US3696110A - Certain hyoscyaminium compounds - Google Patents
Certain hyoscyaminium compounds Download PDFInfo
- Publication number
- US3696110A US3696110A US82813A US3696110DA US3696110A US 3696110 A US3696110 A US 3696110A US 82813 A US82813 A US 82813A US 3696110D A US3696110D A US 3696110DA US 3696110 A US3696110 A US 3696110A
- Authority
- US
- United States
- Prior art keywords
- hyoscyaminium
- bromide
- compounds
- gastric
- quaternary ammonium
- 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 claims description 12
- -1 benzyl halide Chemical class 0.000 claims abstract description 15
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 6
- JABDOYKGZCPHPX-XSCYYCMVSA-M butropium bromide Chemical compound [Br-].CCCCOc1ccc(C[N+]2(C)[C@H]3CC[C@@H]2C[C@@H](C3)OC(=O)[C@H](CO)c2ccccc2)cc1 JABDOYKGZCPHPX-XSCYYCMVSA-M 0.000 claims description 5
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 abstract description 14
- 150000003839 salts Chemical class 0.000 abstract description 10
- 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 abstract description 8
- 229930005342 hyoscyamine Natural products 0.000 abstract description 8
- 229960003210 hyoscyamine Drugs 0.000 abstract description 8
- 229930003347 Atropine Natural products 0.000 abstract description 6
- 229960000396 atropine Drugs 0.000 abstract description 6
- 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 abstract description 6
- 230000000903 blocking effect Effects 0.000 abstract description 6
- 239000007864 aqueous solution Substances 0.000 abstract description 4
- 230000003287 optical effect Effects 0.000 abstract description 4
- 230000001734 parasympathetic effect Effects 0.000 abstract description 4
- 150000003242 quaternary ammonium salts Chemical class 0.000 abstract description 4
- 208000007101 Muscle Cramp Diseases 0.000 abstract description 3
- 208000007107 Stomach Ulcer Diseases 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 208000000718 duodenal ulcer Diseases 0.000 abstract description 3
- 230000002496 gastric effect Effects 0.000 abstract description 3
- 201000005917 gastric ulcer Diseases 0.000 abstract description 3
- 238000010254 subcutaneous injection Methods 0.000 abstract description 3
- 239000007929 subcutaneous injection Substances 0.000 abstract description 3
- 230000000973 chemotherapeutic effect Effects 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 230000008602 contraction Effects 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000001004 anti-acetylcholinic effect Effects 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
- 238000001816 cooling Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000010287 polarization Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BDFZQEDEJPQJNB-UHFFFAOYSA-N 1-(bromomethyl)-4-butoxybenzene Chemical compound CCCCOC1=CC=C(CBr)C=C1 BDFZQEDEJPQJNB-UHFFFAOYSA-N 0.000 description 1
- QAYLIWBLUTYRTC-UHFFFAOYSA-N 1-(bromomethyl)-4-ethoxybenzene Chemical compound CCOC1=CC=C(CBr)C=C1 QAYLIWBLUTYRTC-UHFFFAOYSA-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
- 241000242873 Scopolia Species 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- RKUNBYITZUJHSG-PJPHBNEVSA-O [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate Chemical compound C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-PJPHBNEVSA-O 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229940088506 buscopan Drugs 0.000 description 1
- 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 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
- 230000000052 comparative effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B42—BOOKBINDING; ALBUMS; FILES; SPECIAL PRINTED MATTER
- B42D—BOOKS; BOOK COVERS; LOOSE LEAVES; PRINTED MATTER CHARACTERISED BY IDENTIFICATION OR SECURITY FEATURES; PRINTED MATTER OF SPECIAL FORMAT OR STYLE NOT OTHERWISE PROVIDED FOR; DEVICES FOR USE THEREWITH AND NOT OTHERWISE PROVIDED FOR; MOVABLE-STRIP WRITING OR READING APPARATUS
- B42D17/00—Hanging or securing devices for books, newspapers or the like
Definitions
- the new quaternary ammonium salts according to the present invention exhibit a strong parasympathetic blocking activity with low toxicity. They therefore are advantageously utilizable for chemotherapeutical treatment of patients suffering from diseases such as, for example, gastric cramp, gastric ulcer, duodenal ulcer and the like.
- Aqueous solutions of these salts are stable and are administrated to patients through venous and subcutaneous injections as well as oral administration.
- This invention relates to a process for synthesizing new quaternary salts of atropine or its optical isomer called hyoscyamine base and represented by the formula wherein R is lower alkyl or alkenyl group and X is 3. Anti-acetylcholine effect against the contraction halogen atom.
- Atropine and its optical isomer called hyoscyamine base are the essential components of the main 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 dryness of mouth, retention of urine, disturbance of heart rhythm and an injurious effect on central nervous system.
- Typical solvents which have been found preferable to carry out the above reaction include lower alcohol, acetone, ether and the like.
- the reaction takes place readily at room temperature. In order to prevent from racemisation of the reacting materials, it is advisable to carry out the reaction at low temperature.
- reaction mixture had a turbid appearance followed by separation of white crystals.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
A class of new quaternary ammonium salts derived from atropine or its optical isomer called hyoscyamine base with p-alkoxy or alkenoxy-substituted benzyl halide. The new quaternary ammonium salts according to the present invention exhibit a strong parasympathetic blocking activity with low toxicity. They therefore are advantageously utilizable for chemotherapeutical treatment of patients suffering from diseases such as, for example, gastric cramp, gastric ulcer, duodenal ulcer and the like. Aqueous solutions of these salts are stable and are administrated to patients through venous and subcutaneous injections as well as oral administration.
Description
United States Patent 1 3,696,110
Tanaka et al. 1 Oct. 3, 1972 [54] CERTAIN HYOSCYAMINIUM [56] References Cited CO UNDS OTHER PUBLICATIONS [72] inventors: Satoru Tanaka; Kazunorl Ilulnmto, smithuisl chem Abstracts. VOL 66, Item both Of Tokyo, Japan [73] Assignee: Gisal Kabushiki Kalsha, Tokyo, The Merck index, Seventh Edition, Page 547, 1960 Japan The Merck index, Eighth Edition, Page 558, i968 [22] Filed: Oct. 21, 1970 Pd E r Man L. R0
[ PP 32,813 Attorney-Wenderoth, Lind & Ponack Related U.S. Application Data Continuation of Ser. No. 858,110, Sept. 15, I969, abandoned.
Foreign Application Priority Data ABSTRACT A class of new quaternary ammonium salts derived from atropine or its optical isomer called hyoscyamine base with p-alkoxy or alkenoxy-substituted benzyl halide. The new quaternary ammonium salts according to the present invention exhibit a strong parasympathetic blocking activity with low toxicity. They therefore are advantageously utilizable for chemotherapeutical treatment of patients suffering from diseases such as, for example, gastric cramp, gastric ulcer, duodenal ulcer and the like. Aqueous solutions of these salts are stable and are administrated to patients through venous and subcutaneous injections as well as oral administration.
5 Cldms, No Drawings CERTAIN I-IYOSCYAMINIUM COMPOUNDS This is a continuation of U.S. application, Ser. No. 858,] filed Sept. 15, I969, now abandoned.
This invention relates to a process for synthesizing new quaternary salts of atropine or its optical isomer called hyoscyamine base and represented by the formula wherein R is lower alkyl or alkenyl group and X is 3. Anti-acetylcholine effect against the contraction halogen atom.
Atropine and its optical isomer called hyoscyamine base are the essential components of the main 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 dryness of mouth, retention of urine, disturbance of heart rhythm and an injurious effect on central nervous system.
It was found as the result of several researches which had recently been conducted that the aforementioned drawbacks especially the undesired side effect on central nervous system caused by these researches which had recently been conducted that the afore-mentioned drawbacks especially the undesired side effect 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 salts. The quaternary salts of atropine such as atropine methyl bromide and butyl scopolaminium bromide in commercial name Buscopan, for example, are now available in market.
It cannot, however, be pronounced that difficulty of the side effect on central nervous system presented by these quaternary salts was satisfactorily eliminated.
It has now been found according to our extensive researches in this field that the aforementioned drawbacks or difficulty can satisfactorily be removed by providing the new quaternary salts of atropine or hyoscyamine base with p-alkoxy or p-alkenoxy-substituted benzyl halide.
The followings are comparative data with respect to the pharmacological effects and toxicities (as acute toxicity LD of p-butoxybenzyl hyoscyaminium bromide as one of the typical quaternary salts according to the present invention and the hitherto known butyl scopolaminium bromide.
I Experiment on Isolated Stomac of Rat According to Magnus Method 1. Direct Effect:
a. With 1 X 10- g/ml of p-butoxybenzyl hyoscyaminium bromide, 74.7 percent control and with l X 10" g/ml of the compound, 42.5 percent control of spontaneous motility were respectively observed.
b. With 1 X 10" g/ml of butyl scopolaminium bromide, no appreciable control was observed.
2. Blocking Effect on the Contraction caused by l X l0 g/ml of Barium Chloride:
caused by l X l0" g/ml of acetylcholine:
a. With 1 X 10" g/ml of p-butoxybenzyl ,hyoscyaminium bromide, 72.5 percent control of the contraction were observed.
b. With l X l0" g/ml of butyl scopolaminium bromide, only 15 .0 percent control of the contraction were observed.
ll. Experiment on the Isolated Small lntestin of Mouse According to Magnus' Method 1. Blocking Effect on the Contraction caused by 5 x 10" glml of Barium Chloride:
a. With 1 X [0" g/ml of p-butoxybenzyl hyoscyaminium bromide, 40.0 percent control of contraction, and with l X l0" g/ml of butyl scopolaminium bromide, only 27.1 percent control of the contraction were respectively observed.
2. Anti-acetylcholine Effect on the Contraction caused by l X l0 g/ml of Acetylcholine:
a. With 1 X 10" g/ml of butyl scopolaminium bromide, 22.6 percent control of the contraction were observed.
lII. Acute Toxicity on Male Mouse Weighing ca 20 Grams intravenous injection (LD 12.0 mg/kg (1 l.0-l 3.1
s/ s) Subcutaneous injection (LD 660 mg/kg wherein Rznd X have the same meanings as previously defined.
Typical solvents which have been found preferable to carry out the above reaction include lower alcohol, acetone, ether and the like. The reaction takes place readily at room temperature. In order to prevent from racemisation of the reacting materials, it is advisable to carry out the reaction at low temperature.
Since p-alkoxy or alkenoxy benzyl halide is generally unstable in some extent and is liable to be contaminated with resinous matters thus formed, it is desirable to use it soon after purification by distillation.
In practice, however, no appreciable lowering in yield of the contemplated quaternary salts was observed even though the reaction was conducted with crude substance.
Because no report or reports are found in the literatures so far as our knowledge is concerned with respect to the particular p-alkoxy or alkenoxy benzyl hyoscyaminium halides according to the present invention, the compounds are regarded as new substances.
They are tolerably water-soluble. The aqueous solutions thus obtained are relatively stable to heat. ln
aqueous solutions, the compounds have no tendency to cause racemisation. The fact offers one of the serious advantages in the production of pharmaceutical preparations.
The following examples illustrate the invention.
EXAMPLE 1 Preparation of p-Methoxybenzyl Hyoscyaminium Bromide To 40 milliliters of ice-cooled ethanol solution containing 6 grams of hyoscyamine base were added drop by drop with stirring under ice-cooling l milliliters of an ethanol solution containing grams of p-methoxybenzyl bromide. After stirring for two hours, separation of white crystals appeared. The stirring was continued for additional 5 hours at room temperature. The crystals separated out were then recovered by filtration. The crude crystals were dissolved in 40 milliliters of methanol and 200 milliliters of ethyl ether were then added to the solution. There was recovered 7.5 grams of the white needles having the melting point at 1 90- 200 C.
Upon elementary analysis, the product gave the following results:
For C,,H,,NO Br; molecular weight 490.45;
C H N Calculated (12): 61.22 6.58 2.86 Found (Q1): 6|.27 6.33 3.02
Rotatory polarization of the product was l in" -5(0 0.5 in water) EXAMPLE 2 Preparation of p-Ethoxybenzyl Hyoscyaminium Bromide To 50 milliliters of an acetone solution containing 8.4 grams of hyoscyamine base were added drop by drop 10 millimeters of an acetone solution containing 7.4 grams of p-ethoxybenzyl bromide while ice-cooling. After stirring for a while, white crystals separated out. The reaction mixture was stirred at room temperature for additional 5 hours. The crystalline substance was recovered by filtration, which was then recrystallized from isopropanol. 10.4 Grams of the purified product were obtained in a form of white needles which had the melting point of 164- 166 C.
Analysis of the product gave the following results:
For C H, N0,Br; molecular weight: 504.47; H N
C Calculated (5): 61.89 6.80 2.78 Found ('5): 61.62 7 l7 2.84
EXAMPLE 3 For C, H N0 Br; molecular weight: 516.48;
H N Calculated (as 62.78 6.64 2.11 Found (I): 62.30 6.73 2.73
EXAMPLE 4 Preparation of p-Butoxybenzyl Hyoscyaminium Bromide To milliliters of an isopropanol solution containing 11.8 grams of hyoscyamine base were added drop by drop with stirring l0 milliliters of an isopropanol solution containing 1 1 grams of p-n-butoxybenzyl bromide.
After a while, the reaction mixture had a turbid appearance followed by separation of white crystals.
After stirring for 5 hours at room temperature, the crystals were recovered by filtration, which were then recrystallized from milliliters of isopropanol. There was obtained 15.8 grams of white needles having the melting point of l 58-160 C.
Analysis of the product gave the following properties:
For C H NOJIr; molecular weight: 532.50;
H N Calculated 63.10 7.20 2.63 Found 63.34 7.31 2.69 Rotatory polarization:
lul --21 .7 (c 0.5 in water) What is claimed is: l. Atropinium and hyoscyaminium quaternary salts represented by the formula:
s oQcm-racm 9-0-0 04 ri-cmoa
Claims (4)
- 2. A compound according to claim 1, which is, p-methoxybenzyl hyoscyaminium bromide.
- 3. A compound according to claim 1, which is, p-ethoxybenzyl hyoscyaminium bromide.
- 4. A compound according to claim 1, which is, allyloxybenzyl hyoscyaminium bromide.
- 5. A compound according to claim 1, which is, p-butoxybenzyl hyoscyaminium bromide.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1153169 | 1969-02-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3696110A true US3696110A (en) | 1972-10-03 |
Family
ID=11780535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US82813A Expired - Lifetime US3696110A (en) | 1969-02-18 | 1970-10-21 | Certain hyoscyaminium compounds |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US3696110A (en) |
| CH (1) | CH510030A (en) |
| DE (1) | DE1950378C2 (en) |
| FR (1) | FR2034553B1 (en) |
| GB (1) | GB1235957A (en) |
| NL (1) | NL142674B (en) |
| SE (1) | SE351848B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0002051A1 (en) * | 1977-11-16 | 1979-05-30 | Eisai Co., Ltd. | Use of butoxybenzylhyoscyamine bromide in pharmaceutical compositions against deafness and tinnitus |
| US20050226920A1 (en) * | 2004-04-13 | 2005-10-13 | Kirk Voelker | Method of decreasing nicotine withdrawal symptoms during smoking cessation. |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1062704B (en) * | 1956-08-07 | 1959-08-06 | Licencia Talalmanyokat | Process for the production of quaternary atropines |
| DE1163845B (en) * | 1960-10-18 | 1964-02-27 | Egyesult G>ogyszer es Tapszer g>ar Budipest λ ertr Dr C W I otter hos und Dr Ing FI W Lotterhos Pat Anwalte Frankfurt"^ | Process for the preparation of p-alkylbenzyl-tropinium derivatives. |
| AT246339B (en) * | 1960-10-18 | 1966-04-12 | Egyt Gyogyszervegyeszeti Gyar | Process for the preparation of new p-alkylbenzyltropinium derivatives |
| DE1165037B (en) * | 1961-11-21 | 1964-03-12 | Dr. Schwarz Arzneimittelfabrik G.m.b.H., Monheim (RhId.) | Process for the preparation of esters of quaternary atropinium salts. |
| FR1539224A (en) * | 1966-09-02 | 1968-09-13 | Boehringer Sohn Ingelheim | Process for making tropic acid derivatives |
-
1969
- 1969-10-06 DE DE1950378A patent/DE1950378C2/en not_active Expired
- 1969-10-07 GB GB49126/69A patent/GB1235957A/en not_active Expired
- 1969-12-09 CH CH1830569A patent/CH510030A/en not_active IP Right Cessation
-
1970
- 1970-02-06 NL NL707001733A patent/NL142674B/en not_active IP Right Cessation
- 1970-02-09 FR FR7004493A patent/FR2034553B1/fr not_active Expired
- 1970-02-13 SE SE01874/70A patent/SE351848B/xx unknown
- 1970-10-21 US US82813A patent/US3696110A/en not_active Expired - Lifetime
Non-Patent Citations (3)
| Title |
|---|
| Smithuis, Chem. Abstracts, Vol. 66, Item No. 79,545 a, 1967 * |
| The Merck Index, Eighth Edition, Page 558, 1968 * |
| The Merck Index, Seventh Edition, Page 547, 1960 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0002051A1 (en) * | 1977-11-16 | 1979-05-30 | Eisai Co., Ltd. | Use of butoxybenzylhyoscyamine bromide in pharmaceutical compositions against deafness and tinnitus |
| FR2409263A1 (en) * | 1977-11-16 | 1979-06-15 | Eisai Co Ltd | MEDICINAL PRODUCT BASED ON BUTOXYBENZYLHYOSCYAMINE BROMIDE FOR USE IN THE TREATMENT OF DEAFDESS AND EAR TINNING |
| US20050226920A1 (en) * | 2004-04-13 | 2005-10-13 | Kirk Voelker | Method of decreasing nicotine withdrawal symptoms during smoking cessation. |
Also Published As
| Publication number | Publication date |
|---|---|
| DE1950378A1 (en) | 1970-08-27 |
| FR2034553B1 (en) | 1974-02-01 |
| NL7001733A (en) | 1970-08-20 |
| SE351848B (en) | 1972-12-11 |
| CH510030A (en) | 1971-07-15 |
| FR2034553A1 (en) | 1970-12-11 |
| NL142674B (en) | 1974-07-15 |
| GB1235957A (en) | 1971-06-16 |
| DE1950378C2 (en) | 1985-10-03 |
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