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

Definitions

• Compound A was tested in doses of 5, 2, 1, 0.5, 0.25 mg./kg.; compound B in doses of 1, 0.25, 0.1 mg./kg.; compound C in doses of 1, 0.5, 0.25, 0.1 mg./kg.
• Compound A showed a strong and lasting antihypertensive effect at every dose.
• Compound B showed remarkable and lasting efiect at the tensive activity.
• Compound C was effective at all doses higher than 0.1 mg./kg.
• a comparison was also carried out between compound A and the well-known hypotensive agent hydralazine. Both compounds were tested on rabbits anesthesized This invention is concerned with new pharmacologically active compounds, and with a method for preparing them. with sodium pentobarbital.
• the preparation of the compounds of the invention runs through two reaction steps.
• the starting 3,6-dichloro-pyridazine I by reaction with about two equimolecular amounts of a primary or secondary amine, in an anhydrous organic solvent, gives a monoamino derivative, which is hereinbelow represented with formula II.
• a monoamino derivative which is hereinbelow represented with formula II.
• R' is a member selected from the class consisting of hydrogen, lower alkyl and hydroxy-lower alkyl groups
• R" is a member selected from the class consisting of lower alkyl, hydroXy-lower alkyl and phenyl groups
• R 0 NH and R" taken together form an optionally lower-alkyl substituted heterocyclic ring with 1-2 heteroatoms.
• the heterocyclic ring is morpholine
• I compound is 3-hydrazino-6-morpholino-pyridazine.
• the compounds of the invention have proved useful 0 as hypotensive agents.
• 3-hydrazino-6-morpholino-pyridazine (A), 3-hydrazino-6-piperidino-pyrida- II zine (B) and 3-hydrazino-6-bis-(Z-hydroxyethyl)-amino pyridazine (C) were administered by intravenous route NZN to dogs anesthesized with 35 rng./kg. of sodium pentobar- HI r. J
• the following examples illustrate the invention.
• EXAMPLE 1 Preparation of 3-hydrazino-6-morpholino-pyridazine An amount of 149 g. (1 mole) of 3,6-dichloropyridazine and 174 g. of morpholinc (2 moles) are mixed in 750 ml. of anhydrous ethanol. The mixture is refluxed for 2 hours: the two compounds completely dissolve. The solution is cooled and the precipitated solid is separated by filtration. The precipitate is taken up with water and again filtered. The collected solid is crystallized from water, thus obtaining 174 g. of pure product (yield 75%), M.P.; l38140 C. This product is 3-chloro-6-morpholinopyridazine.
• the dihydrochloride prepared by bubbling HCl in a diethyl ether solution of the free base and collecting the precipitate, melts at 236 C.
• the product is 3-hydrazino-6-bis- (Z-hydroxethyl)-amino-pyridazine dihydrochloride. (the free base, when isolated by usual procedure, is not stable). Yield 9.8 g. (66% M.P. 187.5-188.5 C.
• the free base can be isolated by usual procedures, f.i. by adding an alkali hydroxide or carbonate to the aqueous solution of the dihydrochloride and extracting with diethyl ether.
• the free base is scarcely stable at ordinary temperature and decomposes promptly on heating.
• R is a member selected from the class consisting of hydrogen, lower alkyl and hydroxy-lower alkyl groups
• R is a member selected from the class consisting of lower alkyl, hydroxy-lower alkyl and phenyl groups
• R and R" taken together with the N-atom form a member of the group consisting of morpholino, piperidino and 4-methyl-piperazino, and its non-toxic mineral acid addition salts.
• a compound as in claim 1, wherein the 3,6-disubstituted pyridazine is 3-hydrazino-6-bis-(2-hydroxyethyl)- amino-pyridazine hydrochloride.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Medicinal Chemistry (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)

Applications Claiming Priority (1)

Publications (1)

Family

ID=10426106

Family Applications (1)

Country Status (8)

Cited By (3)

Families Citing this family (2)

Citations (1)

• 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/fr unknown
  • 1966-10-05 BE BE687835D patent/BE687835A/xx not_active IP Right Cessation
  • 1966-10-07 FR FR79159A patent/FR1496046A/fr not_active Expired
  • 1966-10-07 DE DE19661595910 patent/DE1595910A1/de active Pending
  • 1966-10-07 ES ES0332061A patent/ES332061A1/es not_active Expired
  • 1966-10-07 BR BR183481/66A patent/BR6683481D0/pt unknown

Patent Citations (1)

Also Published As

Similar Documents