FI62666C - Foerfarande foer framstaellning av terapeutiskt aktivt 6-klor-2-(1'-piperazinyl)pyrazin och salter daerav - Google Patents
Foerfarande foer framstaellning av terapeutiskt aktivt 6-klor-2-(1'-piperazinyl)pyrazin och salter daerav Download PDFInfo
- Publication number
- FI62666C FI62666C FI760978A FI760978A FI62666C FI 62666 C FI62666 C FI 62666C FI 760978 A FI760978 A FI 760978A FI 760978 A FI760978 A FI 760978A FI 62666 C FI62666 C FI 62666C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- chloro
- compound
- piperazinyl
- pyrazine
- Prior art date
Links
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 title claims description 16
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 title claims description 8
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 230000004913 activation Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 24
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 14
- -1 6-chloro-2-pyrazinyl Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 3
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 238000009472 formulation Methods 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000010992 reflux Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 9
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 8
- 235000011167 hydrochloric acid Nutrition 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
- HYHBKLWDTGTBME-UHFFFAOYSA-N pyrazin-1-ium;chloride Chemical compound Cl.C1=CN=CC=N1 HYHBKLWDTGTBME-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- LSEAAPGIZCDEEH-UHFFFAOYSA-N 2,6-dichloropyrazine Chemical compound ClC1=CN=CC(Cl)=N1 LSEAAPGIZCDEEH-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000002830 appetite depressant Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000002798 polar solvent Substances 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 206010033307 Overweight Diseases 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 2
- CJAWPFJGFFNXQI-UHFFFAOYSA-N 2-chloro-6-(1-piperazinyl)pyrazine Chemical compound ClC1=CN=CC(N2CCNCC2)=N1 CJAWPFJGFFNXQI-UHFFFAOYSA-N 0.000 description 2
- ZMVHGTJAFGHEBY-UHFFFAOYSA-N 2-chloro-6-(4-methylpiperazin-1-yl)pyrazine Chemical compound C1CN(C)CCN1C1=CN=CC(Cl)=N1 ZMVHGTJAFGHEBY-UHFFFAOYSA-N 0.000 description 2
- OMWQDRPFWJDOSI-UHFFFAOYSA-N 3-chloro-4-oxidopyrazin-1-ium 1-oxide Chemical compound [O-][N+]1=CC=[N+]([O-])C(Cl)=C1 OMWQDRPFWJDOSI-UHFFFAOYSA-N 0.000 description 2
- PSYWKYZOKOCKMC-UHFFFAOYSA-N 4-(6-chloropyrazin-2-yl)piperazine-1-carbaldehyde Chemical compound ClC1=CN=CC(N2CCN(CC2)C=O)=N1 PSYWKYZOKOCKMC-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical class NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000012320 chlorinating reagent Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- WAKKYDYEXHZKFX-UHFFFAOYSA-N methyl 5-bromo-3-chloropyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=C(Br)N=C1Cl WAKKYDYEXHZKFX-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 235000010269 sulphur dioxide Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical class O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 1
- IPHFEAMSIOVYCA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene;hydrochloride Chemical compound Cl.C1=CC=C2CCCCC2=C1 IPHFEAMSIOVYCA-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 description 1
- ONTRHJAWFXBKPO-UHFFFAOYSA-N 2,6-dichloro-1-oxidopyrazin-1-ium Chemical compound [O-][N+]1=C(Cl)C=NC=C1Cl ONTRHJAWFXBKPO-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- XDIQJKFDYXTSKQ-UHFFFAOYSA-N 2-[(6-chloropyrazin-2-yl)-(cyanomethyl)amino]acetonitrile Chemical compound ClC1=CN=CC(N(CC#N)CC#N)=N1 XDIQJKFDYXTSKQ-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- JTPXVCKCLBROOJ-UHFFFAOYSA-N 2-amino-6-chloropyrazine Chemical compound NC1=CN=CC(Cl)=N1 JTPXVCKCLBROOJ-UHFFFAOYSA-N 0.000 description 1
- YHHKEXPNBPDPOW-UHFFFAOYSA-N 2-bromo-n-(2-bromoethyl)ethanamine;hydrobromide Chemical compound Br.BrCCNCCBr YHHKEXPNBPDPOW-UHFFFAOYSA-N 0.000 description 1
- WMFVTBWTDDQNRO-UHFFFAOYSA-N 2-chloro-1-oxidopyrazin-1-ium Chemical compound [O-][N+]1=CC=NC=C1Cl WMFVTBWTDDQNRO-UHFFFAOYSA-N 0.000 description 1
- PFIZGLUIYAZQFU-UHFFFAOYSA-N 2-chloro-6-piperazin-1-ylpyrazine;hydron;chloride Chemical compound Cl.ClC1=CN=CC(N2CCNCC2)=N1 PFIZGLUIYAZQFU-UHFFFAOYSA-N 0.000 description 1
- GGYHNCSPMSJACW-UHFFFAOYSA-N 2-methyl-1-[3-(trifluoromethyl)phenyl]butan-1-amine Chemical compound CCC(C)C(N)C1=CC=CC(C(F)(F)F)=C1 GGYHNCSPMSJACW-UHFFFAOYSA-N 0.000 description 1
- HCGFLVDMFDHYJD-UHFFFAOYSA-N 2-piperazin-1-ylpyrazine Chemical compound C1CNCCN1C1=CN=CC=N1 HCGFLVDMFDHYJD-UHFFFAOYSA-N 0.000 description 1
- QSROXGLQWDHTHR-UHFFFAOYSA-N 3,5-dichloro-1-oxidopyrazin-1-ium Chemical compound [O-][N+]1=CC(Cl)=NC(Cl)=C1 QSROXGLQWDHTHR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical class CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 1
- YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical class O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- QJKPRBQZMCWDJB-UHFFFAOYSA-N ClC1=NC(=CN=C1)Cl.Cl.N1=CC=NC=C1 Chemical compound ClC1=NC(=CN=C1)Cl.Cl.N1=CC=NC=C1 QJKPRBQZMCWDJB-UHFFFAOYSA-N 0.000 description 1
- RWBYNBZGQCVJSB-UHFFFAOYSA-N ClC1=NC=CN=C1.[N+]1(=CC=NC=C1)[O-] Chemical compound ClC1=NC=CN=C1.[N+]1(=CC=NC=C1)[O-] RWBYNBZGQCVJSB-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- XOLBLPGZBRYERU-UHFFFAOYSA-N SnO2 Inorganic materials O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- ZGSDJMADBJCNPN-UHFFFAOYSA-N [S-][NH3+] Chemical compound [S-][NH3+] ZGSDJMADBJCNPN-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 229960001582 fenfluramine Drugs 0.000 description 1
- 229960005191 ferric oxide Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- BSRDNMMLQYNQQD-UHFFFAOYSA-N iminodiacetonitrile Chemical compound N#CCNCC#N BSRDNMMLQYNQQD-UHFFFAOYSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 235000013980 iron oxide Nutrition 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- NNCALKDEIWAWBU-UHFFFAOYSA-N methyl 5-amino-3-chloropyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=C(N)N=C1Cl NNCALKDEIWAWBU-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- CWQXQMHSOZUFJS-UHFFFAOYSA-N molybdenum disulfide Chemical compound S=[Mo]=S CWQXQMHSOZUFJS-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
- PTLRDCMBXHILCL-UHFFFAOYSA-M sodium arsenite Chemical compound [Na+].[O-][As]=O PTLRDCMBXHILCL-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229940044609 sulfur dioxide Drugs 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- XLOMVQKBTHCTTD-UHFFFAOYSA-N zinc oxide Inorganic materials [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
- 229960001296 zinc oxide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Child & Adolescent Psychology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57005275A | 1975-04-21 | 1975-04-21 | |
| US57005275 | 1975-04-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI760978A7 FI760978A7 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1976-10-22 |
| FI62666B FI62666B (fi) | 1982-10-29 |
| FI62666C true FI62666C (fi) | 1983-02-10 |
Family
ID=24277994
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI760978A FI62666C (fi) | 1975-04-21 | 1976-04-09 | Foerfarande foer framstaellning av terapeutiskt aktivt 6-klor-2-(1'-piperazinyl)pyrazin och salter daerav |
Country Status (36)
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091098A (en) * | 1977-04-25 | 1978-05-23 | Merck & Co., Inc. | 3-(1-PIPERAZINYL)-1,2,4-BENZOTRIAZINES AND N-oxides |
| US4163849A (en) | 1978-03-17 | 1979-08-07 | Merck & Co., Inc. | Piperazinylpyrazines |
| US4252816A (en) * | 1979-12-03 | 1981-02-24 | Merck & Co., Inc. | Tetrahydro-1H-1,4-diazepino(1,7-a)benzimidazoles useful as analgesic agents |
| US4339579A (en) | 1980-12-29 | 1982-07-13 | American Home Products Corporation | 2,6-Bis-(pyrrolopyrazinyl)pyrazines |
| EP0094498A3 (en) * | 1982-05-06 | 1985-04-03 | American Cyanamid Company | Antiatherosclerotic 1-piperazine derivatives |
| US4547505A (en) * | 1983-03-25 | 1985-10-15 | Degussa Aktiengesellschaft | N-Phenyl-N-'-cycloalkylalkanoylpiperazine useful as analgetics and process for its production |
| US4788290A (en) * | 1987-12-11 | 1988-11-29 | American Home Products Corporation | Serotonergic pyrazine derivatives |
| EP0580465A1 (fr) * | 1992-06-25 | 1994-01-26 | Sanofi | Nouvelle utilisation thérapeutique d'hétérocyclyl-pipérazines comme 5-HT3 agonistes et nouveaux dérivés |
| HU226859B1 (en) * | 1997-10-27 | 2009-12-28 | Neurosearch As | Phenyl- or heteroaryl-homopiperazines, their use and medicaments containing them |
| WO2000064885A1 (en) * | 1999-04-26 | 2000-11-02 | Neurosearch A/S | Heteroaryl diazacycloalkanes, their preparation and use |
| IL151020A0 (en) * | 2000-02-16 | 2003-02-12 | Neurogen Corp | Substituted arylpyrazines |
| US6825198B2 (en) * | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| CN1305871C (zh) | 2002-07-19 | 2007-03-21 | 比奥维特罗姆股份公司 | 用于治疗与5－ht2a受体有关疾病的新哌嗪基－吡嗪酮衍生物 |
| SE0202287D0 (sv) * | 2002-07-19 | 2002-07-19 | Biovitrum Ab | New compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2606906A (en) * | 1948-10-14 | 1952-08-12 | American Cyanamid Co | 1-(2-pyridyl) piperazine and process of preparing same |
-
1976
- 1976-04-07 SE SE7604093A patent/SE421695B/xx not_active IP Right Cessation
- 1976-04-07 EG EG76205A patent/EG12387A/xx active
- 1976-04-07 DK DK164476A patent/DK143899C/da not_active IP Right Cessation
- 1976-04-08 NO NO761207A patent/NO146599C/no unknown
- 1976-04-09 FI FI760978A patent/FI62666C/fi not_active IP Right Cessation
- 1976-04-09 NL NL7603800A patent/NL167692C/xx not_active IP Right Cessation
- 1976-04-12 IL IL49391A patent/IL49391A/xx unknown
- 1976-04-13 GR GR50538A patent/GR59900B/el unknown
- 1976-04-13 AU AU12966/76A patent/AU496854B2/en not_active Expired
- 1976-04-13 PH PH18329A patent/PH12274A/en unknown
- 1976-04-14 CA CA250,732A patent/CA1059128A/en not_active Expired
- 1976-04-14 FR FR7610958A patent/FR2308367A1/fr active Granted
- 1976-04-15 GB GB15644/76A patent/GB1492528A/en not_active Expired
- 1976-04-15 CY CY1090A patent/CY1090A/xx unknown
- 1976-04-15 DD DD192399A patent/DD124599A5/xx unknown
- 1976-04-16 CS CS762549A patent/CS195726B2/cs unknown
- 1976-04-19 ES ES447150A patent/ES447150A1/es not_active Expired
- 1976-04-19 JP JP51043763A patent/JPS51136688A/ja active Granted
- 1976-04-20 DE DE2617205A patent/DE2617205C3/de not_active Expired
- 1976-04-20 SU SU762346054A patent/SU638260A3/ru active
- 1976-04-20 AR AR262930A patent/AR210349A1/es active
- 1976-04-20 AT AT288376A patent/AT353795B/de not_active IP Right Cessation
- 1976-04-20 CH CH492676A patent/CH619462A5/de not_active IP Right Cessation
- 1976-04-20 PL PL1976188912A patent/PL99664B1/pl unknown
- 1976-04-20 LU LU74795A patent/LU74795A1/xx unknown
- 1976-04-20 BE BE166282A patent/BE840904A/xx not_active IP Right Cessation
- 1976-04-20 ZA ZA762320A patent/ZA762320B/xx unknown
- 1976-04-20 RO RO7685688A patent/RO73278A/ro unknown
- 1976-04-20 YU YU01006/76A patent/YU100676A/xx unknown
- 1976-04-20 BG BG032968A patent/BG34185A3/xx unknown
- 1976-04-21 PT PT65027A patent/PT65027B/pt unknown
- 1976-04-21 HU HU76ME00001967A patent/HU172684B/hu unknown
- 1976-04-21 IE IE828/76A patent/IE42979B1/en unknown
-
1977
- 1977-06-01 ES ES459405A patent/ES459405A1/es not_active Expired
- 1977-06-01 ES ES459406A patent/ES459406A1/es not_active Expired
- 1977-06-01 ES ES459407A patent/ES459407A1/es not_active Expired
-
1980
- 1980-10-02 KE KE3088A patent/KE3088A/xx unknown
- 1980-10-30 HK HK603/80A patent/HK60380A/xx unknown
-
1981
- 1981-12-30 MY MY225/81A patent/MY8100225A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI62666C (fi) | Foerfarande foer framstaellning av terapeutiskt aktivt 6-klor-2-(1'-piperazinyl)pyrazin och salter daerav | |
| US7579365B2 (en) | Indolyl-3-glyoxylic acid derivatives having antitumor action | |
| US3696197A (en) | Pharmaceutical compositions containing homopyrimidazole derivatives | |
| EP0079545B1 (en) | Benzimidazole derivatives, process for the preparation thereof and pharmaceutical composition containing the same | |
| HU184989B (en) | Process for preparing derivatives of 2-/4-/diphenyl-methyl/-piperazin-1-yl/-acetic acid | |
| HU211256A9 (en) | New benzimidazolone derivatives | |
| JPH0735371B2 (ja) | 新規なオキサゾロピリジン誘導体、これらの製造法およびそれらを含む製薬組成物 | |
| JP2002504103A (ja) | ３−置換された３、４−ジヒドロチエノ［２、３−ｄ］ピリミジン誘導体 | |
| HU190635B (en) | Process for preparing benzoxazoline-derivatives and the pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions comprising the same as active substance | |
| US3944551A (en) | N-Coumaranyl and chromanyl -methyl-or sulfur analogs thereof-N'- thiazolyl piperazines | |
| FI94953B (fi) | Menetelmä terapeuttisesti käyttökelpoisten 2-aminopyrimidiini-4-karboksamidijohdannaisten valmistamiseksi | |
| PL119641B1 (en) | Process for preparing novel,condensed derivatives of pyrimidine pirimidina | |
| LV10716B (en) | Novel derivatives of triazolopyridine and triazoloquinoline aminoalkylthio compounds, methods for preparation thereof, medicinal preparations containing same, their use as analgetics | |
| HU201057B (en) | Process for producing 6-phenyl-3-(piperazinyl-alkyl)-1h,3h-pyrimidin-2,4-dion derivatives and pharmaceutical compositions containing them | |
| FI77456C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 3-/2-/4-(2-metoxifenyl) -1-piperazinyl/etyl/-2,4-(1h,3h)-kinazolindionderivat. | |
| US4065451A (en) | 1,3-Dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one, substituted diamino acetate esters and their acid salts | |
| ES2215312T3 (es) | Derivados de pirido(3',4':4,5)tieno(2,3-d)-pirimidina 3-substituidos, su obtencion y empleo. | |
| US4022779A (en) | Amino derivatives of pyrido(3,4-b)pyrazine carboxylic acids and esters | |
| EP3277687B1 (en) | 7-(morpholin-4-yl)pyrazole[1,5-a]pyrimidine derivatives which are useful for the treatment of immune or inflammatory diseases or cancer | |
| CN110950807B (zh) | 联芳基类化合物、其制备方法、药物组合物及其应用 | |
| HU196998B (en) | Process for producing basically substituted pyridine derivatives and pharmaceuticals comprising same | |
| JPH1017555A (ja) | ６−アミノ−５−メチルウラシル誘導体 | |
| KR790001500B1 (ko) | 피페라지닐 피라진 화합물의 제법 | |
| US3838122A (en) | 2-heterocyclic-1,3-benzodiazepines | |
| US4727074A (en) | 2-(phenylmethylene)-1-(diaminoalkoxy) cycloalkanes and their pharmaceutical uses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: MERCK & CO INC. |