US3847924A - Certain scopolammonium compounds - Google Patents
Certain scopolammonium compounds Download PDFInfo
- Publication number
- US3847924A US3847924A US00365728A US36572873A US3847924A US 3847924 A US3847924 A US 3847924A US 00365728 A US00365728 A US 00365728A US 36572873 A US36572873 A US 36572873A US 3847924 A US3847924 A US 3847924A
- Authority
- US
- United States
- Prior art keywords
- scopolammonium
- compound
- compounds
- observed
- certain
- 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 title description 13
- 150000003839 salts Chemical group 0.000 claims abstract description 3
- 150000002367 halogens Chemical group 0.000 abstract 1
- 230000008602 contraction Effects 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 229940126062 Compound A Drugs 0.000 description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical class C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 6
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 5
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 5
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 5
- 229960002646 scopolamine Drugs 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000001004 anti-acetylcholinic effect Effects 0.000 description 2
- 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 2
- 229960000396 atropine Drugs 0.000 description 2
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 2
- 229910001626 barium chloride Inorganic materials 0.000 description 2
- -1 benzyl halide Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000001734 parasympathetic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- RKUNBYITZUJHSG-FXUDXRNXSA-N (S)-atropine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@H]3CC[C@@H](C2)N3C)=CC=CC=C1 RKUNBYITZUJHSG-FXUDXRNXSA-N 0.000 description 1
- GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 1
- 241001106067 Atropa Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 241000242873 Scopolia Species 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- PIPAJLPNWZMYQA-RYTJFDOTSA-N [(1S,5R)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate Chemical compound C([C@H]1CC[C@@H](C2)[N+]1(C)C)C2OC(=O)C(CO)C1=CC=CC=C1 PIPAJLPNWZMYQA-RYTJFDOTSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 229940088506 buscopan Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 206010013990 dysuria Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 229930005342 hyoscyamine Natural products 0.000 description 1
- 229960003210 hyoscyamine Drugs 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 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
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
Definitions
- scopolamine, atropine and hyoscyamine base are the essential components of the alkaloids contained in belladonna and scopolia. These compounds exhibit a strong parasympathetic blocking activity and they therefore are utilized for the purpose of therapeutical treatment of diseases such as gastric cramp, gastric ulcer, duodenal ulcer and the like. Unfortunately it was found that they show undesirable side effects such as thirst, dysuria, and palpitation and the injurious effects on central nervous system, such as illusion, hemicrania, nausea and the like.
- Compound A N-(p-butoxybenzyl)scopolammonium bromide
- Compound B the hitherto known butyl scopolammonium bromide
- R and X have the same meanings as previously defined with respect to the formula given to the opening paragraph.
- Typical solvents which have been found preferable to carry out the above reaction include lower alcohol, acetone, ether, chloroform and the like.
- the reaction takes place readily at room temperature. In order to avoid the racemisation of the scopolamine compounds, it is advisable to carry out the reaction at a low temperature.
- the resulting N-(p-loweralkoxybenzyl)scopolammonium bromides are easily soluble in Water.
- the aqueous solutions thus obtained are stable to heat with no tendency of causing racemisation. The fact olfers one of the serious advantages in the production of pharmaceutical preparations.
- R is a lower alkyl group and X is a halogen atom.
- a compound according to claim 1 which is pmethoxybenzyl scopolarnmonium bromide.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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 |
|---|---|---|---|
| JP47057633A JPS4919012A (enrdf_load_stackoverflow) | 1972-06-12 | 1972-06-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3847924A true US3847924A (en) | 1974-11-12 |
Family
ID=13061285
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00365728A Expired - Lifetime US3847924A (en) | 1972-06-12 | 1973-05-31 | Certain scopolammonium compounds |
Country Status (11)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3952108A (en) * | 1972-04-18 | 1976-04-20 | Istituto De Angeli S.P.A. | Scopolamine derivatives for treating ulcers and spasms |
| AU760009B2 (en) * | 1997-10-24 | 2003-05-08 | Newlaxant Llc | Bis-quaternary ammonium derivatives as neuromuscular relaxants |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0622991Y2 (ja) * | 1990-02-28 | 1994-06-15 | 沖電気工業株式会社 | 化合物半導体ウエハ |
| RU2414615C1 (ru) * | 2009-08-28 | 2011-03-20 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Газотурбинный двигатель |
| RU2450144C1 (ru) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Газотурбинный двигатель |
| RU2450141C1 (ru) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Газотурбинный двигатель |
| RU2450143C1 (ru) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Газотурбинный двигатель |
| RU2450142C1 (ru) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Газотурбинный двигатель |
| RU2459967C1 (ru) * | 2011-04-05 | 2012-08-27 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Двухконтурный газотурбинный двигатель |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH77A (de) * | 1889-01-09 | Christian Herren | Wurzelschneidmaschine |
-
1972
- 1972-06-12 JP JP47057633A patent/JPS4919012A/ja active Pending
-
1973
- 1973-05-31 US US00365728A patent/US3847924A/en not_active Expired - Lifetime
- 1973-06-06 NL NL7307903A patent/NL7307903A/xx not_active Application Discontinuation
- 1973-06-07 SE SE7308071A patent/SE403113B/xx unknown
- 1973-06-07 CH CH827873A patent/CH572933A5/xx not_active IP Right Cessation
- 1973-06-08 PH PH14709A patent/PH10925A/en unknown
- 1973-06-12 CA CA173,797A patent/CA1006519A/en not_active Expired
- 1973-06-12 GB GB2789573A patent/GB1378127A/en not_active Expired
- 1973-06-12 AU AU56805/73A patent/AU468339B2/en not_active Expired
- 1973-06-12 FR FR7321306A patent/FR2187354B1/fr not_active Expired
- 1973-06-12 DE DE2329893A patent/DE2329893A1/de active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3952108A (en) * | 1972-04-18 | 1976-04-20 | Istituto De Angeli S.P.A. | Scopolamine derivatives for treating ulcers and spasms |
| AU760009B2 (en) * | 1997-10-24 | 2003-05-08 | Newlaxant Llc | Bis-quaternary ammonium derivatives as neuromuscular relaxants |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2187354B1 (enrdf_load_stackoverflow) | 1977-09-09 |
| CA1006519A (en) | 1977-03-08 |
| PH10925A (en) | 1977-10-05 |
| AU468339B2 (en) | 1976-01-08 |
| GB1378127A (en) | 1974-12-18 |
| DE2329893A1 (de) | 1974-01-03 |
| NL7307903A (enrdf_load_stackoverflow) | 1973-12-14 |
| AU5680573A (en) | 1974-12-12 |
| JPS4919012A (enrdf_load_stackoverflow) | 1974-02-20 |
| SE403113B (sv) | 1978-07-31 |
| FR2187354A1 (enrdf_load_stackoverflow) | 1974-01-18 |
| CH572933A5 (enrdf_load_stackoverflow) | 1976-02-27 |
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