DE2002024A1 - New pyridazine-1-oxides and processes for their preparation - Google Patents

Description

CIBA A K Tl ENGESE LLSCHA FT, BA SE L (S C H WEI2)

Case 6665/1 + 2 / E / - ^:

Germany

Keue pyridazine-1-oxides and process for their preparation

The invention relates to new pyridazine-1-oxides the general formula. . . ..

= CH-

-SO,

A f a * i ι r. * / Λ. 1 1. ι ι —Ώ · '

\ J ■ ■ ■ r ^ JvJ it "^ v J 3 \ - ' "

in which B ¹ and B "either hydrogen atoms" or together an optionally substituted 1,5-butadienylene (l ', ^J }) radical, R * denotes hydrogen, a lower alkyl radical or an optionally substituted phenyl radical, ^ for an hydrogenator or a lower alkyl radical. stands,

00 9831/1918

the symbols alk mean lower / alkylene radicals which separate the oxygen atoms by at least 2 carbon atoms and η stands for an integer from 2 to 9, in particular 2 or 3, and processes for their preparation.

A lower alkyl radical is, for example, a methyl, ethyl, propyl, isopropyl, butyl or pentyl radical.

The lower alkylene radicals Alk are in particular straight or branched lower alkylene radicals, such as 1,2-ethy-φ len, 1,2-propylene, 1,2-butylene, 1,3-propylene, 1,3-butylene or 2,3-butylene radicals. .

As substituents of the Phenylresteä are primarily alkyl groups, especially lower alkyl groups, such as the above-mentioned alkoxy groups, especially. Lower alkoxy groups, e.g. those which are derived from the specified lower alkyl groups, Halogen atoms., Such as fluorine, chlorine or Bromine atoms, and the Trifluoromethylgrijppe into consideration. The. Substitution can be one, two or more than one.

Substituents of the 1,3-butadienylene (l, ⁱ l) radical are, for example, the substituents given above for the phenyl radical, or hydroxyl, nitro or amino groups. These amino groups can be further substituted, for example by acyl radicals, such as alkanoyl radicals, especially lower alkanoyl radicals, such as acetyl radicals, or benzoyl radicals. The 1,3-butadienylene (1, ^) · radical can be substituted one, two or more times.

The new compounds have valuable pharmacological properties in particular antibacterial and antiparasitic intrinsic

009831/1918

societies. Above all, they show an effect against staphylococci, e.g. staph. aureus, Coli bacilli such as E. coil, Salmonella, for example Salmonella typhimurium and Pasteurella species, as shown in animal experiments, for example on mice, when administered subcutaneously in doses of 30-300 mg / kg and when administered orally in doses of 100-300 mg / kg shows. However, the new compounds are also effective against schistosomes, as shown in animal experiments, for example, on mice given daily doses of 300-100 mg / kg pp on 7 consecutive days. The new compounds are accordingly useful as antibacterial and anti-parasitic agents. In particular, they are suitable for treating the diseases caused by the pathogens mentioned. The new compounds are also valuable intermediates for the production of other useful SCÖf; fe, especially pharmacologically active compounds,

Particularly valuable are connections of the '/.-,

formula

■ 0-f-Alk-O - ^ - Ü '■' ■ '"/".

wherein Alk sübstibuierte ethylene (l, 2) optionally by Methylgrüppen - or propylene (l _J 3) -resbo means R. ¹ is a methyl group, a phenyl group or unsubstitüierte especially hydrogen "means, - Rg'eine · -Nicderalky ! group, one

0098 3 1/1918

■ - 4 - V,

Lower alkoxy group, a halogen atom or, in particular, a Hydrogen atom means, η for 2 or 3 and R for one Lower alkyl group.

Particularly noteworthy are the connections of the Formula shown at the outset, in which the symbols Alk represent radicals of the formula 1

CH CH t

- I.

are, in which R 1 and R ^ denote hydrogen atoms or methyl radicals, and compounds of the formula shown at the outset / in which the symbols Alk represent the radicals of the formula

R "R. R_

^{stand, in which R 1} to R are hydrogen or methyl radicals, and in which B 1 and B "are hydrogen atoms and R ^{1 is} a W unsubstituted phenyl radical, a methyl group or, above all, hydrogen. ^

4- (3,6,9-Trioxadecyloxy) -i- [2- (5-nitro-2-furyl) vinyl] -phthalazine-2-oxide is particularly effective, 3- (3 * 6,9-trioxaundecyloxy) -6- [2- (5-nitro-2-furyl) vinyl] pyridazine-1-oxide and especially 3- (3,6,9-trioxadecyloxy) -6- [2- (5-nitro-2-furyl) vinyl] pyridazine-1-oxide the formula

009831/1918

e.g. at the house with: subcutaneous administration in doses from jK> mg / kg a clear effect against E. coil as well as with subeutane administration in doses of 30 mg / kg on 3 consecutive the following days a clear effect against SaI * shows monella typhimuyium.

The new compounds are known per se Methods received. It is preferable to proceed in such a way that one pyridazines of the formula

where B ', 0 ", R', R ₁ AIk and η have the meanings given above, N-oxidized.

The oxidation is carried out inübl.icher manner, 'for example, _t; with N-oxidizing agents, v / ie hydrogen peroxide, ozone,

'Inorganic peracids, e.g.,' persulfuric acids, such as Caro's Acid, or especially organic peroxy compounds all organic peracids, such as peressic acid, pertrifluoro

~ 6 -

acetic acid, perbenzoic acid or phthalmonoperic acid, which also can be substituted, e.g. by halogen atoms, such as chlorine atoms, for example chlorophthalmonoperic acid or m-chlorobenzoic acid, or tertiary hydroperoxide compounds, such as tert, butyl or cumene peroxide, optionally in the presence of Catalysts such as vanadium, titanium or molybdenum compounds.

··
But you can also proceed in such a way that you have connections

of the formulas.

and.

0 (-

directly or stepwise reacted with one another, wherein X ₀ and Y ₀ in the reaction leaving a vinylene (1,2) 'bridge of the formula-' explained above. ·

-C = CH-

are removable radicals and B ¹ , B ¹ *, R ^f , R, Alk and η have the meanings given.

For example, 5-nitrofuran compounds can be used gene of the formula

00983 1/1918

O ₂ N-

-CH = X

with compounds of the formula

Ö-f- ^

react, where B ¹ , B ", R ¹ , R, Alk and η have the meanings given and in each case one of the two radicals X und.Y means an oxygen atom, while the other means two hydrogen atoms a metal atom can be replaced, ie the compound can also be used in the form of its metal salts, such as alkali metal salts, for example lithium, iiatrium or magnesium salts, the second valence of the magnesium being used by halogen, for example chlorine or

. Bromine, is saturated. .

, X, or Y can also stand for a radical of the formula bP (Ap), where Ar is an aryl radical, in particular a

. Phenyl radical and the other radical X or Y stands for an oxygen atom. The reaction can in this case, for example, be carried out by the method of Wittig and Sehöllkopf, conveniently in an inert solvent, for example an ether such as diethyl ether, methylene chloride or an alcohol, or in water, preferably under weakly alkaline conditions, optionally at elevated temperature and filtering off

0 09 831/1918

of the triarylphosphine oxide formed.

Vorzugswelse one proceeds in such a way that one ver bonds of the formula

in which B ', B ", R ^!, R, n and Alk have the meanings given, with 5-nitrofurfural or a reactive derivative thereof, such as an acetal, thioaeetal or acylal, for example the diacetate, or a bisulfite compound.

The reaction is carried out in a customary manner, if appropriate in the presence of condensing agents or catalysts, e.g. depending on the nature of the carbonyl component in the presence of water, alcohol or acid-releasing agents, carried out at ordinary or advantageously elevated temperature, whereby e.g. the undesired reaction products, such as water or alcohols, can be continuously removed from the reaction mixture.

But it is also possible to use compounds of the formulas

O ₀ N-

-CH = C

^X > -X · and Y ¹ - ^ - AIk- (Hh-R

009831/1918

-to be implemented with each other for B ¹ , B ¹ ^ R ¹ , B ^ Alk and η the above

have given meanings and X ¹ and Y ¹ are residues which can be split off in the reaction leaving an ether bridge rO-. One of the radicals X ¹ and Y ^{1 is} preferably an exchangeable radical and the other is a hydroxyl group. Exchangeable residues are primarily reactive esterified hydroxyl groups, e.g. hydroxyl groups esterified with strong organic or inorganic acids / in particular halogen atoms, such as. "Chlorine or bromine atoms, or Sulfonylöxygruppen, yorzugsweise arylsulfonyloxy groups such as toluenesulfonyloxy -. When Y ¹ is hydroxyl group, then X ¹ can also be a free

or etherified kercapto group, e.g. a benzyl mercapto

A group or a lower alkyl mercapto group such as ethyl or ethyl mercapto group, an ammonium group, e.g. a tri-alkylammonium group such as the trimethylammonium group or a lower alkylsulfonyl group such as the methylsulfonyl group .. .- ^{: f ;;} - -

The reaction takes place in the usual way , expediently, and moderately using a solvent, _for example a lower alkanol, such as methane oil.

the compound containing the hydroxyl group in the form of a Salt, for example an alkali metal salt, such as sodium or; Potassium salt or one works in the presence of a basic condensation medium such as pyridine or alkali metal carbonate or acetate or alkali metal methylate, e.g. sodium methylate *

Another method consists in - that one

bonds of the formula

B ¹

Ö f-Alk-O - ^ - R '

where B ¹ , B ", R ', R, η and Alk have the meanings given, nitrated. In particular, the customary nitrating agents are used, for example nitric acid, optionally with the addition of sulfuric acid. ¹ The nitration is advantageously carried out under mild conditions, e.g. lower temperature and in solvents such as lower alkanecarboxylic acids or their anhydrides, e.g. in glacial acetic acid, ie one ni- - *

of
triated with mixed anhydride of nitric acid and

™ a lower alkanoic acid such as acetic acid.

The reactions mentioned are carried out in the usual way Presence or absence of dilution, condensation and / ' or catalytic agents, when depressed, more common. * or elevated temperature, possibly in a closed place Oefäss and / or carried out under an inert gas atmosphere.

The invention also encompasses those embodiments of the method in which one clicks on any one intermediate product obtainable in a process step, e.g.

a compound of the formula

009831/1918

-AIk- (Hh-R "

where A is a 1-R'-ethylene radical which has radicals which can be split off with formation of a double bond, such as, for example, optionally etherified or acylated oxy groups / and B ¹ JB ″, R ¹ , R, η and Alk have the meanings given, and the missing ones Process steps, such as, for example, introducing the double bond with elimination of the radicals mentioned, for example in the case mentioned the elimination of alcohol, acid or water, or in which the starting materials are optionally used in the form of salts and / or are formed under the reaction conditions For example, the aldehyde can be liberated from a functional derivative such as a bisulfite compound or a hydrazone under suitable reaction conditions. These reactions are also carried out in the usual way. /

For the reactions according to the invention .vor? -. · such starting materials are used which result in the preferred compounds mentioned above.

The starting materials are known or can be used according to an; known methods can be obtained. For example, this is how you get the Compounds of the formula used as starting materials for the oxidation

Ö09831 / 191Ö

O — C-

in which B ″, B ¹ , R ^r , R, All and η have the meaning given above, preferably by using compounds of the formulas.

and

reacted directly or in stages with one another, where Β ', Β ¹¹ ,! ** Alk _# n, X _o and Y _{0 have} the meanings given above. The implementation takes place in two ways analogously to that given above. But you can also use compounds of the formula

R

C =

in which B ', B ", R ¹ , R, Alk and η have the meanings given above, nitrate or compounds of the formulas

009831/1918

implement with each other, in which & ^^ * yR have the specified SetSeuttnigeii. These reactions "are preferably as ■ -above " ■ amtgegetoen durcligefülirfc *

"Meienigeii der genanniien ilusgangsstoife in which B ¹ and B * represent hydrogen and η represents an integer of 4 Ms 9, aB * 4,5 or 6, and those in

where B ¹ and B ⁿ together represent the 1,3 -butadienylene (1,4} radical and η Ϊ ttr a number from 2 to 9 are new. Like their 1-oxides, they have anti-parasitic and anti-bacterial properties lind also form an object of the invention... _: "-" ·

Lie new compounds can, for example, in the form of pharmaceuticals ^; Zeutischer preparations find use, which they in mixture with one for the enteral, parenteral or topical. Application suitable pharmaceutical organic or 'inorganic, solid or liquid carrier material contain. ^v the same for the formation are those substances that do not react with the novel compounds, such as, for example, water, gelatin, lactose, starch, stearyl alcohol, Mägnesiümstearat, talc, vegetable ÖIE, benzyl alcohols, gum, propylene glycols, petroleum jelly or other known excipients , The pharmaceutical? Eutic preparations can for example as tablets, dragdes, • capsules, ointments, creams or in liquid form as solutions

009031/1918

(e.g. as an elixir or syrup), suspensions or emulsions. If necessary, they are sterilized and / or contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers, solubilizers or salts for changing the osmotic pressure or buffers. They can also contain other therapeutically valuable substances. The pharmaceutical preparations are obtained according to the usual methods. '

The new compounds can also be used in veterinary medicine, for example in one of the forms mentioned above or in the form of feed or additives for animal feed. For example, the usual extenders and thinners or animal feed are used. \

The new compounds can also be used as disinfectants or preservatives, for example for disinfecting the skin, instruments, bandages, linen or the like, and also for disinfecting or preserving food or feed. They can be used alone or in a mixture with the customary stretching or carrier materials.

The invention is described in more detail in the following examples. The temperatures are given in degrees Celsius.

009831/1918

ilspleljl

One solves Ii, ^ g ^ - (^^^
nitro-2-furyl) vinyl] pyridazine in 20 ml of methylene chloride, treated with 7.3 g of 85% m-chloroperbenzoic acid and stirred for 20 hours at room temperature. The reaction solution is then evaporated in vacuo. The residue is stirred up with ether, the undissolved portion is suction filtered and recrystallized from ethanol. This gives the> - (3,6,9-trioxa-decyloxy) -6- [2- (5-nitrb-2-furyl) vinyllpyridazine-1-oxide of the formula.

from F. 136-

- 16 Example 2

One dissolves 65O mg ^ - (^, ö ^
(5-nitro-2-furyl) vinyl] phthalazine in 50 ml of methylene chloride, 520 mg of m-chloroperbenzoic acid are added and the mixture is refluxed for 6 hours. The reaction solution is then evaporated in vacuo. The residue is stirred up with ether, the undissolved portion is filtered off with suction and recrystallized from ethanol. This gives the ¹ t - (>, 6 _J 9-trioxadecyloxy) -l- [2- (5-nitro-2-furyl) vinylI-phthalazine-2-oxide of the formula

GH = CH

N-

from P.

The 4- (3,6,9-trioxadecyloxy) -1- (2- (5-nitro-2-furyl) vinyl] phthalazine used as starting material can be made as follows:

36 g of l-chloro - ^ - methyl-phthalazin v / ground heated with a solution of ^l \, 6 g of sodium in 330 ml methoxytriglycol during hours in Dornbenrohr to 135th The reaction solution is then .wird 'evaporated in vacuo. The residue

The mixture is stirred up with water and extracted with methylene chloride.

009831/1918

-. '■ if -

After evaporation of the methylene chloride solution, "the oily Fractionated residue. The 4 - (5j6,9-T'rioxadecyloxy) l-methyl-phthalazine of the formula

from Kp (0.05 mm) I97 ⁰ »

3 S 4- (5,6,9-trioxadecyloxy-i-methyl-phthalazine and 7.05 g of nitrofurural are heated in 50 ml of acetic anhydride for 5 hours to 100% . The reaction solution is then evaporated in vacuo Ice water and dilute sodium hydrogen carbonate solution are added to the residue. The 4- (3 _i 6,9-Trioxa'-decyiox ^) -1 »r2 - (! 5'-nitro-24 furyl) -vinylJ-phthala2in separates out formula

009831/1918

C.

from P. 117-120, which after recrystallization from methylene chloride petroleum ether melts at 120-21 °.

The aqueous alkaline solution can be concentrated by extracting with methylene chloride with the addition of petroleum ether, further material of the above formula can be obtained.

In an analogous manner, by oxidation of 5- (5,6,12,15,18,21,24,27-Nonaoxaoctacosyloxy) -6- (2- (5-nitro-2-furyl) vinyl] pyridazine the> O, 6,9,12,15, 18,21,24,27-nonaoxaoctacosyloxy) -6- [2- (5-nitro-2-furyl) vinyl] pyridazine-1-oxide be won.

009831/1918

Example>

'■ - "'"'■' 9 g ^ -D ^^. Ia
1- (2- (5-nitro-2-furyl) -vinyi] -plithalazine are refluxed in 100 ml of methylene chloride with 5 / 5gim-chloroperbenzoic acid for 6 hours The residue is dissolved in a little methyl chloride, the undissolved material is filtered off and the residue is again evaporated. i2, i5, i8-Hexaoxanonadecyloxy) -1- (2- (5-nitro-2-furyl) vinyl / phthalazine-2-oxide of the formula

GH = CH-

I!

The NMR spectrum in deuterochloroform shows the following characteristic bands: 8.75 (d) 7.7 (0) 7.52) d) 6, e6 (d) 5 ^ (s) ppm.

"." "'·".',. The 4- (5,6, -9, 12,15,18-hexaoxanohadecyloxy) -1- [2- (5-nitro-2-furyl) vinyl] phthalazine can be made as follows:

00 9831/1918

59 * 2 g of hexaethylene glycol monomethyl ether are added dropwise to an M ₁ load of 9.6 g of a 50% dispersion of sodium hydride in oil and 200 ml of absolute dioxane. After the calculated amount of hydrogen has developed, the solution prepared in this way is added to a solution of 35 * 7 g of 1-chloro-4-methyl-phthalazine and heated to 140 ° for 10 hours in a closed tube. The precipitated common salt is filtered off and the dioxane solution is evaporated to dryness in vacuo. The back

When it stood, water was added and the mixture was extracted with chloroform.

The chloroform solution is dried and evaporated. The residue is subjected to fractional distillation. The 4- (3 * 6.9 * 12.15,18-hexaoxanonadecyloxy) -1-methyl-phthalazine is obtained in this way from bp 185 / 0.018 mm.

14 g of 4- (3,6,9,12,15,18-hexaoxanonadecyloxy) -1-methyl-phthalazine and 4.5 g of 5-nitrofurfural are in 50 ml of acetic anhydride for 2 hours under a nitrogen atmosphere heated to 140 °. After cooling, φ is concentrated to dryness in vacuo, and the residue is crystallized from isopropanal. The 4- (3,6,9,12,15,18-hexaoxanonadecyloxy) is obtained -1- [2- (5-nitro-2-furyl) vinyl] phthalazine of the formula

From F. 85-87

I 009831/1918

O (CII OM ₂ O) CH

Example 4

Tablets containing 500 mg .5- (5,6,9-Trloxadecyloxy) -6- [2- (5-nitro-2-furyl) -vinyl] -pyridazine-1-oxide can be used in; the following composition can be produced: - ■ · ■. '-'-' ■ ·

■ - · - · - ■ '■' -. '^;'" per tablet

5- (5> 6> 9-trloxa-deeyloxy) - '.

6- [2- (5-nitro ^ 2-furyl) vinyl] pyridazine i-oxide "

Wheat sticks ■ ^; - ■ - ■■ · ■

Colloidal silica with _; . - ■ -. r. hydrolyzed starch

Magnesium stearate ^:

Talk "■■■><■■'■'. * ■. ' '- ■. · "" ■■■

500, 0 mg 7Ö , 0 mg 50 , 0 Wg ■ ■ ·: $: , 0 mg ^: ; ■: ■■ 19. , 0 mg , 0 mg

Manufacture _; . ;

Half of the wheat starch is put on the water bath with de? 4 times the amount of water, gelatinized. The active ingredient is kneaded with this paste, bi.g ,, a plastic mass. has arisen. Then the. , colloidal silica. · Incorporated in portions with hydro- and lysed starch. The plastic mass is passed through a sieve of. k - 5 "nim Ma ^ driven mesh size and dried at 45 C, The dried granulate is beaten durcfr a sieve of 0.8-1, -4 rnrn MaschehVifeite and the remaining disintegrants, glidants and lubricants are added after.. Further homogenization, standard catfish tablets with a diameter of 11.5 mm and a weight of 425 mg are pressed.

009831/1918

Claims (6)

Claims Process for the preparation of pyridazine-1-oxides of the general formula (D where B 'and B "are either hydrogen atoms or together an optionally substituted l ^ - rest mean, R 'hydrogen, a lower "Alleyl" radical or an optionally substituted phenyl radical, R for a hydrogen atom or a lower alkyl " rest, the symbols Alk are lower alkylene radicals that separate the oxygen atoms by at least 2 carbon atoms, and η is an integer from 2 to 9, characterized in that pyridazines of the formula (II), 0 - (- 009831/1918 in which-B ', Β ", R ¹ , R, Alk and η have the meanings given above, N -oxidized, or compounds of the formulas AIk-O (III) and reacted directly or in stages with one another, in which X and Y in the reaction, leaving a vinylene (1,2} bridge the formula -G = CH- are removable radicals and B ¹ , B ″, R ¹ , R, Alk and η have the meanings given; or compounds of the formulas R ¹ B " -GH = C- (V) and Y ¹ - (VI) reacted with one another, where B ¹ , B ", R ¹ , R, Alk and η have the meanings given above and X ¹ and Y ^f are radicals which can be split off in the reaction leaving an Aetlierbrücke -O-, or compounds of the formula 009831/1918 O — H-AIk-O-J — R ' where B ^r , B ", R ¹ , -R, η and Alk have the meanings given, nitrated. 2. The method according to claim 1, characterized in that that the oxidation to 1-oxide with N-oxidizing agents performs. y » Process according to claims 1 and 2, characterized in that the oxidation to the 1-oxide is carried out with organic peracids. "" 4. The method according to claim 1, characterized in that that you can get compounds of the formula 0 - (- AIk-O -) - R
η 009831/1918 (VII) ; · - 200202A wherein B ¹ / B ", R ', R, n / and Alk have the meanings given in claim 1, with §-Nltrofurfural or a reactive functional derivative" thereof reacts / 5. The method according to claim k _} characterized in that the pyridazine compound of the formula VII is used in the form of a metal salt. -. '· 6. The method according to claim 1, characterized in that that you can make compounds of the formulas. C = Y and reacts with one another, with one of the residues. JC and Y. for an oxygen atom and, the other for, a residue of the formula -P (Ar), in which Ar is an aryl radical. 7. The method according to claim 6, characterized in that Ar stands for the phenyl radical, 8. The method according to claim 1, characterized net that one uses compounds of the formulas V and VI in which X ^{1 is} a halogen atom and Y 'is a hydroxyl group. · 009831/1918 9. The method according to claims 1 and 8, characterized in that the compound of formula VI in the form an alkali salt is used. · '■ 10.. Process according to Claim 1, characterized in that nitration is carried out with nitric acid in glacial acetic acid. 11. The method according to any one of claims 1-5 and 8-10, characterized in that one on any one Stage of the process compound available as an intermediate * V goes out and carries out the missing steps, or a starting material forms under the reaction conditions. 12. The method according to any one of claims 6 and 7> characterized in that one goes from one to some level of the Process available as an intermediate compound starts out and carries out the missing steps, or a starting material forms under the reaction conditions. IjJ. Method according to claim II, characterized in that that one in a compound of the formula 009831/1918 ^ β; ό, ί " ^2r ". 200202V wherein A is a 1-R ¹ -ethylehrest, which has residues which can be split off with formation of a double bond, and B ', B ", R ¹ ,' R * η and Alk have the meanings given in claim 1, splitting off the radicals mentioned . ■ "■ '■. l4. · Method according to one of claims 1-5 / 8-11 and characterized in that one compounds of the formula = CH- -NO. (D 0-f-Alk- <H ~ R where η is 2 or 5, R is lower. Alkyl radicals, R ¹ denotes hydrogen, a methyl group or an unsubstituted phenyl group and Alk denotes radicals of the formula —GH —- CH- stands in which R and R denote hydrogen atoms or methyl radicals. _15th Method according to one of Claims 6, 7 and 12, characterized in that compounds of the formula y 009 831/1918 R ¹ -A8- (I) where η stands for 2 or 5, R stands for lower alkyl radicals, R ^{r stands for} hydrogen, a methyl group or an unsubstituted phenyl group and Alk stands for radicals of the formula ■ üH — CH- R ₂ stands in which R, and Rp hydrogen atoms or methyl radicals mean. 16. The method according to any one of claims 1-5 * 8-11 and: characterized in that the 5- (5 * 6,9-trioxadecyloxy) 6- [2- (5-nitro-2-furyl) -vinyl] -pyridazine-1-oxide of the formula -NO 009831/1918 0-GH ₂ -Clt ₂ -O-CH ₂ -Clr ^ O - CII ₂ --O [[ _? --O-GH. ₃ manufactures. . 20Q2024 1? · Method according to one of claims 6, 7 and 12, characterized / that the 3W (> ,, 6 _r 9-triQxadeeylaxy) -6- [2- (5-nifero-r2-furyl) -vinylJ ^ pyridazine -l-oxide of the formula 18> method naßi> one of claims 1-5 _# B-3-1 and X5, characterized by the fact that the ^^ Ö ^. 19 «Vepfatipen liaQh one of the / Insprqhe 6 * 7 and. 101 characterized by the fact that the 4- (3 ^ 6 ^ 9 ^ TrlQxa.de.cyl.Qxy) rr 20. The compounds produced according to one of claims 1 to 19.
23 ,, Pyridazine-1-oxides of the general formula R ¹ -NO 2. I '. (ι) ^r 00 9 83 171 ti 8 · ^: ■ Ϊ. ■ Λ- where B ¹ and B "are either hydrogen atoms or together · an optionally substituted 1,3-butadienylene- (1,4) radical, R 'denotes hydrogen, a lower alkyl radical or an optionally substituted phenyl radical, R denotes a hydrogen atom or represents a lower alkyl radical, the symbols Alk mean lower alkylene radicals which separate the oxygen atoms by at least 2 carbon atoms and η stands for an integer from 2 to 9, Phthalazine-2-oxides of the formula AIk-O -) - R η wherein Alk is optionally substituted by methyl groups, ethylene (l, 2) - or propylene (l, 3) means radicals, R ¹ represents hydrogen, a methyl group or an unsubstituted phenyl group, Rg represents a hydrogen atom, a lower alkyl, a Niederalko-xygruppe or denotes a halogen atom, η denotes 2 or 3 ^un <i ^{R f} w ^{r is} lower alkyl groups . Pyridazine-1-oxides of the formula 009831/1918 (ι) where η stands for 2 or 3 ", R stands for lower alkyl radicals, R ^{1 stands for} hydrogen, a methyl group or an unsubstituted phenyl group and Alk stands for radicals of the formula -CH CH- stands, where R, and R _? Denote hydrogen atoms or methyl radicals, or radicals of the formula R, R "R- '* * | 3 ι * | 5 . - —CH- CH CH-, wherein R- to R ₁ - are hydrogen or methyl radicals. Pyridazine-1-oxides of the formula (I) 0 0 9 8 3 1/1918 -JC- where η is 2 or 3, R is a methyl or ethyl group., R '. Hydrogen and Alk is an ethylene (1,2) radical. 25. 3- (3 _J 6,9-trioxadecyloxy) -6-f2- (5-nitro-2-furyl). Vinyl] -pyridazine-1-oxide. 26. 4 ~ (3,6-Trioxadecyloxy _J 9) -l- [2- (5-nitro ~ 2-furyl) -vinylJ-phthalazin-2-oxide. 27. ² f- (5.6 _J 9.12 _J 15,18-hexaoxanonadecyloxy) -1- [2 ₇ (5-nitro-. • * 2-furyl) vinyl] phthalazine 2-oxide. The compounds described in the examples. 29. Pharmaceutical preparations containing compounds of the type shown in claims 21 to 26 together with a carrier material. 50. Pharmaceutical preparations containing compounds of the type shown in claim 27 together with a carrier material. 51 ·. Process for the preparation of pyridazines the general formula 009831/1918 wherein B 'and B "are either hydrogen atoms or together an optionally substituted 1,3-butadienylene- (1,4) radical, R' is hydrogen, a lower alkyl radical or an optionally substituted phenyl radical, R represents a hydrogen atom or a lower one Alkyl radical, the symbols Alk mean lower alkylene radicals which separate the oxygen atoms by at least 2 carbon atoms and η stands for an integer from ¹ Y to 9 and can also be 2 or 5 if B ¹ and B "optionally substituted .1,3-butadienylene (1,4) radical, characterized in that compounds of the formulas' and 0-f-Alk-O-) - R directly or stepwise with one another, where B ', B ", R, Alk and η have the meanings given above and X and Y have the meanings given in Claim 1, or compounds of the formula R '\ rt = CH- 00 9 83.1 / 1918 wherein B ', B ", R', R, Alk and η have the meanings given above have nitrated or compounds of the formulas and Y '- (- Λ Ik-O -) - R reacted with one another, in which B ', B ", R ¹ , R, Alk and η have the ^{meanings given above and X f} and Y' have the meanings given in claim 1." · 32 · The method according to claim 31, characterized in, that you can get compounds of the formula B ^f 0 - (- AIk-O-) -R wherein B ¹ , B ", Alk, R, R 'and η have the meanings given in claim% , reacted with 5-nitrofurfural or a reactive derivative thereof *. 35. The method according to any one of claims 51 and J2, characterized in that the ² l - (2,6,9-trioxcidecyloxy) ~ l- [2- (5-nitro-2-furyl) vinyl] phthalazln or the ^ - (3,6,9, 12,15, 18-hexaoxanonadecyloxy) -1- [2- (5-nitro-2-furyl ^> i-vinyl] phthalazine. 009831/1918 Pyridazine of the general formula ir * " where B ¹ and B ″ denote either hydrogen atoms or together an optionally substituted 1,3-butadiehylen- (l, * l) ^{radical, R 1} denotes hydrogen, a lower alkyl radical or an optionally substituted phenyl radical, R denotes a hydrogen atom or a lower alkyl radical, the symbols Alk mean lower alkylene radicals which separate the oxygen atoms by at least 2 carbon atoms and η stands for an integer from ^ to 9 _s and can also be 2 or 3, if B ¹ and B "optionally substituted l ^ -Butadienylen-Cl., ^ Jj -rest mean. 55. 4- (3,6,9-trioxadecyloxy) -1- [2- (5-nitro-2-furyl) vinyl] phthalazine and ⁱ f- (3j6j9il2 / 15jl8-hexaoxanonadecyloxy) -1- [2- (5-nitro-2-furyl) -vinyl] -phthalazln. 36. Pharmaceutical preparations containing compounds of the type shown in.den Claims 3 ^ and 35 together with a carrier material .. 009 8 3 1/1918 57.Disinfectants and preservatives, characterized by a content of pyridazine-1-oxides of the general formula (ι), O (-AIk-O) - ■ ■ - R where B 'and B "are either hydrogen atoms or together an optionally substituted 1,3-butadienylene- (1, R 'denotes hydrogen, a lower alkyl radical or an optionally substituted phenyl radical means R represents a hydrogen atom or a lower one Alkyl radical, the symbols Alk are lower alkylene radicals, which the oxygen a.tome by at least 2 carbon atoms separate, mean and η for an integer. 2 to 9 stands, 58. Disinfectants and preservatives, characterized by a content of pyridazines general formula 009831/1918 200202Λ η. where B ¹ and Β · ^{Μ are} either hydrogen atoms or together an optionally substituted 1./5-buta,dienylene (1,4) radical, R ^{f is} hydrogen, a lower "". ■ Alkyl radical or an optionally substituted phenyl radical meansj R stands for a hydrogen atom or a lower alkyl radical, the symbols Alk mean lower alkylene radicals which separate the oxygen atoms by at least 2 carbon atoms and η stands for an integer from 4 to 9, and also 2 or 3 if B ¹ and B ″ denote an optionally substituted 1,3-butadienylene (1> 4) radical.