DE3613571A1 - N-(2'-Aminophenyl)benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases - Google Patents

N-(2'-Aminophenyl)benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases

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Publication number
DE3613571A1
DE3613571A1 DE19863613571 DE3613571A DE3613571A1 DE 3613571 A1 DE3613571 A1 DE 3613571A1 DE 19863613571 DE19863613571 DE 19863613571 DE 3613571 A DE3613571 A DE 3613571A DE 3613571 A1 DE3613571 A1 DE 3613571A1
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Germany
Prior art keywords
aminophenyl
benzamide
compounds
general formula
group
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
DE19863613571
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German (de)
Inventor
Ute Weiershausen
Gerhard Dr Satzinger
Karl-Otto Dr Vollmer
Wolfgang Dr Herrmann
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Goedecke GmbH
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Goedecke GmbH
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Application filed by Goedecke GmbH filed Critical Goedecke GmbH
Priority to DE19863613571 priority Critical patent/DE3613571A1/en
Priority to NZ219974A priority patent/NZ219974A/en
Priority to DK198487A priority patent/DK170771B1/en
Priority to CA000534920A priority patent/CA1334760C/en
Priority to CS872736A priority patent/CS262448B2/en
Priority to PH35157A priority patent/PH23928A/en
Priority to SU874202372A priority patent/SU1486054A3/en
Priority to ES87105846T priority patent/ES2095824T3/en
Priority to JP62096357A priority patent/JPH0825977B2/en
Priority to NO871640A priority patent/NO168353C/en
Priority to HU871729A priority patent/HU197295B/en
Priority to FI871733A priority patent/FI87766C/en
Priority to AT87105846T priority patent/ATE53572T1/en
Priority to EP87105846A priority patent/EP0242851B1/en
Priority to DD87301997A priority patent/DD263286A5/en
Priority to DE8787105846T priority patent/DE3763191D1/en
Priority to IL82265A priority patent/IL82265A/en
Priority to ZA872829A priority patent/ZA872829B/en
Priority to IE104687A priority patent/IE60332B1/en
Priority to CN 90104997 priority patent/CN1015417B/en
Priority to PT84737A priority patent/PT84737B/en
Priority to CN87103096A priority patent/CN1012498B/en
Priority to AT0265187A priority patent/AT388913B/en
Publication of DE3613571A1 publication Critical patent/DE3613571A1/en
Priority to GR90400340T priority patent/GR3000562T3/en
Priority to US07/594,592 priority patent/US5137918A/en
Withdrawn legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The application relates to novel compounds of the general formula II <IMAGE> in which R denotes halogen or a lower alkylalkoxy or lower acylamino group. They are suitable for the treatment of neoplastic diseases and can be prepared according to analogous processes.

Description

In der DE-OS 33 05 755 werden Verbindungen der allgemeinen Formel IIn DE-OS 33 05 755 compounds of the general formula I

als wirksam bei der Bekämpfung von malignen, proliferativen und autoimmunen Erkrankungen beschrieben. Besonders wirksam sind das 4-Amino-N-(2′-aminophenyl)-benzamid und seine N-Monomethylderivate.as effective in fighting malignant, proliferative and autoimmune diseases described. They are particularly effective 4-amino-N- (2'-aminophenyl) benzamide and its N-monomethyl derivatives.

Überraschenderweise wurde nun gefunden, daß die zunächst pharmakologisch für essentiell gehaltene, basische p-Amino-funktion nicht nur nicht verantwortlich für die therapeutische Wirksamkeit der erfindungsgemäßen Substanzen ist, sondern ihre Abwesenheit oder ihre chemische Veränderung in neutral reagierende Gruppen durch Substitution bzw. ihr Ersatz durch nicht-basische Reste zu wirksamen Verbindungen mit überlegener Verträglichkeit führen.Surprisingly, it has now been found that the pharmacological initially for essential, basic p-amino function not only not responsible for the therapeutic effectiveness of the invention Is substances, but their absence or their chemical Change in neutral reacting groups through substitution or their replacement with non-basic residues to form effective compounds lead superior tolerance.

Gegenstand der Erfindung sind somit neue N-2(Aminophenyl)-benzamid-Derivate zur Therapie maligner, proliferativer und autoimmuner Erkrankungen der allgemeinen Formel IIThe invention thus relates to new N-2 (aminophenyl) benzamide derivatives for the treatment of malignant, proliferative and autoimmune diseases of the general formula II

worin
R Halogen oder eine Niederalkylalkoxy- oder Niederacylaminogruppe bedeutet. Niederalkyl- /Niederacyl- umfaßt dabei einen unsubstituierten oder mit Hydroxyl substituierten C1-C4-Rest.wherein
R represents halogen or a lower alkylalkoxy or lower acylamino group. Lower alkyl / lower acyl comprises an unsubstituted or hydroxyl-substituted C 1 -C 4 radical.

Bevorzugt sind dabei Verbindungen der allgemeinen Struktur II, die einen Niederacylaminorest R besitzen, wiePreference is given to compounds of the general structure II which have a lower acylamino radical R, such as

  • 1) 4-Acetamino-N-(2′-aminophenyl)-benzamid1) 4-Acetamino-N- (2'-aminophenyl) benzamide
  • 2) 4-Isobutyrylamino-N-(2′-aminophenyl)-benzamid2) 4-isobutyrylamino-N- (2'-aminophenyl) benzamide
  • 3) 4-Formylamino-N-(2′-aminophenyl)-benzamid3) 4-Formylamino-N- (2'-aminophenyl) benzamide
  • 4) 4-(β-Hydroxypropionyl)amino-N-(2′-aminophenyl)-benzamid4) 4- (β-hydroxypropionyl) amino-N- (2'-aminophenyl) benzamide

Die 4-Acylamino-Verbindungen 1) bis 4) sowie die anderen oben aufgeführten, durch eine Halogen- oder Niederalkylalkoxygruppe substituierten N-(2′-Aminophenyl)-benzamid-Derivate der allgemeinen Formel II sind neu. Bekannt ist jedoch eine Verbindung mit R = H (Beilstein 13, HW S. 20), ohne daß deren pharmakologischen Wirkung bisher beschrieben wurde.The 4-acylamino compounds 1) to 4) and the other listed above, substituted by a halogen or lower alkylalkoxy group N- (2'-aminophenyl) benzamide derivatives of the general formula II are new. However, a connection with R = H is known (Beilstein 13, HW p. 20), without their pharmacological effect has been described so far.

Ein weiterer Gegenstand der Erfindung ist daher die Verwendung von Verbindungen der allgemeinen Formel II, wobei jedoch R zusätzlich auch Wasserstoff sein kann, bei der Bekämpfung neoplastischer Erkrankungen.Another object of the invention is therefore the use of Compounds of the general formula II, but R additionally can also be hydrogen in the fight against neoplastic diseases.

Die Verbindungen der allgemeinen Formel II können hergestellt werden, indem man Verbindungen der allgemeinen Formel III a und b:The compounds of the general formula II can be prepared by using compounds of the general formula III a and b:

in welcher A eine reaktive Säuregruppe darstellt, R die obengenannte Bedeutung hat und X eine mit einer Schutzgruppe versehene Aminogruppe oder eine Nitrogruppe bedeutet,
in an sich bekannter Weise miteinander umsetzt, die so erhaltenen Verbindungen der allgemeinen Formel IV,in which A represents a reactive acid group, R has the meaning given above and X represents an amino group provided with a protective group or a nitro group,
reacting with one another in a manner known per se, the compounds of the general formula IV thus obtained,

in welcher X und R die obengenannte Bedeutung haben
reduziert oder durch Abspaltung der Schutzgruppe in die entsprechenden Verbindungen der Formel II überführt.in which X and R have the meaning given above
reduced or converted into the corresponding compounds of formula II by splitting off the protective group.

Die erfindungsgemäßen Wirkstoffe werden vorteilhaft in Form eines pharmazeutischen Präparats verabreicht, welches die Wirkstoffe in freier Form oder in Form einer Mischung mit einem z. B. für die topische, enterale (z. B. orale oder rectale) oder parenterale (intramuskuläre oder intravenöse) Applikation geeigneten pharmazeutischen organischen oder anorganischen festen oder flüssigen Trägermaterial enthält. Für die Bildung derselben kommen solche Stoffe in Frage, die mit den neuen Verbindungen nicht reagieren, wie z. B. Gelatine, Lactose, Stärke, Stearylalkohol, Magnesiumstearat, Talk, pflanzliche Öle, Benzylalkohole, Prophylenglykole, Vaseline oder andere Arzneimittelträger. The active compounds according to the invention are advantageously in the form of a pharmaceutical Prepared drug, which contains the active ingredients in free form or in the form of a mixture with a z. B. for topical, enteral (e.g. oral or rectal) or parenteral (intramuscular or intravenous) application of suitable pharmaceutical organic or contains inorganic solid or liquid carrier material. For the Formation of the same is possible for those substances that are compatible with the new ones Connections do not respond, e.g. B. gelatin, lactose, starch, Stearyl alcohol, magnesium stearate, talc, vegetable oils, benzyl alcohols, Propylene glycols, petroleum jelly or other excipients.  

Die pharmazeutischen Präparate können z. B. als Tabletten, Drag´es, Kapseln, Suppositorien, Salben, Cremes oder in flüssiger Form als Suspensionen oder Emulsionen vorliegen. Gegebenenfalls sind sie sterilisiert und/oder enthalten Hilfsstoffe, wie Konservierungs-, Stabilisierungs-, Netz- oder Emulgiermittel, Lösungsvermittler oder Salze zur Veränderung des osmotischen Druckes oder Puffer. Sie können auch weitere Wirkstoffe enthalten.The pharmaceutical preparations can e.g. B. as tablets, drages, Capsules, suppositories, ointments, creams or in liquid form as Suspensions or emulsions are present. If necessary, they are sterilized and / or contain auxiliary substances such as preservatives, stabilizers, Wetting or emulsifying agents, solubilizers or salts to change the osmotic pressure or buffer. You can also contain other active ingredients.

Die anzuwendende Dosis hängt von der Art des zu therapierenden Krankheitsgeschehens und von individuellen Faktoren ab.The dose to be used depends on the type of disease to be treated and on individual factors.

Im allgemeinen werden Dosen von 10 bis 300 mg, insbesondere 20 bis 50 mg verabreicht. In besonderen Fällen kann die Einzeldosis auch höher liegen.Generally, doses of 10 to 300 mg, especially 20 to 50 mg administered. In special cases, the single dose can also be higher.

Die Umsetzung der Verbindungen gemäß Formel IIIa mit Verbindungen der Formel IIIb erfolgt in an sich bekannter Weise. Als reaktive Säuregruppen A dienen vor allem die Säurehalogenide, -anhydride oder -imidazolide oder Estergruppen, die eine Umsetzung mit der Aminogruppe erlauben. A bedeutet somit bevorzugt Halogen, Imidazolyl-, Acyl- oder niedere Alkoxyreste.The reaction of the compounds of formula IIIa with compounds of Formula IIIb is carried out in a manner known per se. As reactive acid groups A mainly serve the acid halides, anhydrides or imidazolides or Ester groups that allow reaction with the amino group. A means thus preferably halogen, imidazolyl, acyl or lower alkoxy radicals.

Als Schutzgruppen für X dienen die in der Peptidchemie üblichen Reste, wie z. B. der Benzyl- oder der Carbobenzoxy-Rest.The residues customary in peptide chemistry serve as protective groups for X, such as B. the benzyl or carbobenzoxy radical.

Die Reduktion kann unter Verwendung geeigneter Katalysatoren (Platin oder Palladium) mit Wasserstoff so durchgeführt werden, daß einerseits die freien Nitrogruppen zu primären Aminogruppen reduziert werden und andererseits die an den Aminogruppen befindlichen Schutzgruppen hydrogenolytisch abgespalten werden.
The reduction can be carried out using suitable catalysts (platinum or palladium) with hydrogen in such a way that, on the one hand, the free nitro groups are reduced to primary amino groups and, on the other hand, the protective groups on the amino groups are eliminated by hydrogenolysis.

Beispiel 1example 1 4-Acetamino-N-(2′-aminophenyl)-benzamid4-acetamino-N- (2'-aminophenyl) benzamide

Die Herstellung erfolgt aus p-Acetylaminobenzoesäure über das Säurechlorid, dessen Umsetzung mit o-Nitroanilin und die anschließende katalytische Reduktion der Nitrogruppe.
Schmp. 243°C (Ethanol).The preparation takes place from p-acetylaminobenzoic acid via the acid chloride, its reaction with o-nitroaniline and the subsequent catalytic reduction of the nitro group.
Mp 243 ° C (ethanol).

Beispiel 2Example 2 4-Isobutyrylamino-N-(2′-aminophenyl)-benzamid4-isobutyrylamino-N- (2'-aminophenyl) benzamide

Die Herstellung erfolgt aus p-Isobutyrylaminobenzoesäure über das Säurechlorid, dessen Umsetzung mit o-Nitroanilin und die anschließende katalytische Reduktion der Nitrogruppe.
Schmp. 249°C (Methanol).The preparation takes place from p-isobutyrylaminobenzoic acid via the acid chloride, its reaction with o-nitroaniline and the subsequent catalytic reduction of the nitro group.
Mp 249 ° C (methanol).

Biologisches Verhalten im VergleichsversuchBiological behavior in the comparison test

4-Acetamino-N-(2′-aminophenyl)-benzamid wurde als Beispiel der erfindungsgemäßen Wirkstoffe im Vergleich zum Standard 4-Amino-N- (2′-aminophenyl)-benzamid, für welchen in vitro und in vivo ausgeprägte Inhibition verschiedener experimenteller Tumoren bekannt ist, auf Antitumorwirkung geprüft.4-Acetamino-N- (2'-aminophenyl) benzamide was used as an example of Active substances according to the invention compared to the standard 4-amino-N- (2'-aminophenyl) benzamide, for which in vitro and in vivo pronounced inhibition of various experimental tumors is known, tested for anti-tumor effects.

Die Testung wurde in vitro im "Colorimetric Cytotoxicity Assay" an L 1210 Tumorzellen durchgeführt. Substanzen mit ID50 Werten 250 ug/ml werden in diesem Testsystem als cytostatisch aktiv beurteilt.The test was carried out in vitro in the "Colorimetric Cytotoxicity Assay" on L 1210 tumor cells. Substances with ID 50 values of 250 µg / ml are assessed as cytostatically active in this test system.

Es konnte gezeigt werden (s. Tab. 1), daß der erfindungsgemäße Wirkstoff 4-Acetamino-N-(2′aminophenyl)-benzamidIt could be shown (see Tab. 1) that the invention Active ingredient 4-acetamino-N- (2'aminophenyl) benzamide

  • 1. ausgeprägt cytostatisch wirkt1. has a pronounced cytostatic effect
  • 2. eine mit dem Vergleichsstandard etwa gleiche cytostatische Aktivität aufweist.2. a cytostatic approximately the same as the comparison standard Has activity.

TestsubstanzED50 µg/mlTest substance ED 50 µg / ml

4-Acetamino-N-(2′-aminophenyl)-benzamid3.75 4-Amino-N-(2′-aminophenyl)-benzamid2.784-acetamino-N- (2'-aminophenyl) benzamide3.75 4-Amino-N- (2'-aminophenyl) benzamide2.78

Überraschenderweise wurde gefunden, daß der erfindungsgemäße Wirkstoff 4-Acetamino-N-(2′-aminophenyl)-benzamid bei akuter intragastraler Verabreichung beträchtlich weniger toxisch ist als der Vergleichsstandard. Dies wurde im orientierenden Versuch (n = 4) an männlichen Mäusen zur Ermittlung der LD50 bei 7 Tage- Beobachtung nachgewiesen (s. Tab. 2).
TestsubstanzLD50 mg/kgSurprisingly, it was found that the active ingredient 4-acetamino-N- (2'-aminophenyl) benzamide is considerably less toxic than the comparative standard when administered acute intragastric. This was demonstrated in the orientation test ( n = 4) on male mice to determine the LD 50 after 7 days of observation (see Table 2).
Test substance LD 50 mg / kg

4-Acetamino-N-(2′-aminophenyl)-benzamid1600 4-Amino-N-(2′-aminophenyl)-benzamid6254-acetamino-N- (2'-aminophenyl) benzamide1600 4-amino-N- (2'-aminophenyl) benzamide625

In pharmakokinetischen Versuchen an Ratten konnte eine verminderte Resorption als mögliche Ursache der wesentlich verbesserten akuten Verträglichkeit des erfindungsgemäßen Wirkstoffs im Vergleich zum Standard ausgeschlossen werden: Die intestinale Resorption der Substanz erfolgt rasch, vollständig und dosislinear. In pharmacokinetic trials in rats, one decreased Absorption as a possible cause of the much improved acute tolerance of the active ingredient according to the invention compared to the standard to be excluded: the intestinal Absorption of the substance is rapid, complete and dose-linear.  

Die Bioverfügbarkeit des erfindungsgemäßen Wirkstoffs ist 100%: Es wurde kein statistisch signifikanter Unterschied der AUCs nach Gabe von 10 mg/kg i. v. und i. g. bei Ratten gefunden (s. Abb. 1).The bioavailability of the active ingredient according to the invention is 100%: No statistically significant difference in AUCs after administration of 10 mg / kg iv and ig was found in rats (see Fig. 1).

Abb. 1: AUC, Ratte, nach Verabreichung von 4-Acetamino-N-(2′-aminophenyl)- benzamid.
* i. g. Verabreichung (2 mg/kg; 10 mg/kg; 50 mg/kg)
• i. v. Verabreichung (10 mg/kg) Fig. 1: AUC, rat, after administration of 4-acetamino-N- (2′-aminophenyl) benzamide.
* ig administration (2 mg / kg; 10 mg / kg; 50 mg / kg)
Iv administration (10 mg / kg)

Neben seiner besseren Verträglichkeit zeichnet sich der erfindungsgemäße Wirkstoff gegenüber dem Vergleichsstandard auch durch eine längere Halbwertzeit aus (s. Abb. 2, 3), wodurch es möglich ist, cytostatische Wirkspiegel über längere Zeiträume aufrecht zu erhalten.In addition to its better tolerability, the active substance according to the invention is also distinguished by a longer half-life compared to the comparison standard (see FIGS. 2, 3), which makes it possible to maintain cytostatic activity levels over longer periods.

Abb. 2: Mittlerer Plasmaspiegel von 4-Amino-N-(2′-aminophenyl)- benzamid bei Ratten nach einmaliger Verabreichung von 10 mg/kg i. g. (n = 4).
Halbwertzeit (t1/2) ∼ 15 Minuten. Fig. 2: Average plasma level of 4-amino-N- (2′-aminophenyl) benzamide in rats after a single administration of 10 mg / kg ig ( n = 4).
Half-life (t1 / 2) ∼ 15 minutes.

Abb. 3: Mittlerer Plasmaspiegel von 4-Acetamino-N-(2′-aminophenyl)- benzamid bei Ratten nach einmaliger Verabreichung von + 10 mg/kg i. v. (n = 5), o 2 mg/kg i. g. (n = 5), 10 mg/kg i. g. (n = 6), 50 mg/kg i. g. (n = 5).
Halbwertzeit (t1/2) ∼ 4,2-4,5 Stunden. Fig. 3: Average plasma level of 4-acetamino-N- (2′-aminophenyl) benzamide in rats after a single administration of + 10 mg / kg iv ( n = 5), o 2 mg / kg ig ( n = 5) , 10 mg / kg ig ( n = 6), 50 mg / kg ig ( n = 5).
Half-life (t1 / 2) ∼ 4.2-4.5 hours.

4-Acetamino-N-(2′-aminophenyl)-benzamid als eine die erfindungsgemäße Wirkstoffgruppe repräsentierende Substanz stellt demnach gegenüber dem Vergleichsstandard 4-Amino-N-(2′-aminophenyl)-benzamid ein in wesentlichen biologischen Parametern deutlich verbessertes, dabei gleich wirksames Cytostatikum dar.4-acetamino-N- (2'-aminophenyl) benzamide as one of the invention Substance representing substance group accordingly represents compared to the comparison standard 4-amino-N- (2'-aminophenyl) benzamide a significantly improved in essential biological parameters, is an equally effective cytostatic.

Die erfindungsgemäßen Substanzen haben demnach therapeutische Bedeutung und stellen Mittel dar zurThe substances according to the invention accordingly have therapeutic ones Meaning and represent means for

  • - systemischen und/oder topischen Behandlung maligner Neoplasien- systemic and / or topical treatment of malignant Neoplasia
  • - Behandlung benigner proliferativer Erkrankungen- Treatment of benign proliferative diseases
  • - Behandlung von Störungen des zellulären und humoralen Immunsystems.- Treatment of cellular and humoral disorders Immune system.

Die Möglichkeit der Kombination mit Therapeutika, von denen zu erwarten ist, daß sie die gewünschten Effekte verstärken und günstig beeinflussen, ist mit eingeschlossen.The possibility of combining with therapeutic agents, one of which is is expected to amplify the desired effects and influencing favorably is included.

Claims (8)

1.) N-2′-(Aminophenyl)-benzamid-Derivate der allgemeinen Formel II worin
R Halogen oder eine Niederalkylalkoxy- oder Niederacylaminogruppe bedeutet.1.) N-2 '- (aminophenyl) benzamide derivatives of the general formula II wherein
R represents halogen or a lower alkylalkoxy or lower acylamino group. 2.) Verbindungen nach Anspruch 1, worin R ein Acylaminorest mit bis zu 4 Kohlenstoffatomen ist.2.) Compounds according to claim 1, wherein R is an acylamino radical with up to 4 carbon atoms. 3.) 4-Acetamino-N-(2′-aminophenyl)-benzamid.3.) 4-Acetamino-N- (2'-aminophenyl) benzamide. 4.) 4-Isobutyrylamino-N-(2′-aminophenyl)-benzamid.4.) 4-isobutyrylamino-N- (2'-aminophenyl) benzamide. 5.) 4-Formylamino-N-(2′-aminophenyl)-benzamid.5.) 4-Formylamino-N- (2'-aminophenyl) benzamide. 6.) 4-(β-Hydroxypropionyl)amino-N-(2′-aminophenyl)-benzamid.6.) 4- (β-hydroxypropionyl) amino-N- (2'-aminophenyl) benzamide. 7.) Verfahren zur Herstellung von Verbindungen der allgemeinen Formel I, dadurch gekennzeichnet, daß man Verbindungen der allgemeinen Formel III a und b: in welcher A eine reaktive Säuregruppe darstellt, R die obengenannte Bedeutung hat und X eine mit einer Schutzgruppe versehene Aminogruppe oder eine Nitrogruppe bedeutet,
in an sich bekannter Weise miteinander umsetzt, die so erhaltenen Verbindungen der allgemeinen Formel IV, in welcher X und R die obengenannte Bedeutung haben,
reduziert oder durch Abspaltung der Schutzgruppe in die entsprechenden Verbindungen der Formel II überführt.7.) Process for the preparation of compounds of general formula I, characterized in that compounds of general formula III a and b: in which A represents a reactive acid group, R has the meaning given above and X represents an amino group provided with a protective group or a nitro group,
reacting with one another in a manner known per se, the compounds of the general formula IV thus obtained, in which X and R have the meaning given above,
reduced or converted into the corresponding compounds of formula II by splitting off the protective group. 8.) Verwendung von Verbindungen der allgemeinen Formel I, in welcher R Wasserstoff, Halogen, eine Niederalkylalkoxy- oder eine Niederacylaminogruppe bedeutet bei der Bekämpfung neoplastischer Erkrankungen.8.) Use of compounds of general formula I in which R Hydrogen, halogen, a lower alkylalkoxy or a lower acylamino group means in the fight against neoplastic diseases.
DE19863613571 1986-04-22 1986-04-22 N-(2'-Aminophenyl)benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases Withdrawn DE3613571A1 (en)

Priority Applications (25)

Application Number Priority Date Filing Date Title
DE19863613571 DE3613571A1 (en) 1986-04-22 1986-04-22 N-(2'-Aminophenyl)benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases
NZ219974A NZ219974A (en) 1986-04-22 1987-04-14 N-(2'-aminophenyl)-benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases
DK198487A DK170771B1 (en) 1986-04-22 1987-04-15 N- (2'-aminophenyl) benzamide derivatives, their preparation and use in the preparation of a pharmaceutical composition and such preparation
CA000534920A CA1334760C (en) 1986-04-22 1987-04-16 N-(2'-aminophenyl)-benzamide-derivatives, process for their preparation and their use in the control of neoplastic diseases
CS872736A CS262448B2 (en) 1986-04-22 1987-04-16 Process for preparing derivatives of n-/2-aminophenyl/-benzamide
PH35157A PH23928A (en) 1986-04-22 1987-04-20 N'-(2'-aminophenyl)benzamide derivatives and method of use thereof
SU874202372A SU1486054A3 (en) 1986-04-22 1987-04-20 Method of producing benzamides
EP87105846A EP0242851B1 (en) 1986-04-22 1987-04-21 N-(2'-aminophenyl)-benzamide derivatives, process for their manufacture and their application in the treatment of neoplastic illness
IL82265A IL82265A (en) 1986-04-22 1987-04-21 N-(2'-aminophenyl)-benzamide derivatives,their preparation and pharmaceutical compositions containing them
NO871640A NO168353C (en) 1986-04-22 1987-04-21 ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE N- (2'-AMINOPHENYL) -BENZAMIDE DERIVATIVES
HU871729A HU197295B (en) 1986-04-22 1987-04-21 Process for production of new derivatives of n-/2'-aminphenil/-benzamid and medical preparatives containing those as active substance
FI871733A FI87766C (en) 1986-04-22 1987-04-21 FORM OF THERAPEUTIC ACTIVATION OF THERAPEUTIC ACTIVE N- (2'-AMINOPHENYL) BENZENE DERIVATIVES
AT87105846T ATE53572T1 (en) 1986-04-22 1987-04-21 N-(2'-AMINOPHENYL)-BENZAMIDE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE IN COMBATING NEOPLASTIC DISEASES.
ES87105846T ES2095824T3 (en) 1986-04-22 1987-04-21 PROCEDURE FOR THE OBTAINING OF N-2 'DERIVATIVES - (AMINOPHENYL) -BENZAMIDE AND ITS USE FOR THE FIGHT AGAINST NEOPLASTIC DISEASES.
DD87301997A DD263286A5 (en) 1986-04-22 1987-04-21 METHOD FOR PRODUCING N- (2'-AMINOPHENYL) -BENZAMIDE DERIVATIVES
DE8787105846T DE3763191D1 (en) 1986-04-22 1987-04-21 N- (2'-AMINOPHENYL) -BENZAMIDE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE IN THE FIGHT AGAINST NEOPLASTIC DISEASES.
JP62096357A JPH0825977B2 (en) 1986-04-22 1987-04-21 N- (2 ''-aminophenyl) -benzamide derivative, process for producing the same and pharmaceutical composition containing the same
ZA872829A ZA872829B (en) 1986-04-22 1987-04-22 N-(2'-aminophenyl)-benzamide-derivatives,process for their preparation and their use in the control of neoplastic diseases
IE104687A IE60332B1 (en) 1986-04-22 1987-04-22 N-(2'aminophenyl)-benzamide-derivatives, process for their preparation and their use in the control of neoplastic diseases
CN 90104997 CN1015417B (en) 1986-04-22 1987-04-22 Process for preparing medicine combination containing formamide derivatives
PT84737A PT84737B (en) 1986-04-22 1987-04-22 PROCESS FOR THE PREPARATION OF N- (2'-AMINOFENYL) -BENZAMIDE AND PHARMACEUTICAL COMPOSITIONS DERIVATIVES CONTAINING THEM
CN87103096A CN1012498B (en) 1986-04-22 1987-04-22 Process for n-(2'amino phenyl)-benzamide derivative and its drug composition
AT0265187A AT388913B (en) 1986-04-22 1987-10-08 NEW N- (2'-AMINOPHENYL) -BENZAMIDE DERIVATIVES AND MEDICINAL PRODUCTS CONTAINING THEM
GR90400340T GR3000562T3 (en) 1986-04-22 1990-06-14 N-(2'-aminophenyl)-benzamide derivatives, process for their manufacture and their application in the treatment of neoplastic illness
US07/594,592 US5137918A (en) 1986-04-22 1990-10-09 N-(2'-aminophenyl)-benzamide derivatives process for the preparation thereof and pharmaceutical compositions containing them

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DE19863613571 DE3613571A1 (en) 1986-04-22 1986-04-22 N-(2'-Aminophenyl)benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases

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ZA872829B (en) 1987-10-08
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