Classifications

• • 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
  • C07D403/12—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 linked by a chain containing hetero atoms as chain links
• • 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
  • C07D237/14—Oxygen atoms
• • 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
  • C07D413/12—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 linked by a chain containing hetero atoms as chain links

Definitions

• C07d 51/04 COXY-6-hydrazinopyridazines which have a marked 158 1 Field of Search 260/250 A ti-hypeflensive activity, and a 5 much higher than that of the clinically used drug hydralazine.
• the com- 5 References Cited pounds of the invention are prepared by reacting 3 UNITED STATES PATENTS aminoalcoxy-6-hal0genopyridazines with hydrazine.
• l0 mula (I) are prepared by reacting compounds of the The invention provides N-substituted 3-aminoalcoxyformula: o-hydrazinopyridazines which have a marked antihypertensive activity and a LD much higher than that of the clinically used drug hydralazine.
• the new compounds of this invention are the N- substituted 3-aminoalcoxy-6-hydrazinopyridazines. of 2 fl 11 general formula: R
• R NHHHZ r wherein R. R and are as defined above and X is chlo- )1 rine or bromine, with a hydrazme. wh
• the com- R pounds of formula (II) are heated with hydrazine to a 1 2 temperature from 20C to the boiling point of the mix- 5 ture. preferably between 70 and l l5C.
• the reaction wherein n is an integer from 2 to 6, R is hydrogen. can be conducted using an excess ofhydrazine,or using lower alkyl. or lower hydroxyalkyl.
• R is lower alkyl. an inert organic solvent, such as ethanol. propanol.
• the compounds of formula (I) may be employed as dibromopyridazine with an aminoalcohol of formula: such or in the form ofacid addition salts, obtained from i I the bases by treatment with mineral acids, such as hydrochloric. hydrobromic. or sulfuric acid, or organic acids. such as acetic. succinic, benzoic. or p-toluene- N J 3 -UH sulfonic acid.
• the hypotensive effect of the compounds of formula 40 3 (I) has been proved by administering them intrave- 1 nously in aqueous solution to anaesthetized cats and measuring the decrease in their arterial blood pressure.
• R. R and n are as defined above.
• the reaction The antihypertensive action of the new compounds has can be accomplished. according to the nature of the been measured by inducing renal hypertension in rats aminoalcohol employed. either by heating the halogeby the method of Grollman (Proc. Soc. Exptl. Biol. and no-pyridazine with the compound of formula ([11) in Med.. 57. lO2.
• anhydrous sodium or potassium carterial blood pressure following oral administration of bonate in an aprotic high-boiling solvent, such as dian aqueous solution of a compound of the invention as methylformamide. or else by heating the a salt, e.g. the hydrochloride. halogenopyridazine with an anhydrous alkali metal salt
• a salt e.g. the hydrochloride. halogenopyridazine with an anhydrous alkali metal salt
• the reaction temtheir corresponding approximate intraperitoneal LD perature is not critical and may range from 50C to the in the rat are grouped in the following Table together boiling point of the selected solvent.
• compounds of formula (I) are separated from the reac- TABLE Compound Mouse Anaesthetized Cat Awake hyperof tensive rat Example No. LD Effective Half Efi'ective dosage effect osage mg/kg mg/kg time: mg/kg intraperitoneal intravenous minutes orally 1 300 0.0! I20 0:5 2 800 0.2 150 3 900 0.1 130 Hydralazine 0.5 100 tion mixture and purified by conventional methods for organic bases.
• EXAMPLE 1 3-( 2-Anilinoethoxy )-6-hydrazinopyridazine a. 3-(2-anilinoethoxyl-o-chloropyridazine 3.76 Grams of N-(Z-hydroxyethyl)-aniline and grams 2.98 of 3,6-dichloropyridazine are added to 40 ml of anhydrous dimethylformamide containing 10 grams of potassium carbonate and the mixture is heated to lC for hours with stirring. The insoluble mineral salts are filtered off, and the filtrate is concentrated to dryness under vacuum.
• the aqueous phase is separated and rendered alkaline while cold with a 30% aqueous sodium hydroxide solution.
• the oil that separates is extracted with diethyl ether.
• the extract is dried over anhydrous K CO and the solvent is removed by distillation.
• the residue is fractionally distilled under ⁇ acuum. thus gi ⁇ ing 60 g (70% of theoretical) of 3-1B-dimethylaminopropoxy)- b.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Citations (3)

• 1971
  • 1971-12-10 GB GB5762071A patent/GB1324579A/en not_active Expired
  • 1971-12-16 JP JP46101527A patent/JPS5117553B1/ja active Pending
  • 1971-12-24 DE DE19712164618 patent/DE2164618A1/de active Pending
  • 1971-12-27 FR FR7146756A patent/FR2139798B1/fr not_active Expired
• 1972
  • 1972-01-17 US US218531A patent/US3891641A/en not_active Expired - Lifetime
  • 1972-01-18 BE BE778206A patent/BE778206A/xx unknown

Patent Citations (3)

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