EP0258264A1 - N,n'-(bisfurfuryl)-2-furylmethandiamin, seine herstellung und seine verwendung - Google Patents

N,n'-(bisfurfuryl)-2-furylmethandiamin, seine herstellung und seine verwendung

Info

Publication number
EP0258264A1
EP0258264A1 EP19870900067 EP87900067A EP0258264A1 EP 0258264 A1 EP0258264 A1 EP 0258264A1 EP 19870900067 EP19870900067 EP 19870900067 EP 87900067 A EP87900067 A EP 87900067A EP 0258264 A1 EP0258264 A1 EP 0258264A1
Authority
EP
European Patent Office
Prior art keywords
bisfurfuryl
hydrofuramide
furfurylmethanediamine
furfural
acid
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Withdrawn
Application number
EP19870900067
Other languages
German (de)
English (en)
French (fr)
Inventor
Gustav Sotek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP0258264A1 publication Critical patent/EP0258264A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical

Definitions

  • the invention relates to N, N '- (bisfurfuryl) -2-furfurylmethane diamines and processes for their preparation and their use.
  • hydrofuramide N, N'-di-2-furfuryl-2-furfurylindendiaine
  • N, N '- (bisfurfuryl) -2-furfurylmethanediamine has a melting point of 107 to 109 ° C, a molecular weight of 272 and an elemental analysis of 54.2% C, 5.26% H, 6.03% N and 34.45% 0.
  • the process according to the invention for the preparation of the new compounds is characterized by the following steps: reacting a hydrofuramide optionally substituted on the furfuran ring (s) with a borohydride and isolating the reduction product:
  • a hydrofuramide is preferably reacted in the liquid phase, optionally in a polar, hydrophilic solvent, with an alkali metal or alkaline earth metal hydride salt and the hydrogenated reaction product is obtained by methods known per se, such as extraction, fractional distillation, chromatography or. similar, separated.
  • the hydrogenated reaction product can particularly preferably be separated off by separating the liquid obtained by reacting the hydrofuramide with a borohydride in a liquid phase into an organic and an inorganic phase, and then fractionally distilling the organic phase.
  • hydrofuramide is dissolved in tetrahydrofuran and the solution is slowly added to the solution with cooling and stirring with an alkali metal borohydride solution; After the reaction has ended, the reaction mixture is neutralized with acid, preferably an aqueous solution of an acid, and the organic phase which forms is separated off and distilled.
  • the hydrofuramide can be obtained by reacting ammonia with furfural.
  • the conversion of ammonia and furfural preferably takes place in the liquid phase.
  • Furfural can be introduced into an ethanolic ammonia solution while cooling and the separating solid, the hydrofuramide, can be obtained by methods known per se, such as filtration, centrifugation, decanting or the like.
  • Salts of N, N '(bisfurfuryl) -2-furfurylmethanediamine can be obtained by: reacting the N, N' (bisfurfuryl) -2-furfurylmethanediamine with stoichiometric amount of acid.
  • N, N'- (bisfurfuryl) -2-furfurylmethanediamine can be dissolved in an organic solvent, reacted with a stoichiometric amount of acid solution, and the salt which separates out can be separated off.
  • a preferred use of the compounds according to the invention is as a medicament.
  • N, N '(bisfurfuryl) -2-furfurylmethanediamines are also to be understood as meaning salts of this class of compounds and derivatives thereof, as can be prepared, for example, by using substituted furfurals.
  • the new compounds are characterized by a surprising physiological activity.
  • the N, N '(bisfurfuryl) -2-furfurylmethanediamine reduces the viscosity of blood.
  • the new active ingredient brings about an increase in the cholesterol esterase values which, for example, decrease from 78 units to 34 to 40 units in the case of degeneration diseases.
  • an increase in the albumin content in the serum is found when the active ingredient according to the invention is used.
  • the new active ingredients are suitable for oral administration as well as for parenteral use, infusion. As an indicator. Areas of application are recommended, inter alia, for all diseases which are associated with an increase in the viscosity of the blood, such as angina pectoris, cardiac arrhythmia, circulatory disorders, Parkinsonism. They are also suitable for the treatment of all kinds of liver diseases, including the consequences of alcoholism.
  • the compound is also stable at room temperature so that there are no storage problems.
  • the pH is then adjusted to 10 using 30% sodium hydroxide solution and the anoraganic salts which have precipitated are suctioned off.
  • the reaction mixture separates into two phases.
  • the tetrahydrofuran phase is separated off and concentrated under a water jet pump vacuum.
  • the residue is added to "70 ml Diisopopylether and crystallized.
  • the crystals dersrrt obtained are filtered off with suction.
  • the Filter ⁇ cake is taken up in 150 ml of acetone and boiled for 30 minutes under reflux.
  • the solids are filtered hot with suction and the acetone was completely evaporated.
  • the crystalline return The stand is taken up in 80 ml of diisopropyl ether and suction filtered, and the solid is washed with diisopopyl ether and dried at 40 ° C.
  • the hydrofuramide obtained in this way had the following properties:
  • the effectiveness of the substance is examined by a pharmacological screening program.
  • mice 12 mice were anesthetized with chloroform and treated ip with 0.15 test substance. 30 minutes after administration of the test substance, the heartbeat rate of 9 mice was below 200 / min (ECG).
  • Tachycardia was induced in 12 rats by administering 0.01 mg / kg isoproterenol (IV). 6 rats / kg of the test substance N, N '(bisfurfuryl) 2-furfurylmethanediamine were administered to 12 rats per os. An ECG was taken 30 minutes after the substance was administered and 70% of the animals showed a clear inhibition of tachycardia.
  • mice Fourteen mice were fed a high cholesterol-cholic acid diet for 7 days.
  • the hypercholesterolemic animals were divided into two groups of 7 animals (control group). On the 6th and 7th day after starting the diet, 0.2 mg test substance / animal was administered orally. After fasting at night, a reduction in blood cholesterol levels of over 15% was measured compared to the mice in the control group.
  • ⁇ ntiedema effect 7 rats were given 5 mg / kg of N, N '(bisfurfuryl) -2-furfurylmethane diamine per os and 0.1 ml of a 1% suspension of canigeenan injected into the paws after one hour. Compared to a control group of rats, suppression of paw edema by more than 30% was observed in rats treated with the test substance.
  • mice 10 mice were fed with 0.2 g test substance. One hour after the test substance was administered, 5 mice were treated with oxazolone on the shaved abdomen.
  • the ears were irritated by applying oxazolone to one ear.
  • the irritated ear showed a swelling of over 50% compared to the uh-treated ear of the same mouse.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Furan Compounds (AREA)
EP19870900067 1985-12-30 1986-12-30 N,n'-(bisfurfuryl)-2-furylmethandiamin, seine herstellung und seine verwendung Withdrawn EP0258264A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19853546319 DE3546319A1 (de) 1985-12-30 1985-12-30 N,n' (bisfurfuryl)-2-furfurylmethandiamin, seine herstellung und seine verwendung
DE3546319 1985-12-30

Publications (1)

Publication Number Publication Date
EP0258264A1 true EP0258264A1 (de) 1988-03-09

Family

ID=6289678

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19870900067 Withdrawn EP0258264A1 (de) 1985-12-30 1986-12-30 N,n'-(bisfurfuryl)-2-furylmethandiamin, seine herstellung und seine verwendung

Country Status (4)

Country Link
EP (1) EP0258264A1 (enrdf_load_stackoverflow)
JP (1) JPS63502504A (enrdf_load_stackoverflow)
DE (1) DE3546319A1 (enrdf_load_stackoverflow)
WO (1) WO1987004160A1 (enrdf_load_stackoverflow)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5292903A (en) * 1991-08-22 1994-03-08 The United States Department Of Agriculture As Represented By The Secretary Of Agriculture One step method for the preparation of difurfuryl diamines

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3565560A (en) * 1968-07-16 1971-02-23 Frederick W Proewig Pharmaceutical preparation containing hydrofuramide and method of using it
DE2700432A1 (de) * 1977-01-07 1978-07-20 Brauegg Arzneimittel Kg Bernd Neuer wirkstoff zur verwendung als arzneimittel mit wertvollen therapeutischen effekten n,n'-difurfuryliden-2- furan-methandiamin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8704160A1 *

Also Published As

Publication number Publication date
WO1987004160A1 (en) 1987-07-16
DE3546319A1 (de) 1987-09-17
JPS63502504A (ja) 1988-09-22
DE3546319C2 (enrdf_load_stackoverflow) 1988-12-08

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