CO5261507A1 - INDOLINONES REPLACED IN POSITION 5, ITS PREPARATION AND ITS USE AS MEDICATIONS - Google Patents

INDOLINONES REPLACED IN POSITION 5, ITS PREPARATION AND ITS USE AS MEDICATIONS

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CO5261507A1
CO5261507A1 CO00077919A CO00077919A CO5261507A1 CO 5261507 A1 CO5261507 A1 CO 5261507A1 CO 00077919 A CO00077919 A CO 00077919A CO 00077919 A CO00077919 A CO 00077919A CO 5261507 A1 CO5261507 A1 CO 5261507A1
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alkyl
group
amino
phenyl
sulfonyl
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CO00077919A
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Spanish (es)
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Roth Gerald Jurgen
Armin Heckel
Rainer Walter
Meel Jacobus Van
Norbert Redemann
Gisela Schnapp
Tontsch-Grun Ulrike
Walter Spevak
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Boehringer Ingelheim Pharma K
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Publication of CO5261507A1 publication Critical patent/CO5261507A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Indolinonas sustituidas en posición 5 de la fórmula general<EMI FILE="00077919_1" ID="1" IMF=JPEG >En la que X significa un átomo de oxígeno o azufre, R1 significa un átomo de hidrógeno o un radical de profármaco,R2 significa un grupo hidroxi, alcoxi C1-3, ariloxi, fenil-alcoxi C1-3, ciano, (HO)2PO, (OH)(alcoxi C1-4)PO, (HO)(ariloxi)PO, (HO)(benciloxi)PO, (alcoxi C1-4)2PO,(ariloxi)2PO, (benciloxi)2PO, (alquilen C1-3-dioxi)PO, H(alcoxi C1-4)PO, H(ariloxi)PO, H(benciloxi)PO, mercapto, alquil C1-3-mercapto, aril-mercapto, fenil-alquil C1-3-mercapto, alquil C1-3-sulfinilo, aril-sulfinilo, fenil-alquil C1-3-sulfinilo, alquil C1-3-sulfonilo, aril-sulfonilo, fenil-alquil C1-3-sulfonilo, sulfo, alcoxi C1-3-sulfonilo, ariloxi-sulfonilo, fenil-alcoxi C1-3-sulfonilo, amino-sulfonilo, alquil C1-4-amino-sulfonilo, aril-amino-sulfonilo, heteroaril-amino-sulfonilo, fenil-alquil C1-3-amino-sulfonilo, di-(alquil C1-4)-amino-sulfonilo, di-(aril)-amino-sulfonilo, di-(fenil-alquil C1-3)-amino-sulfonilo, N-(alquil C1-3)-aril-amino-sulfonilo, N-(alquil C1-3)-heteroaril-amino-sulfonilo, N-(alquil C1-3)-fenil-alquil C1-3-amino-sulfonilo o un grupo cicloalquilen-imino-sulfonilo de 4 a 7 miembros, R3 significa un átomo de hidrógeno, un grupo alquilo C1-6, cicloalquilo C3-7, trifluorometilo o heteroarilo, un grupo fenilo o naftilo, un grupo fenilo o naftilo mono- o di-sustituido con un átomo de flúor, cloro, bromo o yodo, o con un grupo trifluorometilo, alquilo C1-3 o alcoxi C1-3, realizándose en el caso de la disustitución que los sustituyentes pueden ser iguales o diferentes y que los grupos fenilo y naftilo sin sustituir, mono- y di-sustituidos, que precedentemente se han mencionado, pueden estar sustituidos adicionalmente con un grupo hidroxi, hidroxi-alquilo C1-3 o alcoxi C1-3-alquilo C1-3, - 2 -con un grupo ciano, ciano-alquilo C1-3, ciano-alquenilo C2-3, ciano-alquinilo C2-3, carboxi, carboxi-alquilo C1-3, carboxi-alquenilo C2-3, carboxi-alquinilo C2-3, alcoxi C1-3-carbonilo, alcoxi C1-3-carbonil-alquilo C1-3, alcoxi C1-3-carbonil-alquenilo C2-3 o alcoxi C1-3-carbonil-alquinilo C2-3,con un grupo alquil C1-3-carbonilo, alquil C1-3-carbonil-alquilo C1-3, alquil C1-3-carbonil-alquenilo C2-3 o alquil C1-3-carbonil-alquinilo C2-3, con un grupo amino-carbonilo, amino-carbonil-alquilo C1-3, amino-carbonil-alquenilo C2-3, amino-carbonil-alquinilo C2-3, alquil C1-3-amino-carbonilo, alquil C1-3-amino-carbonil-alquilo C1-3, alquil C1-3-amino-carbonil-alquenilo C2-3, alquil C1-3-amino-carbonil-alquinilo C2-3, di-(alquil C1-3)-amino-carbonilo, di-(alquil C1-3)-amino-carbonil-alquilo C1-3, di-(alquil C1-3)-amino-carbonil-alquenilo C2-3 o di-(alquil C1-3)-amino-carbonil-alquinilo C2-3, con un grupo nitro, nitro-alquilo C1-3, nitro-alquenilo C2-3 o nitro-alquinilo C2-3,con un grupo amino, alquil C1-3-amino, di-(alquil C1-3)-amino, amino-alquilo C1-3, alquil C1-3-amino-alquilo C1-3 o di-(alquil C1-3)-amino-alquilo C1-3, con un grupo alquil C1-3-carbonil-amino, alquil C1-3-carbonil-amino-alquilo C1-3, N-(alquil C1-3)-alquil C1-3-carbonil-amino o N-(alquil C1-3)-alquil C1-3-carbonil-amino-alquilo C1-3, con un grupo alquil C1-3-sulfonil-amino, alquil C1-3-sulfonil-amino-alquilo C1-3, N-(alquil C1-3)-alquil C1-3-sulfonil-amino o N-(alquil C1-3)-alquil C1-3-sulfonil-amino-alquilo C1-3, con un grupo alquil C1-3-amino-sulfonilo, alquil C1-3-amino-sulfonil-alquilo C1-3, N-(alquil C1-3)-alquil C1-3-amino-sulfonilo o N-(alquil C1-3)-alquil C1-3-amino-sulfonil-alquilo C1-3, con un grupo cicloalquilen-imino, cicloalquilen-imino-carbonilo, cicloalquilen-imino-sulfonilo, cicloalquilen-imino-alquilo C1-3, cicloalquilen-imino-carbonil-alquilo C1-3 o cicloalquilen-imino-sulfonil-alquilo C1-3 en cada caso con 4 a 7 miembros de anillo, realizándose en cada caso que el grupo metileno situado en posición 4 en un grupo cicloalquilen-imino de 6 ó 7 miembros puede estar reemplazado por un átomo de oxígeno o azufre, o por un grupo sulfinilo, sulfonilo, -NH o -N(alquilo C1-3), o con un grupo heteroarilo o heteroaril-alquilo C1-3,R4 significa un grupo fenilo, un grupo fenilo sustituido con un átomo de flúor, cloro, bromo o yodo, con un grupo ciano, nitro, alquilo C1-3 o trifluorometilo, con un grupo alcoxi C1-3 sustituido eventualmente con 1 a 3 átomos de flúor, con un grupo amino-alcoxi C2-3, alquil C1-3-amino-alcoxi C2-3, di-(alquil C1-3)-amino-alcoxi C2-3 o bencil-amino-alcoxi C2-3, con un grupo cicloalquilen-imino-alcoxi C2-3 con 4 a 7 miembros de anillo, o con un grupo alquil C1-3-mercapto, carboxi, alcoxi C1-3-carbonilo, tetrazolilo o heteroarilo, un grupo fenilo sustituido con un grupo cicloalquilen-imino de 4 a 7 miembros, en el que un grupo metileno unido con el grupo imino puede estar reemplazado por un grupo carbonilo o sulfonilo, o la parte de cicloalquileno puede estar condensada con un anillo de fenilo, ouno o dos átomos de hidrógeno pueden estar reemplazados en cada caso por un grupo alquilo C1-3 y/o en cada caso el grupo metileno situado en posición 4 de un grupo cicloalquilen-imino de 6 ó 7 miembros puede estar sustituido con un grupo carboxi, alcoxi C1-3-carbonilo, amino-carbonilo, alquil C1-3-amino-carbonilo, di-(alquil C1-3)-amino-carbonilo, fenil-alquil C1-3-amino o N-(alquil C1-3)-fenil-alquil C1-3-amino, o puede estar reemplazado por un átomo de oxígeno o azufre, por un grupo sulfinilo, sulfonilo, -NH, -N(alquilo C1-3), -N(fenilo), -N(alquil C1-3-carbonilo) o -N(benzoílo), un grupo alquil C1-4-fenilo, que en la parte de alquilo está sustituido con un grupo amino, alquil C1-4-amino, di-(alquil C1-4)-amino, N-(fenil-alquil C1-4)-alquil C1-4-amino, ?-hidroxi-alquil C2-4-amino, di-(?-hidroxi-alquil C2-4)-amino o cicloalquil C3-7-amino, con un grupo cicloalquilen-imino de 4 a 7 miembros, en el que un grupo metileno unido con el grupo imino puede estar reemplazado por un grupo carbonilo o sulfonilo, o la parte de cicloalquileno puede estar condensada con un anillo de fenilo o con un grupo oxazolo, imidazolo, tiazolo, piridino, pirazino o pirimidino eventualmente sustituido con un átomo de flúor, cloro, bromo o yodo, con un grupo nitro, alquilo C1-3, alcoxi C1-3 o amino, o uno o dos átomos de hidrógeno pueden estar reemplazados en cada caso con un grupo alquilo C1-3, cicloalquilo C5-7 o fenilo y/o en cada caso el grupo metileno situado en posición 4 de un grupo cicloalquilen-imino de 6 ó 7 miembros puede estar sustituido con un grupo hidroxi, carboxi, alcoxi C1-4-carbonilo, amino-carbonilo, - 3 -alquil C1-3-amino-carbonilo, di-(alquil C1-3)-amino-carbonilo, fenil-alquil C1-3-amino o N-(alquil C1-3)-fenil-alquil C1-3-amino, o puede estar reemplazado por un átomo de oxígeno o azufre, por un grupo sulfinilo, sulfonilo, -NH, -N(alquilo C1-3), -N (fenilo), -N(alquil C1-3-carbonilo) o -N(benzoílo), con un grupo cicloalquenilen-imino de 5 a 7 miembros, en el que el doble enlace está aislado con respecto del átomo de nitrógeno, con un grupo fenil-amino, N-(alquil C1-3)-fenil-amino, fenil-alquil C1-3-amino, N-(alquil C1-3)-fenil-alquil C1-3-amino o di-(fenil-alquil C1-3)-amino, con un grupo hidroxi, alcoxi C1-3, tetrazolilo, carboxi, alcoxi C1-3-carbonilo, amino-carbonilo, alquil C1-3-amino-carbonilo, di-(alquil C1-3)-amino-carbonilo, alquil C1-3-carbonil-amino o N-(alquil C1-3)-alquil C1-3-carbonil-amino o con un grupo cicloalquilen-imino-carbonilo de 4 a 7 miembros, un grupo fenilo sustituido con el grupo de la fórmula N(R a ) CO (CH 2 ) n R b (II),en la que Ra significa un átomo de hidrógeno o un grupo alquilo C1-3, n significa uno de los números 0, 1, 2 ó 3 y Rb significa un grupo amino, alquil C1-4-amino, fenil-amino, N-(alquil C1-4)-fenil-amino, bencil-amino, N-(alquil C1-4)-bencil-amino odi-(alquil C1-4)-amino, un grupo cicloalquilen-imino de 4 a 7 miembros,realizándose en cada caso que el grupo metileno situado en posición 4 de un grupo cicloalquilen-imino de 6 ó 7 miembros puede estar reemplazado por un átomo de oxígeno o azufre, o por un grupo sulfinilo, sulfonilo, -NH, -N(alquilo C1-3), -N(fenilo), -N(alquil C1-3-carbonilo) o -N(benzoílo), o, si n representa uno de los números 1, 2 ó 3, también significa un átomo de hidrógeno, o un grupo fenilo sustituido con el grupo de la fórmula N(R c ) (CH 2 ) m (CO) o R d (III),en la que Rc significa un átomo de hidrógeno, un grupo alquilo C1-3, un grupo alquil C1-3-carbonilo, aril-carbonilo, fenil-alquil C1-3-carbonilo, alquil C1-3-sulfonilo, aril-sulfonilo o fenil-alquil C1-3-sulfonilo, m significa uno de los números 1, 2, 3 ó 4, o significa uno de los números 0 ó 1 y Rd significa un grupo amino, alquil C1-4-amino, fenil-amino, N-(alquil C1-4)-fenil-amino, bencil-amino, N-(alquil C1-4)-bencil-amino o di-(alquil C1-4)-amino, un grupo cicloalquilen-imino de 4 a 7 miembros,pudiendo la parte de cicloalquileno estar condensada con un anillo de fenilo o pudiendo en cada caso el grupo metileno situado en posición 4 de un grupo cicloalquilen-imino de 6 ó 7 miembros estar reemplazado por un átomo de oxígeno o azufre, por un grupo sulfinilo, sulfonilo, -NH, -N(alquilo C1-3), -N(fenilo), -N(alquil C1-3-carbonilo) o -N(benzoílo), significa un grupo alcoxi C1-3 o un grupo di-(alquil C1-4)-amino-alquil C1-3-amino eventualmente sustituido en posición 1 con un grupo alquilo C1-3, o también, si R3 no posee el significado de un átomo de hidrógeno, o de un grupo alquilo C1-6, cicloalquilo C1-7 o trifluorometilo, también significa un grupo aril-sulfonil-amino-fenilo o N-(alquil C1-3)-aril-sulfonil-amino-fenilo, pudiendo todos los grupos fenilo enlazados simplemente o condensados, que están contenidos en los radicales mencionados para R4, estar mono- o di-sustituidos con átomos de flúor, cloro, bromo o yodo, o con grupos alquilo C1-5, trifluorometilo, alcoxi C1-3, carboxi, alcoxi C1-3-carbonilo, amino-sulfonilo, nitro o ciano, pudiendo los sustituyentes ser iguales o diferentes, o pudiendo dos átomos de hidrógeno contiguos de los grupos fenilo estar reemplazados por un grupo metilen-dioxi, y R5 significa un átomo de Indolinones substituted in position 5 of the general formula <EMI FILE = "00077919_1" ID = "1" MFI = JPEG> In which X means an oxygen or sulfur atom, R1 means a hydrogen atom or a prodrug radical, R2 means a hydroxy group, C1-3 alkoxy, aryloxy, phenyl-C1-3 alkoxy, cyano, (HO) 2PO, (OH) (C1-4 alkoxy) PO, (HO) (aryloxy) PO, (HO) (benzyloxy ) PO, (C1-4 alkoxy) 2PO, (aryloxy) 2PO, (benzyloxy) 2PO, (C1-3 alkylene dioxy) PO, H (C1-4 alkoxy) PO, H (aryloxy) PO, H (benzyloxy) PO, mercapto, C1-3 alkyl mercapto, aryl mercapto, phenyl C1-3 alkyl mercapto, C1-3 alkyl sulfinyl, aryl sulfinyl, phenyl C1-3 alkyl sulfinyl, C1-3 alkyl sulfonyl , aryl-sulfonyl, phenyl-C 1-3 alkyl sulfonyl, sulfo, C 1-3 alkoxy sulfonyl, aryloxy sulfonyl, phenyl C 1-3 alkoxy sulfonyl, amino sulfonyl, C 1-4 alkyl amino sulfonyl, aryl -amino-sulfonyl, heteroaryl-amino-sulfonyl, phenyl-C1-3-alkyl-sulfonyl, di- (C1-4-alkyl) -amino-sulfonyl, di- (aryl) -amino-sulfonyl, di- (phenyl- C1-3 alkyl) -amino-sulfo nyl, N- (C1-3 alkyl) -aryl-amino-sulfonyl, N- (C1-3 alkyl) -heteroaryl-amino-sulfonyl, N- (C1-3 alkyl) -phenyl-C1-3-alkyl- sulfonyl or a 4- to 7-membered cycloalkylene-imino-sulfonyl group, R 3 means a hydrogen atom, a C 1-6 alkyl group, C 3-7 cycloalkyl, trifluoromethyl or heteroaryl, a phenyl or naphthyl group, a mono phenyl or naphthyl group - or di-substituted with a fluorine, chlorine, bromine or iodine atom, or with a trifluoromethyl group, C1-3 alkyl or C1-3 alkoxy, being carried out in the case of the substitution that the substituents may be the same or different and that the unsubstituted, mono- and di-substituted phenyl and naphthyl groups mentioned above may be further substituted with a hydroxy, hydroxy-C1-3alkyl or C1-3alkoxy-C1-3alkyl group, -2 with a cyano, cyano-C1-3 alkyl, cyano-C2-3 alkenyl, cyano-C2-3 alkynyl, carboxy, carboxy-C1-3 alkyl, carboxy-C2-3 alkenyl, carboxy-C2-3 alkynyl, alkoxy group C1-3-ca Rbonyl, C1-3 alkoxycarbonyl C1-3alkyl, C1-3alkoxycarbonylC2-3alkyl or C1-3alkoxycarbonylC2-3alkyl, with a C1-3alkylcarbonyl group, C1 alkyl -3-C 1-3 alkylcarbonyl, C 1-3 alkylcarbonyl C2-3 alkynyl or C 1-3 alkylcarbonylC2-3 alkynyl, with an aminocarbonyl group, aminocarbonylC 1-3 alkyl, C2-3 aminocarbonylcarbonyl, C2-3 aminocarbonylcarbonyl, C1-3alkylaminocarbonyl, C1-3alkylcarbonyl-C1-3alkyl, C1-3alkyl-aminocarbonyl- C2-3 alkenyl, C1-3 alkyl-amino-carbonyl-C2-3 alkynyl, di- (C1-3 alkyl) -amino-carbonyl, di- (C1-3 alkyl) -amino-carbonyl-C1-3 alkyl, di- (C1-3 alkyl) -amino-carbonyl-C2-3 alkenyl or di- (C1-3 alkyl) -amino-carbonyl-C2-3 alkynyl, with a nitro group, nitro-C1-3 alkyl, nitro- C2-3 alkenyl or C2-3 nitro-alkynyl, with an amino group, C1-3alkyl-amino, di- (C1-3alkyl) -amino, amino-C1-3alkyl, C1-3alkyl-amino-alkyl C1-3 or di- (C1-3 alkyl) -amino-C1-3 alkyl, with a C1-3 alkylcarbonyl amino group, alkyl C1-3-carbonyl-amino-C1-3alkyl, N- (C1-3alkyl) -C1-3alkyl-amino or N- (C1-3alkyl) -C1-3alkyl-carbonyl-amino- C1-3 alkyl, with a C1-3 alkyl sulfonyl amino group, C1-3 alkyl sulfonyl amino C1-3 alkyl, N- (C1-3 alkyl) C1-3 alkyl sulfonyl amino or N - (C1-3alkyl) -C1-3alkyl-sulfonyl-amino-C1-3alkyl, with a C1-3alkyl-sulfonyl group, C1-3alkyl-sulfonyl-C1-3alkyl, N- (C1-3 alkyl) -C1-3-amino-sulfonyl or N- (C1-3-alkyl) -C1-3-amino-sulfonyl-C1-3 alkyl, with a cycloalkylene-imino, cycloalkylene-imino- group carbonyl, cycloalkylene-imino-sulfonyl, cycloalkylene-imino-C1-3alkyl, cycloalkylene-imino-carbonyl-C1-3alkyl or cycloalkylene-imino-sulfonyl-C1-3alkyl in each case with 4 to 7 ring members, being performed in each case that the methylene group located in position 4 in a 6 or 7 membered cycloalkylene imino group may be replaced by an oxygen or sulfur atom, or by a sulfinyl, sulfonyl, -NH or -N (alq C1-3 uyl), or with a heteroaryl or heteroaryl-C1-3 alkyl group, R4 means a phenyl group, a phenyl group substituted with a fluorine, chlorine, bromine or iodine atom, with a cyano, nitro, C1 alkyl group -3 or trifluoromethyl, with a C1-3 alkoxy group optionally substituted with 1 to 3 fluorine atoms, with a C2-3 amino-alkoxy group, C1-3 alkyl-C2-3 amino-alkoxy, di- (C1- alkyl) 3) -amino-C2-3 alkoxy or benzyl amino-C2-3 alkoxy, with a C2-3 cycloalkylene-imino-alkoxy group with 4 to 7 ring members, or with a C1-3 alkyl mercapto group, carboxy , C1-3-alkoxycarbonyl, tetrazolyl or heteroaryl, a phenyl group substituted with a 4- to 7-membered cycloalkylene imino group, in which a methylene group linked to the imino group may be replaced by a carbonyl or sulfonyl group, or the cycloalkylene part may be condensed with a phenyl ring, one or two hydrogen atoms may be replaced in each case by a C1-3 alkyl group and / or in each case the meti group leno located in position 4 of a 6 or 7 membered cycloalkylene imino group may be substituted with a carboxy group, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3alkylcarbonyl alkyl, di- (C1- alkyl) 3) -amino-carbonyl, phenyl-C1-3-alkyl or N- (C1-3-alkyl) -phenyl-C1-3-alkyl, or it may be replaced by an oxygen or sulfur atom, by a sulfinyl group , sulfonyl, -NH, -N (C1-3 alkyl), -N (phenyl), -N (C1-3 alkylcarbonyl) or -N (benzoyl), a C1-4 alkyl phenyl group, which in the alkyl part is substituted with an amino group, C1-4 alkyl-amino, di- (C1-4 alkyl) -amino, N- (phenyl-C1-4 alkyl) -C 1-4 alkyl-amino,? -hydroxy- C2-4-amino, di - (? -hydroxy-C2-4-alkyl) -amino or C3-7-cycloalkyl group, with a 4- to 7-membered cycloalkylene-imino group, in which a methylene group linked to the imino group may be replaced by a carbonyl or sulfonyl group, or the cycloalkylene part may be condensed with a phenyl ring or with an oxazolo group, i midazolo, thiazolo, pyridino, pyrazino or pyrimidino possibly substituted with a fluorine, chlorine, bromine or iodine atom, with a nitro group, C1-3 alkyl, C1-3 alkoxy or amino, or one or two hydrogen atoms may be replaced in each case with a C1-3 alkyl, C5-7 cycloalkyl or phenyl group and / or in each case the methylene group located in position 4 of a 6 or 7 membered cycloalkylene imino group may be substituted with a hydroxy, carboxy group , C1-4 alkoxycarbonyl, aminocarbonyl, -3-C1-3alkylcarbonyl, di- (C1-3alkyl) -aminocarbonyl, phenyl-C1-3alkyl or N- (alkyl C1-3) -phenyl-C1-3-alkyl, or may be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH, -N (C1-3 alkyl), -N (phenyl) group , -N (C 1-3 alkylcarbonyl) or -N (benzoyl), with a 5-7 membered cycloalkenylene imino group, in which the double bond is isolated from the nitrogen atom, with a phenyl group- amino, N- (C1-3 alkyl) -fe nyl-amino, phenyl-C1-3-alkyl, N- (C1-3-alkyl) -phenyl-C1-3-alkyl or di- (phenyl-C1-3-alkyl) -amino, with a hydroxy group, alkoxy C1-3, tetrazolyl, carboxy, C1-3 alkoxycarbonyl, aminocarbonyl, C1-3alkylcarbonyl, di- (C1-3alkyl) -aminocarbonyl, C1-3alkylcarbonyl amino or N- (C1-3 alkyl) -C 1-3 alkyl-carbonyl-amino or with a 4- to 7-membered cycloalkylene-imino-carbonyl group, a phenyl group substituted with the group of the formula N (R a) CO (CH 2) n R b (II), in which Ra means a hydrogen atom or a C1-3 alkyl group, n means one of the numbers 0, 1, 2 or 3 and Rb means an amino group, C1-4 alkyl -amino, phenyl-amino, N- (C1-4 alkyl) -phenyl-amino, benzyl-amino, N- (C1-4 alkyl) -benzyl-amino-odi- (C1-4 alkyl) -amino, a cycloalkylene group -imino of 4 to 7 members, realizing in each case that the methylene group located in position 4 of a cycloalkylene-imino group of 6 or 7 members can be replaced by an oxygen or sulfur atom, or by a sulfinyl, sulfonyl, -NH, -N (C1-3 alkyl), -N (phenyl), -N (C1-3-alkylcarbonyl) or -N (benzoyl) group, or, if n represents one of the numbers 1, 2 or 3, also means a hydrogen atom, or a phenyl group substituted with the group of the formula N (R c) (CH 2) m (CO) or R d (III), in which Rc means a hydrogen atom, a C1-3 alkyl group, a C1-3 alkylcarbonyl group, arylcarbonyl, phenylC1-3alkylcarbonyl, C1-3alkyl sulfonyl, aryl sulfonyl or phenyl C1- alkyl 3-sulfonyl, m means one of the numbers 1, 2, 3 or 4, or means one of the numbers 0 or 1 and Rd means an amino group, C1-4-alkyl, phenyl-amino, N- (C1-alkyl -4) -phenyl-amino, benzyl-amino, N- (C1-4alkyl) -benzyl-amino or di- (C1-4alkyl) -amino, a 4- to 7-membered cycloalkylene-imino group, the part being able to of cycloalkylene being condensed with a phenyl ring or in each case the methylene group located in position 4 of a 6 or 7 ml cycloalkylene imino group embros be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH, -N (C1-3 alkyl), -N (phenyl), -N (C1-3-alkylcarbonyl) or -N ( benzoyl), means a C1-3 alkoxy group or a di- (C1-4 alkyl) -amino-C1-3-amino alkyl optionally substituted in position 1 with a C1-3 alkyl group, or also, if R3 does not possess the meaning of a hydrogen atom, or of a C1-6 alkyl, C1-7 cycloalkyl or trifluoromethyl group, also means an aryl-sulfonyl-amino-phenyl or N- (C1-3 alkyl) -aryl-sulfonyl-amino group -phenyl, all phenyl groups simply linked or condensed, which are contained in the radicals mentioned for R4, being mono- or di-substituted with fluorine, chlorine, bromine or iodine atoms, or with C1-5 alkyl groups, trifluoromethyl , C1-3 alkoxy, carboxy, C1-3 alkoxycarbonyl, amino-sulfonyl, nitro or cyano, the substituents may be the same or different, or two adjacent hydrogen atoms of the f groups may be enyl be replaced by a methylene dioxy group, and R5 means an atom of

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