DE1595910A1 - 3,6-Disubstituted pyridazines and processes for their preparation - Google Patents
3,6-Disubstituted pyridazines and processes for their preparationInfo
- Publication number
- DE1595910A1 DE1595910A1 DE19661595910 DE1595910A DE1595910A1 DE 1595910 A1 DE1595910 A1 DE 1595910A1 DE 19661595910 DE19661595910 DE 19661595910 DE 1595910 A DE1595910 A DE 1595910A DE 1595910 A1 DE1595910 A1 DE 1595910A1
- Authority
- DE
- Germany
- Prior art keywords
- pyridazine
- amino
- hydrazino
- dihydrochloride
- general formula
- 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.)
- Pending
Links
Classifications
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/22—Nitrogen and oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- 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)
- Plural Heterocyclic Compounds (AREA)
Description
DR. JUR. DIPL-CHEM. WALTER BEIL _. ,,,„. Ä.Ä DR. JUR. DIPL-CHEM. WALTER BEIL _. ,,, ". Ä . Ä
ALFRED HOEPPENER 1 J. Juli 19IS ALFRED HOEPPENER 1 J. July 19IS
DR. JUR. DIPL.-CHEM. H.-J. WOLFFDR. JUR. DIPL.-CHEM. H.-J. WOLFF
DR. IUR. HANS CHR. BEILDR. IUR. HANS CHR. AX
«23 FRANKFURT AM MAIN-HOCHST AOELONSTIASSI SI«23 FRANKFURT AM MAIN-HOCHST AOELONSTIASSI SI
. Unser· Nr. 13 177. Our No. 13 177
Lepetit S.p.A. Mailand / ItalienLepetit S.p.A. Milan / Italy
3.6-Diaubstitulerte Pyridazine und Verfahren zu3.6-Diaubstituted Pyridazines and Procedures too ihrer Herstellungtheir manufacture
Gegenstand der Erfindung Bind 3,6-dieubetituierte Pyridazine der allgemeinen formelThe invention relates to bind 3,6-di-substituted pyridazines the general formula
in der R1 Wasserstoff, eine niedere Alkyl- oder niedere Hydroxyalkylgruppe und R" eine niedere Alkyl-, niedere Hydroxyalkyl- oder eine Phenylgruppe bedeutet, wobei R1 und R" zusammen auch einen gegebenenfalls durch niedere Alkylgruppen substituierten heterocyclischen Ring Kit 1 bis 2 Heteroatomen darstellen können, und deren nicht-toxische Säureanlagerungssalze sowie ein Verfahren zur Herstellung dieser Verbindungen.in which R 1 denotes hydrogen, a lower alkyl or lower hydroxyalkyl group and R "denotes a lower alkyl, lower hydroxyalkyl or a phenyl group, where R 1 and R" together also represent a heterocyclic ring Kit 1 to 2 heteroatoms which is optionally substituted by lower alkyl groups can represent, and their non-toxic acid addition salts and a process for the preparation of these compounds.
909887/1S37 fctau* Unterlagen iAit tu909887 / 1S37 fctau * documents iAit tu
8AD ORIGINAL8AD ORIGINAL
in einem wasserfreien organischen Lösungsmittel mit etwa 2 Moläquivalenten eines Amins der allgemeinen Formel R1R11NH umsetzt, das erhaltene 6-aminosubetituierte 3-Chlorpyridazin der allgemeinen Formelin an anhydrous organic solvent with about 2 molar equivalents of an amine of the general formula R 1 R 11 NH, the resulting 6-amino-substituted 3-chloropyridazine of the general formula
unter Rückfluß mit Hydrazinhydrat erhitzt und gegebenenfalls das erhaltene 6-amino-3-hydrazino-8ubetituierte Pyridazin in Säureanlagerungssalze überführt.heated under reflux with hydrazine hydrate and optionally the 6-amino-3-hydrazino-8-substituted pyridazine obtained converted into acid addition salts.
Sie erfindungsgemäßen Verbindungen stellen wirksame blutdrucksenkende Mittel dar. Die Untersuchung der blutdrucksenkenden Wirkung von ^-Hydrazino-ö-morpholino-pyridazin (A)1 3-Hydrazino-6-piperidino-pyridazin (B) und 3-Hydrasino-6-bis-(2-hydroxyäthyl)-aaino-pyrida*in (C), die intraTenöe an mit 35 mg/kg Pentobarbitalnatrium anäethetisierte Hunde verabreicht wurden, ergaben die in Tabelle I aufgeführten Werte:The compounds according to the invention are effective antihypertensive agents. The investigation of the antihypertensive effect of ^ -hydrazino-ö-morpholino-pyridazine (A) 1 3-hydrazino-6-piperidino-pyridazine (B) and 3-hydrasino-6-bis- ( 2-hydroxyethyl) -aaino-pyrida * in (C), which were administered intraTenoe to dogs anaesthetized with 35 mg / kg pentobarbital sodium, gave the values listed in Table I:
909887/1637909887/1637
SAD ORIGINALSAD ORIGINAL
Aus diesen Werten geht hervor, daß die genannten Verbindungen eine starke graduelle und anhaltende blutdrucksenkende Wirkung haben. Yeränderungen in der Atmung wurden nicht festgestellt. Die gleichen Verbindungen wurden auch an Ratten Mit Hierenüberdruck untersucht, der nach dem Verfahren von Grollman (Proc. Soc. Exptl. Biol. Med., Band 57, Seite 102 (1944) hervorgerufen worden war. Die Verbindungen wurden einmal täglich fünf Tage lang oral in wässriger Lösung verabreicht. Die Verbindung JL wurde in Dosen von 5, 2, 1, 0,5 und 0,25 mg/kg, die Verbindung B in Dosen von 1, 0,25 und 0,1 mg/kg und die Verbindung C in Dosen von 1, 0,5, 0,25 und 0,1 mg/kg untersucht. Die Verbindung A zeigte bei jeder Dosis eine starke anhaltende blutdrucksenkende Wirkung. Die Verbindung B hatte bei einer Dosis von 1 und 0,25 mg/kg eine bemerkenswert anhaltende Wirkung und bei 0,1 »g/kg ein· geringere Wirkung. Die Verbindung C war bei allen Dosen über 0,1 mg/kg wirksam, ferner wurde einFrom these values it can be seen that the compounds mentioned have a strong gradual and sustained antihypertensive effect Have an effect. No changes in breathing were noted. The same compounds were also used in rats Investigated with Hieren overpressure, which according to the method of Grollman (Proc. Soc. Exptl. Biol. Med., Volume 57, p 102 (1944). The compounds were administered orally in aqueous solution once a day for five days administered. Compound JL was administered in doses of 5, 2, 1, 0.5 and 0.25 mg / kg, compound B in doses of 1, 0.25 and 0.1 mg / kg and the compound C in doses of 1, 0.5, 0.25 and 0.1 mg / kg were examined. Compound A showed strong sustained antihypertensive properties at each dose Effect. Compound B had a remarkably sustained effect at a dose of 1 and 0.25 mg / kg and at 0.1 »g / kg a lower effect. The connection C was effective at all doses above 0.1 mg / kg, and also became a
909887/1637909887/1637
Vergleich zwischen der Verbindung A und dem bekannten blutdrucksenkenden Mittel Hydralazin durchgeführt. Beide Verbindungen wurden an Kaninchen untersucht, die mit Pentobarbitalnatrium anästhetisiert worden waren*Comparison between compound A and the well-known antihypertensive agent hydralazine was carried out. Both compounds were tested in rabbits anesthetized with sodium pentobarbital *
Verbin- Anzahl Dosis, Blutdruck Änderung des Blutdrucks, dung der Ka- mg/kg zu Beginn, mm Hg nach Minuten nichen i.v. mm Hg 10 30 60 120Connection number Dose, blood pressure Change in blood pressure, dung of Ka- mg / kg at the beginning, mm Hg after minutes nichen i.v. mm Hg 10 30 60 120
-34 -41 -43 -39-34 -41 -43 -39
-14 -27 -31 -28 -35 -49 -47 -44-14 -27 -31 -28 -35 -49 -47 -44
-9-19-20-9-19-20
-15 -27 -28 -27-15 -27 -28 -27 -11 -17 -18 -10-11 -17 -18 -10
Aus den obigen Werten ist ersichtlich, daß die bemerkenswerte blutdrucksenkende Wirkung auch bei sehr geringen Dosen lang anhält, nämlich länger als 2 Stunden. Die Verbindung A zeigte bei gleicher Dosis stets eine größere Wirkung als Hydralazin.From the above values it can be seen that the remarkable antihypertensive effect persists even at very low doses, namely longer than 2 hours. Compound A always showed a greater effect at the same dose as hydralazine.
Die folgenden Beispiele erläutern das erfindungegemäße Verfahr en ιThe following examples explain the process according to the invention
149 g (1 Mol) 3,6-Dlehlorpyridazin und 174 g (2 MeI) Morpholin werden in 750 ecm wasserfreiem Äthanol gemischt. Das Gemisch wird 2 Stunden unter Rückfluß erhitzt, worauf Tollständige Lösung eintritt. Die Lösung wird gekühlt und der ausgefällte Peststoff «»filtriert. Die fällung wir*149 g (1 mol) 3,6-dlehlorpyridazine and 174 g (2 mol) morpholine are mixed in 750 ecm anhydrous ethanol. The mixture is refluxed for 2 hours, whereupon complete solution occurs. The solution is cooled and the precipitated pest «» filtered. The felling we *
909887/163 7 V ; /.909887/163 7 V ; /.
BAD ORIGINALBATH ORIGINAL
azinazin
azinazin
azinazin
In Wasser aufgenommen und erneut filtriert. Der gewonnene feststoff wird aus Wasser umkrlstalllslert. Man erhält 174 g reines Produkt (Ausbeute 75 *)| I 138-UO0O.Taken up in water and filtered again. The solid matter obtained is crystallized from water. 174 g of pure product are obtained (yield 75%) | I 138-UO 0 O.
40 g des erhaltenen 3-Chlor-6-morpholino-pyridazins werden In 370 ocm 98 jtigem Hydrazinhydrat suspendiert. Das Gemisoh •wird 2 Stunden unter Rückfluß erhitzt, dann gekühlt, die ausgeschiedene fällung gewonnen, mit etwa 50 ocm Hydrazinhydrat gewaschen und aus Toluol umkristallisiert. Die Ausbeute beträgt 28 g (75 t)| f 145-150° C.40 g of the 3-chloro-6-morpholino-pyridazine obtained are suspended in 370 ml of 98% hydrazine hydrate. The Gemisoh • is heated under reflux for 2 hours, then cooled, the precipitate which has separated out is recovered, washed with about 50 ocm hydrazine hydrate and recrystallized from toluene. The yield is 28 g (75 t) | f 145-150 ° C.
Das durch Einleiten von Chlorwasserstoff in eine Diäthylätherlösung der freien Base und Gewinnung der fällung hergestellte Dihydrochlorid schmilzt bei 236° C.The dihydrochloride produced by introducing hydrogen chloride into a diethyl ether solution of the free base and recovering the precipitate melts at 236 ° C.
Beispiel 2 3-Hydrasino-6-bis-(2-hydroxyäthyl)-amino-pyridazin Example 2 3-hydrasino-6-bis- (2-hydroxyethyl) -amino-pyridazine
Sine Lösung von 61 g 3»6-Dichlor-pyridazin und 87 g bis-(2-Ohloräthyl)-aain in 750 oca Cyclohexanol wird 3 Stunden unter Rückfluß erhitst. Das Lösungsmittel wird im Takuum entfernt und der Rückstand in 150 ecm Wasser aufgenommen. Die Lösung wird sweiaal mit Petroläther extrahiert, um die noch vorhandene geringe Menge Cyclohexanol zu entfernen· Dann wird mit Natriumchlorid ausgesalzen und mit Athylacetat extrahiert. Di« erhaltene Lösung wird nach dem Trocknen über Natriumsulfat zur Trockne eingeengt und der Rückstand aus Isopropylalkohol umkristallisiert. Man erhält 60 g 3-Chlor-6-bis-(2-hydroxyäthyl)-pyridazin (Ausbeute 70 5t)i P 96-98° C.Its solution of 61 g of 3 »6-dichloropyridazine and 87 g of bis- (2-chloroethyl) -aain in 750 oca cyclohexanol is 3 hours heated under reflux. The solvent is removed in vacuo and the residue is taken up in 150 ecm of water. The solution is extracted sweiaal with petroleum ether in order to obtain the Remove any small amount of cyclohexanol that is still present. It is then salted out with sodium chloride and extracted with ethyl acetate. The solution obtained is evaporated to dryness after drying over sodium sulfate and the residue is recrystallized from isopropyl alcohol. You get 60 g of 3-chloro-6-bis (2-hydroxyethyl) pyridazine (yield 70 5t) i P 96-98 ° C.
11g dieses Produktes werden mit 300 ecm 98 tigern Hydrazinhydrat gemischt und zwei Stunden unter Rückfluß erhitzt. Das Gemisch wird 12 Stunden bei Raumtemperatur stehen gelassen. Dann wird im Takkum eingeengt. Der Rückstand wird11 g of this product are mixed with 300 ecm 98 tiger hydrazine hydrate and heated under reflux for two hours. The mixture is left to stand at room temperature for 12 hours. Then it is narrowed in the Takkum. The residue will
909887/1637909887/1637
BAD ORIGINALBATH ORIGINAL
In heißem Äthanol aufgenommen. Wenn die Lösung kalt ist, wird die fällung abfiltriert und aus dem FiItrat das Lösungsmittel im Yakuun entfernt. Der Rückstand wird in 60 cc« heißem Isopropylalkohol gelöst und dann über iullererde filtriert. Bei Zugabe einer Lösung von Chlorwasserstoff in Diäthyläther fällt das Produkt aus dem TiItrat aus. Eb wird aus wasserfreiem Äthanol umkristallisiert und besteht aus 3-Hydrazino-6-bis-(2-hydroxyäthyl)-amino-pyrldazin-dihydroohlorid (die freie Base ist nicht beständig, wenn sie nach üblichen Verfahren isoliert wird). Die Ausbeute beträgt 9,8 g (66 *)t Ϊ 187,5-188,5° CTaken up in hot ethanol. When the solution is cold, the precipitate is filtered off and the solvent in the yakuun is removed from the filtrate. The residue is dissolved in hot isopropyl alcohol at 60 cc and then filtered over earth. When a solution of hydrogen chloride in diethyl ether is added, the product precipitates from the TiItrat. Eb is recrystallized from anhydrous ethanol and consists of 3-hydrazino-6-bis- (2-hydroxyethyl) -amino-pyrldazine dihydrochloride (the free base is not stable if it is isolated by conventional methods). The yield is 9.8 g (66 *) t Ϊ 187.5-188.5 ° C
Beispiel 3 3-Hydrazin/ö-6-(N-phenyl-N-aethyl)-amino-pyridazin Example 3 3-hydrazine / δ-6- (N-phenyl-N-ethyl) -amino-pyridazine
3 g 3,6-Dichlor-pyridazin und 4,28 g N-Methy1-anilin werden in 15 ecm siedendem Butanol gelöst und 3 Stunden unter Rückfluß erhitzt. Das Lösungsmittel v/ird im Vakuum entfernt und der Rückstand in Wasser aufgenommen. Biese Lösung wird mehrmals mit Diäthyläther extrahiert. Aus der erhaltenen Lösung erhält man nach der Entfernung des organischen Lösungsmittels im Vakuum das Rohprodukt, das aus Diisopropyläther umkristallisiert wird und aus 3-Chlor-6-(N-phenyl-M-methyl)-amino-pyridazin besteht; Ausbeute 3,9 g (75 5*)l 1 89-91° C3 g of 3,6-dichloropyridazine and 4.28 g of N-methy1-aniline are dissolved in 15 ecm boiling butanol and refluxed for 3 hours. The solvent is removed in vacuo and the residue is taken up in water. This solution is extracted several times with diethyl ether. After removal of the organic solvent in vacuo, the resulting solution gives the crude product, which is recrystallized from diisopropyl ether and consists of 3-chloro-6- (N-phenyl-M-methyl) -amino-pyridazine; Yield 3.9 g (75 5 *) l 1 89-91 ° C
1,5 g dieses Produktes werden in 26 ecm 98 Seigern Hydrazinhydrat gelöst. Das Gemisch wird 10 Stunden unter Rückfluß erhitzt. Dann wird das Lösungsmittel im Vakuum entfernt. Der Rückstand wird in Chloroform aufgenommen und zweimal mit einer gesättigten wässrigen Natriumchloridlösung gewaschen. Die organische Schicht wird getrocknet und das Chloroform abdestilliert. Der ölige Rückstand wird in Methanol gelöst und mit einer Diäthylätherlösung von Chlorwasserstoff behandelt. Beim Abkühlen scheidet sich eine fällung aus, die aus Äthanol umkristallisiert wird. Sie besteht au· 5-1.5 g of this product are in 26 ecm 98 Seigern hydrazine hydrate solved. The mixture is refluxed for 10 hours. Then the solvent is removed in vacuo. The residue is taken up in chloroform and washed twice with a saturated aqueous sodium chloride solution. The organic layer is dried and the chloroform is distilled off. The oily residue is dissolved in methanol dissolved and treated with a diethyl ether solution of hydrogen chloride. When it cools down, a precipitate separates out, which is recrystallized from ethanol. It consists of 5-
909887/1637909887/1637
BADBATH
Hydrazine» -6-(N-phenyl-H-iae thyl) -amino-pyridazin-dihydrociilorlä. Ausbeute 1,3 g (65 *)» 1 206-208° C. Die freie Bae· kann nach üblichen Verfahren, z.B. durch Zugabe eines Alkalihydroxide oder -carbonate zu der wässrigen Lösung des Dihydrochloride und Sxtrahieren mit Diäthyläther gewonnen «erden. Die freie Base ist jedoch bei nornalen Temperaturen kaum beständig und zerfällt rasch beia Ephitzen.Hydrazines »-6- (N-phenyl-H-iae thyl) -amino-pyridazine-dihydrociilorla. Yield 1.3 g (65 *) "1206-208 ° C. The free Bae · can according to customary methods, for example by addition of an alkali metal hydroxides or carbonates, to the aqueous solution of the dihydrochloride and Sxtrahieren extracted with diethyl ether" ground. The free base, however, is hardly stable at normal temperatures and quickly disintegrates when exposed to heat.
Nach dem Verfahren des Beispiels 1 wurden ferner hergestellt!Following the procedure of Example 1 were also prepared!
4) 3-Bydraxino-6-piperidino-pyridazint Ausbeute 75 1»\ ? 140-145° Cι4) 3-Bydraxino-6-piperidino-pyridazint Yield 75 1 »\ ? 140-145 ° C
5) 3-Hydraeino-6-(4-nethyl-piperazino)-pyridazin| Ausbeute 70 i>\ F 165-167° C.5) 3-Hydraeino-6- (4-ethyl-piperazino) -pyridazine | Yield 70 i> \ F 165-167 ° C.
909887/1637909887/1637
BAD ORIGINALBATH ORIGINAL
Claims (7)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB42818/65A GB1157642A (en) | 1965-10-08 | 1965-10-08 | 3-Hydrazino-6-Amino-Pyridazines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1595910A1 true DE1595910A1 (en) | 1970-02-12 |
Family
ID=10426106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19661595910 Pending DE1595910A1 (en) | 1965-10-08 | 1966-10-07 | 3,6-Disubstituted pyridazines and processes for their preparation |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3535317A (en) |
| BE (1) | BE687835A (en) |
| BR (1) | BR6683481D0 (en) |
| CH (1) | CH467269A (en) |
| DE (1) | DE1595910A1 (en) |
| ES (1) | ES332061A1 (en) |
| FR (1) | FR1496046A (en) |
| GB (1) | GB1157642A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1054107B (en) * | 1970-12-15 | 1981-11-10 | Isf Spa | NEW 3, HYDRAZINOPYRIDAZINE 6, SUBSTITUTED FOR ANTI-HYPERTEN SIVA ACTIVITIES AND THEIR PREPARATION |
| ZA741396B (en) * | 1973-03-07 | 1975-01-29 | Isf Spa | New 6-substituted 3-carbethoxyhydrazinopyridazines and their preparation |
| IT1063908B (en) * | 1976-06-11 | 1985-02-18 | Isf Spa | HYDRAZINOPYRIDIAZINE DERIVATIVES |
| HU176972B (en) * | 1977-06-13 | 1981-06-28 | Gyogyszerkutato Intezet | Process for producing new piridazinyl-hydrasone derivatives |
| US4247551A (en) | 1979-09-17 | 1981-01-27 | Gruppo Lepetit S.P.A. | N-Pyrrolyl-pyridazineamines and their use as antihypertensive agents |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2484029A (en) * | 1945-12-21 | 1949-10-11 | Ciba Pharm Prod Inc | Hydrazine derivatives of pyridazine compounds |
-
1965
- 1965-10-08 GB GB42818/65A patent/GB1157642A/en not_active Expired
-
1966
- 1966-09-26 US US581753A patent/US3535317A/en not_active Expired - Lifetime
- 1966-10-04 CH CH1426966A patent/CH467269A/en unknown
- 1966-10-05 BE BE687835D patent/BE687835A/xx not_active IP Right Cessation
- 1966-10-07 ES ES0332061A patent/ES332061A1/en not_active Expired
- 1966-10-07 DE DE19661595910 patent/DE1595910A1/en active Pending
- 1966-10-07 FR FR79159A patent/FR1496046A/en not_active Expired
- 1966-10-07 BR BR183481/66A patent/BR6683481D0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES332061A1 (en) | 1967-07-16 |
| BR6683481D0 (en) | 1973-12-26 |
| BE687835A (en) | 1967-03-16 |
| CH467269A (en) | 1969-01-15 |
| US3535317A (en) | 1970-10-20 |
| FR1496046A (en) | 1967-09-22 |
| GB1157642A (en) | 1969-07-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DD211555A5 (en) | PROCESS FOR PREPARING NEW 4-AMINO-6,7-DIMETHOXYCHINOLINE DERIVATIVES | |
| DD159071A5 (en) | METHOD FOR THE PREPARATION OF PYRIDOXIN DERIVATIVES AND THEIR USE IN THERAPEUTICA | |
| DE1620449B2 (en) | SUBSTITUTED BENZIMIDAZOLES AND METHOD FOR PREPARING IT | |
| DE2458638C2 (en) | 4'-substituted 2-methyl-3-piperidinopropiophenone derivatives, processes for their production and pharmacological preparations which contain them | |
| DE1595910A1 (en) | 3,6-Disubstituted pyridazines and processes for their preparation | |
| DE1795741A1 (en) | PROCESS FOR THE PREPARATION OF AN INTERMEDIATE SUITABLE FOR THE PRODUCTION OF 3-FORMYLRIFAMYCINE SVDERIVATIVES | |
| DE3223877C2 (en) | ||
| AT363074B (en) | METHOD FOR PRODUCING NEW 1-AMINO-LOW-ALKYL-3,4-DIPHENYL-1H-PYRAZOLES AND THEIR SALTS | |
| DE2819896A1 (en) | CHROME DERIVATIVES, METHOD FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THE SAME | |
| DE1229096B (en) | Process for the preparation of 2-substituted 3-amino-pyrazole-4-carboxylic acid-N '- [5-nitrofuryl- (2) -methylidene] -hydrazides | |
| DE2403786A1 (en) | NEW DERIVATIVES OF CUMARINE | |
| DE1283841B (en) | Basically substituted ethers of ethanolamine | |
| DE1795384C3 (en) | 1 H-2,3-Benzoxazines, processes for their production and pharmaceuticals | |
| DE1595910C (en) | 3,6-Disubstituted pyridazines and processes for their preparation | |
| DE2536170B2 (en) | ||
| DE2035161C3 (en) | L-Leucyl-L-leucyl-L-valyl-L-tyrosinol and its acid addition salts with pharmacologically acceptable acids | |
| DE2526405C2 (en) | β-piperidinoethyl basinate and process for its preparation | |
| EP0000727A1 (en) | 3-(4-(1,3-Diazacycloalkene-2-yl)-phenyl)-1,2-benzisothiazoles, process for their preparation and medicaments containing them. | |
| DE1695905C (en) | 1 Carbamoyl 5 phenyl 1,2 dihydro 3 H 1,4 benzodiazepinone (2) derivatives and process for their preparation | |
| AT288413B (en) | Process for the production of new basic xanthone derivatives and their salts | |
| DE1303930C2 (en) | 2- (2-CHLORO-4-METHYL- OR-AETHYL- ANILINO) -1,3- DIAZACYCLOPENTEN- (2), THEIR SALTS AND A PROCESS FOR THEIR PRODUCTION | |
| AT255409B (en) | Process for the preparation of new substituted benzimidazole derivatives and their salts | |
| AT322563B (en) | PROCESS FOR THE PREPARATION OF NINE 6-SUBSTITUTED 3-HYDRAZINOPYRIDAZINES AND THEIR ACID ADDITION SALTS | |
| DE2515548A1 (en) | QUATERNAERE AMMONIUM SALTS OF N-DIALKYLAMINOALKYL-N- (2-INDANYL) -ANILINES AND METHOD FOR THEIR PRODUCTION | |
| AT236934B (en) | Process for the production of new hydrazones from 5-nitro-furfural |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E77 | Valid patent as to the heymanns-index 1977 |