US3847924A - Certain scopolammonium compounds - Google Patents
Certain scopolammonium compounds Download PDFInfo
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- 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
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- 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)
Abstract
WHEREIN R IS A LOWER ALKYL GROUP AND X IS A HALOGEN ATOM.
(3-(HO-CH2-CH(-C6H5)-COO-),6,7-(-O-),8-(R-O-(1,4-
PHENYLENE)-),8-(H3C-)-NORTROPANIUM) X(-)
1. SCOPOLAMMONIUM QUATERNARY SALTS REPRESENTED BY THE FORMULA:
Description
United States Patent 3,847,924 CERTAIN SCOPOLAMMONIUM COMPOUNDS Satoru Tanaka and Kazunori Hashimoto, Tokyo, Japan, assignors to Eisai Co., Ltd., Tokyo, Japan No Drawing. Filed May 31, 1973, Ser. No. 365,728 Claims priority, application Japan, June 12, 1972, 47/ 57,633 Int. Cl. C07d 43/ 06 U.S. Cl. 260-292 3 Claims ABSTRACT OF THE DISCLOSURE This invention relates to the new quaternary ammonium salts of scopolamine represented by the formula:
59 O -cH -n-cri II O-C-CH-CH OH wherein R is a lower alkyl group and X is a halogen atom, and a process for the preparation thereof.
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.
It was found as the result of several researches which had recently been conducted that the aforementioned drawbacks especially the undesired side effects on central nervous system caused by these compounds can considerably be reduced, although their aimed original parasympathetic blocking activity is also somewhat reduced, when these compounds are administrated in a form of their conventional quaternary ammonium salts. The quaternary ammonium salts of atropine such as N-methyl atropinium bromine and N-butyl scopolammonium bromide in the commercial name of Buscopan, for example, are now available in market.
It cannot, however, be pronounced that the side effects on the central nervous system presented by these quaternary ammonium salts was satisfactorily eliminated.
It has now been found according to our extensive researches in this field that the aforementioned drawbacks can satisfactorily be removed by providing the new quaternary ammonium salts which were gained by the reaction of scopolamine base with p-alkoxy-substituted benzyl halide.
The followings are the comparative data with respect to the pharmacological effects and toxicities (as acute toxicity LDso) of N-(p-butoxybenzyl)scopolammonium bromide, hereinafter-called Compound A, as one of the typical quaternary ammonium salts according to the present invention and the hitherto known butyl scopolammonium bromide, herein after called Compound B.
I. Experiment on Isolated Stomach of Rat According to Magnus Method 1. Direct effect:
(a) With 1 10- g./ml. of Compound A, 70.5 percent control of the spontaneous motility was observed.
(b) With 1x10- g./ml. of Compound B, no appreciable control was observed.
2. Blocking effect on the contraction caused by 1 l0 g./ml. of barium chloride:
(a) With 1 10- g./ml. of Compound A, 68.3 percent control of the contraction was observed.
(b) With 1 l0 g./ml. of Compound B, only 15.0
percent control of the contraction was observed.
3. Anti-acetylcholine effect against the contraction caused by 1x10 g./ml. of acetylchloine:
(a) With 1 10-" g./ml. of Compound A, 64.5 percent control of the contraction was observed.
(b) With 1 l0 g./ml. of Compound B, only 15.0
percent control of the contraction was observed.
II. Experiment of the Isolated Small Intestine of Mouse According to Magnus Method 1. Blocking effect on the contraction caused by 5X10 g./ml. of barium chloride:
(a) With 1 l0 g./ml. of Compound A, 32.4 percent control of contraction was observed.
(b) With 1 10- g./ml. of Compound B, only 27.1 percent control was observed.
2. Anti-acetylcholine effect on the contraction caused by 1 10-" g./m1. of acetylcholine:
(a) With l 10- g./ml. of Compound A, 76.8 percent control of the contraction was observed.
(b) With 1X10 g./ml. of Compound B, 15.1 percent control was observed.
III. Acute Toxicity on Male Mouse Weighing ca.
20 Grams Compound A B Subcutaneous injection (LDso), mg./kg 750 580 Oral administration (LDao), mg./kg 2, 200 1, 800
wherein 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.
The following examples illustrate the invention.
EXAMPLE 1 Preparation of N- (p-methoxybenzyl Scopolamrnonium Bromide To 70 milliliters of a chloroform solution containing 10 grams of scopolamine base were added drop by drop under ice-cooling 3O milliliters of a chloroform solution containing 7 grams of p-methoxybenzyl bromide. After the completion of the addition, the reaction mixture was stirred for one hour under ice-cooling. The stirring was continued for additional one hour at room temperature for carrying out the reaction. After the completion of the reaction, 100 milliliters of isopropyl ether were added to the solution. Crystals which separated out were recovered by filtration. The crystals were recrystallized from chloroform-isopropyl ether to obtain the purposed product in needles which had the melting point of 7580 C. with foaming and decomposition. Yield were 12.8 grams which corresponded to 72.3% of the theory.
Elementary analysis of the product and the calculation for C H BrNO -2H O; Molecular weight 540.46 gave:
To 50 milliliters of a chloroform solution containing 9 grams of scopolamine were added 30 milliliters of a C H N Calculated (percent)- 57. 73 6.92 2. Found (percent) 57.77 6.90 2. 24
Rotatory plarization of the product was:
[a] r 12.6 (c=0.5, l=0.1 in ethanol).
What is claimed is: 1. Scopolammoniurn quaternary salts represented by the formula:
6) wa s-0&
o-ii-cn-cn oa o wherein R is a lower alkyl group and X is a halogen atom.
2. A compound according to claim 1, which is pmethoxybenzyl scopolarnmonium bromide.
3. -A compound according to claim 1, which is pbutoxybenzyl scopolarnmonium bromide.
References Cited UNITED STATES PATENTS 3,696,] 10 10/1972 Tanaka et al 260292 ALAN L. ROTMAN, Primary Examiner US. Cl. X.R. 424265
Claims (1)
1. SCOPOLAMMONIUM QUATERNARY SALTS REPRESENTED BY THE FORMULA:
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP47057633A JPS4919012A (en) | 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)
| Country | Link |
|---|---|
| US (1) | US3847924A (en) |
| JP (1) | JPS4919012A (en) |
| AU (1) | AU468339B2 (en) |
| CA (1) | CA1006519A (en) |
| CH (1) | CH572933A5 (en) |
| DE (1) | DE2329893A1 (en) |
| FR (1) | FR2187354B1 (en) |
| GB (1) | GB1378127A (en) |
| NL (1) | NL7307903A (en) |
| PH (1) | PH10925A (en) |
| SE (1) | SE403113B (en) |
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 (en) * | 1990-02-28 | 1994-06-15 | 沖電気工業株式会社 | Compound semiconductor wafer |
| RU2414615C1 (en) * | 2009-08-28 | 2011-03-20 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Gas turbine engine |
| RU2450143C1 (en) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Gas turbine engine |
| RU2450142C1 (en) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Gas turbine engine |
| RU2450141C1 (en) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Gas turbine engine |
| RU2450144C1 (en) * | 2011-03-16 | 2012-05-10 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Gas turbine engine |
| RU2459967C1 (en) * | 2011-04-05 | 2012-08-27 | Открытое акционерное общество "Научно-производственное объединение "Сатурн" (ОАО "НПО "Сатурн") | Double-flow gas turbine engine |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH77A (en) * | 1889-01-09 | Christian Herren | Root cutting machine |
-
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/en 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 GB GB2789573A patent/GB1378127A/en not_active Expired
- 1973-06-12 DE DE2329893A patent/DE2329893A1/en active Pending
- 1973-06-12 FR FR7321306A patent/FR2187354B1/fr not_active Expired
- 1973-06-12 AU AU56805/73A patent/AU468339B2/en not_active Expired
- 1973-06-12 CA CA173,797A patent/CA1006519A/en not_active Expired
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 |
|---|---|
| NL7307903A (en) | 1973-12-14 |
| CH572933A5 (en) | 1976-02-27 |
| SE403113B (en) | 1978-07-31 |
| FR2187354A1 (en) | 1974-01-18 |
| GB1378127A (en) | 1974-12-18 |
| PH10925A (en) | 1977-10-05 |
| CA1006519A (en) | 1977-03-08 |
| AU468339B2 (en) | 1976-01-08 |
| FR2187354B1 (en) | 1977-09-09 |
| DE2329893A1 (en) | 1974-01-03 |
| AU5680573A (en) | 1974-12-12 |
| JPS4919012A (en) | 1974-02-20 |
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