AR039562A1 - OXO-AZABICICLIC COMPOUNDS - Google Patents

OXO-AZABICICLIC COMPOUNDS

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Publication number
AR039562A1
AR039562A1 ARP030100749A ARP030100749A AR039562A1 AR 039562 A1 AR039562 A1 AR 039562A1 AR P030100749 A ARP030100749 A AR P030100749A AR P030100749 A ARP030100749 A AR P030100749A AR 039562 A1 AR039562 A1 AR 039562A1
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Argentina
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group
alkyl
hydrogen
oxygen
atom
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ARP030100749A
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Spanish (es)
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Bernard Gaudilliere
Henry Jacobelli
Catherine Kostlan
Yue-Wen-Song
Jack Jie Li
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Warner Lambert Co
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Publication of AR039562A1 publication Critical patent/AR039562A1/en

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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
    • 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

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  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Compuestos oxo-azabicíclicos y su uso para la preparación de una composición farmacéutica para tratar la inhibición de la metaloproteasa de la matriz de tipo 13, mediante la administración a un cuerpo vivo de una cantidad eficaz de dicho compuesto. La composición farmacéutica es útil para el tratamiento de una enfermedad seleccionada de artritis, osteoartritis y otras de acuerdo con la memoria. Composición farmacéutica que comprende una cantidad eficaz de dicho compuesto solo o en combinación con uno o más excipientes o portadores farmacéuticamente aceptables. Reivindicación 1: Un compuesto seleccionado de aquellos de fórmula (1), caracterizado porque: X1, X2, y X3, independientemente uno de otro, representan un átomo de nitrógeno o un grupo -CR3 en donde R3 representa un grupo seleccionado de hidrógeno, alquilo C1-6, amino, monoalquilamino C1-6, dialquilamino C1-6, hidroxi, alcoxi C1-6, y halógeno, con la condición de que no más de dos de los grupos X1, X2, y X3 simultáneamente representa un átomo de nitrógeno; G1 representa un grupo seleccionado entre las fórmulas (2) y (3) en donde: el átomo de carbono con el número 2 está unido al grupo N-R1 del anillo, R4 y R5, idénticos o diferentes, independientemente uno del otro, representa un grupo seleccionado de hidrógeno, alquilo C1-6, arilo, arilalquilo C1-6, cicloalquilo, cicloalquilalquilo C1-6, heteroarilo, heteroarilalquilo C1-6, heterocicloalquilo, y heterocicloalquilalquilo C1-6, R6 representa un grupo seleccionado de: hidrógeno, trifluorometilo, OR7, NR7R8, en donde R7 y R8, idénticos o diferentes independientemente uno del otro, representan hidrógeno o alquilo C1-6; alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, arilalquilo C1-6, cicloalquilalquilo C1-6, heteroarilo, heteroarilalquilo C1-6, heterocicloalquilo, y heterocicloalquilalquilo C1-6, estos grupos siendo opcionalmente substituidos por uno o más grupos, que pueden ser idénticos o diferentes independientemente uno del otro, seleccionados de halógeno, amino, monoalquilamino C1-6, dialquilamino C1-6, cada grupo alquilo es idéntico o diferente independientemente uno del otro, ciano, trihalogenoalquilo C1-6, acilo C1-6, -C(-O)OR7, -OR7 y -SR7, en donde R7 es lo definido anteriormente, G2 representas un grupo seleccionado de triple enlace carbono-carbono, -CH=C=CH-, C=O, C=S, S(O)n1 en donde n1 representa un entero de 0 a 2 inclusive, y un grupo de fórmula (4), en donde el átomo de carbono con el número 1 está unido al biciclo del compuesto de fórmula (1), Y1 representa un grupo seleccionado de oxígeno, azufre, -NH y -Nalquilo C1-6, e Y2 representa un grupo seleccionado de oxígeno, azufre, -NH y -Nalquilo C1-6, n representa un entero de 0 a 6 inclusive, Z1 representa -CR9R10, en donde R9 y R10, idénticos o diferentes independientemente uno del otro, representan un grupo seleccionado de hidrógeno, alquilo C1-6, trihalogenoalquilo C1-6, halógeno, -OR7, -SR7, y -C(-O)OR7, en donde R7 es lo definido anteriormente, amino, monoalquilamino C1-6, dialquilamino C1-6 en donde cada grupo alquilo es idéntico o diferente independientemente uno del otro, y en donde cuando n es mayor o igual a 2, la cadena hidrocarbonada Z1 opcionalmente contiene uno a dos enlaces múltiples aislados o conjugados, y/o en donde cuando n es mayor o igual a 2, uno de dichos -CR9R10 pueden opcionalmente ser reemplazados con un grupo seleccionado de oxígeno, S(O)n1 en donde n1 es lo definido anteriormente, -NH y -Nalquilo C1-6, A representa un grupo seleccionado de arilo, heteroarilo, cicloalquilo, y heterocicloalquilo, estos grupos son monociclos o biciclos de 5- o 6-miembros compuestos de dos monociclos de 5- o 6-miembros, R1 representa un grupo seleccionado de: hidrógeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, estos grupos pueden estar opcionalmente substituidos con uno o más grupos, que pueden ser idénticos o diferentes independientemente uno del otro, seleccionado de amino, ciano, trihalogenoalquilo C1-6, cicloalquilo, -C(=O)NR7R8, -C(=O)OR8, OR8, SR8, en donde R7 y R8, que pueden ser idénticos o diferentes independientemente uno del otro, representa hidrógeno o alquilo C1-6, y el grupo de fórmula (5), en donde p es un entero de 0 a 8 inclusive, Z2 representa -CR11R12 en donde R11 y R12, idénticos o diferentes independientemente uno del otro, representa un grupo seleccionado de hidrógeno, alquilo C1-6, fenilo, trihalogenoalquilo C1-6, halógeno, amino, OR7, SR7 y -C(-O)OR7 en donde R7 representa hidrógeno o alquilo C1-6, y en donde cuando p es mayor o igual a 2, la cadena hidrocarbonada Z2 opcionalmente contiene uno a dos enlaces múltiples aislados o conjugados, y/o cuando n es mayor o igual a 2, uno de dichos -CR11R12 pueden opcionalmente ser reemplazado con un grupo seleccionado de oxígeno, S(O)n1 en donde n1 es lo definido anteriormente, -NH, -Nalquilo C1-6, y carbonilo, B representa un grupo seleccionado de arilo, heteroarilo, cicloalquilo, y heterocicloalquilo, estos grupos son monociclos o biciclos de 5 o 6 miembros compuestos de dos monociclos de 5 o 6 miembros, q es un entero de 0 a 7 inclusive, el grupo(s) G3, que puede ser idéntico o diferente independientemente uno del otro, se selecciona(n) de alquilo C1-6, halógeno, CN, NO2, CF3, OCF3, -(CH2)kNR13R14, -N(R13)C(=O)R14, -N(R13)C(=O)OR14, -N(R13)SO2R14, -N(SO2R13)2, -OR13, -S(O)k1R13, -SO2-N(R13)-(CH2)k2-NR14R15, -(CH2)kSO2NR13R14, -X4(CH2)kC(=O)OR13, -(CH2)kC(=O)OR13, -C(=O)O-(CH2)k2-NR13R14, -C(=O)O-(CH2)k2-C(=O)OR16, -X4(CH2)kC(=O)NR13R14, -(CH2)kC(=O)NR13R14, -R17-C(=O)OR13, -X5-R18, y -C(=O)-R19-NR13R14 en donde: X4 representa un grupo seleccionado de un átomo de oxígeno, un átomo de azufre opcionalmente substituidos por uno o dos átomos de oxígeno, y un átomo de nitrógeno substituido por un átomo de hidrógeno o un grupo alquilo C1-6, k es un entero de 0 a 3 inclusive, k1 es un entero de 0 a 2 inclusive, k2 es un entero de 1 a 4 inclusive, R13, R14 y R15, que pueden ser idénticos o diferentes independientemente uno del otro, están seleccionados de hidrógeno y alquilo C1-6, R16 representa un grupo seleccionado de alquiloC1-6, -R19-NR13R14, -R19-NR13-C(=O)-R19-NR14R15, y -C(=O)O-R19-NR13R14 en donde R19 representa un grupo alquileno C1-6 lineal o ramificado, y R13, R14 y R15 son lo definido anteriormente, R17 representa un grupo cicloalquilo C3-6, X5 representa un grupo seleccionado de un solo enlace, -CH2-, un átomo de oxígeno, un átomo de azufre opcionalmente substituido por uno o dos átomos de oxígeno, y un átomo de nitrógeno substituido por un átomo de hidrógeno o un grupo alquilo C1-6, R18 representa un grupo seleccionado de: monociclo de 5 o 6 miembros arilo, heteroarilo, que es opcionalmente substituido por uno o más grupos, que pueden ser idénticos o diferentes, seleccionados de alquilo C1-6, halógeno, hidroxi, ciano, tetrazolilo, amino, y -C(=O)OR7 en donde R7 representa hidrógeno o alquilo C1-6, y monociclo de 5- o 6- miembros cicloalquilo, heterocicloalquilo, que es opcionalmente substituido por uno o más grupos, que pueden ser idénticos o diferentes, seleccionados de alquilo C1-6, halógeno, hidroxi, oxo, ciano, tetrazolilo, amino, y -C(=O)OR7 en donde R7 representa hidrógeno o alquilo C1-6, m es un entero de 0 a 7 inclusive, el grupo(s) R2, que pueden ser idénticos o diferentes independientemente uno del otro, se seleccionan de alquilo C1-6, halógeno, -CN, NO2, SCF3, -CF3, -OCF3, -NR7R8, -OR8, -SR8, -SOR8, -SO2R8, -(CH2)kSO2NR7R8, -X7(CH2)kC(=O)OR8, -(CH2)kC(=O)OR8, -X7(CH2)kC(=O)NR7R8, -(CH2)kC(=O)NR7R8, y -X8-R20 en donde: X7 representa un grupo seleccionado de oxígeno, azufre opcionalmente substituido por uno o dos átomos de oxígeno, y un átomo de nitrógeno substituido por un átomo de hidrógeno o un grupo alquilo C1-6, k es un entero de 0 a 3 inclusive, R7 y R8, que pueden ser idénticos o diferentes independientemente uno del otro, se seleccionan de hidrógeno y alquilo C1-6, X8 representa un grupo seleccionado de un solo enlace, -CH2-, un átomo de oxígeno, un átomo de azufre opcionalmente substituido por uno o dos átomos de oxígeno, y un átomo de nitrógeno substituido por un átomo de hidrógeno o un grupo alquilo C1-6, R20 representa un monociclo de 5- o 6- miembros arilo, heteroarilo, cicloalquilo, o heterocicloalquilo que es opcionalmente substituido por uno o más grupos, que pueden ser idénticos o diferentes, seleccionados de alquilo C1-6, halógeno, hidroxi y amino, y cuando el anillo es heterocíclico, comprende de 1 a 4 heteroátomos seleccionados de nitrógeno, oxígeno y azufre, opcionalmente, las formas racémicas de ellos, isómeros de ellos, N-óxidos de ellos y la sales farmacéuticamente aceptables de ellos, entendiéndose que cuando no se describe ninguna especificación: un grupo arilo indica un sistema monocíclico o bicíclico aromático que contiene de 5 a 10 átomos de carbono, y en el caso de un sistema bicíclico, uno de los anillos es de carácter aromático, y el otro anillo puede ser aromático o parcialmente hidrogenado, un grupo heteroarilo indica un grupo arilo descripto anteriormente en donde de 1 a 4 átomos de carbono son reemplazados por 1 a 4 heteroátomos seleccionados de oxígeno, azufre y nitrógeno, un grupo cicloalquilo indica un sistema monocíclico o bicíclico que contiene de 3 a 10 átomos de carbono, este sistema es saturado o parcialmente insaturado pero sin carácter aromático, y un grupo heterocicloalquilo indica un grupo cicloalquilo definido anteriormente en donde de 1 a 4 átomos de carbono son reemplazados por 1 a 4 heteroátomos seleccionados de oxígeno, azufre, y nitrógeno.Oxo-azabicyclic compounds and their use for the preparation of a pharmaceutical composition to treat the inhibition of type 13 matrix metalloprotease, by administration to a living body of an effective amount of said compound. The pharmaceutical composition is useful for the treatment of a disease selected from arthritis, osteoarthritis and others according to memory. Pharmaceutical composition comprising an effective amount of said compound alone or in combination with one or more pharmaceutically acceptable excipients or carriers. Claim 1: A compound selected from those of formula (1), characterized in that: X1, X2, and X3, independently of one another, represent a nitrogen atom or a -CR3 group wherein R3 represents a selected group of hydrogen, alkyl C1-6, amino, C1-6 monoalkylamino, C1-6 dialkylamino, hydroxy, C1-6 alkoxy, and halogen, with the proviso that no more than two of the groups X1, X2, and X3 simultaneously represent a nitrogen atom ; G1 represents a group selected from formulas (2) and (3) in which: the carbon atom with the number 2 is attached to the N-R1 group of the ring, R4 and R5, identical or different, independently of each other, represents a group selected from hydrogen, C 1-6 alkyl, aryl, C 1-6 arylalkyl, cycloalkyl, C 1-6 cycloalkylalkyl, heteroaryl, C 1-6 heteroarylalkyl, heterocycloalkyl, and C 1-6 heterocycloalkylalkyl, R 6 represents a group selected from: hydrogen, trifluoromethyl , OR7, NR7R8, wherein R7 and R8, identical or different independently of each other, represent hydrogen or C1-6 alkyl; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, C 1-6 arylalkyl, C 1-6 cycloalkylalkyl, heteroaryl, C 1-6 heteroarylalkyl, heterocycloalkyl, and C 1-6 heterocycloalkylalkyl, these groups being optionally substituted by one or more groups, which may be identical or different independently of each other, selected from halogen, amino, C1-6 monoalkylamino, C1-6 dialkylamino, each alkyl group is identical or different independently from each other, cyano, C1-6 trihalogenoalkyl, acyl C1-6, -C (-O) OR7, -OR7 and -SR7, where R7 is defined above, G2 represents a selected group of carbon-carbon triple bond, -CH = C = CH-, C = O, C = S, S (O) n1 where n1 represents an integer from 0 to 2 inclusive, and a group of formula (4), where the carbon atom with the number 1 is attached to the bicycles of the compound of formula (1 ), Y1 represents a group selected from oxygen, sulfur, -NH and -C 1-6 alkyl, and Y2 represents a group selected from oxygen or, sulfur, -NH and -C1-6alkyl, n represents an integer from 0 to 6 inclusive, Z1 represents -CR9R10, where R9 and R10, identical or different independently of each other, represent a group selected from hydrogen, alkyl C1-6, trihalogeno C1-6 alkyl, halogen, -OR7, -SR7, and -C (-O) OR7, where R7 is defined above, amino, C1-6 monoalkylamino, C1-6 dialkylamino where each alkyl group is identical or different independently of each other, and where when n is greater than or equal to 2, the hydrocarbon chain Z1 optionally contains one to two isolated or conjugated multiple bonds, and / or where when n is greater than or equal to 2, one of said -CR9R10 can optionally be replaced with a selected group of oxygen, S (O) n1 where n1 is as defined above, -NH and -C1-6alkyl, A represents a group selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, these groups are 5- or 6-membered monocycles or bicycles composed of two 5- or 6-membered monocycles, R 1 represents a group selected from: hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, these groups may be optionally substituted with one or more groups, which may be identical or different independently of each other, selected from amino, cyano, trihalogeno C1-6 alkyl, cycloalkyl, -C (= O) NR7R8, -C (= O) OR8, OR8, SR8, where R7 and R8, which may be identical or different independently of each other, represents hydrogen or C1-6 alkyl, and the group of formula (5), where p is an integer from 0 to 8 inclusive, Z2 represents -CR11R12 wherein R11 and R12, identical or different independently one of the other represents a group selected from hydrogen, C1-6 alkyl, phenyl, trihalogenoalkyl C1-6 alkyl, halogen, amino, OR7, SR7 and -C (-O) OR7 wherein R7 represents hydrogen or C1-6 alkyl, and where when p is greater than or equal to 2, the hydrocarbon chain Z2 optionally contains one to two isolated multiple bonds or conjugates, and / or when n is greater than or equal to 2, one of said -CR11R12 may optionally be replaced with a selected group of oxygen, S (O) n1 wherein n1 is as defined above, -NH, -C1 -alkyl 6, and carbonyl, B represents a group selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, these groups are 5 or 6 member monocycles or bicycles composed of two 5 or 6 member monocycles, which is an integer from 0 to 7 inclusive , the group (s) G3, which may be identical or different independently from each other, is selected from C1-6 alkyl, halogen, CN, NO2, CF3, OCF3, - (CH2) kNR13R14, -N (R13 ) C (= O) R14, -N (R13) C (= O) OR14, -N (R13) SO2R14, -N (SO2R13) 2, -OR13, -S (O) k1R13, -SO2-N (R13 ) - (CH2) k2-NR14R15, - (CH2) kSO2NR13R14, -X4 (CH2) kC (= O) OR13, - (CH2) kC (= O) OR13, -C (= O) O- (CH2) k2 -NR13R14, -C (= O) O- (CH2) k2-C (= O) OR16, -X4 (CH2) kC (= O) NR13R14, - (CH2) kC (= O) NR13R14, -R17-C (= O) OR13, -X5-R18, and -C (= O) -R19-NR13R14 where: X4 represents a selected group of an atom d and oxygen, a sulfur atom optionally substituted by one or two oxygen atoms, and a nitrogen atom substituted by a hydrogen atom or a C1-6 alkyl group, k is an integer from 0 to 3 inclusive, k1 is an integer from 0 to 2 inclusive, k2 is an integer from 1 to 4 inclusive, R13, R14 and R15, which can be identical or different independently from each other, are selected from hydrogen and C1-6 alkyl, R16 represents a group selected from C1-alkyl -6, -R19-NR13R14, -R19-NR13-C (= O) -R19-NR14R15, and -C (= O) O-R19-NR13R14 where R19 represents a linear or branched C1-6 alkylene group, and R13, R14 and R15 are as defined above, R17 represents a C3-6 cycloalkyl group, X5 represents a group selected from a single bond, -CH2-, an oxygen atom, a sulfur atom optionally substituted by one or two atoms of oxygen, and a nitrogen atom substituted by a hydrogen atom or a C1-6 alkyl group, R18 represents a select group do of: 5 or 6-membered aryl, heteroaryl monocycle, which is optionally substituted by one or more groups, which may be identical or different, selected from C1-6 alkyl, halogen, hydroxy, cyano, tetrazolyl, amino, and -C (= O) OR7 wherein R7 represents hydrogen or C1-6 alkyl, and 5- or 6- membered cycloalkyl, heterocycloalkyl monocycle, which is optionally substituted by one or more groups, which may be identical or different, selected from C1 alkyl -6, halogen, hydroxy, oxo, cyano, tetrazolyl, amino, and -C (= O) OR7 wherein R7 represents hydrogen or C1-6 alkyl, m is an integer from 0 to 7 inclusive, the group (s) R2 , which may be identical or different independently of each other, are selected from C1-6 alkyl, halogen, -CN, NO2, SCF3, -CF3, -OCF3, -NR7R8, -OR8, -SR8, -SOR8, -SO2R8, - (CH2) kSO2NR7R8, -X7 (CH2) kC (= O) OR8, - (CH2) kC (= O) OR8, -X7 (CH2) kC (= O) NR7R8, - (CH2) kC (= O) NR7R8, and -X8-R20 where: X7 represents a selected group of oxygen, sulfur opc ionically substituted by one or two oxygen atoms, and a nitrogen atom substituted by a hydrogen atom or a C1-6 alkyl group, k is an integer from 0 to 3 inclusive, R7 and R8, which may be identical or different independently from each other, hydrogen and C1-6 alkyl are selected, X8 represents a group selected from a single bond, -CH2-, an oxygen atom, a sulfur atom optionally substituted by one or two oxygen atoms, and an atom of nitrogen substituted by a hydrogen atom or a C1-6 alkyl group, R20 represents a 5- or 6- membered aryl, heteroaryl, cycloalkyl, or heterocycloalkyl monocycle which is optionally substituted by one or more groups, which may be identical or different, selected from C1-6 alkyl, halogen, hydroxy and amino, and when the ring is heterocyclic, it comprises 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, optionally, the racemic forms thereof, isomers of them, their N-oxides and the pharmaceutically acceptable salts thereof, it being understood that when no specification is described: an aryl group indicates an aromatic monocyclic or bicyclic system containing from 5 to 10 carbon atoms, and in the case of a bicyclic system, one of the rings is aromatic, and the other ring can be aromatic or partially hydrogenated, a heteroaryl group indicates an aryl group described above where 1 to 4 carbon atoms are replaced by 1 to 4 selected heteroatoms of oxygen, sulfur and nitrogen, a cycloalkyl group indicates a monocyclic or bicyclic system containing from 3 to 10 carbon atoms, this system is saturated or partially unsaturated but without aromatic character, and a heterocycloalkyl group indicates a cycloalkyl group defined above where 1 to 4 carbon atoms are replaced by 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrog eno.

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