039113A (en) * | 1964-08-06 | 1966-08-17 | Ucb Sa | New n-substituted lactams |
| US4144246A (en) * | 1976-11-15 | 1979-03-13 | Parke, Davis & Company | Pyrrolidineacetic acid esters |
| BE864269A (fr) * | 1977-03-03 | 1978-06-16 | Parke Davis & Co | Nouveaux n-(aminoalkyl substitue)-2-oxo-1-pyrrolidine-acetamides et procedes pour les produire |
| DE2757680A1 (de) * | 1977-12-23 | 1979-06-28 | Troponwerke Gmbh & Co Kg | Neue 2-oxo-1-pyrrolidinessigsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| EP0089900B1 (en) * | 1982-03-24 | 1985-12-27 | Prodes S.A. | New n-((2-oxo-1-pyrrolidinyl)acetyl)piperazines, the methods of producing such new compounds and their salts as well as pharmaceutical preparations for therapeutic use containing these compounds or salts |
-
1987
- 1987-01-21 PH PH34749A patent/PH23078A/en unknown
- 1987-01-26 EP EP87810045A patent/EP0236263B1/de not_active Expired - Lifetime
- 1987-01-26 DE DE8787810045T patent/DE3783247D1/de not_active Expired - Fee Related
- 1987-01-26 FI FI870329A patent/FI870329A7/fi not_active IP Right Cessation
- 1987-01-26 AT AT87810045T patent/ATE84033T1/de not_active IP Right Cessation
- 1987-01-26 ES ES87810045T patent/ES2053578T3/es not_active Expired - Lifetime
- 1987-01-27 IL IL81394A patent/IL81394A/xx not_active IP Right Cessation
- 1987-01-28 CA CA000528330A patent/CA1312081C/en not_active Expired - Lifetime
- 1987-01-28 DD DD87299511A patent/DD260066A5/de unknown
- 1987-01-28 PT PT84204A patent/PT84204B/pt not_active IP Right Cessation
- 1987-01-29 DK DK047187A patent/DK47187A/da not_active Application Discontinuation
- 1987-01-29 HU HU87277A patent/HU202862B/hu not_active IP Right Cessation
- 1987-01-29 NZ NZ219101A patent/NZ219101A/xx unknown
- 1987-01-29 ZA ZA87650A patent/ZA87650B/xx unknown
- 1987-01-29 AU AU68097/87A patent/AU599951B2/en not_active Ceased
- 1987-01-29 NO NO870374A patent/NO870374L/no unknown
- 1987-01-29 IE IE23087A patent/IE61100B1/en not_active IP Right Cessation
- 1987-01-30 KR KR870000728A patent/KR870007159A/ko not_active Ceased
- 1987-01-30 JP JP62018790A patent/JPS62185068A/ja active Granted
-
1989
- 1989-06-19 US US07/370,093 patent/US4945092A/en not_active Expired - Fee Related
-
1993
- 1993-03-19 GR GR920402948T patent/GR3007411T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI870329A0 (fi) | 1987-01-26 |
| NZ219101A (en) | 1990-03-27 |
| CA1312081C (en) | 1992-12-29 |
| JPH0558631B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-08-27 |
| FI870329A7 (fi) | 1987-07-31 |
| US4945092A (en) | 1990-07-31 |
| AU6809787A (en) | 1987-08-06 |
| IL81394A0 (en) | 1987-08-31 |
| KR870007159A (ko) | 1987-08-17 |
| DK47187A (da) | 1987-07-31 |
| EP0236263A2 (de) | 1987-09-09 |
| PT84204A (en) | 1987-02-01 |
| IE870230L (en) | 1987-07-30 |
| ZA87650B (en) | 1987-09-30 |
| IE61100B1 (en) | 1994-10-05 |
| IL81394A (en) | 1991-08-16 |
| GR3007411T3 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-07-30 |
| EP0236263A3 (en) | 1989-04-19 |
| HUT43058A (en) | 1987-09-28 |
| PT84204B (pt) | 1989-09-14 |
| PH23078A (en) | 1989-04-10 |
| DE3783247D1 (de) | 1993-02-11 |
| AU599951B2 (en) | 1990-08-02 |
| ATE84033T1 (de) | 1993-01-15 |
| NO870374D0 (no) | 1987-01-29 |
| NO870374L (no) | 1987-07-31 |
| JPS62185068A (ja) | 1987-08-13 |
| EP0236263B1 (de) | 1992-12-30 |
| ES2053578T3 (es) | 1994-08-01 |
| DD260066A5 (de) | 1988-09-14 |
| DK47187D0 (da) | 1987-01-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HMM4 | Cancellation of final prot. due to non-payment of fee |