DE2130234A1 - (pyrazin-2-yl-carboxamido)-ethyl benzene - sulphonyl urea - Google Patents
(pyrazin-2-yl-carboxamido)-ethyl benzene - sulphonyl ureaInfo
- Publication number
- DE2130234A1 DE2130234A1 DE19712130234 DE2130234A DE2130234A1 DE 2130234 A1 DE2130234 A1 DE 2130234A1 DE 19712130234 DE19712130234 DE 19712130234 DE 2130234 A DE2130234 A DE 2130234A DE 2130234 A1 DE2130234 A1 DE 2130234A1
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- Germany
- Prior art keywords
- general formula
- compound
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- alkyl
- alkoxy
- 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.)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Neues Pyrazinylhainstoffderivat und Verfahren zu seiner Herstellung Zusatz zum Patent...(Patentanmeldung P 20 49 806.0-44) Die vorliegende Erfindung betrifft einen neuen Acylaminoäthylbenzolsulphonylharnstoff mit antidiabetischer Wirksamkeit, Verfahren zu seiner Herstellung und dieses Harnstoffderivat enthaltende pharmazeutische Produkte Das Patent... (Patentanmeldung P 20 49 806.0-44) betrifft neue Acylaminoäthylbenzolsulphonylharnstoffe der allgemeinen Formel ZSO2NHCONHR1 worin Z eine Gruppe der allgemeinen Formel ist, model in der Gruppe Z jecle der gruppen X, die gielon oder verschieden sein kennen, ein Wasserstoff- oder ein Halogenatom oder eine gesättigte oder ungesättigte Alkyl- oder Alkoxy-Gruppe oder eine Hydroxy- oder eine Amino-Gruppe oder eine Phenyl-Gruppe ist, die Alkyl-, Halogen- oder Alkoxy-substituiert sein kann, und R1 eine Gruppe der Formel -NR2R3 ist, worin R2 eine Alkyl-Gruppe und R3 eine Alkyl- oder eine Benzyl-Gruppe ist, oder R1 eine Alkyl- oder Alkoxy-substituierte oder unsubstituierte, gesättigte oder ungesättigte Cycloalkyl- oder bicyclische Cycloalkyl-Gruppe ist, wobei die Cycloalkyl-Gruppe bzw. die bicyclische Cycloalkyl-Gruppe ein Stickstofatom im Ring enthält, die pharmakologisch annehmbaren Salze dieser Verbindungen der Formel (I), diese Produkte als Wirkstoff entw haltende pharmazeutische Präparate und Verfahren zu ihrer Herstellung. Dort erläuterte Beispiele für Stickstoff-haltige Cycloalkyl-Gruppen sind sowie als bicyclische Cycloalkyl-Gruppe solche der Formel Es wurde nun gefunden, daß eine weitere von der allgemetnen Formel I umfaßte, aber nicht beschriebene -Verbindung besondere wertvolle Eigenschaften besitzt. Es ist dies der N-(4-Nethylpiperidino)-N'-{4-#ß-(5-methylpyrazin-2'-yl-carboxamido)-äthyl# benzolsulphonyl} -harnstoff der Formel Das erfindungsgemäße Verfahren zur Herstellung der Verbindung der Formel I ist d a d u r c h g e k e n n z e i c h n e t , daß man (a) eine Verbindung der allgemeinen Formel ZSO2X mit einer Verbindung der allgemeinen Formel H2NCONHR1 oder (b) eine Verbindung der allgemeinen Formel ZSO2RH2 mit einer der Verbirdungen der allgemeinen Formeln ONCR1 H@NCONHR1 oder R4 OOCNHR1 od er (c) eine Verbindung der allgemeinen Formel ZSO2NCO mit einer Verbindung der allgemeinen Formel H2NR1 oder (d) eine Verbindung der allgemeinen Formel ZSO2NHCOOR4 mit einer Verbindung der allgemeinen Formel H2NR1 oder (e) eine Verbindung der allgemeinen Formel ZSO2NHCONH2 mit einer der Verbindungen der allgemeinen Formel H2NR1 oder XR1 umsetzt, wobei in den vorstehenden Formeln Z der Rest und R1 der Rest ist, X ein Halogenatom ist und R4 eine Alkyl-Gruppe ist, und die erhaltenen Umsetzungsprodukte, falls erwünscht, in pharmakologisch annehmbare Salze derselben umwandelt.New pyrazinyl urea derivative and process for its production Addition to patent ... (Patent application P 20 49 806.0-44) The present invention relates to a new acylaminoethylbenzenesulphonylurea with antidiabetic activity, process for its preparation and pharmaceutical products containing this urea derivative The patent ... (Patent application P 20 49 806.0-44) relates to new acylaminoethylbenzenesulphonylureas of the general formula ZSO2NHCONHR1 wherein Z is a group of the general formula is, model in the group Z each of the groups X, which can be gielon or different, a hydrogen or a halogen atom or a saturated or unsaturated alkyl or alkoxy group or a hydroxyl or an amino group or a phenyl group which can be alkyl, halogen or alkoxy substituted, and R1 is a group of the formula -NR2R3, where R2 is an alkyl group and R3 is an alkyl or a benzyl group, or R1 is an alkyl or alkoxy -substituted or unsubstituted, saturated or unsaturated cycloalkyl or bicyclic cycloalkyl group, the cycloalkyl group or the bicyclic cycloalkyl group containing a nitrogen atom in the ring, the pharmacologically acceptable salts of these compounds of the formula (I), these products as Pharmaceutical preparations containing active ingredients and processes for their manufacture. Examples of nitrogen-containing cycloalkyl groups explained there are and, as a bicyclic cycloalkyl group, those of the formula It has now been found that another compound, which is comprised by the general formula I but is not described, has particularly valuable properties. It is the N- (4-Nethylpiperidino) -N '- {4- # ß- (5-methylpyrazin-2'-yl-carboxamido) -ethyl-benzenesulphonyl} -urea of the formula The process according to the invention for the preparation of the compound of the formula I is characterized in that (a) a compound of the general formula ZSO2X with a compound of the general formula H2NCONHR1 or (b) a compound of the general formula ZSO2RH2 with one of the compounds of the general formulas ONCR1 H @ NCONHR1 or R4 OOCNHR1 or (c) a compound of the general formula ZSO2NCO with a compound of the general formula H2NR1 or (d) a compound of the general formula ZSO2NHCOOR4 with a compound of the general formula H2NR1 or (e) a compound of the general formula ZSO2NHCONH2 with one of the compounds of the general formula H2NR1 or XR1, where in the above formulas Z is the remainder and R1 the rest X is a halogen atom and R4 is an alkyl group, and if desired converting the reaction products obtained into pharmacologically acceptable salts thereof.
Die Ausgangsprodukte für das erfindungsgemäße Verfahren können durch Acylierung eines geeigneten substituierten Äthylamins mit einer geeigneten Pyrazin-2-carbonsäure hergestellt werden.The starting materials for the process according to the invention can by Acylation of a suitable substituted ethylamine with a suitable pyrazine-2-carboxylic acid getting produced.
Die Verbindung der Formel (I) hat eine sehr gute antidiabetische Wirksamkeit und kann daher entweder allein oder in Verbindung mit hypoglykaemisch wirkenden Biguaniden bei der Behandlung von Diabetes mellitus eingesetzt werden. Sie ist schon in Dosen von nur wenigen Milligramm wirksam.The compound of the formula (I) has a very good antidiabetic activity and can therefore act either alone or in conjunction with hypoglycemic Biguanides are used in the treatment of diabetes mellitus. She is beautiful effective in doses as low as a few milligrams.
Nicht durch Inzucht gezüchtete Ratten der Rasse CFE SPF mit cinem Gewicht zwischen 130 und 160 g und wahllos aus einer größeren Anzahl von Ratten ausgewählt erhielten 10 Stunden vor Beginn des Tests keine Nahrung. Für jede untersuchte Dosie wurde eine Gruppe von 6--Tieren eingesetzt. Die zu untersuchende Verbindung wurde mittels Sonden verabreicht, und zwar in Methocel (Methylcellulose? in einer Konzentration von 0,5 % suspendiert. Die untersuchten Dosen betrugen 7,5, 1,5 und 0,3 mg/kg.CFE SPF breed non-inbred rats with cinem Weight between 130 and 160 g and randomly from a larger number of rats selected were not fed 10 hours before the start of the test. For each examined A group of 6 animals was used. The compound under investigation was administered via tubes in Methocel (methylcellulose? in a Suspended concentration of 0.5%. The doses tested were 7.5, 1.5 and 0.3 mg / kg.
Zur Glukosebestimmung wurden Blutproben 30 bzw. 180 Minuten nach Verabreichung der Verbindung entnomme. Die Blutproben wurden durch Decapitation gewonnen. Der Blutzuckergehalt wurde nach der colorimetrischen Methode mit o-Toluidin nach R.N.Blood samples were taken 30 and 180 minutes after administration to determine glucose from the connection. The blood samples were obtained by decapitation. Of the Blood sugar content was determined by the colorimetric method with o-toluidine according to R.N.
Dubowsky, Clin. Chem. 8 (1967), 215 bestimmt.Dubowsky, Clin. Chem. 8, 215 (1967).
Die prozentuale Verminderung des Blutzuckerspiegels nach Verabreichung der untersuchten Verbindung wurde gegen vor Verabreichung der Test substanz erhaltene und bestimmte Blutzuckerspiegel mit den in der folgenden Tabelle wiedergegebenen Resultaten berechnet: Tabelle Dosis (ing/kg) Minuten nach Verabreichung 30 180 7,5 1,5 52 % 46 % 0,3 37 % 22 % Die vorliegende Erfindung betrifft weiterhin pharmazeutische Zubereitungen, die die Verbindung der Formel I und einen pharmazeutisch annehmbaren Träger und/oder Verdünnungsmittel enthalten.The percentage decrease in blood sugar level after administration the tested compound was obtained against before the administration of the test substance and certain blood sugar levels with those given in the following table Results calculated: Table dose (ing / kg) minutes after administration 30 180 7.5 1.5 52% 46% 0.3 37% 22% The present invention further relates to pharmaceuticals Preparations containing the compound of formula I and a pharmaceutically acceptable Contain carrier and / or diluent.
Die vorliegende Erfindung wird durch das folgende Beispiel erläutert: Beispiel 3,8 g N-{4-#ß-(5'-Methylpyrazin-2'-yl-carboxamido)-äthyl# benzolsulphonyl3-methylurethan (F.p. 192° C) wurden in 70 ml Methanol gelöst und mit 1,3 g 1-Amino-4-methyl-piperidin umgesetzt. Das Methanol wurde durch Destillation unter vermindertem Druck abgetrennt und der Rückstand 30 Minuten auf 1200 C erhitzt. Nach Umkristallisation aus Methanol wurden 2,2 g N-(4-Methyl-piperidino)-N'-[4-{ß-(5'-methylpyrazin-2'-ylcarboxamido)-äthyl}-benzolsulphonylharnstoff mit dem Schmelzpunkt 180 - 183 C erhalten.The present invention is illustrated by the following example: Example 3.8 g of N- {4- # β- (5'-methylpyrazin-2'-yl-carboxamido) -ethyl-benzenesulphonyl-3-methyl urethane (M.p. 192 ° C) were dissolved in 70 ml of methanol and 1.3 g of 1-amino-4-methyl-piperidine implemented. The methanol was separated by distillation under reduced pressure and the residue at 1200 ° C. for 30 minutes heated. After recrystallization 2.2 g of N- (4-methylpiperidino) -N '- [4- {ß- (5'-methylpyrazin-2'-ylcarboxamido) -ethyl} -benzenesulphonylurea were obtained from methanol with a melting point of 180-183 C.
P a t e n t a n s p r ü c h e:P a t e n t a n s p r ü c h e:
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19712130234 DE2130234C3 (en) | 1971-06-18 | 1971-06-18 | An N- [4- (B-pyrazine-2-carboxamido-ethyobenzenesulfonyl] -urea and pharmaceutical preparations containing the same |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19712130234 DE2130234C3 (en) | 1971-06-18 | 1971-06-18 | An N- [4- (B-pyrazine-2-carboxamido-ethyobenzenesulfonyl] -urea and pharmaceutical preparations containing the same |
Publications (3)
Publication Number | Publication Date |
---|---|
DE2130234A1 true DE2130234A1 (en) | 1973-01-04 |
DE2130234B2 DE2130234B2 (en) | 1978-06-15 |
DE2130234C3 DE2130234C3 (en) | 1979-02-22 |
Family
ID=5811119
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19712130234 Expired DE2130234C3 (en) | 1971-06-18 | 1971-06-18 | An N- [4- (B-pyrazine-2-carboxamido-ethyobenzenesulfonyl] -urea and pharmaceutical preparations containing the same |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE2130234C3 (en) |
-
1971
- 1971-06-18 DE DE19712130234 patent/DE2130234C3/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
DE2130234C3 (en) | 1979-02-22 |
DE2130234B2 (en) | 1978-06-15 |
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Legal Events
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C3 | Grant after two publication steps (3rd publication) | ||
8328 | Change in the person/name/address of the agent |
Free format text: REDIES, B., DIPL.-CHEM. DR.RER.NAT., PAT.-ANW., 4000 DUESSELDORF |