DE2037964A1 - New nitrate derivatives and pharmaceutical preparations containing them - Google Patents

Description

Today's nitrone derivatives and pharmaceuticals containing them Preparations The invention relates to new Hitronderiyate with ex-

associated microbial activity. Also concerns the invention also includes pharmaceutical preparations that the new hit derivatives contain "

So far there are derivatives of H-substituted (5-nitro-2-furfurylidene) amine compounds known for their antimicrobial activity. However, these connections do not exist either unsafe toxicity and / or clay gel in effectiveness, so that their use is limited by these properties.

One object of the invention is new compounds with rewarded antibacterial, antifungal and anti-protoxal activities. "

Another object of the invention is new Hitrone derivatives that have the above properties.

Another object of the invention is new Hit derivatives that are useful as drugs both for humans and also for veterinary weekends and which continued in the fields of food, agricultural

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203796A

economy and the like »« gtw & nSt

In particular, Si® invention relates to Hitronder Irate according to the general »» eisi «a

IB ₂ (I)

where E _{1 is} a halogen, aryl phenyl substituent, E _{2 is} a phenyl group A- (X) _21, where A is a Α11ε | ^ρ 1®ιιγ®®Ί ssit 1 Me about 6 carbon atoms, X ®in Wasseretoffatoia ^ ®im @ hydroxyl group, furyl group, Allqrleulf © nylgyupp @ with ®ia @ r alkyl grouping clay 1 to about 4 carbon atoms _@ tiae aroylo ^ r group or an alkanoyloxj group ® old bucket Alkjlgruppierusig τοη 1 bie about 3 carbon formers imä η eim »ganss Sah! τοη represent about 1 blp about 3 «

Example «ffe 3ubetl * to®nten © Btapraehsad H ^ in the gate standing formula I are given naolif @ lg @ nd. The following Litte 1st _t je4ö @ fa may be understood as a limitation of the invention, but rather leiiglish sur explanation

Methyl ethyl propyl isopropyl butyl isobutyl Pentyl Htxyl Heptyl

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2-hydroxypropyl

1-Methy1-2-hydroxyethyl

1 _f 3-dihydroxy-2-propyl

2-hydroxyethyl

1,1-dihydroxyl-2-hydroxyethyl 2-? Urfuryl

Phenyl

2-methane sulfonyloxyethyl

2-acetyloxyethyl

2-benioyloxyethyl

2- (2-Carboxybensoyloxy) -ethyl Ä

and similar groupings.

Entepreohend dta Yoretenden are the following Compounds Examples of compounds entepreohend the general formula and are used only for illustration purposes

a - </ l-BroM-2- (5-nitro-2-furyl) -Tiny 3 / -Ι- «β-thylnitrone

a- / 1 -Bro »-2- (5-ntro-2-furyl) -tinyl / -I- (2-hydroxypropyl) -nitrone

-Bro "-2- (5-nitro-2-furyl) -Tiny \ / - I- (1-" ethyl-2-hydroxyethyl) -nitrone

-Bro "-2- (5-nitro-2-furyl) -tinyl / -I- (1,3-4inydroxy-2-propyl) -nitrone

α- / 1 -Bro «-2- (5-nitro-2-furyl) -rinyX / -! - (2-hydroxyethyl) - { nitrone

a- / i-Bro »r2- (5-nitro-2-furyl) -Tinyl7-I- (2-furfuryl) -nitrone a- / 1-Bro «-2- (5-nitro-2-furyl) -tinyl / -R-phenylnitrone

a - /! - Broa-2- (5-nitro-2-furyl) -riny] / - I- (2- «ethaniulf © nyloxyethyl> -nitrone

a- ^ T-Bro »-2- (5-nitro-2-furyl) -rinyi7-1- (2-» oetyloxyethyl) -nitrone

«- /? - (2-furyl) -2- <5-nitro-2-furyl) -Tinyl7-I-ethylnitrone

009 887/22 5 3

α- / ϊ "- (2-furyl) -2- (5-nitro-2-furyl) -tinyl / -H- (2-hydroxyethyl) -nitrone

α- / ΐ- (2-furyl) -2- (5-nitro-2-furyl) -Yiny ^ / - * - (2-furfuryl) -nitrone

α - ^ - (5-Hitro-2-furyl) -1-phtnylTiny ^ 7-H- (1-methyl-2-hydroxyethy1) -nitrone

a- / 5- (5-Hitro-2-furyl) -1-phtnylrinyi7-li (2-hydroxypropyl) -nitrone

α- ^ 2- (5-nitro-2-fluoryl) -1-phenyl-tinyi, 7-H-methylnitrone

a - ^ - (5-Mitro-2-furyl) -1-phtnylYiny] / -] | -hydroxyethyl) -nitrone

a./5-(5-Iitro-2-furyl)-1-phtnylTinyl/-H-(2-furfuryl) nitrone

Thus compounds of the formula I are tnttprtohtnd by using a carbonyl derivative «of the formula

ι I

OH-O-CHO (II)

E ₁

where R ^ breaks the Torttekes & d «meaning, with a ! -substituted hydroxylamine of the following formula

HO-IH ₂ (III)

where R ₂ the rusty meaning 'r:, ltx%, l & @ rg »etellt it sehliest ai ^ k at B $ nj &? © kondta @ ati®s & 9rfaction an and the 5" Iit? o-2-furylTisg ^> ämitr®ndtriTat <& «R Formula I is in good yields

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Sit at room temperature or may Umsetsung duroh Erhitsen dta Etaktionigtei "oh ·· τοη on trhöhtt temperature in about 20 Bertioh bit TTWA 100 ⁰ C wtrdtn performed. One can use τοη «aüilx ^ iobm solvents, jtdooh wtrdtn btrorsugt bti itr production of the compound I water, methanol, ethanol, Bioxane, Tetrahydrofuran, Bimtthylaulfoxyd and Pimtthylfomaeid applied. Sa iat out "uwti * tn" int catalytieoht depends on Esaigtäurt au dtm tactlonieyattm lugtattit, so that tint tohwaoheaurt care is trsitXt. Duroh dittt iaurt Btdingung treckt aioh tint Bt » ( Soluntunigung dtr condtniationtrtaktion, jtdooh itt dit application dta katalytieohtn materials but dtr gtwüntehttn connections nioht trfordtrlioh»

Ea iatn to make sure that one also daa frtit Hydroxylamine old auoh tin Sals the same in dtr gleiohtn Wtiat uaattstn can and gltioht Srgtbniaat trhalt. Bat SaIs aolltt jtdooh in combination ait auartiohtnd Baat Ttrwtndtt wtrdtn, so that the hydroxylamine from the SaIa frtigtattst is · Torsugawtiat rerwtndtt one inorganiciaoht Bases, wit latrium hydroxide, potassium carbonate and latrium bicarbonate, odtr organisoht Baeen, wit Vatriumaottat, Pyridine, sriäthylamine or dtrgl ·, odtr Otmiaoht hitrron.

Bit Torlitgtndtn Ttrbindtn can wtittrhln um- ™

gtattst wtrdtn, wtnn R ^ ^{ti: n} · ¹ ^ ¹ b * - * 3 hydroxyl groups subatitultrtt alkyl group means, with an alkyl sulfonic acid with 1 bia 4 carbon atoms in dtr alkyl group, tintr aryloarboxylic acid or tintr carbon atomic acid in the with about 3 ttttn Alkyl group or reactive dtrirattn, so that the special derivatives of the compounds mentioned here are formed.

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htit tiftöä gttlgattsa L6e% sagsmitt @ l, ® amsgsfltet to that Ait sptsifie @ h gewiaeeltem Dtrivatt wtrdtn®

It iit ameii WM © gtiSfemea © ioß Earn ®lntn

the sptsiell
Ss is aiioh (SarftMf & isiiswoä @ oa ₀ iQß

demanded

or lÄitaea i © s E © QÄti®moßoaio © kos in AlMMgigk®it voa dta sptsi £ is @ h £ & Beflia / gnieoM S®s> ^) ot; © il, igaa Wiasi © tsraag. -

fall, »üQa © i® Sfia ^ s-

bti € «§ :? ^ © iistiMöiill © ® Waos ^ siaa ^ © iasQtste hardly tint tes-tlteo orgaalseacf'Baste wt ©

for vtrwtndet w @ rd®m * if © im seuxtaalogoald aagaw «Mt becomes; tenxi m & n gewiasohtsrnfalle as Py r id in _t p-Soluelsialf © a © äiir · ₀ l®? telflm @ ^ Ttrwtadta · Palis dit Y®TOst @ £ wig alt eimtr Sä ^ r® is led »is advocated Srifta @ r @ e8i ^ §Ä% r®aiü ^ rdrid as Btsohltuaigtr tingts ^ tst «Biestr BtsehltiiyBlgtr ka & a tntvtdtr la tlatr ftqui ^ altiittn Mssgt @ ä®r im ®ia« r transfer «> sehttssigta Mtagt besüglieii dtr H @ xtrbi ^ tad aagfwaadt vtrdta. WIT TorstthtaS dargeltgt »needs ditstr

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Accelerators do not necessarily have to be Ttrwtndtt.

Desired failures can be done in solvent bti ditttr Dictionary tingtattst wtrdtn. St itt Jtdooh notioht necessary, tin Lttaungaaitttl su Ttrwtndtn, wtnn tntwtdtr dit acid or dtrtn reaction rate or dit Accelerator la Ioraalsuatand flttaaigktlttn tind · St It is important to note that the soldering agent must be used is applied, wtlchtt tnttprtohtnd dtn tpteifitehtn Eigtnaohafttn and dtn Arttn dtr AutgangtrtaktiontttilnthBtr t is chosen Btitpitlt for dtr-like L salary taitttl tind Btnsolt Xthtr, dioxane, pyridine and similar odtr Qtnitoht hitrron,

Dit ntutn Ttrbindentn dtr invention trwitttn tioh btiondtra effective bti dtr treatment τοη Xrankhtittn with aikrobitlltm origin. Bit Iltrondtrlratt gtaäl dtr Invention tind bttondtra effective bti dtr treatment τοη bacteritlltn, fungaltn or protoiotlltn disease. SIt Torlitgtndtn Ttrbindtn trwitttn tioh old äutttrat strong and rtlatir kltiat Botltrungtn hitrron are for action autrtiohtnd · Dit Torlitgtndtn Ttrbindingtn kttnntn bti dtr Btaktigung both “Ton Ntntoh old auoh Titr tntwtdtr topisoh, oral or durefe injection gtgtbtnfallt After compounding in pulp, ointments, fluidity odtr partnttraltn solderingtn old gttigntttn carrier and commonly used pnarmaeeutitohen aids be used. It is also pointed out, the dit Torlitgtndtn Ttrbindentn in a similar width, wlt dit other litrofurandtriTatt on dtn areas dtr Hahraaltttlt dtr Landwirtsohaft and the like, Ttrwtndtt Wtrdtn kttnntn where the removal or prevention of the Vaohβturns τοη microbial organisms is necessary

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The following examples provide a further explanation of the invention without the invention being imputed to them is limited.

example 1

Production of a- / i-bromo-2- (5-nltro-2-furvl) «» vinvl / ^ H-phenvlnitron (compound 1)

To a solution of 2.46 g of oc-bromo-ß- (5-nitro-2-furyl) -aorolein and 500 al of ethanol were added 1.42 g of phenylhydroxylamine and 0.2 ml of glacial acetic acid. The Umeetsung was kept stirring the mixture for a period of time carried out for about 2 hours at room temperature. The resulting precipitate was filtered off and taken from acetyl nitrile recrystallized, leaving 1.7 g of the desired Connection in the form of reddish orange hadels with a Sohmi point of 159 to 161 "C were obtained.

Example 2 Production of a- / i-bromo-2- (5-nitro-2-furyl) -

vinyl / -I- (2-methanesulfonylocyethyl) -nitrone (Connection 2)

The same procedure as in Example 1 was repeated, except that I- (2-methanesulfonylozyäthyl) hydroxylamine was used instead of phenylhydroxylamine. Green-yellow plates of the desired compound with an oil point of 152 to 153 ⁴ C were obtained.

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203796A

Btiapjtl 3

Production of τοη a- ^ i-bromo-2- (5-nitro-2-furyl) -Tinyl / -I- (2-aottyloxyethyl) - "nitrone (Compound 5)

The procedure described in Btispitl 1 was repeated, but instead of τοη pheny! hydroxylamine became II «. (2-aoetyloxyethyl) hydroxylamine used. There were pale yellow! Rebukes the desired connection bit Melting point τοη 131 bit 133 "C obtained.

Btitpitl 4 '

Production of τοη a- / i-Bro «-2- (5-nitro-2-furyl) -vinyl / -I-ethylnitrone (Ytr bond 4)

4 "92 g of a-Broa-ö- dissolved (5-nitro-2-furyl) -acroltin wurdtn in 80 al of ethanol BTL ¹ 65 C with stirring. 2.16 g of H-methylhydroxylamine hydrochloride and 2.1 g of sodium acetate were discharged and the reaction was kept at room temperature. Sa · Gemisoh was stirred for 6 hours. The precipitate was filtered off and the piltrate was concentrated to half a volume under Ttrringertta pressure. The residue obtained after cooling gave crystals that bit dta Toretthtndtn Hitder-Bοhlag were combined The crystals were recrystallized from ethanol, with 4.4 g of the desired ytrbonding from τgtlbtlbtlbtlbtlbtlbtlbtlbtlbtlbtlbtln bit a 3ohatIdtn bit a 3ohatIdtn from ethanol ⁰ C was obtained with Ztrattiung.

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ίο- 2C3 7364

Example 5 Production rom α-

The procedure as®h
but a-Phtnyl "e- (5 ° Kitr ©""2-furyl) -aeroIeiii instead of a-Broe-1- (5-nitro-2-furyl) -ftQrol" in watered. Sit gtwUnsoht · Ttr binding was kept in the form of τοη yellow plates with tin · * bottom point τοη 165 to 166 ¹ C underneath.

Beiipltl 6

of a- ^ 1- (2-puryl) «2- (5-nitro-2-furyl) -Yiny ^ /« »! ~ a« thylnitron (Ytrbond 6)

According to example 4, "wifd" rholt ₍ j · - dooh a- (2-furyl) -ß- (5 »aitro-2-furyl) -» m @ ^ © l «ia» nettll® τοη a-Bvo » »E» (5-nitro-2 «> fu77l) ->& 0 £ oieiii in« i «tst. Si · desired« Ytrbinding wu? 4 # in? ®s «τοη red orange Sad®la with tin« »melting point τοη 179 at 1SO ⁰ C with an extrusion.

BoJBPJel

Manufacture τοη ice and

furjl) -1-phenylTiny] / -! · (2-hjd? oxyethyl) »nitrone (Compound 7)

For a solution τοη 3 "H g eii" a "-Fhenyl-0- (5-nitro-2-furyl) -acrolein in 80 ml of ethanol a Ltftuag τοη 1.20 g of I- (2-Hydroxyäihyl) -hydroxyi & ala in 10 ^ igtr SaIs-

009 887/22 5 3

acid and 3 _f 67 g of sodium acetate added with stirring. The Qtmieoh was then heated to 50 to 55 ⁰ C. For about 1 hour, the reaction mixture was concentrated under reduced pressure and the residue was extracted with chloroform, washed with water and dried, whereupon chloroform was distilled off. Di · · remaining crystal were au uakristallleiert · a · öeaieoh au ethanol and hexane to give 3.13 g of the desired compound tob CiB type in Fora of yellow plates ait a melting point of clay were obtained 114 to 116 C ^11.

The mother liquor was evaporated to dryness and the RUokatand uakriatalliaiert on chloroform, whereby 0.15 g of the desired compound of the Trana type in the form yellow ladein with a Sohmeltpunkt τοη 162 to 164 <C were obtained.

leisriel 6

Production of τοη o- / T-Brem-2- (5-nitro-2-furyl) -Tinyi7-I- (2-hydroxyllthyl) -nitron (Compound 8)

The procedure of Example 7 was repeated, however α-Bromo-8- (5-nitro-2-furrl) -acrolein instead of τοη ois-a-phenTl-e- (5-nltro-2-furTl) -aorolein reserved. The desired compound was obtained with a melting point of 160 to 162 ° C.

Example 9

Production τοη ois- and trane-a - / ^ - (2-puryl) -2- (5-nitro-2-furyl) -Tiny \ / - H- (2-hydroxyethyl) -nitron (compound 9)

009887/2253

Bat Yerfahrtn naoh Example 1 was repeated, jedooh oie- odtr trans-a- (2-iuryl) -ß- (5-nitro-2-furyl) -aorolein instead of τοη ois-a-phenyl-ß- (5-nitro- 2-furyl) aoroltine is used. Si · gewüneohten OIE and trans forms of the compound as an orange yon ladein having a melting point or 169 to 17O ⁰ C with decomposition, 120 receive to 122 ⁰ C with decomposition.

Example 10

Production of τοη a- / i »Bromo-2- (5-nitro-2-furyl) -Tinyl7-H- (2-hydroxypropyl) -nitron (Compound 10)

The procedure according to Example 8 was repeated but I- (2-Hydrozypropyl) -hydroxylamin instead of τοη N- (2-Hydroxyäthyl) -hydroxylamine Terwendet. Ee green yellow! Needles of the desired compound with a melting point τοη 124 get to 126 ⁰ C "

Example 11

Production of τοη a- / i-bromo-2- (5-nitro-2-furyl) -tinyl / -I- (1-methyl-2-hydroxyethyl) -nitrone (Compound 11)

The method NaOH Example 8 was repeated, jedooh I- (1-methyl-2-hydroxyethyl) hydroxylamine instead τοη I- (2-hydroxyethyl) hydroxylamine · Terwendet were yellow ladein of the desired compound having a melting point of 191 to 193 τοη ¹ C received.

009887/2253

Example 12

Production τοη a - ^ - bromo-2- (5-nitro-2-furyl) Tinyl / -H- (2-furfuryl) -nitrone (compound 12)

The procedure according to Example 0 was repeated, using N- (2-furfuryl) -hydroxylamine instead of τοη H- (2-hydroxyethyl) -hydroxylamine. Green-yellow needles of the desired connection with a Sohmel point τοη 158 to 159 ⁰ C were obtained.

Example 13

Production τοη a- / 2- (5-nitro-2-furyl) -1-phenyl-Tiny3 / -N- (1-me ethyl-2-hydroxyethyl) nitrone (compound 13)

The process of Example 11 was repeated, except that α-phenyl-β- (5-nitro-2-furyl) -acrolein was used instead of α-broa-β- (5-nitro-2-furyl) -aorolein. Yellow needles of the desired connection with a Sohmel point τοη 152 to 154 ⁰ C were obtained.

Example U

Production τοη <* - / §- (5-Nitro-2-furyl) -1-phenyl-TinyV ^> -N- (2-hydro3typropyl) -nitron (compound H)

The procedure according to Example 13 was repeated, using N- (2-hydroxypropyl) hydroxylamine instead of τοη N- (1-Hethyl-2-hydroxyethyl) -hydroxylamine Terwendet · Dabe i

009887/2253

-H- 2l3 "36 A

Yellow needles of the desired compound with a Sohmel point τοη 136 to 157 ¹ C were obtained.

Example 15

Manufacture τοη a- / i-bromo-2- (5-nitro-2-furyl) -Tiny3, / - N- ( 1,3-dihydroxy-2-propyl) nitrone (compound 15)

The procedure according to Example 12 was repeated, except that N- (1,3-dihydroxypropyl) -hydroxylamine was used instead of N- (2-furfuryl) -hydroxylamine. Green-yellow needles of the desired compound with a melting point τοη 186 to 187 ⁴ C were obtained.

Example 16

Production τοη eis- and trans-a- / 2- (5-nitr © -2-furyl) -1-phenylTinylZ-N- (2-furfuryl) -ni tron (connection 16)

The process of Example 12 was repeated, but with ois- or trans-a-phenyl-B- (5-nitro-2-furyl) -aorolein instead of τοη a-Broa-B- (5-nitro-2-furyl) -aorolein The ice shape of the desired connection was used in the form of τοη orange plates with a Sehmeispunkt τοη 138 to HCK! and the trane-fora in the form of yellow-orange needles sait a Sohmel point τοη 168 to 169 ⁰ C received. .

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ORIGfNAL «slSFECTED

Btispitl 17

Production of τοη ois- and trans-a- / i- (2-furyl) -2- (5-nitro-2-furyl ) vinyl, / - I- (2-furfuryl) nitrone Connection 17)

The procedure was repeated in Example 16, but ois- or trans-α- (2-furyl) -ß- (5-nitro-2-furyl) -aorolein instead of τοη oi - or trans-a-Phsnyl-ß- ( 5-nitro-2-furyl) acrolein is used. Ee needles with a Sehmeli point τοη 157 to 158 ⁰ C (cis type) and 140 bit UI ⁰ C (trans type) were obtained «

Example 18

Production of τοη a- / i-bromo-2- (3-nitro-2-furyl) -tinyl / -I-2-ethaneulfonyl-oryethyl) -nitrone

To a solution τοη 1.0 g of a -> / i-bromo-2- (5-nitro-2-furyl) -Tinyl7-S- (2-hTdroxyäthyl) -nitron in θ al anhydrous pyridine were with cooling 0.5 g methanesulfonyl chloride sugesetst. The reaction mixture was allowed to stand with stirring at room temperature for 1 hour. Ban was sugegeben water sum Reaktionsgemisoh and the precipitated yellow crude crystals filtered off, washed {overall with water and recrystallized from ethanol to give 1.02 g of the desired compound as a yellow-green plates τοη having a melting point were obtained from 152 to 153 ⁰ C.

009 887/22 5 3

Example 19

Production of τοη a- / T-bromo-2- (5-nitro-2-furyl) -I- (2-aeetyloxyethyl) nitrone

To a solution of 1.0 g of a - ^ - bromo-2- (5-nitro-2-furyl) -yynyl / -H- (2-hydroxyethyl) -nitrone in 8 ml of anhydrous pyridine, 1 ml of acetic anhydride was added with cooling . The reaction was carried out by stirring at room temperature for about 2 hours. Then water was added to the reaction mixture and stirring was continued for 30 minutes to decompose the excess acetic anhydride. The precipitated crystals were filtered off and washed with water. The crude crystals obtained were recrystallized from ethanol and gave 1.5 g of the desired compound in the form of yellow-orange needles with a melting point of 131 to 133 ¹ C.

Example 20

This example illustrates the excellent antimicrobial Activities of the compounds according to the invention on the basis of τοη results τοη in vitro experiments. The compounds of the invention show particularly strong activities against Gram-positive in vitro Bacteria such as Staphylococcus aureus and Myoobaeterium tuberculosis, gran-negative bacteria, such as Eseherlohla ooll and Shigella flezneri, fungi, such as Candida alblcans and Triohophyton asteroides and protozoa such as TrlohovaginalIs.

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In the following table I are the activities of the compounds according to the invention in ritro against one Variety of clay microorganisms grouped together. You minimal Inhibitory concentration (MIC) was determined according to the known series of dilution methods.

In the following tables, the compounds 1 to 17 correspond to those of the examples, while the Compound A, which serves as a control, from N- (5-nitro-2-furfurylidene) «3-aoetylaniline consists.

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Table I.

■ connection 1 3 2 3 4th 6th 8th 9 10 11 12th 14th 3 15th 16 17th A. Organism -—— ^ 10 10 0.3 1 3 1 0.3 3 1 1 10 3 1 3 3 100 Staphylocous
aureus - 0.03 1 0.1 0.3 0.01 1 0.0? 0.1 - 0.3 1 0.3 - Batilus
• ubtlti 30th 1 1 0.3 3 0.3 K 0.3 1 3 3 ( 1 > 30 30th 30th 009887 / Eseheriohia
eoli - 1 3 - 10 1 3C 0.3 1 - - 1 - - 30th 225 Salmonella
tTPhlKurium 10 3 3 1 3 3 K 10 10 30th K > 10 1 3 30th Sfyeob & oteriua
tuberculosi - - 10 0.3 - 1 - 1 10 - * - 3 - 100 Candida
albicana 10 3 3 10 10 K 10 - 30th M. - 10 - 100 fifiehopbyton
asteroid®s 3 1 1 1 1 K 1 1 3 > 30 3 3
j 30th Triohomonas
vaginal! a

HIC: aeg / ml

2Ö3 7 964-

In Tables II and III are the activities of the compounds in yIto found infection with Salmonella typhimurium and Triohomenas raginalii in Mäuen iu-

together.

Infection with Salmonella typhus

10 mice of each group were intraperitoneally infected with 0.5 ml of a bacterial _{euipenion containing 1000 LD 50} of Salmonella typhimurium * 6.25, 12.5, 25 and 50 mgAg of the Yereuoher binding were terabreioht orally twice a day for 4 days , the first treatment being carried out immediately after infection. After observation for 2 weeks, the efficacy was given by the survival value (survivors of animals). The results are given in Table II.

Table II

~~~ _ connection
Dosage - ^ 5 4th 8th 9 11 8th 50 * gAg
25th
12.5
6.25 10/10
9/10
3/10 6/10
3/10 10/10 6/10
3/10
1/10 9/10
5/10
4/10
2/10 7/10 untreated
Yergleioh O / IO ^BB 50 6.25 «9.5 * 35.4 i 35 .4 17.7 <25

00 9 8 S7. .'25 3

2Ü37964

Infection ait Triohomonas vaginalii

6 mice of each group were injected intraperitoneally with 0.1 ml of a protozoan neoplasm (Triohomonas Taginalia) containing 10 'cells infected and orally 125 and 250 mg / kg of association pre-binding at one time Administered 1 hour after infection. On the 7th day after the infection, the mice were killed and the presence τοη viable protozoa in the intraperitoneal cavity abscesses formed during cultivation are examined. The results are given in Table III.

Table III

- "» «^ jrer binding
Dosage ^^ - ~ --- »^^^ 675 680 664 666 686 671 691 698 699 ■ «Λ«
250
125
62.5 4/6
1/6
0/6 4/6
0/6 5/6
2/5
1/6 3/6 4/6
3/6 3/6 3/6 3/6 3/6 niohtbehmndeltt
Control 0/6

(Number of mice without visible · Pro tozosr / examined Mice)

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Claims (16)

Claims A. Nitrone derivatives with antimicrobial activity according to the formula WED ₂ - CH-C-CH-I-R I wherein R ₁ and R ₂ tine phenyl group or a group A- (X) _{n y} a halogen, furyl or Phenyleubetitutnttη wherein A is an alkylene radical ait 1 to about 6 carbon atoms, X is a hydrogen atom, group a hydroxyl {a Turylgruppe , Alkylsulfonyl group with an alkyl group of about 1 to 4 carbon atoms, an aroyloxy group, or an alkanoyloxy group with an alkyl group of about 1 The about 3 carbon atoms and η represent a whole number τοη about 1 to about 3 » 2. As litronderiTat naoh claim 1 a - / ^ - bromo-2- (5-nitro-2-furyl) -tinyl / -l-methylnitron. 3 · As a litronderirat according to claim 1 a- / i-bromo-2- (5-nitro-2-furyl) -yinyl / -H- (2-hydroxypropyl) -nitrone « 4. As a Hitronderirat naoh claims 1 a- / 1-bromo-2- (5-nitro-2-furyl ) -riny3, / - H- (1-methyl-2-hydroxyethyl) -nitrone. ' 5. As a nitrone rat according to claim 1 a- / i-bromo-2- * C 5-nitro-2-furyl) -rinyl / -H- (1,3-dihydroxy-2-propyl) - nitrone. 6. As a litronderirat according to Claim 1 a- ^ T-bromo-2- (5-nitro-2-furyl ) -yiny ^ -1Τ- (2-hydroxyethyl) nitrone. 0098 87/2253 7 «As a nitrone derivative naoh Anepruoh 1 a - ^ / i-BroM-2- (5-nitro-2-furyl) -Tiny1 / -H- (2-furfuryl) -nitrone. 8. As a litrondtrivat naoh Anepruoh 1 oc - ^ - Brom-2- (5-ni tro-2-furyl) -TinyJ, / - H-phtnylnitron 9 Al HitrondtriTat naoh Anepruoh 1 a- / i-Bron-2- (5-nitro-2-furyl) -Tinyl / -H- (2-Btthaneulfonyloxyäthyl) -nitron 10 Old Nitrondtrivat naoh Anepruoh 1 a- / i-Bromo-2- (5-nitro-2-furyl) -Tinyl / -H- (a-aottyloxyethyl) -nitrone. 11. Al · HitrondtriTat naoh Anepruoh 1 a- / i- (2-Turyl) -2- (5-nitro-2-furyl) -Tinyl / -H-methylnitrone. 12 · As a nitrone triTate according to claim 1 a- / i- (2-furyl) -2- (5-ni tro-2-furyl) -TinylZ-H- (2-hydro3tyMthyl) -nitron 13. Al · nitrone derivative naoh Anepruoh 1 a- / i- (2-furyl) -2- (5-nitro-2-furyl) -tynyl / -M- (2-wrfuryl) -nitrone. 14 Al nitrone derivative naoh Anepruoh 1 a- / 2- (5-Hitro-2-furyl ) -1-phtnylTinyl / -H- (1-methyl-2-hydroxyethyl) -nitrone. 15 Al nitrone derivative naoh Anepruoh 1 a- / 2- (5-nitro-2-furyl ) -1-phenylTinyl / -H- (2-hydroxypropyl) -nitrone. 16. Ale HitrondtriTat naoh Anepruoh 1 a »/ 2- (5-Hitro-2-furyl) -1-phtnylTiny1 / -H-Btthylnitron · 17 Ale HitrondtriTat naoh Anepruoh 1 a- / 2- (5-Hitro-2-furyl) -1-phtnylTinyl / -H- (2-hydroxyethyl) nitrone 16. Ale HitrondtriTat naoh Anepruoh 1 a- / 2- (5-Hitro-2-furyl) -1-phtnylTinyl / -H- (2-furfuryl) -nitrone, 19 · Pharmaceutical accessories »gtktnnstiohntt duroh dtn content ink HitrondtriTate dtr formula WOg. I I -CH-C-CH-H-R "1 009837/2253 wherein R ₁ · 1η · η halogen, puryl or phenyl substituents and R ₂ «in · Phtnylgruppt or« int group A- (X) _n signify, where A is an alkylene group with 1 to about 6 carbon atoms, X is a Waeeeratoffatoa, a hydroxyl group , a furyl group, an alkyleulfonyl group with an alkyl grouping τοη 1 to about 4 carbon atoms, an aroyloxy group or an alkanoylozygruppe with an alkyl grouping τοη 1 to about 5 carbon atoms and η an integer τοη about 1 to about 3. 009887/2253