CY1500A - Dicarboxylic or heterocyclic acid piperidyl ester derivatives - Google Patents
Dicarboxylic or heterocyclic acid piperidyl ester derivatives Download PDFInfo
- Publication number
- CY1500A CY1500A CY1500A CY150083A CY1500A CY 1500 A CY1500 A CY 1500A CY 1500 A CY1500 A CY 1500A CY 150083 A CY150083 A CY 150083A CY 1500 A CY1500 A CY 1500A
- Authority
- CY
- Cyprus
- Prior art keywords
- compound
- formula
- quaternary ammonium
- acid addition
- group
- Prior art date
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- 239000002253 acid Substances 0.000 title claims description 135
- -1 piperidyl ester Chemical class 0.000 title claims description 111
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 232
- 150000003839 salts Chemical class 0.000 claims description 128
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 109
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- 150000002367 halogens Chemical class 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 46
- 229940076279 serotonin Drugs 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 29
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 28
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 23
- 150000001408 amides Chemical class 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 239000005711 Benzoic acid Substances 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 235000010233 benzoic acid Nutrition 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 15
- 239000002243 precursor Substances 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- VUCWMAJEUOWLEY-UHFFFAOYSA-N 1-$l^{1}-azanylpiperidine Chemical group [N]N1CCCCC1 VUCWMAJEUOWLEY-UHFFFAOYSA-N 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- RVEATKYEARPWRE-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Cl)C=C1C(O)=O RVEATKYEARPWRE-UHFFFAOYSA-N 0.000 claims description 7
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- ROGHUJUFCRFUSO-UHFFFAOYSA-N 1h-indole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C=CN2 ROGHUJUFCRFUSO-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- 125000004197 benzothien-3-yl group Chemical group [H]C1=C(*)C2=C([H])C([H])=C([H])C([H])=C2S1 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 4
- YTSLFIKCDKXYEV-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl 5-chloro-2-methoxy-4-(methylamino)benzoate Chemical compound C1=C(Cl)C(NC)=CC(OC)=C1C(=O)OC1C(CC2)CCN2C1 YTSLFIKCDKXYEV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- HEXPZRMQHIMYOK-UHFFFAOYSA-N 2-methoxy-1h-indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(O)=O)=C(OC)NC2=C1 HEXPZRMQHIMYOK-UHFFFAOYSA-N 0.000 claims description 3
- MYTGPPIGVGCCRF-UHFFFAOYSA-N 3-iodo-1h-indole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C(I)=CN2 MYTGPPIGVGCCRF-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 239000003416 antiarrhythmic agent Substances 0.000 claims description 3
- 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
- SXIIAHIAZAMFPW-UHFFFAOYSA-N 2-chloro-1h-indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(Cl)NC2=C1 SXIIAHIAZAMFPW-UHFFFAOYSA-N 0.000 claims description 2
- 101100191375 Xenopus laevis prkra-b gene Proteins 0.000 claims description 2
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 239000000730 antalgic agent Substances 0.000 claims description 2
- 229940125684 antimigraine agent Drugs 0.000 claims description 2
- 239000002282 antimigraine agent Substances 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 125000001302 tertiary amino group Chemical group 0.000 claims description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims 4
- LSGKMZLPZFPAIN-UHFFFAOYSA-N 1h-indole-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CNC2=C1 LSGKMZLPZFPAIN-UHFFFAOYSA-N 0.000 claims 1
- DYVWOGCIQANCRE-UHFFFAOYSA-N 5-fluoro-1-methylindole-3-carboxylic acid Chemical compound FC1=CC=C2N(C)C=C(C(O)=O)C2=C1 DYVWOGCIQANCRE-UHFFFAOYSA-N 0.000 claims 1
- 241001506137 Rapa Species 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical compound [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 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 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000002464 receptor antagonist Substances 0.000 description 7
- 229940044551 receptor antagonist Drugs 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 7
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 6
- JEIZLWNUBXHADF-UHFFFAOYSA-N Pelletierine Chemical compound CC(=O)CC1CCCCN1 JEIZLWNUBXHADF-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
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- 230000009471 action Effects 0.000 description 6
- 229960004365 benzoic acid Drugs 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
- 230000036982 action potential Effects 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229910003002 lithium salt Inorganic materials 0.000 description 5
- 159000000002 lithium salts Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229960001866 silicon dioxide Drugs 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- PFYZWMQUFMFKHC-UHFFFAOYSA-N 5-chloro-2-methoxy-4-(phenylmethoxycarbonylamino)benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC(=O)OCC=2C=CC=CC=2)=C1Cl PFYZWMQUFMFKHC-UHFFFAOYSA-N 0.000 description 4
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- 239000012458 free base Substances 0.000 description 4
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
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- IIJFYTVJRDKVCI-UHFFFAOYSA-N 1h-indole-3-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CNC2=C1 IIJFYTVJRDKVCI-UHFFFAOYSA-N 0.000 description 3
- TXJMYISJXPBNCC-UHFFFAOYSA-N 5-chloro-2-methoxy-4-(methylamino)benzoic acid Chemical compound CNC1=CC(OC)=C(C(O)=O)C=C1Cl TXJMYISJXPBNCC-UHFFFAOYSA-N 0.000 description 3
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- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000002763 arrhythmic effect Effects 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- DHZBEENLJMYSHQ-XCVPVQRUSA-N cantharidin Chemical compound C([C@@H]1O2)C[C@@H]2[C@]2(C)[C@@]1(C)C(=O)OC2=O DHZBEENLJMYSHQ-XCVPVQRUSA-N 0.000 description 2
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- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
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- 230000001404 mediated effect Effects 0.000 description 2
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- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
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- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-M malonate(1-) Chemical compound OC(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-M 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- YUPQMVSYNJQULF-UHFFFAOYSA-N methyl 4-amino-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1OC YUPQMVSYNJQULF-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 229950006793 metitepine Drugs 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- CUGDJULQPUTNFK-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-2-yl)benzamide Chemical class C1C(CC2)CCN2C1NC(=O)C1=CC=CC=C1 CUGDJULQPUTNFK-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- WCJOOKJNLGTDRK-UHFFFAOYSA-N n-methyl-10-azabicyclo[4.3.1]decan-8-amine Chemical compound C1CCCC2CC(NC)CC1N2 WCJOOKJNLGTDRK-UHFFFAOYSA-N 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 230000004044 response Effects 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
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- 238000001228 spectrum Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
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- 150000003512 tertiary amines Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/12—Oxygen atoms acylated by aromatic or heteroaromatic carboxylic acids, e.g. cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH397982 | 1982-06-29 | ||
| CH426782 | 1982-07-13 | ||
| CH695182 | 1982-11-30 | ||
| CH695082 | 1982-11-30 | ||
| CH749582 | 1982-12-22 | ||
| CH749482 | 1982-12-22 | ||
| CH125683 | 1983-03-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CY1500A true CY1500A (en) | 1990-08-03 |
Family
ID=27561049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CY1500A CY1500A (en) | 1982-06-29 | 1983-06-27 | Dicarboxylic or heterocyclic acid piperidyl ester derivatives |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US4803199A (en, 2012) |
| AT (1) | AT391136B (en, 2012) |
| AU (2) | AU570002B2 (en, 2012) |
| CH (2) | CH669792A5 (en, 2012) |
| CY (1) | CY1500A (en, 2012) |
| DE (6) | DE3322574A1 (en, 2012) |
| DK (1) | DK172475B1 (en, 2012) |
| FI (1) | FI74707C (en, 2012) |
| FR (1) | FR2531083B1 (en, 2012) |
| GB (4) | GB2125398B (en, 2012) |
| HK (1) | HK60690A (en, 2012) |
| HU (1) | HU191053B (en, 2012) |
| IL (1) | IL69081A (en, 2012) |
| IT (1) | IT1173724B (en, 2012) |
| NL (2) | NL191991C (en, 2012) |
| NZ (1) | NZ204714A (en, 2012) |
| PT (1) | PT76937B (en, 2012) |
| SE (1) | SE463210B (en, 2012) |
| SG (1) | SG53789G (en, 2012) |
| WO (1) | WO1984000166A1 (en, 2012) |
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| US3405134A (en) * | 1965-08-17 | 1968-10-08 | Colgate Palmolive Co | Quinuclidyl esters of aromatic acids |
| SE331841B (en, 2012) * | 1967-05-23 | 1971-01-18 | Astra Ab | |
| US3702324A (en) * | 1970-06-24 | 1972-11-07 | Stanford Research Inst | 3,4,5-trimethoxybenzamides of substituted anilines and of alkylpiperidines |
| GB1293446A (en) * | 1970-07-23 | 1972-10-18 | Rech S Et D Applic Scient Soge | Quinuclidine derivatives, the preparation thereof and pharmaceutical compositions containing them |
| CH614709A5 (en, 2012) * | 1975-09-25 | 1979-12-14 | Ciba Geigy Ag | |
| DE2548968A1 (de) * | 1975-11-03 | 1977-05-12 | Thomae Gmbh Dr K | Neue amino-benzoesaeureamide |
| NL7611713A (nl) * | 1975-11-03 | 1977-05-05 | Thomae Gmbh Dr K | Werkwijze voor de bereiding van verbindingen en preparaten met waardevolle farmacologische eigen- schappen. |
| GB1593146A (en) * | 1976-11-05 | 1981-07-15 | Beecham Group Ltd | Octahydro-quinolizinyl benzamide derivatives |
| IL59004A0 (en) * | 1978-12-30 | 1980-03-31 | Beecham Group Ltd | Substituted benzamides their preparation and pharmaceutical compositions containing them |
| FR2476088A2 (fr) * | 1979-01-16 | 1981-08-21 | Delalande Sa | Nouveaux derives du nor-tropane, leur procede de preparation et leur application en therapeutique |
| NZ197356A (en) * | 1980-06-18 | 1984-05-31 | Beecham Group Ltd | Ar-alkylsulphinyl-n-(azaicycloalkyl(alkyl)) benzamides |
| FR2493848B2 (fr) * | 1980-11-07 | 1986-05-16 | Delalande Sa | Nouveaux derives des nor-tropane et granatane, leur procede de preparation et leur application en therapeutique |
| FR2499570A1 (fr) * | 1981-02-11 | 1982-08-13 | Delalande Sa | Nouveaux derives du b-amino-3 nor-tropane et leur procede de preparation |
| CA1220141A (en) * | 1981-06-13 | 1987-04-07 | John R. Fozard | Treatment of migraine with tropyl benzoate derivatives |
| GB2100259B (en) * | 1981-06-13 | 1984-10-31 | Merrell Toraude & Co | Treatment of migraine with tropyl benzoate derivatives |
| DE3268378D1 (en) * | 1981-06-17 | 1986-02-20 | Beecham Group Plc | Alkylthio derivatives of azabicyclobenzamides, their preparation and pharmaceutical compositions |
| EP0068700A1 (en) * | 1981-06-29 | 1983-01-05 | Beecham Group Plc | Azobicycloalkylbenzamides, process for their preparation and pharmaceutical compositions containing them |
| EP0069482A1 (en) * | 1981-06-29 | 1983-01-12 | Beecham Group Plc | Azabicycloalkyl benzamides, process for their preparation and pharmaceutical compositions containing them |
| NZ200981A (en) * | 1981-07-17 | 1984-10-19 | Recordati Chem Pharm | 3-methylflavone-8-carboxylic acid derivatives and pharmaceutical compositions |
| GB2111479A (en) * | 1981-10-01 | 1983-07-06 | Beecham Group Plc | Benzamides |
| FI74707C (fi) * | 1982-06-29 | 1988-03-10 | Sandoz Ag | Foerfarande foer framstaellning av terapeutiskt anvaendbara alkylenoeverbryggade piperidylestrar eller -amider av bicykliska karboxylsyror. |
| FR2529548A1 (fr) * | 1982-07-02 | 1984-01-06 | Delalande Sa | Nouveaux derives de l'amino-3 quinuclidine, leur procede et leur application en therapeutique |
| ATE19881T1 (de) * | 1982-12-10 | 1986-06-15 | Merrell Toraude & Co | Tropyl- und pseudotropylalkylbenzoate und ihre verwendung in der behandlung von migraene. |
| GB8302483D0 (en) * | 1983-01-29 | 1983-03-02 | Beecham Group Plc | Compounds |
| EP0135545A1 (en) * | 1983-02-19 | 1985-04-03 | Beecham Group Plc | Azabicycloalkyl benzamide and anilide derivatives |
| FR2546169B1 (fr) * | 1983-05-20 | 1986-03-21 | Delalande Sa | N-oxydes de derives aminocycliques, leur procede de preparation et leur application en therapeutique |
-
1983
- 1983-06-22 FI FI832293A patent/FI74707C/fi not_active IP Right Cessation
- 1983-06-22 FR FR8310433A patent/FR2531083B1/fr not_active Expired
- 1983-06-23 DE DE19833322574 patent/DE3322574A1/de active Granted
- 1983-06-23 DE DE3348334A patent/DE3348334C2/de not_active Expired - Lifetime
- 1983-06-23 DE DE3348332A patent/DE3348332C2/de not_active Expired - Lifetime
- 1983-06-23 DE DE1994175004 patent/DE19475004I2/de active Active
- 1983-06-23 DE DE3348331A patent/DE3348331C2/de not_active Expired - Lifetime
- 1983-06-23 DE DE3348333A patent/DE3348333C2/de not_active Expired - Lifetime
- 1983-06-24 WO PCT/CH1983/000081 patent/WO1984000166A1/de unknown
- 1983-06-24 NL NL8302253A patent/NL191991C/xx not_active IP Right Cessation
- 1983-06-27 CY CY1500A patent/CY1500A/en unknown
- 1983-06-27 PT PT76937A patent/PT76937B/pt unknown
- 1983-06-27 DK DK198302951A patent/DK172475B1/da not_active IP Right Cessation
- 1983-06-27 IT IT48580/83A patent/IT1173724B/it active Protection Beyond IP Right Term
- 1983-06-27 IL IL69081A patent/IL69081A/xx not_active IP Right Cessation
- 1983-06-27 AU AU16286/83A patent/AU570002B2/en not_active Expired
- 1983-06-27 NZ NZ204714A patent/NZ204714A/xx unknown
- 1983-06-27 SE SE8303651A patent/SE463210B/sv not_active IP Right Cessation
- 1983-06-27 GB GB08317365A patent/GB2125398B/en not_active Expired
- 1983-06-28 HU HU832335A patent/HU191053B/hu unknown
- 1983-06-28 AT AT2358/83A patent/AT391136B/de not_active IP Right Cessation
-
1984
- 1984-06-24 CH CH904/84A patent/CH669792A5/de not_active IP Right Cessation
-
1985
- 1985-08-12 GB GB08520188A patent/GB2166728B/en not_active Expired
- 1985-08-12 GB GB08520187A patent/GB2166727B/en not_active Expired
- 1985-08-12 GB GB08520186A patent/GB2166726B/en not_active Expired
-
1987
- 1987-11-25 US US07/125,048 patent/US4803199A/en not_active Expired - Lifetime
- 1987-12-10 AU AU82434/87A patent/AU603399B2/en not_active Expired
-
1988
- 1988-06-24 CH CH3305/88A patent/CH669954A5/de not_active IP Right Cessation
- 1988-11-15 US US07/272,030 patent/US4910207A/en not_active Expired - Lifetime
-
1989
- 1989-08-23 SG SG537/89A patent/SG53789G/en unknown
-
1990
- 1990-01-17 US US07/466,550 patent/US5017582A/en not_active Expired - Lifetime
- 1990-08-09 HK HK606/90A patent/HK60690A/xx not_active IP Right Cessation
-
1997
- 1997-06-02 NL NL970021C patent/NL970021I2/nl unknown
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