NO174504B - Analogifremgangsmaate for fremstilling av terapeutisk virksomme derivater av 1,2,5,6-tetrahydropyridin-3-carboxaldehyd-oxim - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk virksomme derivater av 1,2,5,6-tetrahydropyridin-3-carboxaldehyd-oxim Download PDFInfo
- Publication number
- NO174504B NO174504B NO883521A NO883521A NO174504B NO 174504 B NO174504 B NO 174504B NO 883521 A NO883521 A NO 883521A NO 883521 A NO883521 A NO 883521A NO 174504 B NO174504 B NO 174504B
- Authority
- NO
- Norway
- Prior art keywords
- tetrahydropyridine
- carboxaldehyde
- alkyl
- compound
- general formula
- Prior art date
Links
- QGMSPDCKGXYZNB-UHFFFAOYSA-N n-(1,2,3,6-tetrahydropyridin-5-ylmethylidene)hydroxylamine Chemical class ON=CC1=CCCNC1 QGMSPDCKGXYZNB-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 238000002360 preparation method Methods 0.000 title claims abstract description 4
- 238000000034 method Methods 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- -1 cyclic alkyl radical Chemical class 0.000 claims abstract description 10
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 150000002923 oximes Chemical class 0.000 claims description 19
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 9
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 6
- 230000000718 cholinopositive effect Effects 0.000 abstract description 3
- 230000005923 long-lasting effect Effects 0.000 abstract description 2
- 229920006395 saturated elastomer Polymers 0.000 abstract 2
- 150000005840 aryl radicals Chemical class 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 18
- 239000000203 mixture Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- 239000003480 eluent Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- HJJPJSXJAXAIPN-UHFFFAOYSA-N arecoline Chemical compound COC(=O)C1=CCCN(C)C1 HJJPJSXJAXAIPN-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 206010012735 Diarrhoea Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 210000003405 ileum Anatomy 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- JMJSXMRUWSRVOU-UHFFFAOYSA-N (4-chlorophenyl) 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1=CC(Cl)=CC=C1OC(=O)N1CC(C=O)=CCC1 JMJSXMRUWSRVOU-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound 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
- 206010039966 Senile dementia Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- WPUJEWVVTKLMQI-UHFFFAOYSA-N benzene;ethoxyethane Chemical compound CCOCC.C1=CC=CC=C1 WPUJEWVVTKLMQI-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- YIQBHPFHKPIDSO-UHFFFAOYSA-N n-methoxy-1-(1,2,3,6-tetrahydropyridin-5-yl)methanimine Chemical compound CON=CC1=CCCNC1 YIQBHPFHKPIDSO-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WEWQQXOZLOKJKK-UHFFFAOYSA-N (3,4-dimethoxyphenyl) carbonochloridate Chemical compound COC1=CC=C(OC(Cl)=O)C=C1OC WEWQQXOZLOKJKK-UHFFFAOYSA-N 0.000 description 1
- RYWGPCLTVXMMHO-UHFFFAOYSA-N (4-chlorophenyl) carbonochloridate Chemical compound ClC(=O)OC1=CC=C(Cl)C=C1 RYWGPCLTVXMMHO-UHFFFAOYSA-N 0.000 description 1
- YAXBENSUQFRJMP-UHFFFAOYSA-N (4-propan-2-ylphenyl) 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1=CC(C(C)C)=CC=C1OC(=O)N1CC(C=O)=CCC1 YAXBENSUQFRJMP-UHFFFAOYSA-N 0.000 description 1
- XYXONCCUDWNAHA-UHFFFAOYSA-N (4-propan-2-ylphenyl) carbonochloridate Chemical compound CC(C)C1=CC=C(OC(Cl)=O)C=C1 XYXONCCUDWNAHA-UHFFFAOYSA-N 0.000 description 1
- MMWNTLCGGPKVFR-UHFFFAOYSA-N 1-(1-ethyl-3,6-dihydro-2h-pyridin-5-yl)-n-methoxymethanimine Chemical compound CCN1CCC=C(C=NOC)C1 MMWNTLCGGPKVFR-UHFFFAOYSA-N 0.000 description 1
- HBHSFZRTCIDXAS-UHFFFAOYSA-N 1-adamantyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1C(C=O)=CCCN1C(=O)OC1(C2)CC(C3)CC2CC3C1 HBHSFZRTCIDXAS-UHFFFAOYSA-N 0.000 description 1
- PNLZKVOKOVFGMZ-UHFFFAOYSA-N 1-adamantyl carbonofluoridate Chemical compound C1C(C2)CC3CC2CC1(OC(=O)F)C3 PNLZKVOKOVFGMZ-UHFFFAOYSA-N 0.000 description 1
- SONZQXSTWXOYSD-UHFFFAOYSA-N 1-n,2-n-di(propan-2-yl)benzene-1,2-diamine Chemical compound CC(C)NC1=CC=CC=C1NC(C)C SONZQXSTWXOYSD-UHFFFAOYSA-N 0.000 description 1
- DKULSTMKCYRQCP-UHFFFAOYSA-N 2-phenylethyl carbonochloridate Chemical compound ClC(=O)OCCC1=CC=CC=C1 DKULSTMKCYRQCP-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 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
- HRDCVMSNCBAMAM-UHFFFAOYSA-N 3-prop-2-ynoxyprop-1-yne Chemical compound C#CCOCC#C HRDCVMSNCBAMAM-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- COMBRYCXLDMDCU-UHFFFAOYSA-N 5-aminonaphthalene-1-carbonitrile Chemical compound C1=CC=C2C(N)=CC=CC2=C1C#N COMBRYCXLDMDCU-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DYTNFIADBIXRAI-UHFFFAOYSA-N [2-(2-methylsulfonylethyl)-4-nitrophenyl] hydrogen carbonate Chemical compound CS(=O)(=O)CCC1=CC([N+]([O-])=O)=CC=C1OC(O)=O DYTNFIADBIXRAI-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PGMOXDXQCHVMKO-UHFFFAOYSA-N benzyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1C(C=O)=CCCN1C(=O)OCC1=CC=CC=C1 PGMOXDXQCHVMKO-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- BVMCVERBAFGTMI-UHFFFAOYSA-N butyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CCCCOC(=O)N1CCC=C(C=O)C1 BVMCVERBAFGTMI-UHFFFAOYSA-N 0.000 description 1
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- JFHAMNVZHGKQDQ-UHFFFAOYSA-N ethyl 4,6-dimethyl-2-oxo-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=O)NC1C JFHAMNVZHGKQDQ-UHFFFAOYSA-N 0.000 description 1
- BSXUREZDXPMCDN-UHFFFAOYSA-N ethyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CCOC(=O)N1CCC=C(C=O)C1 BSXUREZDXPMCDN-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229950002932 hexamethonium Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- SHPSBBZEMQBPLU-UHFFFAOYSA-N methyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound COC(=O)N1CCC=C(C=O)C1 SHPSBBZEMQBPLU-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- UYLRCDWTTPGBBD-UHFFFAOYSA-N phenyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1C(C=O)=CCCN1C(=O)OC1=CC=CC=C1 UYLRCDWTTPGBBD-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
- JFXKHTWUKHYJSO-UHFFFAOYSA-N propan-2-yl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)OC(=O)N1CCC=C(C=O)C1 JFXKHTWUKHYJSO-UHFFFAOYSA-N 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- CNJXXCUZXVJTOF-UHFFFAOYSA-N propyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CCCOC(=O)N1CCC=C(C=O)C1 CNJXXCUZXVJTOF-UHFFFAOYSA-N 0.000 description 1
- QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- KUDYDGWGDRZATE-UHFFFAOYSA-N tert-butyl 5-formyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC=C(C=O)C1 KUDYDGWGDRZATE-UHFFFAOYSA-N 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 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
- PYIHTIJNCRKDBV-UHFFFAOYSA-L trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;dichloride Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCCCCC[N+](C)(C)C PYIHTIJNCRKDBV-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT8721687A IT1222526B (it) | 1987-08-21 | 1987-08-21 | Derivati dell' ossima della 1,2,5,6-tetraidropiridin-3-carbossaldeide,loro procedimento di preparazione e loro impiego come sostanze medicinali |
Publications (4)
Publication Number | Publication Date |
---|---|
NO883521D0 NO883521D0 (no) | 1988-08-08 |
NO883521L NO883521L (no) | 1989-02-22 |
NO174504B true NO174504B (no) | 1994-02-07 |
NO174504C NO174504C (de) | 1994-05-18 |
Family
ID=11185397
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO883521A NO174504B (no) | 1987-08-21 | 1988-08-08 | Analogifremgangsmaate for fremstilling av terapeutisk virksomme derivater av 1,2,5,6-tetrahydropyridin-3-carboxaldehyd-oxim |
Country Status (22)
Country | Link |
---|---|
US (1) | US4921868A (de) |
EP (1) | EP0308283B1 (de) |
JP (1) | JPH07107048B2 (de) |
KR (1) | KR960014998B1 (de) |
AT (1) | ATE71938T1 (de) |
AU (1) | AU608643B2 (de) |
CA (1) | CA1340987C (de) |
DE (1) | DE3867986D1 (de) |
DK (1) | DK457388A (de) |
ES (1) | ES2038776T3 (de) |
FI (1) | FI90070C (de) |
GR (1) | GR3004249T3 (de) |
HU (2) | HU201012B (de) |
IE (1) | IE61537B1 (de) |
IL (1) | IL87430A0 (de) |
IT (1) | IT1222526B (de) |
MX (1) | MX12707A (de) |
NO (1) | NO174504B (de) |
NZ (1) | NZ225902A (de) |
PT (1) | PT88302B (de) |
SU (1) | SU1681723A3 (de) |
ZA (1) | ZA886131B (de) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5231107A (en) * | 1987-08-21 | 1993-07-27 | Roussel Uclaf | Derivatives of the oxime of 1,2,5,6-tetrahydropyridine 3-carboxaldehyde, the process for their preparation, their use as medicaments and the compositions containing them |
PT90266B (pt) * | 1988-04-15 | 1994-07-29 | Beecham Group Plc | Processo para a preparacao de compostos azabiciclicos |
US5278170A (en) * | 1989-04-13 | 1994-01-11 | Beecham Group P.L.C. | Azabicylo oxime compounds |
ES2219636T3 (es) * | 1989-04-13 | 2004-12-01 | Beecham Group P.L.C. | Nuevos compuestos. |
IT1240603B (it) * | 1990-03-14 | 1993-12-17 | Roussel Maestretti Spa | Derivati della 1,2,5,6-tetraidropiridina 3- carbossaldeide ossima, loro procedimento di preparazione e loro impiego come sostanza medicinale |
IT1241138B (it) * | 1990-05-15 | 1993-12-29 | Roussel Pharma | Derivati dell'ossina della 1,2,5,6- tetraidropiridin-3-carbossaldeide,loro procedimento di preparazione e loro impiego come sostanze medicinali |
WO1992003435A1 (en) * | 1990-08-24 | 1992-03-05 | Beecham Group Plc | Azabicyclic compounds, process and intermediates for their preparation and pharmaceutical compositions containing them |
GB9019095D0 (en) * | 1990-09-01 | 1990-10-17 | Beecham Group Plc | Novel compounds |
WO1992006959A1 (en) * | 1990-10-12 | 1992-04-30 | Beecham Group Plc | 1,2,5,6-tetrahydropyridine oxime derivatives |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR1258847A (fr) * | 1960-02-12 | 1961-04-21 | Ciba Geigy | Procédé de préparation de nouveaux dérivés pyridiniques, entre autres de l'oxime de la l-méthyl-3 ou 4-acétyl-1, 2, 5, 6-tétrahydropyridine |
IL81610A (en) * | 1986-02-27 | 1990-12-23 | Roussel Uclaf | Derivatives of 1,2,5,6-tetrahydropyridin-3-carboxaldehyde oxime,their preparation and pharmaceutical compositions containing them |
US4786648A (en) * | 1986-12-08 | 1988-11-22 | Warner-Lambert Company | O-substituted tetrahydropyridine oxime cholinergic agents |
IT1203971B (it) * | 1987-04-24 | 1989-02-23 | Roussel Maestretti Spa | Derivati di 1,2,5,6-tetraidropiridina, loro procedimento di preparazione e loro applicazione come medicamenti |
-
1987
- 1987-08-21 IT IT8721687A patent/IT1222526B/it active
-
1988
- 1988-08-08 NO NO883521A patent/NO174504B/no unknown
- 1988-08-12 IL IL8887430A patent/IL87430A0/xx not_active IP Right Cessation
- 1988-08-16 DK DK457388A patent/DK457388A/da not_active Application Discontinuation
- 1988-08-17 MX MX1270788A patent/MX12707A/es unknown
- 1988-08-18 ZA ZA886131A patent/ZA886131B/xx unknown
- 1988-08-18 JP JP63203962A patent/JPH07107048B2/ja not_active Expired - Fee Related
- 1988-08-19 IE IE253888A patent/IE61537B1/en not_active IP Right Cessation
- 1988-08-19 DE DE8888402128T patent/DE3867986D1/de not_active Expired - Fee Related
- 1988-08-19 ES ES198888402128T patent/ES2038776T3/es not_active Expired - Lifetime
- 1988-08-19 AT AT88402128T patent/ATE71938T1/de not_active IP Right Cessation
- 1988-08-19 SU SU4356622A patent/SU1681723A3/ru active
- 1988-08-19 AU AU21100/88A patent/AU608643B2/en not_active Ceased
- 1988-08-19 EP EP88402128A patent/EP0308283B1/de not_active Expired - Lifetime
- 1988-08-19 FI FI883869A patent/FI90070C/fi not_active IP Right Cessation
- 1988-08-19 PT PT88302A patent/PT88302B/pt not_active IP Right Cessation
- 1988-08-19 CA CA000575166A patent/CA1340987C/fr not_active Expired - Fee Related
- 1988-08-19 HU HU884414A patent/HU201012B/hu not_active IP Right Cessation
- 1988-08-22 US US07/234,632 patent/US4921868A/en not_active Expired - Fee Related
- 1988-08-22 KR KR1019880010676A patent/KR960014998B1/ko not_active IP Right Cessation
- 1988-08-22 NZ NZ225902A patent/NZ225902A/xx unknown
-
1992
- 1992-04-02 GR GR910402203T patent/GR3004249T3/el unknown
-
1995
- 1995-06-29 HU HU95P/P00578P patent/HU211913A9/hu unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5219872A (en) | Compounds of 1,2,5,6-tetrahydropyridin-3-carboxaldehyde oxime which are useful as cholinergic agents | |
KR910002883B1 (ko) | 벤조푸란-또는 벤조피란-카르복사미드 유도체의 제조방법 | |
NO177590B (no) | Analogifremgangsmåte for fremstilling av terapeutisk aktive cykliske aminforbindelser | |
NO180540B1 (no) | Analogifremgangsmate for fremstilling av terapeutisk aktiv cyklisk amidderivat | |
EA007225B1 (ru) | Производные n-[фенил(пиперидин-2-ил)метил]бензамида и их применение в терапии | |
US4072686A (en) | 1-(3,3,3-Triarylalkyl)-4-phenyl-piperidinealkanols | |
NO174504B (no) | Analogifremgangsmaate for fremstilling av terapeutisk virksomme derivater av 1,2,5,6-tetrahydropyridin-3-carboxaldehyd-oxim | |
US4902699A (en) | Oxime of 1, 2, 5, 6-tetrahydropyridine compounds their use as medicaments and the compositions containing them | |
US5053416A (en) | Derivatives of 1,2,5,6-tetrahydropyridine substituted by a thiazolyl or oxazolyl radical, their use as medicaments and compositions containing them | |
US5015655A (en) | 1-azabicycloalkane derivatives, their preparation process and their use as medicaments | |
US4021552A (en) | 10-[ω-(BENZOYLPIPERIDINYL)ALKYL]PHENOTHIAZINES | |
IL86157A (en) | History of 1,2,5,6-Tetrahydropyridine, process for their preparation and pharmaceutical preparations containing the same | |
CZ51694A3 (en) | Benzoxazine derivatives, process of their preparation and pharmaceutical composition in which said derivatives are comprised | |
US5219873A (en) | Compounds of 1,2,5,6-tetrahydropyridine which are useful as cholinergic agents | |
US2976291A (en) | Ethers of z | |
US6156752A (en) | Optically active 1,4-dihydropyridine compounds as bradykinin antagonists | |
US4927837A (en) | Derivatives of 3-piperidine carbaldehyde oxime and their use as medicaments | |
US4593037A (en) | 1,3-disubstituted piperidine compounds as neuroleptic agents | |
US4623728A (en) | Intermediates for 1,3-disubstituted piperidine compounds as neuroleptic agents | |
US4101660A (en) | 2-Aminomethyl-5-phenyloxazoles and the pharmaceutically acceptable acid addition salts thereof | |
EP0336555A1 (de) | 4,5,6,7-Tetrahydroisothiazolo (4,5-c)pyridin-Derivate und Isomere | |
US5231107A (en) | Derivatives of the oxime of 1,2,5,6-tetrahydropyridine 3-carboxaldehyde, the process for their preparation, their use as medicaments and the compositions containing them | |
US5183893A (en) | 1-azabicycloalkane derivatives, their preparation process and their use as medicaments | |
SU1498387A3 (ru) | Способ получени производных 1,2,5,6 - тетрагидропиридин-3-карбоксальдегидоксима или их гидрохлоридов | |
US5183896A (en) | Derivatives of 1,2,5,6-tetrahydropyridin-3-carboxaldehyde oxime |