AR038922A1 - 2-HETEROARIL-PYRIMIDINES INHIBITORAS OF CDK, ITS PREPARATION AND ITS USE AS MEDICATIONS - Google Patents

2-HETEROARIL-PYRIMIDINES INHIBITORAS OF CDK, ITS PREPARATION AND ITS USE AS MEDICATIONS

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Publication number
AR038922A1
AR038922A1 ARP030100819A ARP030100819A AR038922A1 AR 038922 A1 AR038922 A1 AR 038922A1 AR P030100819 A ARP030100819 A AR P030100819A AR P030100819 A ARP030100819 A AR P030100819A AR 038922 A1 AR038922 A1 AR 038922A1
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Argentina
Prior art keywords
alkyl
alkoxy
optionally
hydroxy
halogen
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ARP030100819A
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Spanish (es)
Inventor
Ulrich Luecking
Martin Krueger
Rolf Jautelat
Olaf Prien
Gerd Siemeister
Alexander Ernst
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Schering Ag
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Publication date
Priority claimed from DE2002112100 external-priority patent/DE10212100A1/en
Priority claimed from DE10255984A external-priority patent/DE10255984A1/en
Application filed by Schering Ag filed Critical Schering Ag
Publication of AR038922A1 publication Critical patent/AR038922A1/en

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    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
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    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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    • 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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    • 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

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Abstract

Inhibidores de las quinasas dependientes de las ciclinas, su preparación y su uso como medicamento para el tratamiento de diversas enfermedades. Reivindicación 1: Compuestos de la fórmula general (1), donde: Q es un resto de fórmula (2) ó (3); D, E, G, L, M y T son cada uno, independientemente entre sí, carbono, oxígeno, nitrógeno o azufre, donde al menos debe estar contenido en el anillo un heteroátomo; R1 es hidrógeno, halógeno, alquilo C1-6, alquinilo C1-6, nitro, ciano, heteroarilo o el grupo -COR5, -OCF3, -S-CF3 o -SO2CF3; R2 es hidrógeno, alquilo C1-10, alquenilo C2-10, alquinilo C2-10, arilo, heteroarilo o cicloalquilo C3-7 o alquilo C1-10, alquenilo C2-10, alquinilo C2-10, arilo, heteroarilo o cicloalquilo C3-7, opcionalmente mono polisustituido, igual o diferente, por hidroxi, halógeno, alcoxi C1-6, alquiltio C1-6, amino, ciano, alquilo C1-6, alquenilo C2-6, alcoxi(C1-6)-alquilo(C1-6), alcoxi(C1-6)- alcoxi(C1-6)-alquilo(C1-6), cicloalquilo C3-7, -NHalquilo C1-6, -NHcicloalquilo C3-7, -N(alquilo C1-6)2, -SO(alquilo C1-6), -SO2(alquilo C1-6), alcanoilo C1-6, -CONR3R4, -COR5, alquil(C1-6)OAc, fenilo o por el grupo -R6, el anillo del cicloalquilo C3-7 puede estar opcionalmente interrumpido por uno o varios átomos de nitrógeno, oxígeno y/o azufre y/o puede estar interrumpido en el anillo por uno o varios grupos =C=O y/u opcionalmente pueden estar contenidos en el anillo uno o varios enlaces dobles posibles, y el fenilo, arilo o cicloalquilo C3-7 en sí puede estar opcionalmente mono o polisustituido, igual o diferente, por halógeno, hidroxi, alquilo C1-6, alcoxi C1-6, o por el grupo -CF3 u -OCF3, X es halógeno, oxígeno, azufre o el grupo -NH- o -N(alquilo C1-3)-o X y R2 forman juntos un anillo de cicloalquilo C3-10, que opcionalmente puede contener uno o varios heteroátomos y que opcionalmente puede estar mono o polisustituido por hidroxi, alquilo C1-6, hidroxi-alquilo(C1-6) o halógeno; A y B son cada uno, independientemente entre sí, hidrógeno, hidroxi, halógeno o el grupo -SR7, -S(O)R7, -SO2R7, -NHSO2R7, -CH(OH)R7,-CR7(OH)-R7, alquil(C1-6)P(O)OR3OR4 o -COR7; o Ay B forman juntos un anillo cicloalquilo C3-7 que pueden estar opcionalmente interrumpido por uno o varios átomos de nitrógeno, oxígeno y/o azufre y/o puede estar interrumpido en el anillo por uno o varios grupos =C=O, y/u opcionalmente puede estar contenidos en el anillo uno o varios enlaces dobles posibles y el anillo cicloalquilo C3-7 puede estar opcionalmente mono o polisustituido, igual o diferente, por hidroxi, halógeno, alcoxi C1-6, alquiltio C1-6, amino, ciano, alquilo C1-6, alquenilo C2-6, cicloalquilo C3-7, alcoxi(C1-6)alquilo(C1-6), -NHalquilo C1-6, -N(alquilo C1-6)2, -SO(alquilo C1-6), -SO2(alquilo C1-6), alcanoilo C1-6, -CONR3R4, -COR5, alquil(C1-6)OAc, fenilo, o por el grupo R6, donde el fenilo a su vez puede estar opcionalmente mono o polisustituido, igual o diferente, por halógeno, hidroxi, alquilo C1-6, alcoxi C1-6, o por el grupo -CF3 u -OCF3; R3 y R4 son cada uno, independientemente entre sí, hidrógeno, hidroxi, alcoxi C1-6 o alquilo C1-6 opcionalmente mono o polisustituido, igual o diferente, por hidroxi, alcoxi C1-6, alquiltio C1-6, -N(alquilo C1-6)2, el grupo R6 o -N(alquilo C1-6)R6, R3 y R4 forman juntos un anillo cicloalquilo C3-7 que opcionalmente puede estar interrumpido por uno o varios átomos de nitrógeno, oxígeno y/o azufre y/o puede estar interrumpido en el anillo por uno o varios grupos =C=O, y/u opcionalmente pueden estar contenidos opcionalmente en el anillo uno o varios enlaces dobles posibles; R5 es hidroxi, benzoxi, alquilo C1-6, alquiltio C1-6, o alcoxi C1-6; R6 es un benciltio, feniloxi o anillo cicloalquilo C3-7 opcionalmente mono o polisustituido, igual o diferente, por halógeno, hidroxi, alquilo C1-6, alcoxi(C1-6) o -SO2NR3R4, donde el anillo cicloalquilo C3-7 tiene el significado indicado en R2; R7 es alquilo C1-6, alquenilo C2-6, alquinilo C2-6, bencilo, cicloalquilo C3-7, donde el anillo cicloalquilo C3-7 tiene el significado indicado en R2, o el grupo -NR3R4, o alquilo C1-10, alquenilo C2-10, alquinilo C2-10 o cicloalquilo C3-7, opcionalmente mono o polisustituido, igual o diferente, por hidroxi, alcoxi C1-6, halógeno, fenilo, -NR3R4 o fenilo que, a su vez, puede estar opcionalmente mono o polisustituido, igual o diferente, por halógeno, hidroxi, alquilo C1-6, alcoxi C1-6, halo-alquilo C1-6, halo-alcoxi C1-6, o fenilo que, a su vez, puede estar opcionalmente mono o polisustituido, igual o diferente, por halógeno, hidroxi, alquilo C1-6 o alcoxi C1-6, halo-alquilo C1-6, halo-alcoxi C1-6; y n es 0 ó 1, en caso de que n = 0, entonces X es halógeno, así como los isómeros, diastereómeros, enantiómeros y sales de los mismos.Inhibitors of cyclin-dependent kinases, their preparation and their use as a medicine for the treatment of various diseases. Claim 1: Compounds of the general formula (1), wherein: Q is a residue of formula (2) or (3); D, E, G, L, M and T are each, independently of each other, carbon, oxygen, nitrogen or sulfur, where at least one heteroatom must be contained in the ring; R1 is hydrogen, halogen, C1-6 alkyl, C1-6 alkynyl, nitro, cyano, heteroaryl or the group -COR5, -OCF3, -S-CF3 or -SO2CF3; R2 is hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl or C3-7 cycloalkyl or C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, heteroaryl or C3- cycloalkyl 7, optionally mono-polysubstituted, the same or different, by hydroxy, halogen, C1-6 alkoxy, C1-6 alkylthio, amino, cyano, C1-6 alkyl, C2-6 alkenyl, (C1-6) alkoxy (C1-) alkyl 6), (C1-6) alkoxy - (C1-6) alkoxy-(C1-6) alkyl, C3-7 cycloalkyl, -N C1-6 alkyl, -NH C3-7 cycloalkyl, -N (C1-6 alkyl) 2 , -SO (C1-6 alkyl), -SO2 (C1-6 alkyl), C1-6 alkanoyl, -CONR3R4, -COR5, (C1-6) alkyl OAc, phenyl or by the group -R6, the cycloalkyl ring C3-7 may be optionally interrupted by one or several nitrogen, oxygen and / or sulfur atoms and / or may be interrupted in the ring by one or more groups = C = O and / or optionally may be contained in the ring one or several possible double bonds, and the phenyl, aryl or C3-7 cycloalkyl itself may optionally be mono or polysubstituted, same or different, by halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, or by the group -CF3 or -OCF3, X is halogen, oxygen, sulfur or the group -NH- or -N (C1-3 alkyl ) -o X and R2 together form a C3-10 cycloalkyl ring, which may optionally contain one or more heteroatoms and which may optionally be mono or polysubstituted by hydroxy, C1-6 alkyl, hydroxy (C1-6) alkyl or halogen ; A and B are each, independently of each other, hydrogen, hydroxy, halogen or the group -SR7, -S (O) R7, -SO2R7, -NHSO2R7, -CH (OH) R7, -CR7 (OH) -R7, (C1-6) alkyl P (O) OR3OR4 or -COR7; or Ay B together form a C3-7 cycloalkyl ring that may be optionally interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or may be interrupted in the ring by one or more groups = C = O, and / or optionally one or several possible double bonds may be contained in the ring and the C3-7 cycloalkyl ring may optionally be mono or polysubstituted, the same or different, by hydroxy, halogen, C1-6 alkoxy, C1-6 alkylthio, amino, cyano , C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, (C1-6) alkoxy (C1-6) alkyl, -N C1-6 alkyl, -N (C1-6 alkyl) 2, -SO (C1 alkyl -6), -SO2 (C1-6 alkyl), C1-6 alkanoyl, -CONR3R4, -COR5, (C1-6) alkyl OAc, phenyl, or by the R6 group, where the phenyl in turn may optionally be mono or polysubstituted, the same or different, by halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, or by the group -CF3 or -OCF3; R3 and R4 are each, independently of each other, hydrogen, hydroxy, C1-6 alkoxy or optionally mono- or polysubstituted C1-6 alkyl, same or different, by hydroxy, C1-6 alkoxy, C1-6 alkylthio, -N (alkyl C1-6) 2, the group R6 or -N (C1-6 alkyl) R6, R3 and R4 together form a C3-7 cycloalkyl ring which may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or it may be interrupted in the ring by one or more groups = C = O, and / or optionally one or several possible double bonds may optionally be contained in the ring; R5 is hydroxy, benzoxy, C1-6 alkyl, C1-6 alkylthio, or C1-6 alkoxy; R 6 is a benzylthio, phenyloxy or C 3-7 cycloalkyl ring optionally mono or polysubstituted, the same or different, by halogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy or -SO 2 NR 3 R 4, where the C 3-7 cycloalkyl ring has meaning indicated in R2; R 7 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, benzyl, C 3-7 cycloalkyl, where the C 3-7 cycloalkyl ring has the meaning indicated in R 2, or the group -NR 3 R 4, or C 1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl or C3-7 cycloalkyl, optionally mono or polysubstituted, the same or different, by hydroxy, C1-6 alkoxy, halogen, phenyl, -NR3R4 or phenyl which, in turn, may optionally be mono or polysubstituted, the same or different, by halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, halo- C1-6 alkyl, halo-C1-6 alkoxy, or phenyl which, in turn, may optionally be mono or polysubstituted , same or different, by halogen, hydroxy, C 1-6 alkyl or C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy; and n is 0 or 1, in case n = 0, then X is halogen, as well as isomers, diastereomers, enantiomers and salts thereof.

ARP030100819A 2002-03-11 2003-03-11 2-HETEROARIL-PYRIMIDINES INHIBITORAS OF CDK, ITS PREPARATION AND ITS USE AS MEDICATIONS AR038922A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2002112100 DE10212100A1 (en) 2002-03-11 2002-03-11 New 2-aminopyrimidine derivatives are cyclin-dependent kinase inhibitors useful for treating e.g. cancer, autoimmune diseases, cardiovascular diseases, infectious diseases or viral infections
DE10255984A DE10255984A1 (en) 2002-11-26 2002-11-26 New 2-aminopyrimidine derivatives are cyclin-dependent kinase inhibitors useful for treating e.g. cancer, autoimmune diseases, cardiovascular diseases, infectious diseases or viral infections

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