JPH0335319B2 - - Google Patents
Info
- Publication number
- JPH0335319B2 JPH0335319B2 JP56093102A JP9310281A JPH0335319B2 JP H0335319 B2 JPH0335319 B2 JP H0335319B2 JP 56093102 A JP56093102 A JP 56093102A JP 9310281 A JP9310281 A JP 9310281A JP H0335319 B2 JPH0335319 B2 JP H0335319B2
- Authority
- JP
- Japan
- Prior art keywords
- endo
- methyl
- octane
- formula
- propyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract 9
- -1 halide ion Chemical group 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 150000001350 alkyl halides Chemical class 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- ZGKIYLYSHXFWES-UHFFFAOYSA-N pentanoic acid;hydrobromide Chemical compound Br.CCCCC(O)=O ZGKIYLYSHXFWES-UHFFFAOYSA-N 0.000 claims 1
- 230000003389 potentiating effect Effects 0.000 abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 abstract 3
- 230000002048 spasmolytic effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 48
- HOZOZZFCZRXYEK-GSWUYBTGSA-M butylscopolamine bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CCCC)=CC=CC=C1 HOZOZZFCZRXYEK-GSWUYBTGSA-M 0.000 description 41
- 229940088506 buscopan Drugs 0.000 description 34
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 230000002921 anti-spasmodic effect Effects 0.000 description 15
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 14
- 229960001789 papaverine Drugs 0.000 description 14
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 13
- 230000008602 contraction Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- OXTNCQMOKLOUAM-UHFFFAOYSA-N 3-Oxoglutaric acid Chemical compound OC(=O)CC(=O)CC(O)=O OXTNCQMOKLOUAM-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 230000009471 action Effects 0.000 description 7
- 230000000968 intestinal effect Effects 0.000 description 7
- 238000004448 titration Methods 0.000 description 7
- PITHYUDHKJKJNQ-UHFFFAOYSA-N 2-propylpentanoyl chloride Chemical compound CCCC(C(Cl)=O)CCC PITHYUDHKJKJNQ-UHFFFAOYSA-N 0.000 description 6
- 241000700199 Cavia porcellus Species 0.000 description 6
- 230000007059 acute toxicity Effects 0.000 description 6
- 231100000403 acute toxicity Toxicity 0.000 description 6
- 230000001022 anti-muscarinic effect Effects 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 210000001198 duodenum Anatomy 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000004135 Bone phosphate Substances 0.000 description 4
- 241000700198 Cavia Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 4
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 4
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 4
- 229910001626 barium chloride Inorganic materials 0.000 description 4
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 4
- 229960004484 carbachol Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 208000008384 ileus Diseases 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 4
- NIEPDSXRYYXOIA-UHFFFAOYSA-N 8-ethyl-8-azabicyclo[3.2.1]octan-3-one Chemical compound C1C(=O)CC2CCC1N2CC NIEPDSXRYYXOIA-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229930003347 Atropine Natural products 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229960000396 atropine Drugs 0.000 description 3
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000012649 demethylating agent Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000036724 intravesical pressure Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 2
- DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 description 2
- RSUHKGOVXMXCND-UHFFFAOYSA-N 8-benzyl-8-azabicyclo[3.2.1]octan-3-one Chemical compound C1C(=O)CC2CCC1N2CC1=CC=CC=C1 RSUHKGOVXMXCND-UHFFFAOYSA-N 0.000 description 2
- LEMYNEZPTCSVOW-UHFFFAOYSA-N 8-cyclopropyl-8-azabicyclo[3.2.1]octan-3-one Chemical compound C1C(=O)CC2CCC1N2C1CC1 LEMYNEZPTCSVOW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- YQBQUZUVGZHHOC-UHFFFAOYSA-N CCCCC(OC(C)C)=O.Br Chemical compound CCCCC(OC(C)C)=O.Br YQBQUZUVGZHHOC-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000000539 anti-peristaltic effect Effects 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 230000000956 myotropic effect Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- NMRPBPVERJPACX-UHFFFAOYSA-N octan-3-ol Chemical compound CCCCCC(O)CC NMRPBPVERJPACX-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229950009846 scopolamine butylbromide Drugs 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- JOTRMYCCALXLNJ-UHFFFAOYSA-N 3-ethyl-4-methylpentanoic acid Chemical compound CCC(C(C)C)CC(O)=O JOTRMYCCALXLNJ-UHFFFAOYSA-N 0.000 description 1
- WNRQHOYCYRTDMM-UHFFFAOYSA-N 5-methyl-8-azabicyclo[3.2.1]octan-3-ol Chemical compound C1C(O)CC2CCC1(C)N2 WNRQHOYCYRTDMM-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- XMLNCADGRIEXPK-KUMOIWDRSA-M chembl2146143 Chemical compound [Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N+]2(C)C)C(=O)C(CO)C1=CC=CC=C1 XMLNCADGRIEXPK-KUMOIWDRSA-M 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000005090 tracheal smooth muscle Anatomy 0.000 description 1
- 150000003813 tropane derivatives Chemical class 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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
- C07D451/06—Oxygen 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
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT22843/80A IT1140998B (it) | 1980-06-18 | 1980-06-18 | Sali di endo-8-metil-8-sin-alchil-8-azoniabiciclo aperta par. quadrata 3.2.1. chiusa par. quadrata-ottan-3-alchilcarbossilati, processo per la loro preparazione e composizioni terapeutiche che li contengono come principio attivo |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5728086A JPS5728086A (en) | 1982-02-15 |
| JPH0335319B2 true JPH0335319B2 (enExample) | 1991-05-27 |
Family
ID=11201066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9310281A Granted JPS5728086A (en) | 1980-06-18 | 1981-06-18 | Endo-8-methyl-8-syn-alkyl-8-azoniabicyclo- (3,2,1)-octane-3-alkylcarboxylate salts, manufacture and therapeutical composition |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4411902A (enExample) |
| EP (1) | EP0042365B1 (enExample) |
| JP (1) | JPS5728086A (enExample) |
| AT (1) | ATE9347T1 (enExample) |
| AU (1) | AU547923B2 (enExample) |
| CA (1) | CA1161040A (enExample) |
| DE (1) | DE3165993D1 (enExample) |
| IT (1) | IT1140998B (enExample) |
| ZA (1) | ZA813786B (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1194343B (it) * | 1983-07-26 | 1988-09-14 | Valeas Spa | Sali di endo-8,8-dialchil-8-azoniabiciclo (3.2.1) ottan-6,7-esso-epossi-3-alchilcarbossilati,processo per la loro preparazione e composizioni terapeutiche che li contengono come principio attivo |
| US4698217A (en) * | 1985-02-26 | 1987-10-06 | Mobil Oil Corporation | Crystalline silicate ZSM-58 and process for its preparation using a methyltropinium cation |
| AT397962B (de) * | 1985-12-27 | 1994-08-25 | Madaus & Co Dr | Verfahren zur herstellung von azoniaspironortropanolestern |
| US5770738A (en) * | 1992-03-05 | 1998-06-23 | Boehringer Ingelheim Kg | Esters of bi- and tricyclic amino alcohols, their preparation and their use in pharmaceutical compositions |
| AU2916301A (en) * | 1999-10-28 | 2001-05-08 | Isotech Of Illinois, Inc. | Improved bearing isolator |
| US6706726B2 (en) * | 2000-10-14 | 2004-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics which may be used as medicaments as well as processes for preparing them |
| TW200534855A (en) * | 2004-01-13 | 2005-11-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| PE20060826A1 (es) * | 2004-12-06 | 2006-10-08 | Smithkline Beecham Corp | Derivado oleofinico de 8-azoniabiciclo[3.2.1]octano y combinacion farmaceutica que lo comprende |
| RU2714135C1 (ru) * | 2019-11-22 | 2020-02-12 | Федеральное государственное бюджетное учреждение науки "Институт токсикологии Федерального медико-биологического агентства" | Гидрохлорид (1-метилпиперидин-4-ил)-2-пропилпентаноата, обладающий холинолитической и противосудорожной активностью |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3170927A (en) * | 1965-02-23 | O chzoh | ||
| US2962499A (en) * | 1957-07-03 | 1960-11-29 | Endo Lab | Certain esters of tropine and tropinium salts |
| US3145211A (en) * | 1962-01-04 | 1964-08-18 | Sterling Drug Inc | Tropyl esters of alpha-cycloalkylalkanoic acids |
-
1980
- 1980-06-18 IT IT22843/80A patent/IT1140998B/it active
-
1981
- 1981-06-03 US US06/270,008 patent/US4411902A/en not_active Expired - Lifetime
- 1981-06-05 ZA ZA00813786A patent/ZA813786B/xx unknown
- 1981-06-11 DE DE8181830096T patent/DE3165993D1/de not_active Expired
- 1981-06-11 AT AT81830096T patent/ATE9347T1/de not_active IP Right Cessation
- 1981-06-11 EP EP81830096A patent/EP0042365B1/en not_active Expired
- 1981-06-15 CA CA000379706A patent/CA1161040A/en not_active Expired
- 1981-06-18 AU AU71953/81A patent/AU547923B2/en not_active Ceased
- 1981-06-18 JP JP9310281A patent/JPS5728086A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| CA1161040A (en) | 1984-01-24 |
| DE3165993D1 (en) | 1984-10-18 |
| US4411902A (en) | 1983-10-25 |
| AU547923B2 (en) | 1985-11-14 |
| EP0042365A1 (en) | 1981-12-23 |
| AU7195381A (en) | 1981-12-24 |
| EP0042365B1 (en) | 1984-09-12 |
| IT8022843A0 (it) | 1980-06-18 |
| ZA813786B (en) | 1982-07-28 |
| JPS5728086A (en) | 1982-02-15 |
| IT1140998B (it) | 1986-10-10 |
| ATE9347T1 (de) | 1984-09-15 |
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