CS197256B2 - Method of producing basicly substituted 2-alkoxycarbonyl-amino-benzimidazol-5/6/-yl-phenyl ethers and ketones - Google Patents

Method of producing basicly substituted 2-alkoxycarbonyl-amino-benzimidazol-5/6/-yl-phenyl ethers and ketones Download PDF

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CS197256B2
CS197256B2 CS789087A CS908778A CS197256B2 CS 197256 B2 CS197256 B2 CS 197256B2 CS 789087 A CS789087 A CS 789087A CS 908778 A CS908778 A CS 908778A CS 197256 B2 CS197256 B2 CS 197256B2
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aminoaniline
phenoxy
benzoyl
phenylthio
methylethoxy
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CS789087A
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Czech (cs)
Inventor
Heinz Loewe
Josef Urbanietz
Dieter Duewel
Reinhard Kirsch
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Hoechst Ag
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Description

Vynález se týká způsobu výroby bazicky substituovaných 2-alkoxykarbonylaminobenzimid,azol-5(6)-ylfenyletherů a -ketonů.The invention relates to a process for the preparation of basic substituted 2-alkoxycarbonylaminobenzimide, azol-5 (6) -ylphenyl ethers and ketones.

Deriváty 2-alkoxykarbonylaminobenzimidazolu s alkylovými zbytky, acylovými zbytky, fenojxyskupinami a fenylthioskupinami v poloze 5(6) jsou již jako anthelmintika zná»<2-Alkoxycarbonylaminobenzimidazole derivatives with alkyl radicals, acyl radicals, phenoxy and phenylthio groups in the 5-position (6) are already known as anthelmintics »<

'n-y-o v němž'n-y-o in which

R3 znamená alkylový zbytek s 1 až 4 atomy uhlíku,R3 represents a C1-C4 alkyl radical,

X znamená kyslík, síru nebo skupinu \X is oxygen, sulfur or a group \

C=O,C = O,

ZOF

Y znamená přímou nebo rozvětvenou alkylenovou skupinu s 1 až 4 atomy uhlíku aY represents a straight or branched alkylene group having 1 to 4 carbon atoms and

Ri a R2 znamenají alkylový zbytek s 1 až 4 atomy uhlíku, přičemž oba zbytky Ri a R2 spolu s atomem dusíku, na který jsou vázá2 má [srov. P. Actor a další, Nátuře 215, 321 (1967), DOS 2 029 637, DOS 2 164 690).R 1 and R 2 are C 1 -C 4 alkyl, both R 1 and R 2 together with the nitrogen atom to which they are attached 2 has [cf. Actor et al., Nature 215, 321 (1967), DOS 2 029 637, DOS 2 164 690).

Předmětem vynálezu jsou anthelminticky účinné bazicky substituované 2-ialkoxyíktarbonylaminobenzlmidazol-5 (6) -ylfenylethery a -ketony vzorce 1 <ÍC-NHCOORS H (1) ny, mohou znamenat také piperidinový nebo morfolinový kruh.The present invention is effective anthelmintic base-substituted 2-ialkoxyíktarbonylaminobenzlmidazol-5 (6) -ylfenylethery and -ketones of the formula 1 <i NHCOR C-H (1) ny may also be a piperidine or morpholine ring.

Jako alkylové zbytky v substituentech Ri, R2 a R3 přicházejí v úvahu zejména methyl, ethyl, propyl, isopropyl, butyl, sek.butyl a terč.butyl. Jako alkylenová skupina Y přichází v úvahu zejména skupina ethylenová, propylenová, butylenová, methylethylenová, methylpropylenová a dimethylethylenová.Suitable alkyl radicals in the substituents R1, R2 and R3 are, in particular, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl and tert-butyl. Particularly suitable alkylene groups Y are ethylene, propylene, butylene, methylethylene, methylpropylene and dimethylethylene.

Předmětem vynálezu je dále způsob výroby bazicky substituovaných 2-alkoxykarhonyluminobenzimidazol-5( 6 j -ylíenyletherů a -ketonů vzorce 1, v němž Ri, R2, R3, X aThe present invention further provides a process for the preparation of a base-substituted 2-alkoxycarbonyluminobenzimidazol-5 (6'-ylphenyl ethers and ketones of formula 1) wherein R 1, R 2, R 3, X and

Y mají shora uvedené významy, který spo197256Y have the above-mentioned meanings, which spo197256

197238 čivá v tom, že se derivát o-fenylendiaminu vzorce 2197238 is clear in that the o-phenylenediamine derivative of formula 2 is used

v němžin which

Ri, R2, X a Y mají stejné významy jako ve vzorci 1, kondenzuje s kyanamidkarboxylátem vzorce 4R1, R2, X and Y have the same meanings as in Formula 1, condensing with the cyanamide carboxylate of Formula 4

NC—N—COORsNC — N — COORs

H (4), v němžH (4), in which

R3 má stejný význam jako ve vzorci 1, v rozmezí pH 1 až 6, výhodně 2 až 5.R 3 has the same meaning as in formula 1, in the range of pH 1 to 6, preferably 2 to 5.

2-alkoxykarbonyIaminobenzlmidazol-5(6)-ylfenylethery vzorce 1, získané postupem podle vynálezu, se mohou, pokud je to žádoucí, převádět přidáním fyziologicky použitelné kyseliny na odpovídající sůl; jako kyseliny se hodí pro tento účel anorganické kyseliny, jako například kyselina chlorovodíková, kyselina sírová, kyselina fosforečná nebo organické kyseliny, jako například kyselina octová, kyselina mléčná, kyselina aceturová, kyselina jantarová, kyselina vinná, kyselina glukuronová nebo kyselina citrónová.The 2-alkoxycarbonylaminobenzimidazol-5 (6) -ylphenyl ethers of the formula I obtained by the process of the invention can, if desired, be converted into the corresponding salt by addition of a physiologically acceptable acid; acids suitable for this purpose are inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid or organic acids such as acetic acid, lactic acid, acetic acid, succinic acid, tartaric acid, glucuronic acid or citric acid.

Zvláště dobře jsou účinné takové sloučeniny vzorce 1, v němž Ri a R2 znamenají methyl nebo ethyl nebo společně s atomem dusíku, na který jsou vázány tvoři piperidinový kruh, v němž Y znamená skupinu — (CH2)z— nebo — (CH2)3— a Rs znamená methyl, zatímco X znamená kyslík, síru nebo skupinu C—O.Especially well effective are those compounds of formula 1 wherein R 1 and R 2 are methyl or ethyl or together with the nitrogen atom to which they are attached form a piperidine ring wherein Y is - (CH 2) 2 - or - (CH 2) 3 - and R 5 is methyl, while X is oxygen, sulfur or C-O.

Průběh reakce lze znázornit následujícím reakčním schématem:The course of the reaction can be illustrated by the following reaction scheme:

CH3-0 (15) I WCH 3 -O (15) IW

(12)(12)

N-y-o (2).N-γ-o (2).

OTNH’·^OT NH '· ^

ΝΗ^«—ΝΗ ^ «-

N-Y-0 ,11, nc-nc* + (10) (2)4-(4,) ->N-Y-0.11, nc-nc + (10) (2) 4- (4 ') ->

CtC00R3 (9)CtC00R 3

N-Y-0N-Y-O

NC-N-COPR^ H (4) (1) HNC-N-COPR 1 H (4) (1) H

197258197258

Při provádění reakce podle vynálezu se přidá nejprve ester kyseliny chlormravenčí vzorce 9 k vodné suspenzi kyanamidu ve formě soli, výhodně vápenaté soli vzorce 10, přičemž se reakční teplota udržuje chlazením mezi 40 a 60 °C.In carrying out the reaction according to the invention, the chloroformic acid ester of formula 9 is first added to the aqueous suspension of cyanamide in the form of a salt, preferably the calcium salt of formula 10, while maintaining the reaction temperature by cooling between 40 and 60 ° C.

Po odfiltrování vyloučených tmavých vedlejších produktů se ve filtrátu získá kyanamid-karbdxylát vzorce 4.After filtering off the precipitated dark by-products, the cyanamide carbonyl oxylate of formula 4 is obtained in the filtrate.

Takto získaný kyanamidkarboxylát vzorce 4 se smísí s přídavkem derivátu o-fenylendiaminu a směs se přidáním minerální kyseliny, například koncentrované kyseliny chlorovodíkové, upraví na hodnotu pH mezi 1 a 6, výhodně mezi 2 a 4. Za účelem reakce se udržuje reakční směs účelně mezi 30 a 100 st. Celsia, a to podle reaktivity derivátu o-fenylendiaminu po dobu mezi 30 minutami a 10 hodinami. Po ochlazení reakční směsi se vyloučený reakční produkt vzorce 1 izoluje odfiltrováním a promytím.The cyanamide carboxylate 4 thus obtained is mixed with the addition of the o-phenylenediamine derivative and the mixture is adjusted to a pH of between 1 and 6, preferably between 2 and 4 by addition of a mineral acid such as concentrated hydrochloric acid. and 100 st. Celsius, depending on the reactivity of the o-phenylenediamine derivative for between 30 minutes and 10 hours. After cooling the reaction mixture, the precipitated reaction product of formula 1 is isolated by filtration and washing.

Derivát o-fenylendiamipu vzorce 2 se může používat buď ve formě volného aminu, nebo ve formě adiční soli s vhodnou anorganickou nebo organickou kyselinou, jako kyselinou chlorovodíkovou, kyselinou sírovou, kyselinoů octovou, kyselinou šťavelovou nebo pod.The o-phenylenediamip derivative of formula 2 can be used either in the free amine form or in the form of an addition salt with a suitable inorganic or organic acid such as hydrochloric acid, sulfuric acid, acetic acid, oxalic acid or the like.

Jako estery kyseliny chlormravenčí vzorce 9 přicházejí v úvahu například: methylester kyseliny chlormravénčí, ethylester kyseliny chlormravenčí, propylester kyseliny chlormravenčí, isopropylester kyseliny chlormravenčí, butylester kyseliny chlormravenčí, isobutylester kyseliny chlormravenčí a terc.butylester kyseliny chlormravenčí.Suitable chloroformic acid esters of the formula 9 include, for example: methyl chloroformate, ethyl chloroformate, propyl chloroformate, isopropyl chloroformate, butyl chloroformate, isobutyl chloroformate and tert-butyl chloroformate.

Jako deriváty o-fenylendiaminu vzorce 2 přicházejí v úvahu například:Examples of suitable o-phenylenediamine derivatives of formula (2) are:

4- [ 4- (2-dimethy laminoethoxy) f enoxy ] -2-aminoanilin,4- [4- (2-dimethylaminoethoxy) phenoxy] -2-aminoaniline,

4-(4-(3-dimethylaminopropoxy) f eno/xy ] -2-aminoanilin,4- (4- (3-dimethylaminopropoxy) phenoxy) -2-aminoaniline,

4-(4-(4-dimethylaminobutoxy jfenoxy ] -2-aminoanilin,4- (4- (4-dimethylaminobutoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dimethylamino-l-methylethoxy J fenoixy ] -2-aminoanilin,4- [4- (2-dimethylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dimethylamino-2-methylethoxy) fenoixy ] -2-aminoanilin,4- [4- (2-dimethylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dimethylamino-l, 2-dimethy lethoxy j fenoixy j -2-aminoanilin,4- [4- (2-dimethylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-(4-(2-diethy laminoethoxy j fenoixy ] -2-aminoanilin,4- (4- (2-diethylaminoethoxyphenoxy) -2-aminoaniline,

4-[ 4-(3-diethylaminopr opoxy)fenoly]-2-aminoanilin,4- [4- (3-diethylaminopropoxy) phenols] -2-aminoaniline,

4- [ 4- (4-diethy laminobutoxy j f enotxy ] -2-aminoanilin,4- [4- (4-diethylamino-butoxy-phenoxy) -2-amino-aniline,

4- [ 4- (2-diethy lamino-l-methy lethoxyf enolxy ] -2-aminoanilin,4- [4- (2-diethylamino-1-methylethoxyphenolxy) -2-aminoaniline,

4- [ 4- (2-diethy lamino-2-methy lethoxy) f enqxy ] -2-aminoanilin,4- [4- (2-diethylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-diethylamino-l,2-dimethy lethoxy) fenoixy ] -2-amlnoanllin,4- [4- (2-diethylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dipropylaminoetho'xy) fenoixy ] -2-aminoanilin,4- [4- (2-dipropylaminoethoxy) phenoxy] -2-aminoaniline,

4-[4-(3-dipropylaminc»propoxy)f enolxy ]-2-aminoanilin,4- [4- (3-dipropylaminopropoxy) phenoxy] -2-aminoaniline,

4-(4-(4-dipropylaminobutoxy) fenoixy ] -2-aminoanilin,4- (4- (4-dipropylaminobutoxy) phenoxy) -2-aminoaniline,

4-(4-(2-dipr opylamino-l-methy lethoxy ] fenoxy ] -2-aminganilin,4- (4- (2-dipropylamino-1-methylethoxy) phenoxy] -2-aminganiline,

4- [ 4- [ 2-dipropylamino-2-methy lethoxy J fenoxy ] -2-aminoanilin,4- [4- [2-dipropylamino-2-methylethoxy] phenoxy] -2-aminoaniline,

4- [ 4- (2-dipropylamino-l,2-dimethy lethoxy J fenoxy ] -2-aminoanilin,4- [4- (2-dipropylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-diisopropylaminoethoxy) fenoxy ] -2-aminoanilin,4- [4- (2-diisopropylaminoethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (3-diisoproipylaminopropoxy J fenoxy ] -2-aminoanilin,4- [4- (3-diisoproipylaminopropoxy) phenoxy] -2-aminoaniline,

4-(4-(4-diisopropy laminobutoxy j fenoxy ] -2-aminoanilin,4- (4- (4-diisopropylaminobutoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-diisopropylamino-l-methyletho'xy j fenoxy ] -2-aminoanilin,4- [4- (2-diisopropylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4-(4-(2-diisopropylamino-2-methy lethoxy J fenoxy]-2-aminoanilin,4- (4- (2-diisopropylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-diisopropylamino-l,2-dimethylethoxy J fenoxy ] -2-aminoanilin,4- [4- (2-diisopropylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dibuty laminoethoxy j fenoxy ] -2-aminoanilin,4- [4- (2-Dibuto laminoethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (3-dibutylaminopropoxy) fenoxy ] -2-aminoanilin,4- [4- (3-Dibutylaminopropoxy) phenoxy] -2-aminoaniline,

4- [ 4- [ 4-dibuty laminobutoxy) fenoxy ] -2-aminoanilin,4- [4- [4-Dibutylaminobutoxy) phenoxy] -2-aminoaniline,

4-(4-(2-dibutylamino-l-methy lethoxy ] fenoxy ]-2-aminoanilin,4- (4- (2-dibutylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dibutylamino-2-methy lethoxy) fenoxy ]-2-aminoanilin,4- [4- (2-Dibutylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 4- (2-dibuty lamino-1,2-dimethy lethoxy) fenoxy ]-2-aminoanilin,4- [4- (2-Dibuto lamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-(4-(2-piperldy lethoxy j fenoxy ] -2-aminoanilin,4- (4- (2-piperidinoethoxy) phenoxy] -2-aminoaniline,

4-(4-(3-piperidylpr opoxy) fenoxy ] -2-aminoanilin,4- (4- (3-piperidylpropoxy) phenoxy] -2-aminoaniline,

4-(4-( 4-piperidylbutoxy ] fenoxy ] -2-aminoanilin,4- (4- (4-piperidylbutoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-piperidyl-l-methylethoxy j fenoxy ] -2-aminoanilin,4- (4- (2-piperidyl-1-methylethoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-piperidyl-2-methy lethoxy) fenoxy ] -2-aminoanilin,4- (4- (2-piperidyl-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-piperidyl-l,2-dimethylethoxy) fenoxy ]-2-aminoanilin,4- (4- (2-piperidyl-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-morf olylethoxy ] fenoxy j-2-aminoanilin,4- (4- (2-morpholylethoxy) phenoxy) -2-aminoaniline,

4-(4-( 3-morf oly Ipropoxy j fenoxy ] -2-aminoanilin,4- (4- (3-morpholylpropoxy) phenoxy] -2-aminoaniline,

4-(4-( 4-morf olylbutoxy j fenoxy ] -2-aminoanilin,4- (4- (4-morpholylbutoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-morf oly 1-1-methylethoxy) fenoxy ] -2-aminoanilin,4- (4- (2-morpholyl-1-methylethoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-morf olyl-2-methy lethoxy) fenoxy ] -2-aminoanilin,4- (4- (2-morpholyl-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(4-( 2-morf olyl-l,2-dimethylethoxy) fenoxy j-2-aminoanilin,4- (4- (2-morpholyl-1,2-dimethylethoxy) phenoxy) -2-aminoaniline,

4- [ 3- (2-dimethylaminoethoxy j fenoxy ] -2-aminoanilin,4- [3- (2-dimethylaminoethoxy) phenoxy] -2-aminoaniline,

4-(3-( 3-dimethylaminopropoxy) fenoxy ] -2-aminoanilin,4- (3- (3-dimethylaminopropoxy) phenoxy) -2-aminoaniline,

4-(3-( 4-dimethylaminobutoxy j fenoxy ] -2-aminoanilin,4- (3- (4-dimethylaminobutoxy) phenoxy] -2-aminoaniline,

4-(3-( 2-dimethylamino-l-methylethoxy) fenoxy ]-2-aminoanilin,4- (3- (2-dimethylamino-1-methylethoxy) phenoxy) -2-aminoaniline,

197236197236

4- [ 3- (2-dimethylamino-2-methy lethoxy) f enoxy ] -2-aminoanilin,4- [3- (2-dimethylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(3-(2-dimethylamino-l,2-dimethylethoxy) f enoxy ] -2-aminoanilin,4- (3- (2-dimethylamino-1,2-dimethylethoxy) phenoxy) -2-aminoaniline,

4-(3-(2-diethylaminoethoxy) fenoxy]-2-aminoanilin, # 4- (3- (2-diethylaminoethoxy) phenoxy] -2-aminoaniline, #

4- [ 3- (3-diethylaminopropoxy] fenoxy ] -2-aminoanilin,4- [3- (3-diethylaminopropoxy) phenoxy] -2-aminoaniline,

4- [ 3- (4-diethylaminobutoxy} fenoxy ]-2-aminoanilin,4- [3- (4-diethylaminobutoxy) phenoxy] -2-aminoaniline,

4- [ 3- (2-diethylamino-l-methylethoxy) fenoxy ]-2-aminoanilin,4- [3- (2-diethylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 3- (2-diethylamino-2-methylethoxy) fenoxy ]-2-aminoanilin,4- [3- (2-diethylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(3-(2-diethy lamino-1,2-dimethy letholxy) fenoxy ] -2-aminoanilin,4- (3- (2-diethylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 3- (2-dipropylaminoethoxy) fenoxy ] -2-aminoanilin,4- [3- (2-dipropylaminoethoxy) phenoxy] -2-aminoaniline,

4- [ 3- (3-dipropylaminopropoxy) fenoxy ] -2-aminoanilin,4- [3- (3-dipropylaminopropoxy) phenoxy] -2-aminoaniline,

4-(3-(4-dipropylaminobutoxy) fenoxy ]-2-aminoanilin,4- (3- (4-dipropylaminobutoxy) phenoxy] -2-aminoaniline,

4- [ 3- (2-dipropy lamino-l-methy lethoxy) fenoxy ]-2-aminoanilin,4- [3- (2-dipropylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 3- [ 2-dipropy lamino-2-methyletho'xy] fenoxy ]-2-aminoanilin,4- [3- [2-dipropylamino-2-methylethoxy] phenoxy] -2-aminoaniline,

4- [ 3- (2-dipropylamino-l,2-dimethylethoxy) fenoxy]-2-aminoanilin,4- [3- (2-dipropylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-[ 3-(2-diisopropylaminoethoxy}fenoxy ]-2-aminoanilin,4- [3- (2-diisopropylaminoethoxy) phenoxy] -2-aminoaniline,

4- [ 3- (3-diisopropylaminopropoxy) fenoxy ]-2-aminoanilin,4- [3- (3-diisopropylaminopropoxy) phenoxy] -2-aminoaniline,

4-(3-(4-diisopropylaminobutolxy] fenoxy ]-2-aminoanilin,4- (3- (4-xy diisopropylaminobuto l] phenoxy] -2-aminoaniline

4-(3-(2-diisopropylamino-l-methy lethoxy) fenoxy ] -2-aminoanilin,4- (3- (2-diisopropylamino-1-methylethoxy) phenoxy) -2-aminoaniline,

4- [ 3- (2-diisopr opylamino-2-methy lethoxy) fenoxy ] -2-aminoanilin,4- [3- (2-diisopropylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(3-(2-diisopropylamino-l,2-dimethylethoxy) fenoxy ] -2-aminoanilin,4- (3- (2-diisopropylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 3- (2-dibutylaminoethoxy) fenoxy ] -2-aminoanilin,4- [3- (2-Dibutylaminoethoxy) phenoxy] -2-aminoaniline,

4-(3-( 3-dibutylaminopropoxy) fenoxy ] -2-aminoanilin,4- (3- (3-dibutylaminopropoxy) phenoxy) -2-aminoaniline,

4-(3-( 4-dibutylaminobutoxy] fenoxy ] -2-aminoanilin,4- (3- (4-dibutylaminobutoxy) phenoxy] -2-aminoaniline,

4-(3-( 2-dibutylamino-l-methylethoxy] fenPxy]-2-aminoanilin,4- (3- (2-dibutylamino-1-methylethoxy) phenyl] -2-aminoaniline,

4-(3-( 2-dibutylamino-2-methylethoxy) f enoixy ] -2-aminoanilin,4- (3- (2-dibutylamino-2-methylethoxy) phenoxy) -2-aminoaniline,

4- [ 3- (2-dlbutylamino-l,2-dimethylethoxy) f enoxy ] -2-aminoanilin,4- [3- (2-Dibutylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-(3-( 2-piperidylethoxy ]f enoixy ] -2-aminoanilin,4- (3- (2-piperidylethoxy) phenoxy] -2-aminoaniline,

4-(3-( 3-piperidylpropdxy) f eno'xy ] -2-aminoanilin,4- (3- (3-piperidylpropoxy) phenoxy] -2-aminoaniline,

4-(3-( 4-piperidylbutoxy} f enoixy ] -2-aminoanllin,4- (3- (4-piperidylbutoxy) phenoxy] -2-aminoaniline,

4-(3-( 2-piperidyl-l-methylethoxy) fenoxy ]-2-aminoanilin,4- (3- (2-piperidyl-1-methylethoxy) phenoxy) -2-aminoaniline,

4-(3-( 2-piperidyl-2-methylethoxy) f enoixy ] -2-aminoanilin,4- (3- (2-piperidyl-2-methylethoxy) phenoxy) -2-aminoaniline,

4-(3-( 2-piperidyl-l,2-dimethyletho!xy ]fenoxy]-2-aminoanilin,4- (3- (2-piperidyl-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 3- (2-morf olylethoxy) fenoxy ]-2-aminoanilin,4- [3- (2-Morpholyl-ethoxy) -phenoxy] -2-amino-aniline,

4-(3-( 3-morf olylpropoxy) fenoxy ] -2-aminoanilin,4- (3- (3-morpholylpropoxy) phenoxy] -2-aminoaniline,

4-(3-( 4-morfolylbutoxy}fenoxy ]-2-aminoanilin,4- (3- (4-morpholylbutoxy) phenoxy] -2-aminoaniline,

4-(3-( 2-morf oly 1-1-methy lethoixy] fenoxy ] -2-aminoanilin,4- (3- (2-morpholyl-1-methylethoxyl) phenoxy] -2-aminoaniline,

4-(3-( 2-morf oly 1-2-methylethoixy) fenoxy ] -2-aminoanilin,4- (3- (2-morpholyl-2-methylethoxyl) phenoxy] -2-aminoaniline,

4-(3-( 2-morfolyl-l,2-dimethylethoxy) fenoxy]-2-aminoanilin,4- (3- (2-morpholyl-1,2-dimethylethoxy) phenoxy) -2-aminoaniline,

4-(2-(2-dimethylaminoethoxy )fenoxy ]-2-aminoanilin,4- (2- (2-dimethylaminoethoxy) phenoxy] -2-aminoaniline,

4-(2-( 3-dimethylaminorpopoxy) fenoxy ] -2-aminoanilin,4- (2- (3-dimethylaminopropoxy) phenoxy] -2-aminoaniline,

4-(2-( 4-dimethylaminobutoxy) fenoxy ] -2-aminoanilin,4- (2- (4-dimethylaminobutoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-dimethylamino-l-methylethoXy] fenoxy ] -2-aminoanilin,4- (2- (2-dimethylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-dimethy lamino-2-methy lethoxy ]fenoxy ] -2-aminoanilin,4- (2- (2-dimethylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-dimethy lamlno-1,2-dimethy 1ethoxy] -fenoxy ] -2-aminoanilin,4- (2- (2-dimethylamino-1,2-dimethyl-ethoxy) -phenoxy] -2-aminoaniline,

4-(2-( 2-diethylaminoethoxy) f enoixy ]-2-aminoanilin,4- (2- (2-diethylaminoethoxy) phenoxy) -2-aminoaniline,

4-(2-( 3-diethylaminoprópoxy (fenoxy ] -2-aminoanilin,4- (2- (3-diethylaminopropoxy (phenoxy) -2-aminoaniline),

4-(2-( 4-diethylaminobutoxy) f enoixy ] -2-aminoanilin,4- (2- (4-diethylaminobutoxy) phenoxy) -2-aminoaniline,

4-(2-( 2-diethylamino-l-methylethoxy] f enoixy ]-2-aminoanllin,4- (2- (2-diethylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-diethylammo-2-methylethoxy] fenoxy]-2-aminoanilln,4- (2- (2-diethylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-diethylaminoi-l,2-dimethy lethoxy] fenoxy]-2-aminoanilin,4- (2- (2-diethylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-dipropylaminoethoxy] fenoxy]-2-aminoanilin,4- (2- (2-dipropylaminoethoxy) phenoxy] -2-aminoaniline,

4-(2-( 3-dipropylaminopropoxy) fenoxy ] -2-aminoanilin,4- (2- (3-dipropylaminopropoxy) phenoxy) -2-aminoaniline,

4-(2-( 4-dipropylaminobutoxy) fenoxy 1 -2-aminoanilin,4- (2- (4-dipropylaminobutoxy) phenoxy-2-aminoaniline),

4-(2-( 2-dipropylamino-l-methylethotxy] fenoxy ] -2-aminoanilin,4- (2- (2-dipropylamino-1-methylethotxy) phenoxy] -2-aminoaniline,

4-(2-( 2-dipropylamino-2-methylethoxy) f enoixy ] -2-aminoanilin,4- (2- (2-dipropylamino-2-methylethoxy) phenoxy) -2-aminoaniline,

4-(2-( 2-dipropylamino-l,2-dimethylethoxy] fenoxy ] -2-aminoanilin,4- (2- (2-dipropylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-diisopr opy laminoethoxy] fenoxy ] -2-aminoanilin,4- (2- (2-diisopropylamino-ethoxy) phenoxy] -2-aminoaniline,

4-(2-( 3-diisopropylaminopropoxy) fenoXy]-2-aminoanilin,4- (2- (3-diisopropylaminopropoxy) phenoxy) -2-aminoaniline,

4-(2-( 4-diisopropylaminobutoXy) f enoixy ] -2-aminoanilin,4- (2- (4-diisopropylaminobutoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-diisopropylamino-l-methy lethoxy) fenoxy ]-2-aminoanilin,4- (2- (2-diisopropylamino-1-methylethoxy) phenoxy) -2-aminoaniline,

4-(2-( 2-diisopropylamino-2-methylethoxy) fenoxy]-2-aminoanilin,4- (2- (2-diisopropylamino-2-methylethoxy) phenoxy) -2-aminoaniline,

4-(2-( 2-diisopropylamino-l,2-dimeťhylethoxy) f enoixy ] -2-aminoanilin,4- (2- (2-diisopropylamino-1,2-dimethylethoxy) phenoxy) -2-aminoaniline,

4-(2-( 2-dibutylaminoethoxy ] fenoxy ] -2-aminoanilin,4- (2- (2-dibutylaminoethoxy) phenoxy] -2-aminoaniline,

4-(2-( 3-dibutylaminopropoxy} fenoxy ] -2-aminoanilin,4- (2- (3-dibutylaminopropoxy} phenoxy) -2-aminoaniline,

4-(2-( 4-dibutylaminobutoxy) fenoxy ] -2-aminoanilin,4- (2- (4-Dibutylaminobutoxy) phenoxy] -2-aminoaniline,

4-(2-( 2-dibutylamino-l-methylethoxy ] fenoxy ] -2-aminoanilin,4- (2- (2-dibutylamino-1-methylethoxy) phenoxy] -2-aminoaniline,

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4- [ 2- (2-dibutylamino-2-methylethoxy) fenoxy ] -2-aminoanilin,4- [2- (2-Dibutylamino-2-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 2- (2-dibutylamino-l,2-dimethylethoxy) fenoxy ] -2-aminoanilin,4- [2- (2-Dibutylamino-1,2-dimethylethoxy) phenoxy] -2-aminoaniline,

4- [ 2- (2-piperidylethoxy) fenoxy ] -2-aminoanilin,4- [2- (2-piperidylethoxy) phenoxy] -2-aminoaniline,

4- [ 2- (2-piperidylpropoxy) fenoxy ]-2-aminoanilin,4- [2- (2-piperidylpropoxy) phenoxy] -2-aminoaniline,

4- [ 2,- (4-piperidylbutolxy) fenoxy ] -2-aminoanilin,4- [2 - (4-piperidylbutolxy) phenoxy] -2-aminoaniline,

4-(2-(2-piperidyl-l-methylethoxy] fenoxy ] -2-aminoanilin,4- (2- (2-piperidyl-1-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 2- (2-piperidyl-2-methylethoxy) fenoxy ] -2-aminoanilin,4- [2- (2-piperidyl-2-methylethoxy) phenoxy] -2-aminoaniline,

4-(2-(2-piperidyl-l,2-dimethylethoxy) fenoxy ]-2-aminoanilin,4- (2- (2-piperidyl-1,2-dimethylethoxy) phenoxy) -2-aminoaniline,

4- [ 2- (2-morf olylethoxy) f enoixy ] -2-aminoanilin,4- [2- (2-Morpholyl-ethoxy) -phenoxy] -2-amino-aniline,

4- [ 2- (3-morf olylpropoxy) fenolxy]-2-aminoanilin,4- [2- (3-morpholylpropoxy) phenolxy] -2-aminoaniline,

4- [ 2- (4-morf olylbutoxyf enoxy ] -2-aminoanilin,4- [2- (4-morpholylbutoxyphenoxy) -2-aminoaniline,

4- [ 2- (2-morf olyl-l-methylethoxy) fenoxy]-2-aminoanilin,4- [2- (2-morpholyl-1-methylethoxy) phenoxy] -2-aminoaniline,

4- [ 2- (2-mořf olyl-2-methylethoixy) fenoxy ] -2-aminoanilin,4- [2- (2-morpholyl-2-methylethoxyl) phenoxy] -2-aminoaniline,

4- [ 2- (2-morf olyl-l,2-dimethylethoxy) fenolxy ] -2-aminoanilin,4- [2- (2-morpholyl-1,2-dimethylethoxy) phenolxy] -2-aminoaniline,

4-(4-(2-dimethylaminoethoxy)) f enylthio ] -2-aminoanilin,4- (4- (2-dimethylaminoethoxy)) phenylthio] -2-aminoaniline,

4- [ 4- (3-dimethylaminopropoxy) fenylthio ] -2-aminoanilin,4- [4- (3-dimethylaminopropoxy) phenylthio] -2-aminoaniline,

4- [ 4- (4-dimethylaminobutoxy] fenylthio] -2-aminoanilin,4- [4- (4-dimethylaminobutoxy) phenylthio] -2-aminoaniline,

4-(4-(2-dimethylamino-l-methyletho)xy ] fenylthio ] -2-aminoanilin,4- (4- (2-dimethylamino-1-methylethoxyl) phenylthio] -2-aminoaniline,

4-(4-(2-dimethy lamino-2-methy lethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-dimethylamino-2-methylethoxy) phenylthio] -2-aminoaniline,

4-[4-(2-dimethy lamino-1,2-dimethy 1ethoxy) fenylthio ] -2-aminoanilin,4- [4- (2-dimethylamino-1,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-diethylaminoethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-diethylaminoethoxy) phenylthio) -2-aminoaniline,

4-(4-( 3-diethylaminopropoxy ] fenylthio ] -2-aminoanilin,4- (4- (3-diethylaminopropoxy) phenylthio] -2-aminoaniline,

4-(4-( 4-diethylaminobutoXy) fenylthio ] -2-aminoanilin,4- (4- (4-diethylaminobutoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-diethy lamino-l-methylethoxy} fenylthio ]-2-aminoanilin,4- (4- (2-diethylamino-1-methylethoxy} phenylthio) -2-aminoaniline,

4-(4-( 2-diethylamino-2-methy lethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-diethylamino-2-methylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-diethylamino-l, 2-dimethy lethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-diethylamino-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-(4-( 2-dipropylaminoethoxy) fenylthio ]-2-aminoianilin,4- (4- (2-dipropylaminoethoxy) phenylthio) -2-amino aniline,

4-(4-( 3-dipropy laminopropoxy) fenylthio ] -2-amino'anilin,4- (4- (3-dipropylaminopropoxy) phenylthio] -2-aminoaniline,

4-(4-( 4-dipropylaminobutoxy) fenylthio ] -2-aminoanilin,4- (4- (4-dipropylaminobutoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-dipropylamino-l-methy lethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-dipropylamino-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(4-( 2-dipropylamino-2-methylethoxy) feny lthio ]-2-amin0fanilin,4- (4- (2-dipropylamino-2-methylethoxy) phenylthio) -2-amino-phaniline,

4- [ 4- (2-dipropylamino-l,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- [4- (2-dipropylamino-1,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-diisopropylaminoethoxy) fenylthio ] -2-amino:anilin,4- (4- (2-diisopropylaminoethoxy) phenylthio] -2-aminoaniline,

4-(4-( 3-diisopropylaminopropoxyf eny lthio ] -2-aminoanilin,4- (4- (3-diisopropylaminopropoxyphenylthio) -2-aminoaniline,

4- [ 4- (4-diisopropylaminobutoxy) fenylthio ] -2-amino'anilin,4- [4- (4-diisopropylaminobutoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-diisopr opylamino-l-methylethoxyf enylthio ] -2-aminoanilin,4- (4- (2-diisopropylamino-1-methylethoxyphenylthio) -2-aminoaniline,

4-(4-( 2-diisopropylamino-2-methy lethoxy) fenylthio ]-2-aminoanilin,4- (4- (2-diisopropylamino-2-methylethoxy) phenylthio) -2-aminoaniline,

4-(4-( 2-diisopr opy lamino-1,2-dimethy 1ethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-diisopropylamino-1,2-dimethyl-ethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-dibutylaminoetho!xy) fenylthio ] -2-aminoanilin,4- (4- (2-dibutylaminoethoxy) phenylthio] -2-aminoaniline,

4-(4-( 3-dibutylaminopropoxy) fenylthio ] -2-aminoanilin,4- (4- (3-dibutylaminopropoxy) phenylthio] -2-aminoaniline,

4-[ 4-(4-dibutylaminobutoxy)fenylthio ] -2-aminoanilin,4- [4- (4-Dibutylaminobutoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-dibutylamino-l-methy lethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-dibutylamino-1-methylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-dibutylamino-2-methylethoxy) fenylthio ]-2-aminoanilin,.4- (4- (2-Dibutylamino-2-methylethoxy) phenylthio) -2-aminoaniline.

4-(4-( 2-dibutylamino-l,2-dimethylethoixy) fenylthio ]-2-aminoanilin,4- (4- (2-dibutylamino-1,2-dimethylethoxyl) phenylthio] -2-aminoaniline,

4- [ 4- (2-piperidylethoxy) fenylthio ] -2-aminoanilin,4- [4- (2-piperidylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 3-piperidylpropoxy) fenylthio ] -2-aminoanilin,4- (4- (3-piperidylpropoxy) phenylthio) -2-aminoaniline,

4-(4-( 4-piperidylbutoxy) fenylthio ] -2-aminoanilin,4- (4- (4-piperidylbutoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-piperidyl-l-methylethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-piperidyl-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(4-( 2-piperidyl-2-methylethoixy) fenylthio ] -2-aminoanilin,4- (4- (2-piperidyl-2-methylethyl i xy) phenylthio] -2-aminoaniline

4-(4-( 2-piperidyl-l,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-piperidyl-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-[ 4-(2-mhrf oly lethoxy)fenylthio ] -2-aminoanilin,4- [4- (2-chloroethoxy) phenylthio] -2-aminoaniline,

4-(4-( 3-morf olylpropoxy) fenylthio]-2-aminoanilin, 4-[4-(4-morfolylbutoxy)f enylthio ] -2-aminoanilin,4- (4- (3-morpholylpropoxy) phenylthio] -2-aminoaniline, 4- [4- (4-morpholylbutoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-morf olyl-l-methoylelthoxy) fenylthio ] -2-aminoanilin,4- (4- (2-morpholyl-1-methoyl-ethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-morf oly 1-2-methy lethoxy) fenylthio ] -2-aminoanilin,4- (4- (2-morpholyl-2-methylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-morf oly 1-1,2-dimethy lethoxy) fenylthio ]-2-aminoanilin,4- (4- (2-morpholyl-1,2,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4-[ 3- (2-dimethylamino’ethoxy) fenylthio ] -2-aminoanilin,4- [3- (2-dimethylamino-ethoxy) -phenylthio] -2-amino-aniline,

4-[ 3-(3-dimethylaminopropoxy)fenylthio ] -2-aminoanilin,4- [3- (3-dimethylaminopropoxy) phenylthio] -2-aminoaniline,

4-(3-( 4-dimethylaminobutoxy} fenylthio ] -2-aminoanilin,4- (3- (4-dimethylaminobutoxy) phenylthio] -2-aminoaniline,

4- [3- (2-dimethylamino-l-methyletho)xy) fenylthio ] -2-aminoanilin,4- [3- (2-dimethylamino-1-methylethoxyl) phenylthio] -2-aminoaniline,

4-(3-( 2-dimethylamino-2-methylethoxy ] fenylthio ] -2-aminoanilin,4- (3- (2-dimethylamino-2-methylethoxy) phenylthio] -2-aminoaniline,

4-(3-( 2-dimethylamino-l,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-dimethylamino-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-diethylaminoethoxy) fenylthio]-2-aminoanilin,4- (3- (2-diethylaminoethoxy) phenylthio) -2-aminoaniline,

4-(3-( 3-diethylaminopropoxy) fenylthio ] -2-aminoanilin,4- (3- (3-diethylaminopropoxy) phenylthio) -2-aminoaniline,

4-(3-( 4‘-diethylaminobutoixy ] fenylthio ] -2-aminoanilin,4- (3- (4‘-Diethylaminobutoxyl) phenylthio] -2-aminoaniline,

4-[ 3-(2-'diethylamino-l-metlhylethoxy) fenylthio ] -2-aminoanilin,4- [3- (2-diethylamino-1-methyl-ethoxy) -phenylthio] -2-amino-aniline,

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4- [ 3- (2-diethylamino-2-methylethoxy) fenylthio ] -2-aminoanilin,4- [3- (2-diethylamino-2-methylethoxy) phenylthio] -2-aminoaniline,

4-(3-(2-diethy laraino-l,2-dimethyethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-diethylamino-1,2-dimethyethoxy) phenylthio) -2-aminoaniline,

4- [ 3- (2-dipr opy laminoethoxy) fenylthio ]-2-aminoanilin,4- [3- (2-dipropylamino-ethoxy) -phenylthio] -2-amino-aniline,

4- [ 3- (3-dipropylaminopropoxy ] fenylthio ] -2-aminoanilin,4- [3- (3-dipropylaminopropoxy) phenylthio] -2-aminoaniline,

4-(3-(4-dipropylaminobutoxy) fenylthio ] -2-aminoanilin,4- (3- (4-dipropylaminobutoxy) phenylthio) -2-aminoaniline,

4-(3-(2-dipr opylamino-l-methylethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-dipropylamino-1-methylethoxy) phenylthio) -2-aminoaniline,

4- [ 3- (2-dipropylamino-2-methoxy) fenylthio ] -2-aminoanllln,4- [3- (2-dipropylamino-2-methoxy) phenylthio] -2-aminoaniline,

4- [ 3- (2-dipropylamino-l,2-dimethy lethoxy) fenylthio ]-2-aminoanilin,4- [3- (2-dipropylamino-1,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4-(3-( 2-diisopropylaminoethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-diisopropylaminoethoxy) phenylthio) -2-aminoaniline,

4-(3-( 3-diisopropylaminopropoxy) fenylthio ] -2-aminoanilin,4- (3- (3-diisopropylaminopropoxy) phenylthio) -2-aminoaniline,

4-(3-( 4-diisopr opylaminobutoxy) fenylthio ] -2-aminoanilin,4- (3- (4-diisopropylaminobutoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-diisopropylamino-l-methylethoxy) f onylthi o ] -2-aminoanilin,4- (3- (2-diisopropylamino-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-diisopr opy lamino-2-methylethoxy) my lthí o ]-2-aminoanilin, ' - [ 3- (2-diisopropylamin'o-l,2methylethoxy)‘ nylthio]-2-aminoanilin,4- (3- (2-diisopropylamino-2-methylethoxy) methylthio) -2-aminoaniline, - [3- (2-diisopropylamino) -1,2-methylethoxy) phenylthio] -2-aminoaniline,

1- [ 3- (2-dibutylaminoethoxy) Enylthio ] -2-aminoanilin,1- [3- (2-Dibutylamino-ethoxy) -ethylthio] -2-amino-aniline,

4-(3-( 3-dlbutylamnopr opoxy) fenylthio ] -2-aminoanilin,4- (3- (3-Dibutylaminopropoxy) phenylthio] -2-aminoaniline,

4-(3-( 4-dlbutylaminobutoxy] fenylthio ] -2-aminoanilin,4- (3- (4-Dibutylaminobutoxy) phenylthio] -2-aminoaniline,

4-(3-( 2-dibutylamino-l-methylethoxy) fenylthio ] -2-amínoaniIin,4- (3- (2-Dibutylamino-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-dibutylamino-2-methylethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-dibutylamino-2-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-dibutylamino-l,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-dibutylamino-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-piperidy lethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-piperidinoxy) phenylthio] -2-aminoaniline,

4-(3-( 3-piperidylpr opoxy) fenylthio ] -2-aminoanilin,4- (3- (3-piperidylpropoxy) phenylthio) -2-aminoaniline,

4-(3-( 4-piperidylbutoxy) fenylthio ] -2-aminoanilin,4- (3- (4-piperidylbutoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-piperidyl-l-methy lethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-piperidyl-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-piperidyl-2-methy lethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-piperidyl-2-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-piperidy 1-1,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-piperidyl-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-morfoly lethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-morpholyphoxy) phenylthio] -2-aminoaniline,

4-(3-( 3-mor f olylpropoxy) fenylthio ] -2-aminoanilin,4- (3- (3-morpholylpropoxy) phenylthio) -2-aminoaniline,

4-(3-( 4-morf olylbutoxy) fenylthio ] -2-aminoanilin,4- (3- (4-morpholylbutoxy) phenylthio] -2-aminoaniline,

4-(3-( 2-morf olyl-l-methy lethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-morpholyl-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-morf olyl-2-methy lethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-morpholyl-2-methylethoxy) phenylthio) -2-aminoaniline,

4-(3-( 2-morf olyl-1,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- (3- (2-morpholyl-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-dimethylaminoethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-dimethylaminoethoxy) phenylthio) -2-aminoaniline,

4-(2-( 3-dimethylaminopropoxy) fenylthio ] -2-aminoanilin,4- (2- (3-dimethylaminopropoxy) phenylthio) -2-aminoaniline,

4-(2-( 4-dimethylamlnobutoxy) fenylthio]-2-aminoanilin,4- (2- (4-dimethylaminobutoxy) phenylthio] -2-aminoaniline,

4- (2- (2-dimethylamino-l-methylethoxy] fenylthio ] -2-aminoanilin,4- (2- (2-dimethylamino-1-methylethoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-dimethy lamino-2-methy lethoxy) fenylthio ]-2-aminoanilin,4- (2- (2-dimethylamino-2-methylethoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-dimethylamino-l,2-dimethy lethoxy] fenylthio ]-2-aminoanilin,4- (2- (2-dimethylamino-1,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4- (2-(2-diethylaminoethoxy) fenylthio]-2-aminoanilin,4- (2- (2-diethylaminoethoxy) phenylthio) -2-aminoaniline,

4-(2-( 3-diethylaminopropoxy) fenylthio ] -2-aminoanilin,4- (2- (3-diethylaminopropoxy) phenylthio) -2-aminoaniline,

4-(2-( 4-diethylaminobutoxy) fenylthio ] -2-aminoa.nilin,4- (2- (4-diethylaminobutoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-diethylamino-l-methylethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-diethylamino-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-diethy lamino-2-methy lethoxy] fenylthio ]-2-aminoanilin,4- (2- (2-diethylamino-2-methylethoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-diethy lamino-1,2-dimethy lethoxy) fenylthio ]-2-aminoanilin,4- (2- (2-diethylamino-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4- [ 2- (2-dipr opy laminoethoxy) fenylthio ]-2-aminoanilin,4- [2- (2-dipropylamino-ethoxy) -phenylthio] -2-amino-aniline,

4-(2-( 3-dipropylaminopropoxy) fenylthio ] -2-aminoanilm,4- (2- (3-dipropylaminopropoxy) phenylthio) -2-aminoaniline,

4-(-2-( 4-dipropylaminobutoxy) fenylthio ] -2-aminoanilin,4 - (- 2- (4-dipropylaminobutoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-dipr opylamino-l-methylethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-dipropylamino-1-methylethoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-dipropylamino-2-methylethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-dipropylamino-2-methylethoxy) phenylthio) -2-aminoaniline,

4- (2- (2-dipropylamino-l,2-dimethylethoxy) fenylthio ]-2-aminoanilin,4- (2- (2-dipropylamino-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-diisopropylaminoethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-diisopropylaminoethoxy) phenylthio) -2-aminoaniline,

4-(2-( 3-diísopropylamínopr opoxy) fenylthio ] -2-aminoani lín,4- (2- (3-diisopropylaminopropoxy) phenylthio] -2-aminoaniline,

4-(2-( 4-diisopropylbutoxy) fenylthio ] -2-aminoanilin,4- (2- (4-diisopropylbutoxy) phenylthio) -2-aminoaniline,

4- [ 2- (2-díisopr opylamino-l-methylethoxy) fenylthio ] -2-aminoanilin,4- [2- (2-diisopropylamino-1-methylethoxy) phenylthio] -2-aminoaniline,

4- [ 2- (2-diisopropylamino-2-methylethoxy) fenylthio]-2-aminoanilin,4- [2- (2-diisopropylamino-2-methylethoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-diisopropy lamino-1,2-dimethylethoxy) fenylthio 1-2-aminoanil’n,4- (2- (2-diisopropylamino-1,2-dimethylethoxy) phenylthio 1-2-aminoaniline),

4- [ 2- (2-dibutylaminoethoxy) fenylthio ] -2-aminoanilin,4- [2- (2-Dibutylaminoethoxy) phenylthio] -2-aminoaniline,

4-(2-( 3-dibutylaminopropoxy ] fenylthio ] -2-aminoa.nilin,4- (2- (3-dibutylaminopropoxy) phenylthio] -2-aminoaniline,

4-(2-( 4-dibuty laminobutoxy) fenylthio]-2-aminoanilin,4- (2- (4-Dibutylaminobutoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-dibutylamino-l-methylethoxy ] fenylthio ] -2-aminoanilin,4- (2- (2-dibutylamino-1-methylethoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-dibutylamino-2-methy lethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-Dibutylamino-2-methylethoxy) phenylthio) -2-aminoaniline,

4-(2-( 2-dibutyla.mino-l,2-dimethylethoxy) fenylthio]-2-aminoanilin,4- (2- (2-dibutyl-amino-1,2-dimethylethoxy) phenylthio) -2-aminoaniline,

4- [ 2- (2-piperidy lethoxy ] fenylthio ] -2-aminoanilin,4- [2- (2-piperidinoethoxy] phenylthio] -2-aminoaniline,

4-(2-( 3-piperidylpropoxy ] fenylthio ] -2-aminoanilin,4- (2- (3-piperidylpropoxy) phenylthio] -2-aminoaniline,

4-[ 2-(4-piperidylbutoxy)fenylthio ] -2-aminoanilin,4- [2- (4-piperidylbutoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-piperidyl-l-methylethoxy ] fenylthio ]-2-aminoanilin,4- (2- (2-piperidyl-1-methylethoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-piperidyl-2-methylethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-piperidyl-2-methylethoxy) phenylthio) -2-aminoaniline,

4- [ 2- (2-piperidyl-l,2-dimethylethoxy) fenylthio J-2-aminoanilin,4- [2- (2-piperidyl-1,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4-(2-( morfolyethoxy] fenylthio ] -2-aminoani lín,4- (2- (morpholyethoxy) phenylthio] -2-aminoaniline,

4-(2-( 3-morf olylpropoxy j fenylthio ] -2-aminoanilin,4- (2- (3-morpholylpropoxy) phenylthio] -2-aminoaniline,

4-(2-( 4-morf olylbutoxyf enylthio J -2-aminoanilin,4- (2- (4-morpholylbutoxyphenylthio) -2-aminoaniline,

4-(2-( 2-mor f oly 1-1-methy lethoxy) fenylthio ] -2-aminoanilin,4- (2- (2-morpholyl-1-methylethoxy) phenylthio] -2-aminoaniline,

4-(2-( 2-morf olyl-2-methylethoxy) fenylthio ]-2-aminoanilin,4- (2- (2-morpholyl-2-methylethoxy) phenylthio) -2-aminoaniline,

4- [ 2- (2-morfolyl-l,2-dimethylethoxy) fenylthio ] -2-aminoanilin,4- [2- (2-morpholyl-1,2-dimethylethoxy) phenylthio] -2-aminoaniline,

4-(4-( 2-dimethylaminoethoxybenzoyl] -2-aminoanilin,4- (4- (2-dimethylaminoethoxybenzoyl) -2-aminoaniline),

4-(4-( 3-dimethylaminopropoxy) benzoyl ]-2-aminoanilin,4- (4- (3-dimethylaminopropoxy) benzoyl) -2-aminoaniline,

4-(4-( 4-dimethylaminobutoxy) benzoyl ]-2-aminoanilin,4- (4- (4-dimethylaminobutoxy) benzoyl) -2-aminoaniline,

4- [ 4- (2-dimethylamino-l-methy lethoxy) benzoyl ] -2-aminoanilin,4- [4- (2-dimethylamino-1-methylethoxy) benzoyl] -2-aminoaniline,

4-(4-( 2-dimethylamino-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-dimethylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-dimethylamino-l,2-dimethylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-dimethylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-diethylaminoethoxy] benzoyl ] -2-aminoanilin,4- (4- (2-diethylaminoethoxy) benzoyl] -2-aminoaniline,

4-[ 4-(3-diethylaminopropoxy)benzoyl ] -2-aminoanilin,4- [4- (3-diethylaminopropoxy) benzoyl] -2-aminoaniline,

4-(4-( 4-diethylaminobutoxy) benzoyl]-2-aminoanilin,4- (4- (4-diethylaminobutoxy) benzoyl) -2-aminoaniline,

4- [ 4- (2-diethylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- [4- (2-diethylamino-1-methylethoxy) benzoyl] -2-aminoaniline,

4-(4-( 2-diethylamino-2-methy lethoxy) benzoyl] -2-aminoanilin,4- (4- (2-diethylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4- [ 4- (2-diethylamino-l,2-dimethyléthoxy) benzoyl ] -2-aminoanilin,4- [4- (2-diethylamino-1,2-dimethylethoxy) benzoyl] -2-aminoaniline,

4-(4-( 2-dipr opylaminoethoxy ] benzoyl ] -2-aminoanilin,4- (4- (2-dipropylaminoethoxy) benzoyl] -2-aminoaniline,

4-(4-( 3-dipropylaminopropoxy) benzoyl ] -2-aminoanilin,4- (4- (3-dipropylaminopropoxy) benzoyl) -2-aminoaniline,

4-(4-( 4-dipr opylaminobutoxy) benzoyl ] -2-aminoanilin,4- (4- (4-dipropylamino-butoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-dipropylamino-l-methyleťhoxy) benzoyl ] -2-aminoanilin,4- (4- (2-dipropylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4- [ 4- (2-dipropylamino-2 -methylethoxy) benzoyl] -2-aminoanilin,4- [4- (2-dipropylamino-2-methylethoxy) benzoyl] -2-aminoaniline,

4-(4-( 2-dipropylamino-l,2-dimethylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-dipropylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-diisopropylaminoethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-diisopropylaminoethoxy) benzoyl) -2-aminoaniline,

4-(4-( 3-diisopr opylaminopropoxy) benzoyl ] -2-aminoanilin,4- (4- (3-diisopropylaminopropoxy) benzoyl) -2-aminoaniline,

4-(4-( 4-diisopr opylaminobutoxy) benzoyl ] -2-aminoanilin,4- (4- (4-diisopropylaminobutoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-diisopropylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-diisopropylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-diisopr opy lamino-2-methy lethoxy) benzoyl ] -2-aminoaniliri,4- (4- (2-diisopropylamino-2-methylethoxy) benzoyl) -2-aminoaniliri,

4-(4-( 2-diisopropylamino-l,2-dimethylethoxy )benzoyl] -2-aminoanilin,4- (4- (2-diisopropylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4- [ 4- (2-dibutylaminoethoxy) benzoyl ] -2-aminoanilin,4- [4- (2-Dibutylaminoethoxy) benzoyl] -2-aminoaniline,

4-(4-( 3-dibutylaminopropoxy) benzoyl ]-2-aminoanilin,4- (4- (3-dibutylaminopropoxy) benzoyl) -2-aminoaniline,

4-(4-( 4-dibutylaminobutoxy) benzoyl ]-2-aminoanilin,4- (4- (4-dibutylaminobutoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-dibutylamino-l-methylethoxy) benzoyl] -2-aminoanilin,4- (4- (2-dibutylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-dibutylamino-2-methy lethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-dibutylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-dibutylamino-l,2-dimethylethoxy ] benzoyl ]-2-aminoanilin,4- (4- (2-dibutylamino-1,2-dimethylethoxy) benzoyl] -2-aminoaniline,

4-(4-( 2-piperidylethoxy ] benzoyl ] -2-aminoanilin,4- (4- (2-piperidylethoxy) benzoyl] -2-aminoaniline,

4-(4-( 3-piperidylpropoxy ] benzoyl] -2-aminoanilin,4- (4- (3-piperidylpropoxy) benzoyl] -2-aminoaniline,

4-(4-( 4-piperidylbutoxy ] benzoyl]-2-aminoanilin,4- (4- (4-piperidylbutoxy) benzoyl] -2-aminoaniline,

4-(4-( 2-piperidyl-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-piperidyl-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-piper idyl-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-piperidyl-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-piperidyl-l,2-dimethylethoxy) benzoyl] -2-aminoanilin,4- (4- (2-piperidyl-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(4-( 2-morf olylethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-morpholylethoxy) benzoyl] -2-aminoaniline,

4-[ 4-(3-morf olylpropoxy)benzoyl ] -2-aminoanilin,4- [4- (3-morpholylpropoxy) benzoyl] -2-aminoaniline,

4- [ 4- (4-morf oly lbutoxy) benzoyl ] -2-aminoanilin,4- [4- (4-morpholinylbutoxy) benzoyl] -2-aminoaniline,

4- [ 4- (2-morf olyl-l-methylethoxy) benzoyl ] -2-aminoanilin,4- [4- (2-morpholyl-1-methylethoxy) benzoyl] -2-aminoaniline,

4- [ 4- (2-imorf oly 1-2-dimethy lethoxy ] benzoyl ] -2-aminoanilin,4- [4- (2-Imorpholyl-2-dimethylethoxy] benzoyl] -2-aminoaniline,

4-(4-( 2-morf oly 1-1,2-dimethy lethoxy) benzoyl ] -2-aminoanilin,4- (4- (2-morpholyl-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-dimethy laminoethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-dimethylaminoethoxy) benzoyl) -2-aminoaniline,

4-(3-( 3-dimethylaminopropoxy) benzoyl ] -2-aminoanilin,4- (3- (3-dimethylaminopropoxy) benzoyl) -2-aminoaniline,

4-(3-( 4-dimethylaminobutoxy} benzoyl ] -2-aminoanilin,4- (3- (4-dimethylaminobutoxy) benzoyl] -2-aminoaniline,

4-[ 3- (2-dimethylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- [3- (2-dimethylamino-1-methylethoxy) benzoyl] -2-aminoaniline,

4- [ 3- (2-dimethylamino-2-methy lethoxy) benzoyl ] -2-aminoanilin,4- [3- (2-dimethylamino-2-methylethoxy) benzoyl] -2-aminoaniline,

4-[ 3-(2-dimethy lamino-l,2-dimethylethoxy} benzoyl ]-2-aminoanilin,4- [3- (2-dimethylamino-1,2-dimethylethoxy} benzoyl] -2-aminoaniline,

4-(3-( 2-diethylaminoethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-diethylaminoethoxy) benzoyl) -2-aminoaniline,

4-(3-( 3-diethylaminopropoxy) benzoyl ] -2-aminoanilin,4- (3- (3-diethylaminopropoxy) benzoyl) -2-aminoaniline,

4-(3-( 4-diethylaminobutoxy) benzoyl] -2-aminoanilin,4- (3- (4-diethylaminobutoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-diethylamino-l-methylethoxy) benzoyl] -2-aminoanilin,4- (3- (2-diethylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-diethylamino-2-methy lethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-diethylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-diethylamino-l,2-dimethy lethoxy) benzoyl]-2-aminoanilin,4- (3- (2-diethylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-dipr opylaminoethoxy) benzoyl ]-2-aminoanilin,4- (3- (2-dipropylaminoethoxy) benzoyl) -2-aminoaniline,

4-(3-( 3-dipropylaminopropoxy ] benzoyl ] -2-aminoanilin,4- (3- (3-dipropylaminopropoxy) benzoyl) -2-aminoaniline,

4-(3-( 4-dipropylaminobutoxy) benzoyl ] -2-aminoanilin,4- (3- (4-dipropylaminobutoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-dipropylamino-l-methy lethoxy) benzoyl]-2-aminoanilin,4- (3- (2-dipropylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

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4-(3-( 2-dipr opylamino-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-dipropylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4- [ 3- (2-dipropylamino-l,2-dimethylethoxy) benzoyl ] -2-aminoanilin,4- [3- (2-dipropylamino-1,2-dimethylethoxy) benzoyl] -2-aminoaniline,

4-(3-( 2-diisopropylaminoethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-diisopropylaminoethoxy) benzoyl) -2-aminoaniline,

4-(3-( 3-diisopropy lamlnopropoxy ] benzoyl ] -2-aminoanilin,4- (3- (3-diisopropylaminopropoxy) benzoyl] -2-aminoaniline,

4-(3-( 4-diisopropylbutoxy) benzoyl ] -2-aminoánilin,4- (3- (4-diisopropylbutoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-diisopropylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-diisopropylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-diisopropylamino-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-diisopropylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-diisopropylamino-l,2-dimethylethoxy] benzoyl ] -2-aminoanllin,4- (3- (2-diisopropylamino-1,2-dimethylethoxy) benzoyl] -2-aminoaniline,

4-(3-( 2-dibutylaminoethoxy} benzoyl ] -2-aminoanllin,4- (3- (2-dibutylaminoethoxy) benzoyl] -2-aminoaniline,

4-(3-( 3-dibutylaminopropoxy) benzoyl ] -2-aminoanilin,4- (3- (3-dibutylaminopropoxy) benzoyl) -2-aminoaniline,

4-[ 3-(4-dibutylamlnobutoxy) benzoyl ] -2-aminoanilin,4- [3- (4-Dibutylaminobutoxy) benzoyl] -2-aminoaniline,

4- [ 3-2-dibutylamino-l-methylethoxy) benzoyl]-2-aminoanilin,4- [3-2-dibutylamino-1-methylethoxy) benzoyl] -2-aminoaniline,

4-(3-( 2-dibutylamino-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-dibutylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-dibutylamino-l,2-dimethylethoxy) benzoyl ]-2-aminoanilin,4- (3- (2-dibutylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-piperidylethoxy ] benzoyl ] -2-aminoanilin,4- (3- (2-piperidylethoxy) benzoyl] -2-aminoaniline,

4-(3-( 3-piperidylpropoxy ] benzoyl ]-2-aminoanilin,4- (3- (3-piperidylpropoxy) benzoyl] -2-aminoaniline,

4-(3-( 4-piperidylbutoxy) benzoyl ] -2-aminoanilin,4- (3- (4-piperidylbutoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-plperidyl-l-metliylethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-Plperidyl-1-methyl-ethoxy) -benzoyl) -2-amino-aniline,

4-(3-( 2-piperidyl-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (3- (2-piperidyl-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-piperidyl-l,2-dimethylethoxy) benzoyl]-2-aminoanilin,4- (3- (2-piperidyl-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(3-( 2-morfolylethoxy ] benzoyl ] -2-aminoanilin,4- (3- (2-morpholylethoxy) benzoyl] -2-aminoaniline,

4-(3-( 3-morf olylpropoxy ] benzoyl ] -2-aminoanilin,4- (3- (3-morpholylpropoxy) benzoyl] -2-aminoaniline,

4-(3-( 4-morf olylbutoxy) benzoyl ]-2-aminoanilin,4- (3- (4-morpholylbutoxy) benzoyl) -2-aminoaniline,

4- [ 3- (2-morf olyl-2-methylethoxy) benzoyl ] -2-aminoanilin,4- [3- (2-morpholyl-2-methylethoxy) benzoyl] -2-aminoaniline,

4-(3-( 2-morf oly 1-2-methylethoNy) benzoyl ] -2-aminoanilin,4- (3- (2-morpholyl-2-methylethonyl) benzoyl) -2-aminoaniline,

4- [ 3- (2-morf olyl-l,2-dimethylethoxy} benzoyl ] -2-aminoanilin,4- [3- (2-morpholyl-1,2-dimethylethoxy} benzoyl] -2-aminoaniline,

4-(2-( 2-dimethylaminoethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-dimethylaminoethoxy) benzoyl) -2-aminoaniline,

4- [ 2-(3-dimethylaminopropoxy) benzoyl ] -2-aminoanllin,4- [2- (3-dimethylaminopropoxy) benzoyl] -2-aminoaniline,

4-(2-( 4-dimettiylaminobutoxy) benzoyl ] -2-aminoanilin,4- (2- (4-dimethylaminobutoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-dimethylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-dimethylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4- [ 2- (2-dimethylamino-2-methylethoxy) benzoyl ] -2-aminoanilin,4- [2- (2-dimethylamino-2-methylethoxy) benzoyl] -2-aminoaniline,

4-(2-( 2-dimethylamlno-l,2-dimethylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-dimethylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-diethylaminoethoxy ] benzoyl] -2-aminoanilin,4- (2- (2-diethylaminoethoxy) benzoyl] -2-aminoaniline,

4-[ 2-(3-diethylaminopropoxy )benzoyl ] -2-aminoanilin,4- [2- (3-diethylaminopropoxy) benzoyl] -2-aminoaniline,

4-(2-( 4-diethylaminobutoxy) benzoyl ] -2-aminoanilin,4- (2- (4-diethylaminobutoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-diethylamino-l-methylethoxy} benzoyl ] -2-aminoanilin,4- (2- (2-diethylamino-1-methylethoxy} benzoyl) -2-aminoaniline,

4-(2-( 2-diethylamino-2-methylethoxy) benzoyl ]-2-aminoanilin,4- (2- (2-diethylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-diethylamino-l,2-dimethyle thoxy) benzoyl ] -2-aminoanilin,4- (2- (2-diethylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-dipropylaminoettioxy) benzoyl ] -2-aminoanilin,4- (2- (2-dipropylamino-thioxy) -benzoyl) -2-amino-aniline,

4-(2-( 3-dipropylaminopropoxy} benzoyl ] -2-aminoanilin,4- (2- (3-dipropylaminopropoxy} benzoyl) -2-aminoaniline,

4-[ 2- (4-dipropylaminobutoxy) benzoyl]-2-aminoanilin,4- [2- (4-dipropylaminobutoxy) benzoyl] -2-aminoaniline,

4-(2-( 2-dipropylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-dipropylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-dipr opylamino-2-methylethoxy) benzoyl ]-2-aminoanilin,4- (2- (2-dipropylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-dipropylamino-l,2-dimethylethoxy) benzoyl ]-2-aminoanilin,4- (2- (2-dipropylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-diisopropylaminoethoxy ] -2-aminoanilin,4- (2- (2-diisopropylaminoethoxy) -2-aminoaniline)

4-(2-( 3-diisopropylaminopropoxy ] benzoyl ] -2-aminoanilin,4- (2- (3-diisopropylaminopropoxy) benzoyl] -2-aminoaniline,

4-(2-( 4-diisopropylaminobutoxy) benzoyl ] -2-aminoanilin,4- (2- (4-diisopropylaminobutoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-diisopropylamino-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-diisopropylamino-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-diisopropylamino-2-methylethoxy) benzoyl ]-2-aminoanilin,4- (2- (2-diisopropylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-[ 2-(2-diisopropylamino-l,2-dimethylethoxy)benzoyl ] -2-aminoanilin,4- [2- (2-diisopropylamino-1,2-dimethylethoxy) benzoyl] -2-aminoaniline,

4-(2-( 2-dibutylaminoethoxy) benzoyl ]-2-aminoanilin,4- (2- (2-dibutylaminoethoxy) benzoyl) -2-aminoaniline,

4-(2-( 3-dibutylaminopropoxy) benzoyl ]-2-aminoanilin,4- (2- (3-dibutylaminopropoxy) benzoyl) -2-aminoaniline,

4-[ 2-(4-dibutylaminobutoxy ]benzoyl ]-2-aminoanilin,4- [2- (4-Dibutylaminobutoxy) benzoyl] -2-aminoaniline,

4-(2-( 2-dibutylamino-l-methylethoxy ]benzoyl ]-2-aminoanilin,4- (2- (2-dibutylamino-1-methylethoxy) benzoyl] -2-aminoaniline,

4-(2-( 2-dibutylamino-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-dibutylamino-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-dibutylamino-l,2-dimethylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-dibutylamino-1,2-dimethylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-piperidylethoxy} benzoyl ] -2-aminoanilin,4- (2- (2-piperidylethoxy} benzoyl) -2-aminoaniline,

4- [ 2- (3-piperidylpropoxy) benzoyl ] -2-aminoanilin,4- [2- (3-piperidylpropoxy) benzoyl] -2-aminoaniline,

4-(2-( 4-piperidylbutoxy) benzoyl ] -2-aminoanilin,4- (2- (4-piperidylbutoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-piperidyl-l-methylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-piperidyl-1-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-piperidyl-2-methylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-piperidyl-2-methylethoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-piperidyl-l,27dimethylethoxy) benzoyl ] -2-aminoanilin,4- (2- (2-piperidinyl-l, 2 7 dimethylethoxy) benzoyl] -2-aminoaniline

4-(2-( 2-morfolylethoxy j benzoyl ] -2-aminoanilin,4- (2- (2-morpholylethoxy) benzoyl] -2-aminoaniline,

4-(2-( 3-morf olylpropoxy) benzoyl ] -2-aminoanilin,4- (2- (3-morpholylpropoxy) benzoyl) -2-aminoaniline,

4-(2-( 4-morf olylbutoxy) benzoyl ] -2-aminoanilin,4- (2- (4-morpholylbutoxy) benzoyl) -2-aminoaniline,

4-(2-( 2-morf oly 1-1-methylethoxy ] benzoyl ]-2-aminoanilin,4- (2- (2-morpholyl-1-methylethoxy) benzoyl] -2-aminoaniline,

4-(2-( 2-morf olyl-2-methylethoxy) benzoyl]-2-aminoanilin a 4-(2-( 2-morfolyl-l,2-dimethylethoxy) benzoyl ] -2-aminoanilin.4- (2- (2-morpholyl-2-methylethoxy) benzoyl] -2-aminoaniline; and 4- (2- (2-morpholyl-1,2-dimethylethoxy) benzoyl) -2-aminoaniline.

Derivát o-fenylendiaminu vzorce 2, který slouží jako výchozí látka, se získá redukcí příslušného aminonitroderivátu vzorce 11, v němž X a Y mají stejný význam jako ve vzorci 1. Redukce se může provádět například hydrogenaei v přítomnosti Raneyova niklu a rozpouštědla, jako methanolu nebo dimethylformamidu při teplotách mezi 20 a 60 °CI nebo působením redukčních činidel, jako dithioničitánu sodného.The o-phenylenediamine derivative of formula 2, which serves as the starting material, is obtained by reduction of the corresponding amino nitro derivative of formula 11 in which X and Y have the same meaning as in formula 1. The reduction can be carried out, for example, by hydrogenation in the presence of Raney nickel and a solvent such as methanol or dimethylformamide at temperatures between 20 and 60 ° C or by the action of reducing agents such as sodium dithionite.

Aminonitroderiváty vzorce 11 se získají reakcí příslušného hydroxynitraminodifenyletheru vzorce 13, v němž X má stejný význam jako ve vzorci 1, účelně ve formě jeho soli s alkalickým kovem, výhodně soli sodné, s bazickou sloučeninou vzorce 12, v němž Y má stejný význam jako ve vzorci 1 a W znamená odštěpnou skup'nu, jako halogen, například chlor, brom nebo jod, nebo zbytek anorganické nebo organické kyslíkaté kyseliny, jako sulfátovou skupinu nebo zbytek kyseliny p-toluensulfonové, účelně v aprotickém dipolárním rozpouštědle, jako je aceton, dimethylformamid nebo dimethylsulfoxid nebo v alkoholu, jako je methanol nebo ethanol za zahřívání na vyšší teplotu, výhodně na bod varu používaného rozpouštědla. Po ukončení reakce se rozpouštědlo odstraní destilací a zbytek se zpracuje působením báze, iako výhodně amoniaku nebo hydroxidu alkalického kovu. jako hydroxidu sodného za použití rozpouštědla, které není mísitelné s vodou, jako je ethylacetát, methylendichlorid nebo chloroform.The amino nitro derivatives of formula 11 are obtained by reacting the corresponding hydroxynitraminodiphenyl ether of formula 13 in which X has the same meaning as in formula 1, conveniently in the form of its alkali metal salt, preferably sodium salt, with a basic compound of formula 12 in which Y has the same meaning as 1 and W represents a leaving group such as halogen, for example chlorine, bromine or iodine, or an inorganic or organic oxygen acid residue, such as a sulfate group or a p-toluenesulfonic acid residue, suitably in an aprotic dipolar solvent such as acetone, dimethylformamide or dimethylsulfoxide or in an alcohol such as methanol or ethanol with heating to a higher temperature, preferably to the boiling point of the solvent used. After completion of the reaction, the solvent is removed by distillation and the residue is treated with a base, preferably ammonia or an alkali metal hydroxide. as sodium hydroxide using a water-miscible solvent such as ethyl acetate, methylene dichloride or chloroform.

Hydroxyiiitraminodifenylethery vzorce 13 se získávají reakcí odpovídající methoxyderivátů vzorce 14, v němž X má stojný význam, jako ve vzorci 1, se silnými minerálními kyselinami, ja-ko výhodně s kyselinou bromovodíkovou nebo organickými sloučeninami, které mohou takovéto kyseliny odštěpovat, jako je pyrídin-hydrochlorid, při zvýšené teplotě, výhodně při bodu varu vodného roztoku této kyseliny nebo roztoku organická sloučeniny ve formě soli v bázi, která je základem této sloučeniny, například v pyridinu v případě pyridin-hydrochloridu, a reakční produkt se izoluje zředěním vodou.Hydroxyitraminodiphenyl ethers of formula 13 are obtained by reacting the corresponding methoxy derivatives of formula 14 in which X is of the same meaning as in formula 1 with strong mineral acids such as hydrobromic acid or organic compounds which can cleave such acids such as pyridine hydrochloride at elevated temperature, preferably at the boiling point of an aqueous solution of the acid or a solution of the organic compound in the base form of the compound, for example in pyridine for pyridine hydrochloride, and the reaction product is isolated by dilution with water.

Sloučeniny podle tohoto vynálezu jsou cennými chemoterapeutiky a jsou vhodné k potírání parasitárních chorob u lidí a zvířat. Tyto sloučeniny jsou zvláště účinné proti měchovcům (Amylostoma), jsou však vynikajícím způsobem účinné taká proti dalším helmintům, jako je například vlasovka (Haemonchus), vlasovka (Ostertagia), vlasovka (Hyostrongylus), vlasovka (Trichostrongylus) vlasovka (Coopsria) jakož i motolice jaterní (Fasciola hepatica) a četné další. Zvláště výrazná je jejich účinnost proti červům (škrkavkám) napadajícím především lidi, masožravce, ale také prežvýkavce a způsobujícím značné zdravotní a hospodářské škody.The compounds of this invention are valuable chemotherapeutic agents and are useful in the control of parasitic diseases in humans and animals. These compounds are particularly effective against hookworms (Amylostoma), but they are also excellent against other helminths such as Haemonchus, Ostertagia, Hyostrongylus, Trichostrongylus as well as fluke liver (Fasciola hepatica) and numerous others. Especially significant is their effectiveness against worms (roundworms) attacking mainly humans, carnivores, but also ruminants and causing considerable health and economic damage.

Sloučeniny vzorce 1 se mohou používat jako anthelmintiika v humánní a veterinární medicíně. Aplikují se podle povahy případu v dávkách mezi 0,5 a 50 mg na 1 kg tělesné hmotnosti 1 až 14 dnů.The compounds of formula 1 can be used as anthelmintics in human and veterinary medicine. They are administered according to the nature of the case at doses between 0.5 and 50 mg per kg body weight for 1 to 14 days.

K orální aplikaci přicházejí v úvahu tablety, dražé, kapsle, prášky, granuláty nebo pasty, které obsahují účinné látky spolu s obvyklými pomocnými látkami a nosnými látkami, jako je škrob, prášková celulóza, mastek, stearan hořečnatý, cukr, želatina, uhličitan vápenatý, jemně dispergovaná kyselina křemičitá, karboxymethylcelulóza nebo podobné látky.For oral administration, tablets, coated tablets, capsules, powders, granules or pastes which contain the active substances together with the usual excipients and carriers such as starch, powdered cellulose, talc, magnesium stearate, sugar, gelatin, calcium carbonate, finely dispersed silicic acid, carboxymethylcellulose or the like.

Pro parenterální aplikaci přicházejí v úvahu roztoky, například olejovité roztoky, které se připravují za použití sezamového oleje, ricinového oleje nebo syntetických triglyceridů, pořípadě s přídavkem tokoferolu jako antloxidačně účinné látky nebo/a za použití povrchově aktivních látek, jako jsou estery sorbitanu s mastnými kyselinami. Vedle toho přicházejí v úvahu vodné suspenze, které se vyrábějí za použití ethoxylovaných esterů sorbitanu s mastnými kyselinami, popřípadě za přídavku zahušťovadel, jako je polyethylenglykol nebo karboxymethylcelulóza.Suitable solutions for parenteral administration are, for example, oily solutions which are prepared using sesame oil, castor oil or synthetic triglycerides, optionally with the addition of tocopherol as an antloxidant, and / or with surfactants such as sorbitan fatty acid esters. . Other suitable suspensions are aqueous suspensions which are prepared using ethoxylated sorbitan fatty acid esters, optionally with the addition of thickeners, such as polyethylene glycol or carboxymethylcellulose.

Koncentrace účinných látek podle vynálezu v přípravcích vyrobených za použití těchto látek se pro účely veterinární medicíny pohybuje výhodně mezi 2 a 20 hmotnostními procenty: pro účely humánních léčiv se koncentrace účinných látek pohybuje výhodně mezi 20 a 80 hmotnostními °/o.The concentration of the active compounds according to the invention in the preparations produced using these compounds is preferably between 2 and 20% by weight for veterinary purposes: for the purposes of human medicaments, the concentration of the active compounds is preferably between 20 and 80% by weight.

Ke zjištění účinku sloučenin podle vynálezu byly prováděny různé chemoterapeutické pokusy na psech nebo ovcích. Psi byli experimentálně infikováni larvami měchovce psího (Ancylostoma caninumj, ovce larvami vlasovky slezové (Haemonchus contortus j a vlasovky kozí (Trichostrongylus colubriformis j. Pokusná zvířata se po dobu pokusu udržují ve vykachlíčkovaných boxech, které se denně důkladně čistí, aby se zamezilo superinfekci. Po uplynutí prepatenční doby (čas mezi infekcí a pohlavní zralostí parazitů s počínajícím se vylučováním produktů množení) se podle modifikovaného Mc Masterova postupu [viz Tierarztl. Umschau 6, 209 až 210 (1951)] určuje počet vajíček na 1 gram výkalu. Bezprostředně potom se provádí ošetření zvířat, obecně 4 až 8 zvířat na 1 skupinu, minimálně však 2 zvířat, a to orálně nebo subkutánně, přičemž se aplikuje suspenze 0,5 až 10,0 mg na 1 kg tělesné hmotnosti vždy ve formě 10 ml suspenze tylózy s obsahem 1 % účinné látky. Vždy 7., 14. a 28. den po ošetření se znovu podle shora popsaného postupu stanovuje počet vajíček ve výkalu a určuje se procentuální změna k výchozí hodnotě. Při přesvědčivém úspěchu se popřípadě provádí sekce pokusných zvířat za vyšetření zažívacího traktu na případně přítomné nematody.Various chemotherapeutic experiments on dogs or sheep were performed to determine the effect of the compounds of the invention. The dogs were experimentally infected with cankerworm larvae (Ancylostoma caninumj, sheep by larvae of Haemonchus contortus and Goatfish (Trichostrongylus colubriformis j.). the retention time (the time between infection and sexual maturity of parasites beginning with the elimination of propagation products) is determined according to a modified Mc Master procedure (see Tierarztl. Umschau 6, 209-210 (1951)) to determine the number of eggs per gram of feces. animals, generally 4 to 8 animals per group, but at least 2 animals, orally or subcutaneously, with a suspension of 0.5 to 10.0 mg per kg of body weight each in the form of 10 ml of a 1% tylose suspension. On the 7th, 14th and 28th day after treatment, the procedure was repeated as described above In the case of conclusive success, a section of the test animals is performed, where appropriate, to examine the digestive tract for any nematodes present.

Výsledek pokusu je patrný z následující tabulky:The result of the experiment is shown in the following table:

Při pokusech byly zjištěny následující úěinky:The following effects were found in the experiments:

Sloučenina podle Parasit příkladu motolice jaterní (Fascila hepaticaj tasemnlce motolice jaterní tasemnlce tasemnice vlasovka (Tr ichostr ongy lus) tasemnice tasemnice tasemnice tasemniceA compound according to the Parasit example of the liver fluke (Fascila hepaticaj tapeworm) woolweed liverworm tapeworm tapeworm (Tr ichostr ongy lus) tapeworm tapeworm tapeworm tapeworm

Dávka mg/kg Usmrcení perorálně parazité v %Dose mg / kg Oral parasites killing in%

30 30 100 100 ALIGN! 10 10 100 100 ALIGN! 30 30 100 100 ALIGN! 10 10 100 100 ALIGN! 10 10 > 90 > 90 2,5 2.5 100 100 ALIGN! 20 20 May 100 100 ALIGN! 20 20 May 100 100 ALIGN! 20 20 May 100 100 ALIGN! 20 20 May 100 100 ALIGN!

Sloučeniny podle vynálezu jsou účinné jak proti tasem,ničím, tak i proti vlasovkám parazitujícím v žaludečním a střevním traktu až do dávek menších než 10 mg/kg. Zejména pokud jde o kombinovaný účinek při relativně nízké dávce, paik při léčbě většího počtu infekcí převyšují známé 5(6J-substituované 2-benzimidazolkarbamáty.The compounds of the present invention are effective against both tassels, teats and hairworms parasitic in the stomach and intestinal tract up to doses of less than 10 mg / kg. Especially with regard to the combined effect at a relatively low dose, paik exceeds the known 5 (6J-substituted 2-benzimidazolecarbamates) in the treatment of multiple infections.

Příklad 1Example 1

K roztoku 4,2 g kyanamidu ve 20 ml vody se přidá 9,0 g methylesteru kyseliny chlormravenčí a 21,8 g 33% roztoku hydroxidu sodného. Reakční směs se míchá 1,5 hodiny, přičemž se teplota udržuje mezi 30 a 35 °C. Potom se přidá roztok 26,5 g 4-[3-(2-piperidylethoxy )f enoxy ]-2-aminoanilinu, ve 200 ml isopropylakoholu a potom se teplota zvýší až na 80 °C. Po přidání 20 ml ledové kyseliny octové se reakční směs zahřívá ještě 3 až 4 hodiny na 90 °C. K horkému roztoku ku se přidá koncentrovaný amoniak přikapáním až k alkalické reakci, přičemž se vyloučí hustá kaše. Tato kaše se odfiltruje a surový produkt se čistí rozpuštěním ve směsi z 400 ml methanolu a 35 ml 2 N kyseliny chlorovodíkové při 50 °C, filtrací za použití aktivního uhlí a opětovným vysrážením produktu amoniakem. Nyní čistý 3-(2-piperidylethoxy )fenyl-2-methoxy,karbonylaminobenzenimidazol-5 (6 j-ylether se odfiltruje a promyje se methanolem a potom vodou. Výtěžek 22 g o teplotě rozkladu 200 st. Celsia.To a solution of 4.2 g of cyanamide in 20 ml of water was added 9.0 g of methyl chloroformate and 21.8 g of 33% sodium hydroxide solution. The reaction mixture was stirred for 1.5 hours while maintaining the temperature between 30 and 35 ° C. Then a solution of 26.5 g of 4- [3- (2-piperidylethoxy) phenoxy] -2-aminoaniline in 200 ml of isopropyl alcohol is added and the temperature is then raised to 80 ° C. After addition of 20 ml of glacial acetic acid, the reaction mixture is heated at 90 ° C for 3 to 4 hours. Concentrated ammonia was added dropwise to the hot solution until an alkaline reaction was added, leaving a thick slurry. The slurry was filtered and the crude product was purified by dissolving it in a mixture of 400 mL of methanol and 35 mL of 2 N hydrochloric acid at 50 ° C, filtering with activated carbon and reprecipitating the product with ammonia. Now pure 3- (2-piperidylethoxy) phenyl-2-methoxy, carbonylaminobenzenimidazol-5 (6'-yl ether) was filtered off and washed with methanol and then with water, yield 22 g, decomposition temperature 200 ° C.

Za účelem přípravy 4-[3-(2-piperidylethoxy )f enoxy ]-2-aminoanilinu se hydrogenuje 17 g 4-[3-(2-piperidylethoxy]fenoxy]-2-aminonitrobenzenu ve 200 ml dimethylformamidu v přítomnosti Raneyova niklu při teplotě 50 °C a tlaku vodíku 5 MPa. Katalyzátor se odfiltruje a filtrát se odpaří k suchu. Po zředění išopropanolem se získá surový 4- [ 3- (2-piperidylethoxyf enoxy ] -2-aminoanilin.In order to prepare 4- [3- (2-piperidylethoxy) phenoxy] -2-aminoaniline, 17 g of 4- [3- (2-piperidylethoxy) phenoxy] -2-aminonitrobenzene was hydrogenated in 200 ml of dimethylformamide in the presence of Raney nickel at a temperature of The catalyst was filtered off and the filtrate was evaporated to dryness, diluted with isopropanol to give crude 4- [3- (2-piperidylethoxyphenoxy) -2-aminoaniline.

Za účelem přípravy 4-[3-(2-piperidylethoxy )f enoxy]-2-aminonitr obenzěnu se rozpustí nejprve 6 g sodíku v 500 ml absolutního ethanolu, přidá se 64 g 4-(3-hydroxyfenoxyj-2-aminonitrobenzenu a roztok se zahustí ve vakuu. Po vysušení pomocí pevného hydroxidu sodného se získá 70 g sodné soli 4-(3-hydroxyfenoxy)-2-aminonitrobenzenu.To prepare 4- [3- (2-piperidylethoxy) phenoxy] -2-aminonitrile of obenzene, first dissolve 6 g of sodium in 500 ml of absolute ethanol, add 64 g of 4- (3-hydroxyphenoxy) -2-aminonitrobenzene, and dissolve the solution. After drying with solid sodium hydroxide, 70 g of 4- (3-hydroxyphenoxy) -2-aminonitrobenzene sodium salt are obtained.

Směs 13,4 g sodné soli 4-(3-hýdroxyfenoxy j-2-aminoniťrobenzenu ve 100 ml acetonu se míchá sé 7,5 g píperidinoethylchloridu 3 hodiny na parní lázní. Potom se rozpouštědlo odpaří ve vakuu, zbytek se rozpustí ve zředěné kyselině octové a zalkalizuje se amoniakem. Za účelem izolace volného 4- [ 3- (2-piperidylethoxy j f enoxy j -2-aminonitrobenzenu se emulze zpracovává za použití ethylačetátu a po odpaření rozpouštědla se získá 17 g sloučeniny v olejovité formě, která se může přímo použít pro hydrogenaci.A mixture of 13.4 g of 4- (3-hydroxyphenoxy) -2-aminonitrobenzene sodium salt in 100 ml of acetone is stirred with 7.5 g of piperidinoethyl chloride for 3 hours on a steam bath, then the solvent is evaporated off under vacuum, the residue is dissolved in dilute acetic acid. In order to isolate the free 4- [3- (2-piperidylethoxy) phenoxy] -2-aminonitrobenzene, the emulsion was treated with ethyl acetate, and after evaporation of the solvent, 17 g of an oily compound was obtained which could be used directly for hydrogenation.

4-(3-( hydroxyf enoxy) -2-aminonitr obenzen se získá tím, že se použije 190 g 4- (3-methoxyf enoxy) -2-aminonitrobenzenu zahřívá s lOnásobným množstvím 48% vodné kyseliny bromovodíkové 2 hodiny k varu pod zpětným chladičem. Potom se rozpouštědlo odpaří ve vakuu, zbytek se vyjme roztokem octanu sodného a směs se míchá nějaký čas na parní lázni. Surový produkt se odfiltruje a čistí se rozpuštěním v ethylacetátu, filtrací za použití malého množství aktivního uhlí, odpařením filtrátu ve vakuu a rozmícháním zbytku s petroletherem. Tímto způsobem se získá 163 g čistého 4-(3-hydroxyfenoxy)-2-aminonitrobenzenu o teplotě tání 137 °C.4- (3- (hydroxyphenoxy) -2-aminonitrile obenzene) is obtained by using 190 g of 4- (3-methoxyphenoxy) -2-aminonitrobenzene with 10 times 48% aqueous hydrobromic acid at reflux for 2 hours The solvent is then evaporated off under vacuum, the residue is taken up with sodium acetate solution and the mixture is stirred on a steam bath for some time. The crude product is filtered off and purified by dissolving in ethyl acetate, filtering with a small amount of activated carbon, evaporating the filtrate under vacuum and stirring. 163 g of pure 4- (3-hydroxyphenoxy) -2-aminonitrobenzene of melting point 137 DEG C. are thus obtained.

Analogickým způsobem se z odpovídajících výchozích látek získají následující sloučeniny:The following compounds are obtained in an analogous manner from the corresponding starting materials:

Příklad 2Example 2

3- (2-dimethylaminoethoxy ] f enyl-2-methóxykarbonylaminobenzimidazol1972563- (2-dimethylaminoethoxy) phenyl-2-methoxycarbonylaminobenzimidazole197256

-5(6)-ylether, teplota tání 190 °C (rozklad se získá z 4-(3-( 2-dimethylaminoethoxy) fenoxy ] -2-aminoanilinu přes 4-(3-hydroxyfenoxy)-2-aminonitrobenzen, teplota tání 137 °C a 4- [ 3- (2-dimethylaminoethoxy) fenoxy ] -2-aminonitrobenzen (olejovitý produkt).190 DEG C. (decomposition from 4- (3- (2-dimethylaminoethoxy) phenoxy) -2-aminoaniline) via 4- (3-hydroxyphenoxy) -2-aminonitrobenzene, m.p. And 4- [3- (2-dimethylaminoethoxy) phenoxy] -2-aminonitrobenzene (oily product).

Přiklad 3Example 3

3- (dimethylaminopr opoxy) f eny 1-2-methoxykar bony laminobenzimiďazol-5 (6) -ylether, teplota tání 173 °C (rozklad) se získá z 4-(3-( 3-dimethylaminopropoxy) fenoxy) -2-aminoanilinu přes 4- (3-hydro'xyf enoxy) -2-aminonitrobenzen, teplota tání 137 °C a 4-f3-(3-dimethylaminopropoxy)fenoxy]-2-aminonitrobenzen, teplota tání 108 °C.3- (dimethylaminopropoxy) phenyl 1-2-methoxycarbonylaminobenzimidazole-5 (6) -yl ether, m.p. 173 ° C (dec.) Was obtained from 4- (3- (3-dimethylaminopropoxy) phenoxy) -2-aminoaniline via 4- (3-hydroxyphenoxy) -2-aminonitrobenzene, m.p. 137 ° C; and 4- [3- (3-dimethylaminopropoxy) phenoxy] -2-aminonitrobenzene, m.p. 108 ° C.

Příklad 4Example 4

4- (2-dimethylaminoethoxy) f enyl-2-methoxykarbonylaminobenzimidazol-5 (6) -ylether, teplota tání 210°C (rozklad) se získá z 4-(4-( 2-dimethylaminoethoxy) fenoxy) -2-aminoanilinu přes 4- (4-hydroxyfenoxy)-2-aminonitrobenzen, teplota tání 205 °C a 4-(4-( 2-dimethylaminoethoxy) fenoxy ] -2-aminonitrobenzen, teplota tání 125 °C.4- (2-dimethylaminoethoxy) phenyl-2-methoxycarbonylaminobenzimidazol-5 (6) -yl ether, m.p. 210 ° C (dec.) Is obtained from 4- (4- (2-dimethylaminoethoxy) phenoxy) -2-aminoaniline via 4 (4-hydroxyphenoxy) -2-aminonitrobenzene, m.p. 205 ° C; and 4- (4- (2-dimethylaminoethoxy) phenoxy] -2-aminonitrobenzene, m.p. 125 ° C.

Příklad 5Example 5

4-(2-diethylaminoethoxy )fenyl-2-methoxykarbonylaminobenzimidazol-5 (6)-ylether, teplota tání 198 °C (rozklad) se získá z 4-(4-( 2-diethylaminoethoxy) fenoxy ] -2-aminoanilinu4- (2-diethylaminoethoxy) phenyl-2-methoxycarbonylaminobenzimidazol-5 (6) -yl ether, m.p. 198 ° C (dec.) Was obtained from 4- (4- (2-diethylaminoethoxy) phenoxy] -2-aminoaniline

PŘEDMĚTSUBJECT

Claims (1)

PŘEDMĚTSUBJECT Způsob výroby bazicky substituovaných 2-alkoxykarbonylaminobenzimidazol-5 (6) -ylfenyletherů a -ketonů obecného vzorce 1 ?’Y'°Xo>-x^WcooR3 * H 11) přes 4- (4-hydroxyfenoxy) -2-aminonitrobenzen, teplota tání 205 °C a 4-(4-( 2-diethylaminoethoxy)fenoxy ] -2-aminonitrobenzen, teplota tání 135 °C.Process for the preparation of basic substituted 2-alkoxycarbonylaminobenzimidazol-5 (6) -ylphenyl ethers and ketones of general formula (I). Y1 ° Xo-x (Wcoo R 3 * H 11) via 4- (4-hydroxyphenoxy) -2-aminonitrobenzene, melting point 205 ° C and 4- (4- (2-diethylaminoethoxy) phenoxy] -2-aminonitrobenzene, mp 135 ° C. Příklad 6Example 6 4- (2-piperidylethoxy) f enyl-2-methoxykar bonylaminobenzimidazol-5 (6) -ylether, teplota tání 195°C (rozklad) se získá z 4-[ 4-(2-piperidylethoxy )f enoxy]-2-aminoanilinu přes 4-(4-hydroxyfenoxy )-2-aminonitrobenzen, teplota tání 205 °C a 4-(4-(2-piperidylethoxy) fenoxy ] -2-aminonitrobenzen, teplota tání 108 °C.4- (2-piperidylethoxy) phenyl-2-methoxycarbonylaminobenzimidazol-5 (6) -yl ether, m.p. 195 DEG C. (decomposition) is obtained from 4- [4- (2-piperidylethoxy) phenoxy] -2-aminoaniline via 4- (4-hydroxyphenoxy) -2-aminonitrobenzene, m.p. 205 ° C; and 4- (4- (2-piperidylethoxy) phenoxy] -2-aminonitrobenzene, m.p. 108 ° C. Příklad 7Example 7 4- (2-diethylaminoethoxy) f enyl-2-methoxykarbonylamindbenzimidazol-5 (6) -ylthioether, teplota tání 163 °C (rozklad) se získá z 4-(4-( 4-2-diethylaminoethoxy) fenylthio ] -2 -aminoanilinu přes 4- (4-hydr oxyf eny lthio ] -2-aminonitrobenzen, teplota tání 190 °C a 4-(4-( 2-diethylaminoethoxy) feny lthio ] -2-aniinonitrobenzen (pryskyřičný produkt)4- (2-diethylaminoethoxy) phenyl-2-methoxycarbonylaminobenzimidazol-5 (6) -ylthioether, m.p. 163 DEG C. (decomposition) is obtained from 4- (4- (4-2-diethylaminoethoxy) phenylthio) -2-aminoaniline via 4- (4-hydroxyphenylthio) -2-aminonitrobenzene, m.p. 190 ° C; and 4- (4- (2-diethylaminoethoxy) phenylthio] -2-aniononitrobenzene (resin product) Příklad 8Example 8 4- (2-diethylaminoethoxy ] f enyl-2-methoxykarbonylaminobenzimidazol-5 (6) -ylketon, teplota tání 218 °C (rozklad) se získá z4- (2-diethylaminoethoxy) phenyl-2-methoxycarbonylaminobenzimidazol-5 (6) -yl ketone, m.p. 218 DEG C. (decomposition) is obtained from m.p. 4-(4-( 2-diethylaminoethoxy) benzoyl ] -2-aminoanilinu přes 5- (4-hydroxybenzoyl) -2-aminonitrobenzen, teplota tání 220 °C a 5-(4-( 2-diethylaminoethoxy) benzoyl ] -2-aminonitrobenzen, teplota tání 93 °C.4- (4- (2-diethylaminoethoxy) benzoyl] -2-aminoaniline via 5- (4-hydroxybenzoyl) -2-aminonitrobenzene, m.p. 220 ° C; and 5- (4- (2-diethylaminoethoxy) benzoyl] -2- aminonitrobenzene, m.p. 93 ° C. VYNÁLEZU v němžOF THE INVENTION in which R3 znamená alkylový zbytek s 1 až 4 atomy uhlíku,R3 represents a C1-C4 alkyl radical, X znamená kyslík, síru nebo skupinu \X is oxygen, sulfur or a group \ C=O, /C = O, / Y znamená přímou nebo rozvětvenou alkylenovou skupinu s 1 až 4 atomy uhlíku aY represents a straight or branched alkylene group having 1 to 4 carbon atoms and Ri a Rz znamenají alkylový zbytek s 1 až 4 atomy uhlíku, přičemž oba zbytky Ri a R2 spolu s atomem dusíku, na který jsou vázány, mohou znamenat také piperidinový nebo morfolinový kruh, a jejich fyziologicky nezávadných solí s kyselinami, vyznačující se tím, že se derivát o-fenylendiaminu obecného vzorce 2R 1 and R 2 are C 1 -C 4 alkyl, wherein R 1 and R 2 together with the nitrogen atom to which they are attached may also represent a piperidine or morpholine ring, and their physiologically acceptable salts with acids, The method according to claim 1, wherein the o-phenylenediamine derivative of general formula 2 is used NC—N—COORsNC — N — COORs IAND H (4), v němžH (4), in which R3 má stejný význam jako ve vzorci 1, v rozmezí pH od 1 do 6, načež se popřípadě získaná sloučenina vzorce 1 převede působením kyseliny na fyziologicky použitelnou sůl.R 3 has the same meaning as in formula 1, in the pH range of 1 to 6, after which the optionally obtained compound of formula 1 is converted by treatment with an acid into a physiologically acceptable salt. v němžin which Ri, R2, X a Y mají stejné významy jako ve vzorci 1, kondenzuje s kyanamidkarboxylátem obecného vzorce 4R1, R2, X and Y have the same meanings as in Formula 1, condensing with the cyanamide carboxylate of Formula 4 Severografia, n. p., závod 7, MostSeverography, n. P., Plant 7, Most
CS789087A 1974-09-10 1978-12-28 Method of producing basicly substituted 2-alkoxycarbonyl-amino-benzimidazol-5/6/-yl-phenyl ethers and ketones CS197256B2 (en)

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CS756069A CS197255B2 (en) 1974-09-10 1975-09-05 Method of producing basicly substituted 2-alkoxycarbonyl-amino-benzimidazol-5/6/-ylphenyl esters and ketones
CS789087A CS197256B2 (en) 1974-09-10 1978-12-28 Method of producing basicly substituted 2-alkoxycarbonyl-amino-benzimidazol-5/6/-yl-phenyl ethers and ketones

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