US 2013/0210815 A1 · SUBSTITUTED IMIDAZOPYRAZINES

Abstract

The present invention relates to substituted imidazopyrazine compounds of general formula (I) in which A, R1, R3 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, as well as to intermediate compounds useful in the preparation of said compounds.

A compound of general formula (I):

in which:
A represents a
group;
Z represents a —C(═O)N(H)R2 or —S(═O)2N(H)R2 group,
or a group selected from:
wherein * indicates the point of attachment of said groups with the rest of the molecule;
R1 represents a hydrogen atom or a halogen atom, or a —CN, C1-C6-alkyl-, —N(R6a)R6b, —NO2, —OR6 or —SR6 group;
R2 represents a hydrogen atom, or a C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, —C1-C6-alkyl-CN, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl- or C3-C6-cycloalkyl- group;
wherein said C3-C6-cycloalkyl- group is optionally substituted, one or more times, identically or differently, with a substituent selected from:
halo-, C1-C3-alkyl-, cyano-, C1-C3-alkoxy-;
R3 represents a hydrogen atom, or a —CN, C1-C6-alkyl-, —(CH2)m—C2-C6-alkenyl, —(CH2)m—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, —(CH2)m-(3- to 7-membered heterocycloalkyl), aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C2-C6-alkenyl-, C3-C6-cycloalkenyl-, C2-C6-alkynyl-, aryl-, C1-C6-alkyl-aryl-, heteroaryl-, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2 or —N(H)C(═O)R6 group;
said C1-C6-alkyl-, —(CH2)m—C2-C6-alkenyl, —(CH2)m—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C2-C6-alkenyl-, C3-C6-cycloalkenyl-, C2-C6-alkynyl-, aryl-, C1-C6-alkyl-aryl- or heteroaryl- group
being optionally substituted, identically or differently, with 1, 2, 3, or 4 R7 groups;
R4a, R4b, R4c, R4d
represent, independently from each other, a hydrogen or halogen atom, or a —CN, C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2, —N(H)C(═O)R6, —N(R6c)C(═O)R6, —N(H)C(═O)N(R6a)R6b, —N(R6c)C(═O)N(R6a)R6b, —N(H)C(═O)OR6, —N(R6c)C(═O)OR6, —N(H)S(═O)R6, —N(R6c)S(═O)R6, —N(H)S(═O)2R6, —N(R6c)S(═O)2R6, —N═S(═O)(R6a)R6b, —OR6, —O(C═O)R6, —O(C═O)N(R6a)R6b, —O(C═O)OR6, —SR6, —S(═O)R6, —S(═O)N(H)R6, —S(═O)N(R6a)R6b, —S(═O)2R6, —S(═O)2N(H)R6a, —S(═O)2N(R6a)R6b or —S(═O)(═NR6c)R6 group;
R5 represents a hydrogen atom, or a C1-C6-alkyl-, C2-C6-alkenyl-, —(CH2)n—C2-C6-alkenyl, —(CH2)n—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, —(CH2)m-(3- to 7-membered heterocycloalkyl), aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, —C1-C6-alkyl-CN, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C2-C6-alkenyl-, C3-C6-cycloalkenyl-, C2-C6-alkynyl-, aryl-, heteroaryl- group;
said C1-C6-alkyl-, C2-C6-alkenyl-, —(CH2)n—C2-C6-alkenyl, —(CH2)n—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, —(CH2)m-(3- to 7-membered heterocycloalkyl), aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, —C1-C6-alkyl-CN, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C2-C6-alkenyl-, C3-C6-cycloalkenyl-, C2-C6-alkynyl-, aryl- or heteroaryl- group
being optionally substituted, identically or differently, with 1, 2, 3, or 4 R8 groups;
R6, R6a, R6b, R6c,
represent, independently from each other, a hydrogen atom, or a C1-C6-alkyl-, HO—C1-C6-alkyl-, C3-C6-cycloalkyl-, C2-C6-alkenyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, aryl-C1-C6-alkyl-, or heteroaryl-C1-C6-alkyl- group;
R7 represents a hydrogen or halogen atom, or a HO—, —CN, C1-C6-alkoxy-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, 3- to 7-membered heterocycloalkyl-, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2, —N(H)C(═O)R6, —N(R6c)C(═O)R6, —N(H)C(═O)N(R6a)R6b, —N(R6c)C(═O)N(R6a)R6b, —N(H)C(═O)OR6, —N(R6c)C(═O)OR6, —N(H)S(═O)R6, —N(R6c)S(═O)R6, —N(H)S(═O)2R6, —N(R6c)S(═O)2R6, —N═S(═O)(R6a)R6b, —O(C═O)R6, —O(C═O)N(R6a)R6b, —O(C═O)OR6, —SR6, —S(═O)R6, —S(═O)N(H)R6, —S(═O)N(R6a)R6b, —S(═O)2R6, —S(═O)2N(H)R6, —S(═O)2N(R6a)R6b or —S(═O)(═NR6c)R6 group;
R8 represents a hydrogen or halogen atom, or a —CN, C1-C6-alkoxy-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, 3- to 7-membered heterocycloalkyl-, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2, —N(H)C(═O)R6, —N(R6c)C(═O)R6, —N(H)C(═O)N(R6a)R6b, —N(R6c)C(═O)N(R6a)R6b, —N(H)C(═O)OR6, —N(R6c)C(═O)OR6, —N(H)S(═O)R6, —N(R6c)S(═O)R6, —N(H)S(═O)2R6, —N(R6c)S(═O)2R6, —N═S(═O)(R6a)R6b, —OR6, —O(C═O)R6, —O(C═O)N(R6a)R6b, —O(C═O)OR6, —SR6, —S(═O)R6, —S(═O)N(H)R6, —S(═O)N(R6a)R6b, —S(═O)2R6, —S(═O)2N(H)R6, —S(═O)2N(R6a)R6b or —S(═O)(═NR6c)R6 group;
m is an integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
and
n is an integer of 1, 2, 3, 4, 5, 6 or 7;
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

23 more elements

Substituted imidazopyrazines

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Substituted imidazopyrazines

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Abstract

Claims13