DE3644246A1 - Process for the preparation of 3-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-(aminosulp honyl)propaneimideamide - Google Patents
Process for the preparation of 3-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-(aminosulp honyl)propaneimideamideInfo
- Publication number
- DE3644246A1 DE3644246A1 DE19863644246 DE3644246A DE3644246A1 DE 3644246 A1 DE3644246 A1 DE 3644246A1 DE 19863644246 DE19863644246 DE 19863644246 DE 3644246 A DE3644246 A DE 3644246A DE 3644246 A1 DE3644246 A1 DE 3644246A1
- Authority
- DE
- Germany
- Prior art keywords
- formula
- methyl
- amino
- aminoiminomethyl
- thiazolyl
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Die Erfindung betrifft ein neues Verfahren zur Herstellung von 3-[[[2-[(Aminoiminomethyl)-amino]-4-thiazolyl]- methyl]-thio]-N-(aminosulfonyl)-propanimidamid der Formel (1) und sämtlichen seiner möglichen tautomeren Formen und dessen pharmazeutisch verträglichen SalzenThe invention relates to a new method of manufacture of 3 - [[[2 - [(aminoiminomethyl) amino] -4-thiazolyl] - methyl] thio] -N- (aminosulfonyl) propanimidamide of the formula (1) and all of its possible tautomeric forms and its pharmaceutically acceptable salts
Diese Substanz besitzt eine bemerkenswerte Aktivität als H₂-Rezeptor-Antagonist und ist therapeutisch als Säuresekretionsinhibitor wertvoll. Sie wird oral zur Behandlung von peptischem Ulcus und anderen magensäurebedingten Erkrankungen verabreicht. Sowohl ihre hohe Aktivität als auch niedrige Toxizität macht diese Verbindung zu einer der wertvollsten Wirkstoffe in diesem therapeutischen Gebiet.This substance has remarkable activity as an H₂ receptor antagonist and is therapeutic as Acid secretion inhibitor valuable. Orally it becomes Treatment of peptic ulcer and other gastric acid-related Diseases administered. Either their high activity as well as low toxicity makes them this connection to one of the most valuable active ingredients in this therapeutic area.
Die JP-PS Kokai 56 55 383 beschreibt die Herstellung der Verbindung der Formel (1) in 64%iger Ausbeute durch Umsetzung von Methyl-3-[[[2-[(aminoiminomethyl)-amino]-4- thiazolyl]-methyl]-thio]-propanimidat der Formel (2) mit 2 Äquivalenten Sulfamid der Formel (3) in Methanol bei Raumtemperatur gemäß folgender GleichungJP-PS Kokai 56 55 383 describes the production of the Compound of formula (1) in 64% yield by reaction of methyl-3 - [[[2 - [(aminoiminomethyl) amino] -4- thiazolyl] methyl] thio] propanimidate of the formula (2) with 2 equivalents of sulfamide of formula (3) in methanol at room temperature according to the following equation
Die vorliegende Erfindung betrifft ein verbessertes Verfahren zur Herstellung der Verbindung der Formel (1), bei dem die Nucleophilie des Sulfamids erhöht worden ist. Dies wurde durch Bindung einer Trialkylsilylgruppe an eines der sulfamidischen Stickstoffatome erreicht. So wird unter Verwendung von N-Trimethylsilylsulfamid der Formel (4) (hergestellt, wie in dem spanischen Patent ES 5 56 322 beschrieben) und einer katalytischen Menge einer Base, wie Natriummethylat, in Methanol die Verbindung der Formel (1) gemäß folgender Gleichung erhaltenThe present invention relates to an improved method for the preparation of the compound of formula (1), in which the nucleophilicity of the sulfamide has been increased is. This was done by attaching a trialkylsilyl group reached on one of the sulfamide nitrogen atoms. So is using N-trimethylsilylsulfamide of formula (4) (prepared as in the Spanish patent ES 5 56 322) and a catalytic amount a base such as sodium methylate in methanol of formula (1) obtained according to the following equation
Alternativ kann die Verbindung der Formel (1) durch Umsetzung des Imidats der Formel (2) mit 2 Äquivalenten Sulfamid der Formel (3) in Anwesenheit von Trimethylmethoxysilan und einer katalytischen Menge einer Base, wie Natriummethylat, in Methanol gemäß folgender Gleichung erhalten werden Alternatively, the compound of formula (1) can be reacted of the imidate of formula (2) with 2 equivalents Sulfamide of formula (3) in the presence of trimethylmethoxysilane and a catalytic amount of a base, like sodium methylate, in methanol according to the following equation be preserved
Beide Reaktionstypen wurden mit verschiedenen Anteilen der Base und des Sulfamid-Derivats durchgeführt. Beste Ausbeuten werden erzielt, wenn entweder 0,05 Äquiv. Natriummethylat und 2 Äquiv. N-Trimethylsilylsulfamid der Formel (4) oder 0,05 Äquiv. Natriummethylat und 2 Äquiv. sowohl des Sulfamids der Formel (3) als auch des Trimethylmethoxysilans der Formel (5) verwendet werden. Die so erhaltenen Ausbeuten (71 bis 74%) sind beträchtlich höher als die in dem vorstehend erwähnten japanischen Patent berichteten. Daher stellt das vorliegend beschriebene Verfahren eine Verbesserung dar.Both types of reactions were with different proportions the base and the sulfamide derivative. best Yields are achieved when either 0.05 equiv. Sodium methylate and 2 equiv. N-Trimethylsilylsulfamide the Formula (4) or 0.05 equiv. Sodium methylate and 2 equiv. both the sulfamide of formula (3) and trimethylmethoxysilane of formula (5) can be used. The Yields thus obtained (71 to 74%) are considerable higher than that in the aforementioned Japanese Patent reported. Therefore, this describes Procedure is an improvement.
Die folgenden Beispiele erläutern die Erfindung. Sie zeigen bevorzugte Bedingungen und sollen keine Einschränkung bedeuten.The following examples illustrate the invention. they show preferred conditions and are not intended to be limiting mean.
In einem ofengetrockneten 25-ml-Kolben, der mit einem
magnetischen Drehstab und einem Calciumchloridrohr ausgestattet
ist, suspendiert man 1,008 g (6 mMol) N-Trimethylsilylsulfamid
in 3 ml wasserfreiem Methanol. Man
gibt 819 mg (3 mMol) Methyl-3-[[[2-[(aminoiminomethyl)-
amino]-4-thiazolyl]-methyl]-thio]-propanimidat (2) auf
einmal zu und rührt die Mischung 2 Tage bei Raumtemperatur.
Hiernach wird der weiße Niederschlag abfiltriert,
der Feststoff mit 10 ml einer 1 : 2 Methanol-Ethanol-Mischung
gewaschen und 5 h bei 25°C und 0,1 mmHg getrocknet,
um 547 mg weißes Pulver in einer Ausbeute von
54% in reiner Form aufgrund der dünnschichtchromatischen
(TLC) Analyse zu ergeben:
Fp. 156 bis 160°C;
Rf 0,2 (CHCl₃/CH₃OH/25% NH₄OH 15/0,4/0,1).
Durch Umkristallisation
aus DMF/Wasser wird eine analytische
Probe erhalten, um das Produkt in Form feiner, weißer
Nadeln zu ergeben:
Fp: 161 bis 165°C.
IR (KBr): 3502, 3397, 3372, 3101, 1635, 1599, 1575,
1531, 1489, 1330, 1319, 1286, 1147, 543 cm-1;
¹H-NMR (60 MHz, DMSO-d₆) δ: (TMS) 8,3 (brs, 1H), 7,3
(brs, 1H), 6,8 (brs), 6,5 (s), 3,6 (s, 2H,
ArCH₂S), 2,9-2,3 (m, 4H, SCH₂CH₂);
Wassergehalt (Karl-Fisher): 0%;In an oven-dried 25 ml flask equipped with a magnetic torsion bar and a calcium chloride tube, 1.008 g (6 mmol) of N-trimethylsilylsulfamide are suspended in 3 ml of anhydrous methanol. 819 mg (3 mmol) of methyl 3 - [[[[- [(aminoiminomethyl) - amino] -4-thiazolyl] methyl] thio] propanimidate (2) are added all at once and the mixture is stirred for 2 days Room temperature. The white precipitate is then filtered off, the solid is washed with 10 ml of a 1: 2 methanol-ethanol mixture and dried for 5 hours at 25 ° C. and 0.1 mmHg to give 547 mg of white powder in a yield of 54% in pure form based on the thin-layer chromatic (TLC) analysis:
Mp 156-160 ° C;
Rf 0.2 (CHCl₃ / CH₃OH / 25% NH₄OH 15 / 0.4 / 0.1).
An analytical sample is obtained by recrystallization from DMF / water to give the product in the form of fine, white needles:
Mp: 161 to 165 ° C.
IR (KBr): 3502, 3397, 3372, 3101, 1635, 1599, 1575, 1531, 1489, 1330, 1319, 1286, 1147, 543 cm -1 ;
1 H-NMR (60 MHz, DMSO-d₆) δ : (TMS) 8.3 (brs, 1H), 7.3 (brs, 1H), 6.8 (brs), 6.5 (s), 3, 6 (s, 2H, ArC H ₂S), 2.9-2.3 (m, 4H, SC H ₂CH₂);
Water content (Karl-Fisher): 0%;
Analyse für C₈H₁₅N₇O₂S₃Analysis for C₈H₁₅N₇O₂S₃
berechnet:C 28,48; H 4,48; N 29,06; S 28,51%; gefunden:C 28,54; H 4,80; N 28,86; S 28,56%.calculated: C 28.48; H 4.48; N 29.06; S 28.51%; found: C 28.54; H 4.80; N 28.86; S 28.56%.
Man führt die gleiche Umsetzung wie in Beispiel 1 unter Verwendung von 3 Äquiv. (1,513 g, 9 mMol) N-Trimethylsilylsulfamid und 4 ml Methanol durch. Unter Anwendung des gleichen Aufarbeitungsverfahrens erhält man 568 mg (56%) Produkt.The same reaction as in Example 1 is carried out Using 3 equiv. (1.513 g, 9 mmol) N-trimethylsilyl sulfamide and 4 ml of methanol. Under application the same work-up procedure gives 568 mg (56%) product.
Einem ofengetrockneten 10-ml-Kolben, der mit einem magnetischen Drehstab und einem Calciumchloridrohr versehen ist und 554 mg (3,3 mMol, 1,1 Äquiv.) N-Trimethylsilylsulfamid in 3 ml wasserfreiem Methanol enthält, führt man 16 mg (0,3 mMol, 0,1 Äquiv.) Natriummethylat und anschließend 819 mg (3 mMol, 1 Äquiv.) Methyl-3-[[[2- [(aminoiminomethyl)-amino]-4-thiazolyl]-methyl]-thio]- propanimidat bei Raumtemperatur zu. Nach 4 h wird die Mischung eine gelbliche Lösung und nach 8 h erscheint ein weißer Niederschlag. Die Mischung wird 2 Tage bei Raumtemperatur gerührt. Die Aufarbeitung wie in Beispiel 1 ergibt 526 mg weißes Pulver (52%), das aufgrund der TLC-Analyse rein ist.An oven-dried 10 ml flask fitted with a magnetic Torsion bar and a calcium chloride tube and 554 mg (3.3 mmol, 1.1 equiv) N-trimethylsilylsulfamide contains in 3 ml of anhydrous methanol, 16 mg (0.3 mmol, 0.1 equiv.) of sodium methylate are passed and then 819 mg (3 mmol, 1 equiv.) methyl-3 - [[[2- [(aminoiminomethyl) amino] -4-thiazolyl] methyl] thio] - propanimidate at room temperature. After 4 hours the Mix a yellowish solution and appear after 8 h a white precipitate. The mixture is at 2 days Room temperature stirred. Working up as in Example 1 gives 526 mg of white powder (52%) due to the TLC analysis is pure.
Die gleiche Umsetzung, wie die in Beispiel 3 beschriebene, wird unter Verwendung von 2,5 Äquiv. (1,260 g, 7,5 mMol) N-Trimethylsilylsulfamid und 0,05 Äquiv. (8 mg, 0,15 mMol) Natriummethylat in 4 ml Methanol durchgeführt. Die vorliegend beschriebene Produktisolierung ergibt 659 mg (65%) aufgrund der TLC-Analyse reines Material.The same implementation as that described in Example 3 is calculated using 2.5 equiv. (1.260 g, 7.5 mmol) N-trimethylsilyl sulfamide and 0.05 equiv. (8 mg, 0.15 mmol) sodium methylate in 4 ml methanol carried out. The product insulation described here gives 659 mg (65%) based on TLC analysis pure material.
Man beschickt einen ofengetrockneten 25-ml-Kolben, der mit einem magnetischen Drehstab und einem Calciumchloridrohr versehen ist, mit 554 mg (3,3 mMol, 1,1 Äquiv.) N-Trimethylsilylsulfamid und 3 ml wasserfreiem Methanol. Man gibt in drei Anteilen dreimal 273 mg (3×1 mMol, 3×0,33 Äquiv.) Methyl-3-[[[2-[(aminoiminomethyl)- amino]-4-thiazolyl]-methyl]-thio]-propanimidat zu den Zeitpunkten 0, 8 bzw. 24 h zu. Die entstandene Mischung wird 24 h bei Raumtemperatur gerührt. Die Aufarbeitung gemäß Beispiel 1 ergibt 363 mg (36%) Produkt in Form eines weißen Pulvers, das aufgrund der TLC-Analyse rein ist. A 25 ml oven-dried flask is charged with a magnetic torsion bar and a calcium chloride tube is provided with 554 mg (3.3 mmol, 1.1 equiv.) N-trimethylsilyl sulfamide and 3 ml of anhydrous methanol. In three portions, 273 mg (3 × 1 mmol, 3 × 0.33 equiv.) Methyl-3 - [[[2 - [(aminoiminomethyl) - amino] -4-thiazolyl] methyl] thio] propanimidate to the Times 0, 8 and 24 h too. The resulting mixture is stirred for 24 h at room temperature. The workup according to Example 1 gives 363 mg (36%) of product in the form of a white powder, which is pure based on TLC analysis is.
Man führt die gleiche Umsetzung wie in Beispiel 5 unter Verwendung von 1,008 g (6 mMol, 2 Äquiv.) N-Trimethylsilylsulfamid durch. Die Aufarbeitung ergibt 516 mg (51%) Produkt.The same reaction as in Example 5 is carried out Use of 1.008 g (6 mmol, 2 equiv) of N-trimethylsilylsulfamide by. Working up gives 516 mg (51%) product.
Zu einer gut gerührten Suspension von 1,008 g (6 mMol, 2 Äquiv.) N-Trimethylsilylsulfamid und 8 mg (0,15 mMol, 0,05 Äquiv.) Natriummethylat in 3 ml wasserfreiem Methanol gibt man in drei Anteilen 3×273 mg (3×1 mMol, 3×0,33 Äquiv.) Methyl-3-[[[2-[(aminoiminomethyl)- amino]-4-thiazolyl]-methyl]-thio]-propanimidat zu den Zeitpunkten 0, 8 bzw. 24 h. Die Mischung wird 24 h bei Raumtemperatur gerührt. Die übliche Aufarbeitung ergibt 740 mg (73%) Produkt in Form eines weißen, aufgrund der TLC-Analyse reinen Pulvers.To a well-stirred suspension of 1.008 g (6 mmol, 2 equiv.) N-trimethylsilylsulfamide and 8 mg (0.15 mmol, 0.05 equiv.) Sodium methylate in 3 ml of anhydrous methanol 3 × 273 mg (3 × 1 mmol, 3 × 0.33 equiv.) Methyl-3 - [[[2 - [(aminoiminomethyl) - amino] -4-thiazolyl] methyl] thio] propanimidate to the Times 0, 8 and 24 h. The mixture is at 24 h Room temperature stirred. The usual workup results 740 mg (73%) product in the form of a white, due to the TLC analysis of pure powder.
Man beschickt einen ofengetrockneten 100-ml-Kolben, der mit einem magnetischen Drehstab und einem Calciumchloridrohr versehen ist, mit 3,845 g (40 mMol, 2 Äquiv.) Sulfamid, 55 mg (1 mMol, 0,05 Äquiv.) Natriummethylat, 5,5 ml (40 mMol, 2 Äquiv.) Trimethylmethoxysilan und 25 ml wasserfreiem Methanol. Zu der Mischung gibt man in drei Anteilen 3×1,82 g (3×6,66 mMol, 3×0,33 Äqu.) Methyl-3-[[[2-[(aminoiminomethyl)-amino]-4-thiazolyl]- methyl]-thio]-propanimidat zu den Zeitpunkten 0, 8 bzw. 24 h. Die Mischung wird hiernach 48 h gerührt und das Produkt gemäß Beispiel 1 isoliert, um 4,80 g (71%) weißes, aufgrund der TLC-Analyse reines Pulver zu ergeben.A 100 ml oven-dried flask is charged with a magnetic torsion bar and a calcium chloride tube is provided with 3.845 g (40 mmol, 2 equiv.) Sulfamide, 55 mg (1 mmol, 0.05 equiv.) Sodium methylate, 5.5 ml (40 mmol, 2 equiv.) Trimethylmethoxysilane and 25 ml of anhydrous methanol. Add to the mixture three portions of 3 x 1.82 g (3 x 6.66 mmol, 3 x 0.33 eq.) Methyl-3 - [[[2 - [(aminoiminomethyl) amino] -4-thiazolyl] - methyl] -thio] -propanimidate at times 0, 8 or 24 hours. The mixture is then stirred for 48 hours and that Product isolated according to example 1, by 4.80 g (71%) white powder, based on TLC analysis.
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES556323A ES8800187A1 (en) | 1986-06-20 | 1986-06-20 | Prepn. of N-aminosulphonyl-propanimide amide derivs. |
| ES8602842A ES2003439A6 (en) | 1986-10-31 | 1986-10-31 | Prepn. of N-aminosulphonyl-propanimide amide derivs. - inhibitors for stomach acid secretion for treatment of peptic ulcers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3644246A1 true DE3644246A1 (en) | 1987-12-23 |
Family
ID=26154308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19863644246 Withdrawn DE3644246A1 (en) | 1986-06-20 | 1986-12-23 | Process for the preparation of 3-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-(aminosulp honyl)propaneimideamide |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE3644246A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3831162A1 (en) * | 1988-06-10 | 1989-12-14 | Hanil Pharmaceutical Ind Co | METHOD FOR PRODUCING 3 - (((2- (DIAMINOMETHYLENE) AMINO) -4-THIAZOLYL) METHYL) THIO-N-SULFAMOYL PROPIONAMIDINE |
| EP0356366A1 (en) * | 1988-07-18 | 1990-02-28 | Centro Marga Para La Investigacion S.A. | A process for the preparation of N-sulfamyl-propionamidine derivatives |
| US5021582A (en) * | 1987-06-22 | 1991-06-04 | Centro Marga Para La Investigacion S.A. | Famotidine polymorphic forms and their preparation process |
| US5128477A (en) * | 1986-08-05 | 1992-07-07 | Richter Gedeon Vegyeszeti Gyar Rt. | Process for the preparation of morphologically homogeneous forms of thiazole derivatives |
| WO2022034121A1 (en) | 2020-08-11 | 2022-02-17 | Université De Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2951675A1 (en) * | 1979-08-02 | 1981-02-05 | Yamanouchi Pharma Co Ltd | NEW GUANIDINOTHIAZOL COMPOUNDS, METHOD FOR THE PRODUCTION THEREOF AND PREPARATION OF MEDICINAL PRODUCTS |
| JPS5655383A (en) * | 1979-10-12 | 1981-05-15 | Yamanouchi Pharmaceut Co Ltd | Amizine derivative and its preparation |
| EP0128736A1 (en) * | 1983-06-07 | 1984-12-19 | Yamanouchi Pharmaceutical Co., Ltd. | Novel 2-guanidinothiazoline compounds, their preparation, and their use as intermediates |
-
1986
- 1986-12-23 DE DE19863644246 patent/DE3644246A1/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2951675A1 (en) * | 1979-08-02 | 1981-02-05 | Yamanouchi Pharma Co Ltd | NEW GUANIDINOTHIAZOL COMPOUNDS, METHOD FOR THE PRODUCTION THEREOF AND PREPARATION OF MEDICINAL PRODUCTS |
| US4283408A (en) * | 1979-08-02 | 1981-08-11 | Yamanouchi Pharmaceutical Co., Ltd. | Guanidinothiazole compounds, process for preparation and gastric inhibiting compositions containing them |
| JPS5655383A (en) * | 1979-10-12 | 1981-05-15 | Yamanouchi Pharmaceut Co Ltd | Amizine derivative and its preparation |
| EP0128736A1 (en) * | 1983-06-07 | 1984-12-19 | Yamanouchi Pharmaceutical Co., Ltd. | Novel 2-guanidinothiazoline compounds, their preparation, and their use as intermediates |
Non-Patent Citations (2)
| Title |
|---|
| US-Z: Chemical Abstracts, 100, 1984, 120 108w * |
| US-Z: Chemical Abstracts, 104, 1986, 109 486e * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5128477A (en) * | 1986-08-05 | 1992-07-07 | Richter Gedeon Vegyeszeti Gyar Rt. | Process for the preparation of morphologically homogeneous forms of thiazole derivatives |
| US5021582A (en) * | 1987-06-22 | 1991-06-04 | Centro Marga Para La Investigacion S.A. | Famotidine polymorphic forms and their preparation process |
| DE3831162A1 (en) * | 1988-06-10 | 1989-12-14 | Hanil Pharmaceutical Ind Co | METHOD FOR PRODUCING 3 - (((2- (DIAMINOMETHYLENE) AMINO) -4-THIAZOLYL) METHYL) THIO-N-SULFAMOYL PROPIONAMIDINE |
| GB2220415A (en) * | 1988-06-10 | 1990-01-10 | Hanil Pharma Ind | Process for producing a sulphamide |
| GB2220415B (en) * | 1988-06-10 | 1991-12-18 | Hanil Pharma Ind | Process for producing a sulphamide |
| EP0356366A1 (en) * | 1988-07-18 | 1990-02-28 | Centro Marga Para La Investigacion S.A. | A process for the preparation of N-sulfamyl-propionamidine derivatives |
| WO2022034121A1 (en) | 2020-08-11 | 2022-02-17 | Université De Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
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