US 2013/0156756 A1 · Substituted Triazolopyridines

Abstract

The present invention relates to substituted triazolopyridine compounds of general formula (I): in which R1, R2, R3, R4, and R5 are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease of uncontrolled cell growth, proliferation and/or survival as well as to the use of intermediate compounds for the preparation of said compounds.

A compound of general formula (I):

in which:
R1 represents an aryl or heteroaryl group
which is substituted, one or more times, identically or differently, with a substituent selected from:
R6—(C1-C6-alkyl)-, R6—(CH2)n(CHOH)(CH2)m—, R6—(C1-C6-alkoxy)-, R6—(CH2)n(CHOH)(CH2)p—O—, R6—(C1-C6-alkoxy-C1-C6-alkyl)-, R6—(C1-C6-alkoxy-C1-C6-alkyl)-O—, R6—O—, —C(═O)R6, —C(═O)O—R6, —OC(═O)—R6, —N(H)C(═O)R6, —N(R7)C(═O)R6, —N(H)C(═O)NR6R7, —N(R7)C(═O)NR6R7, —NR6R7, —C(═O)N(H)R6, —C(═O)NR6R7, R6—S—, R6—S(═O)—, R6—S(═O)2—, —N(H)S(═O)R6, —N(R7)S(═O)R6, —S(═O)N(H)R6, —S(═O)NR6R7, —N(H)S(═O)2R6, —N(R7)S(═O)2R6, —S(═O)2N(H)R6, —S(═O)2NR6R7, —S(═O)(═NR6)R7, —S(═O)(═NR7)R6, —N═S(═O)(R6)R7;
and
which is optionally substituted, one or more times, identically or differently, with a substituent Rxy selected from:
halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, R8—(C1-C6-alkyl)-, R8—(CH2)n(CHOH)(CH2)m—, R8—(C1-C6-alkoxy)-, R8—(CH2)n(CHOH)(CH2)p—O—, R8—(C1-C6-alkoxy-C1-C6-alkyl)-, R8—(C1-C6-alkoxy-C1-C6-alkyl)-O—, R8—O—, —C(═O)R8, —C(═O)O—R8, —OC(═O)—R8, —N(H)C(═O)R8, —N(R7)C(═O)R8, —N(H)C(═O)NR8R7, —N(R7)C(═O)NR8R7, —NR8R7, —C(═O)N(H)R8, —C(═O)NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, —N(H)S(═O)R8, —N(R7)S(═O)R8, —S(═O)N(H)R8, —S(═O)NR8R7, —N(H)S(═O)2R8, —N(R7)S(═O)2R8, —S(═O)2N(H)R8, —S(═O)2NR8R7, —S(═O)(═NR8)R7, —S(═O)(═NR7)R8, —N═S(═O)(R8)R7;
R2 represents an aryl group or heteroaryl group
which is substituted, one or more times, identically or differently, with a substituent selected from:
R9—, R9—(C1-C6-alkyl)-, R9—(CH2)n(CHOH)(CH2)m—, R9—(C1-C6-alkoxy)-, R9—(CH2)n(CHOH)(CH2)p—O—, R9—(C1-C6-alkoxy-C1-C6-alkyl)-, R9—(C1-C6-alkoxy-C1-C6-alkyl)-O—, —O—(CH2)n—C(═O)NR9R7, R9—O—, —C(═O)R9, —C(═O)O—R9, —OC(═O)—R9, —N(H)C(═O)R9, —N(R7)C(═O)R9, —N(H)C(═O)NR9R7, —N(R7)C(═O)NR9R7, —NR9R7, —C(═O)N(H)R9, —C(═O)NR9R7, R9—S—, R9—S(═O)—, R9—S(═O)2—, —N(H)S(═O)R9, —N(R7)S(═O)R9, —S(═O)N(H)R9, —S(═O)NR9R7, —N(H)S(═O)2R9, —N(R7)S(═O)2R9, —S(═O)2N(H)R9, —S(═O)2NR9R7, —S(═O)(═NR9)R7, —S(═O)(═NR7)R9, —N═S(═O)(R9)R7;
and
which is optionally substituted, one or more times, identically or differently, with a substituent selected from:
halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, R8—(C1-C6-alkyl)-, R8—(CH2)n(CHOH)(CH2)m—, R8—(C1-C6-alkoxy)-, R8—(CH2)n(CHOH)(CH2)p—O—, R8—(C1-C6-alkoxy-C1-C6-alkyl)-, R8—(C1-C6-alkoxy-C1-C6-alkyl)-O—, O—(CH2)n—C(═O)NR8R7, R8—O—, —C(═O)R8, —C(═O)O—R8, —OC(═O)—R8, —N(H)C(═O)R8, —N(R7)C(═O)R8, —N(H)C(═O)NR8R7, —N(R7)C(═O)NR8R7, —NR8R7, —C(═O)N(H)R8, —C(═O)NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, —N(H)S(═O)R8, —N(R7)S(═O)R8, —S(═O)N(H)R8, —S(═O)NR8R7, —N(H)S(═O)2R8, —N(R7)S(═O)2R8, —S(═O)2N(H)R8, —S(═O)2NR8R7, —S(═O)(═NR8)R7, —S(═O)(═NR7)R8, —N═S(═O)(R8)R7;
R3 represents a hydrogen atom, a halogen atom, a hydroxy-, amino, cyano-, nitro-, C1-C4-alkyl-, halo-C1-C4-alkyl-, C1-C4-alkoxy-, halo-C1-C4-alkoxy-, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4-alkyl-, halo-C1-C4-alkoxy-C1-C4-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, halo-C2-C6-alkenyl-, halo-C2-C6-alkynyl-, C3-C6-cycloalkyl-, or halo-C3-C6-cycloalkyl- group;
R4 represents a hydrogen atom, a halogen atom, a hydroxy-, amino, cyano-, nitro-, C1-C4-alkyl-, halo-C1-C4-alkyl-, C1-C4-alkoxy-, halo-C1-C4-alkoxy-, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4-alkyl-, halo-C1-C4-alkoxy-C1-C4-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, halo-C2-C6-alkenyl-, halo-C2-C6-alkynyl-, C3-C6-cycloalkyl-, or halo-C3-C6-cycloalkyl- group;
R5 represents a hydrogen atom;
R6 represents a group selected from:
C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —(CH2)q—(C3-C6-cycloalkyl), —(CH2)q-(3- to 10-membered heterocycloalkyl), —(CH2)q-aryl, or —(CH2)q-heteroaryl;
said group being optionally substituted, one or more times, identically or differently, with a substituent selected from:
halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, R8—(C1-C6-alkyl)-, R8—(CH2)n(CHOH)(CH2)m—, R8—(C1-C6-alkoxy)-, R8—(CH2)n(CHOH)(CH2)p—O—, R8—(C1-C6-alkoxy-C1-C6-alkyl)-, R8—(C1-C6-alkoxy-C1-C6-alkyl)-O—, aryl-, R8—O—, —C(═O)R8, —C(═O)O—R8, —OC(═O)—R8, —N(H)C(═O)R8, —N(R7)C(═O)R8, —N(H)C(═O)NR8R7, —N(R7)C(═O)NR8R7, —NR8R7, —C(═O)N(H)R8, —C(═O)NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, —N(H)S(═O)R8, —N(R7)S(═O)R8, —S(═O)N(H)R8, —S(═O)NR8R7, —N(H)S(═O)2R8, —N(R7)S(═O)2R8, —S(═O)2N(H)R8, —S(═O)2NR8R7, —S(═O)(═NR8)R7, —S(═O)(═NR7)R8, —N═S(═O)(R8)R7;
R7 represents a hydrogen atom, a C1-C6-alkyl-, or C3-C6-cycloalkyl- group;
or
R6 and R7,
together with the nitrogen atom to which they are attached, represent a 3- to 10-membered heterocycloalkyl- group, which is optionally substituted, one or more times, identically or differently, with halogen, hydroxy, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl- or C3-C6-cycloalkyl-;
R8 represents a hydrogen atom or a C1-C6-alkyl- group;
R9 represents a group selected from:
C7-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-;
said group being optionally substituted, one or more times, identically or differently, with a substituent selected from:
halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, —(CH2)q—(C3-C6-cycloalkyl), R8—(CH2)n(CHOH)(CH2)m—, R8—(C1-C6-alkoxy)-, R8—(CH2)n(CHOH)(CH2)p—O—, R8—(C1-C6-alkoxy-C1-C6-alkyl)-, R8—(C1-C6-alkoxy-C1-C6-alkyl)-O—, aryl-, R8—O—, —C(═O)R8, —C(═O)O—R8, —OC(═O)—R8, —N(H)C(═O)R8, —N(R7)C(═O)R8, —N(H)C(═O)NR8R7, —N(R7)C(═O)NR8R7, —NR8R7, —C(═O)N(H)R8, —C(═O)NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, —N(H)S(═O)R8, —N(R7)S(═O)R8, —S(═O)N(H)R8, —S(═O)NR8R7, —N(H)S(═O)2R8, —N(R7)S(═O)2R8, —S(═O)2N(H)R8, —S(═O)2NR8R7, —S(═O)(═NR8)R7, —S(═O)(═NR7)R8, —N═S(═O)(R8)R7;
or
R9 and R7,
together with the nitrogen atom to which they are attached, represent a 3- to 10-membered heterocycloalkyl- group, which is optionally substituted, one or more times, identically or differently, with halogen, hydroxy, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, —C(═O)O—R8 or C3-C6-cycloalkyl-;
n, m, p
represent, independently from each other, an integer of 0, 1, 2, 3, 4, or 5;
q represents an integer of 0, 1, 2 or 3;
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

33 more elements

Substituted Triazolopyridines

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Substituted Triazolopyridines

Life of this patent

Abstract

Claims22