GB2025969A - A Process for Preparing N- cyano-N'-methyl-N''-[2-{[(5- methylimidazol-4-yl)-methyl]-thio}- ethyl]-guanidine - Google Patents
A Process for Preparing N- cyano-N'-methyl-N''-[2-{[(5- methylimidazol-4-yl)-methyl]-thio}- ethyl]-guanidine Download PDFInfo
- Publication number
- GB2025969A GB2025969A GB7925042A GB7925042A GB2025969A GB 2025969 A GB2025969 A GB 2025969A GB 7925042 A GB7925042 A GB 7925042A GB 7925042 A GB7925042 A GB 7925042A GB 2025969 A GB2025969 A GB 2025969A
- Authority
- GB
- United Kingdom
- Prior art keywords
- methyl
- cyano
- guanidine
- ethyl
- methylimidazol
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 title abstract description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 7
- 230000028327 secretion Effects 0.000 claims abstract description 7
- 230000002496 gastric effect Effects 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- -1 5-methylimidazol-4-yl Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 4
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- ZORWZOOZJGMSTE-UHFFFAOYSA-N 1-cyano-2-methyl-3-(2-sulfanylethyl)guanidine Chemical compound N#CNC(=NC)NCCS ZORWZOOZJGMSTE-UHFFFAOYSA-N 0.000 abstract description 7
- OVLUBEIAVGIZEN-UHFFFAOYSA-N 1-cyano-3-[2-(2,3-dioxobutylsulfanyl)ethyl]-2-methylguanidine Chemical compound N#CNC(=NC)NCCSCC(=O)C(C)=O OVLUBEIAVGIZEN-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 230000036269 ulceration Effects 0.000 description 2
- JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 description 1
- APZXPRHPPCTRHN-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-1h-imidazole Chemical compound CC=1NC=NC=1CCl APZXPRHPPCTRHN-UHFFFAOYSA-N 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- XMYLSWOTJKUSHE-UHFFFAOYSA-N cyanamide;lead Chemical compound [Pb].NC#N XMYLSWOTJKUSHE-UHFFFAOYSA-N 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- MHGGQXIPBPGZFB-UHFFFAOYSA-N methyl n-cyano-n'-methylcarbamimidothioate Chemical compound CSC(=NC)NC#N MHGGQXIPBPGZFB-UHFFFAOYSA-N 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/22—Radicals substituted by singly bound oxygen or sulfur atoms etherified
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The compound known as Cimethidin, N-cyano-N'-methyl-N''-[2- {[(5-methylimidazol-4-yl)-methyl]- thio}-ethyl]-guanidine, is made by reacting chlorodiacetyl with ethylene glycol, reacting the resultant ketal hemiketal with N-cyano-N'-methyl- N''-(2-mercaptoethyl)-guanidine to form N-cyano-N'-methyl-N''-[2- (butane-2,3-dionyl)thioethyl]- guanidine ethyleneketal hemiketal, hydrolyzing this to give the corresponding alpha -diketone and condensing the latter with formaldehyde and ammonia to produce Cimethidin, which can be incorporated in pharmaceutical compositions for gastric secretion reduction or inhibition.
Description
SPECIFICATION
A Process for Preparing N-Cyano-N'-Methyl N"-[2-{ [(5-Methylimidazol-4-yl )-Methyl]-Thio)-
Ethyl]-Guanidine The invention relates to the preparation of N cyano-N'-methyl-N"-[2-([(5-methylimidazol-4- yl)-methyl]-thio)-ethyl]-guanidine (referred to in the following as "Cimethidin") by the condensation of N-cyano-N'-methyl-N"-[2 (butane-2,3-dionyl)-thioethyl]-guanidine with formaldehyde and ammonia.
It is known that Cimethidin can be prepared by reacting 5-methyl-4-[(2-aminoethyl)-thiomethyl]imidazole with N-cyano-N',S-dimethylisothiourea, by reacting N-cyano-N"-[2-( [(5-methylimidazol- 4-yl)-methyl]-thio)-ethyl]-S-methylisothiou rea with methylamine and by reacting N'-methyl-N" [2-( [(5-methylimidazol-4-yl)-methyl]-thio i-ethyl]- thiourea with lead cyanamide (U.S.Patent
Specification 3,876,647 and German
Offenlegungsschrift 2,344,779); Cimethidin also can be made from N',S-dimethyl-N"-[2-I [(5- methylimidazol-4-yl)-methyi]-thio )-ethyl]-isothiourea and cyanamide (Belgian Patent
Specification 832,665) and from 5-methyl-4chloromethylimidazole and N-cyano-N'-methyl
N"-(2-mercaptoethyl)-guanidine (Dutch Patent
Application 7,51 0,344Y.
Cimethidin inhibits the secretion of gastric acid and of pepsin and shows valuable therapeutic effects in treating duodenal and benign gastric ulcers, recurrent ulcerations and ulcerations arising in stoma, reflux esophagitis and other conditions, where a reduced secretion of gastric acid is desired.
It has been found that Cimethidin can be prepared easily and with a good yield by the condensation of N-cyano-N'-methyl-N"-[2 (butane-2,3-dionyl)-thioethyl3-guanidine, formaldehyde and ammonia. The process according to the invention comprises reacting chlorodiacetyl with ethylene glycol to form the
corresponding ketal heliketal, reacting the latter with N-cyano-N'-methyl-N"-(2-mercaptoethyl)
guanidine to form the corresponding ketal
heliketal of the formula:
subjecting the compound of formula I to acidic hydrolysis to obtain the corresponding a-diketone and then condensing the latter with formaldehyde and ammonia to form the desired Cimethidin.
In carrying out the process of this invention, chlorodiacetyl is first converted to the corresponding ketal hemiketal, preferably by reaction with the ethylene glycol in benzene in the presence of a catalytic amount of ptoluenesulphonic acid and subsequently, after stirring the ketal hemiketal and N-cyano-N'methyl-N"-(2-mercaptoethyl)-guanidine in a lower alcohol, e.g. up to C8, preferably isopropanol, N,N'-dimethyl-formamide or acetonitrile in the presence of 1 to 3 equivalents of sodium or sodium hydride, the precipitate obtained is removed by suction and the mother liquor is evaporated to dryness.The resultant ketal hemiketai as represented by formula I is desirably separated from the residue, e.g. by recrystallisation from an appropriate solvent or by column chromatography, and is then stirred for 2-4 hours at 55 0--570C in acetone with the addition of dilute sulphuric acid. After evaporating the solution to dryness in vacuo, adding 4-6 equivalents of 25% aqueous or ethanolic ammonia and 1-1.5 equivalents of formaldehyde, while stirring the mixture for 1020 hours at 0"--5 OC, the solution is evaporated to dryness and Cimethidin can be isolated from the residue, for instance, by recrystallisation from an appropriate solvent or by column chromatography. The main advantages of this process are the small number of reaction steps, as well as the simplicity of the preparation.The invention resides also in Cimethidin when made by the process of the invention and in pharmaceutical compositions for use in reducing or inhibiting gastric secretion and in treating conditions where reduced gastric secretion is desired, comprising at least one carrier substance and Cimethidin. The invention. is illustrated by the following Examples, which are given by way of expianation rather than limitation.
Example 1
A solution of 4.82 g (0.04 mole) of chlorodiacetyl, 5.5 g (0.088 mole! of ethylene glycol and a catalytic quantity ofptoluenesulphonic acid in 250 ml of dry benzene was heated for 10 hours under reflux. By evaporating the solution to dryness in vacuo, a crude product was obtained from which, after purification (crystallisation, column chromatography), pure chlorodiacetyl ethyleneketal hemiketal was obtained, m.p.
99 101 C.
Example 2
0.484 g (0.021 mole) of sodium was dissolved in 60 ml of isopropanol and 1.11 g (0.007 mole) of N-cyano-N'-methyl-N11-(2-mercaptoethyl)- guanidine were added. After stirring for 30 minutes at room temperature, 1.59 g (0.007 mole) of chlorodiacetyl ethyleneketal hemiketal were added and stirring was continued for 5 hours at the boiling point of the solution. The precipitate obtained was removed by suction, the mother liquor was evaporated to dryness in vacuo and, after purification (crystallisation, column chromatography), N-cyano-N'-methyl-N"-[2 (butane-2,3-dionyl)-thioethyl]-guanidine ethyleneketal hemiketal was obtained from the residue in the form of white hygroscopic crystals, m.p. < 1200C.
Example 3
Analogously to the process described in
Example 2, from 0.92 g (0.021 mole) of 55% sodium hydride, 1.11 g (0.007 mole) of N-cyano
N'-methyl-N"-(2-mercaptoethyl)-guanidine and 1.59 g (0.007 mole) of chlorodiacetyl ethyleneketal hemiketal in 20 ml of N,N'dimethylformamide at 200--250C for 30 hours, N-cyano-N'-methyl-N"-[2-(butane-2,3-dionyl)- thioethyl]-guanidine ethyleneketal hemiketal was obtained.
Example 4
Analogously to the process described in
Example 2, from 0.31 g (0.007 mole) of 55% sodium hydride, 1.11 g (0.007 mole) of N-cyano
N'-methyl-N"-(2-mercaptoethyl)-guanidine and 1.59 g (0.007 mole) of chlorodiacetyl ethyleneketal hemiketal in 50 ml of acetonitrile at the boiling point of the mixture, N-cyano-N' methyl-N"-[2-(butane-2,3-dionyl)thioethyl]- guanidine ethyleneketal hemiketal was obtained.
Example 5
Analogously to the process described in
Example 2, from 0.161 g (0.007 mole) of sodium, 1.11 g (0.007 mole) of N-cyano-N'-methyl-N"-(2- mercaptoethyl)-guanidine and 1.59 g (0.007 mole) of chlorodiacetyl ethyleneketal hemiketal in 20 ml of ethanol at room temperature, N-cyano N'-methyl-N"-[2-(butane-2,3-dionyl)-thioethyl]- guanidine ethyleneketal hemiketal was obtained.
Example 6
A mixture of 0.35 g (0.001 mole) of N-cyano N'-methyí-N"-[2-(butane-2,3-dionyl)-thioethyl]- guanidine ethyleneketal hemiketal, 50 ml of acetone and 15 ml of 1% sulphuric acid was heated to 550--570C for 2-4 hours and then evaporated to dryness in vacuo. The residue was dissolved in 2 ml of water or ethanol and, while at 00--50C, 0.5--0.7 ml (0.007-0.009 mole) of a 25% aqueous or ethanolic solution of ammonia and subsequently 0.08-0.12 ml (0.001- 0.001 5 mole) of 40% formaldehyde were added dropwise and the reaction mixture was stirred for a further 10-20 hours. Then the reaction solution was evaporated to dryness in vacuo and, after purification (crystallisation, column chromatography), N-cyano-N'-methyl-N"-[2-Ir(5- methylimidazol-4-yl)-methyl]-thio)-ethylj- guanidine was obtained from the residue, m.p.
1400--1420C.
Claims (4)
1. A process for preparing N-cyano-N'-methyl N"-[2-( [(5-methylimidazol-4-yl)-methyl]-thio i- ethyl]-guanidine, which comprises reacting chlorodiacetyl with ethylene glycol to form the corresponding ketal hemiketal, reacting the latter with N-cyano-N'-methyí-N"-(2-mercapto-ethyl)- guanidine to form N-cyano-N'-methyl-N8-[2- (butane-2,3-dionyl)-thioethyl]-guanidine ethyleneketal hemiketal of the formula:
subjecting the compound of formula I to acidic hydrolysis to obtain the corresponding a-diketone and then condensing the latter with formaldehyde and ammonia to form the desired N-cyano-N' methyl-N"-[2-j [(5-methylimidazol-4-yl)-methyl] thio)-ethyl]-guanidine.
2. A process according to Claim 1, substantially as described with reference to the foregoing Examples.
3. N-cyano-N'-methyl-N"-[2-{[(5 methylimidazol-4-yI)-methyl-thioj-ethyl]- guanidine, when prepared by a process according to either preceding claim.
4. A pharmaceutical composition for use in reducing or inhibiting gastric secretion and in treating conditions where reduced gastric secretion is desired, comprising at least one carrier substance and the compound of Claim 3.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU1725/78A YU40716B (en) | 1978-07-19 | 1978-07-19 | Process for obtaining n-cyano-n'-methyl-n'-û2-|5-metylimidazole4-yl)-methyl¨-thioethylù guanidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2025969A true GB2025969A (en) | 1980-01-30 |
| GB2025969B GB2025969B (en) | 1982-09-02 |
Family
ID=25555343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7925042A Expired GB2025969B (en) | 1978-07-19 | 1979-07-18 | Process for preparing n - cyano - n'- methyl - n''- (2-(((5 - methylimidazol - 4 - yl) - methylthio) - ethyl) - guanidine |
Country Status (7)
| Country | Link |
|---|---|
| AT (1) | AT366033B (en) |
| CH (1) | CH643246A5 (en) |
| DE (1) | DE2928857B2 (en) |
| GB (1) | GB2025969B (en) |
| IT (1) | IT1121013B (en) |
| SU (1) | SU886744A3 (en) |
| YU (1) | YU40716B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0261818A1 (en) * | 1986-09-01 | 1988-03-30 | Mitsui Petrochemical Industries, Ltd. | Process for preparation of guanidine derivative |
| US5808090A (en) * | 1996-02-22 | 1998-09-15 | Endo Pharmaceuticals Inc. | Process for preventing precipitation in cimetidine injection solutions |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU185298B (en) * | 1981-06-26 | 1984-12-28 | Richter Gedeon Vegyeszet | Process for producing cimetidine |
| HU185636B (en) * | 1981-06-26 | 1985-03-28 | Richter Gedeon Vegyeszet | Process for preparing new cimetidine-hydrate /cimetidine-h/ |
| JPH0629234B2 (en) * | 1986-12-26 | 1994-04-20 | 三井石油化学工業株式会社 | α-acyloxyketone derivative |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1397436A (en) | 1972-09-05 | 1975-06-11 | Smith Kline French Lab | Heterocyclic n-cyanoguinidines |
| GB1533380A (en) | 1974-09-02 | 1978-11-22 | Smith Kline French Lab | Process for the preparation of heterocyclic substituted thioureas and h-cyanoguanidines |
| GB1531221A (en) | 1974-09-02 | 1978-11-08 | Smith Kline French Lab | Process for preparing guanidine derivatives |
-
1978
- 1978-07-19 YU YU1725/78A patent/YU40716B/en unknown
-
1979
- 1979-07-17 DE DE2928857A patent/DE2928857B2/en active Granted
- 1979-07-18 GB GB7925042A patent/GB2025969B/en not_active Expired
- 1979-07-18 CH CH669479A patent/CH643246A5/en not_active IP Right Cessation
- 1979-07-19 SU SU792790358A patent/SU886744A3/en active
- 1979-07-19 AT AT0498379A patent/AT366033B/en not_active IP Right Cessation
- 1979-07-19 IT IT68506/79A patent/IT1121013B/en active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0261818A1 (en) * | 1986-09-01 | 1988-03-30 | Mitsui Petrochemical Industries, Ltd. | Process for preparation of guanidine derivative |
| US4808726A (en) * | 1986-09-01 | 1989-02-28 | Mitsui Petrochemical Industries, Ltd. | Process for preparation of guanidine derivative |
| US5808090A (en) * | 1996-02-22 | 1998-09-15 | Endo Pharmaceuticals Inc. | Process for preventing precipitation in cimetidine injection solutions |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2928857B2 (en) | 1981-07-23 |
| AT366033B (en) | 1982-03-10 |
| IT1121013B (en) | 1986-03-26 |
| ATA498379A (en) | 1981-07-15 |
| GB2025969B (en) | 1982-09-02 |
| IT7968506A0 (en) | 1979-07-19 |
| CH643246A5 (en) | 1984-05-30 |
| DE2928857A1 (en) | 1980-02-07 |
| YU40716B (en) | 1986-04-30 |
| YU172578A (en) | 1982-10-31 |
| DE2928857C3 (en) | 1988-02-11 |
| SU886744A3 (en) | 1981-11-30 |
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