NOVEL PYRAZINE AMIDE COMPOUNDS

摘要

The present invention relates to compounds of formula 1 or pharmaceutically acceptable salt thereof,;;wherein R1, R2, R3, R5, R4, R5, R6 and X− have the meanings as indicated in the specification, to their use as a medicament, to their use in the treatment of a disease selected from among respiratory diseases or complaints and allergic diseases of the airways, to pharmaceutical composition comprising at least one of said compound or a pharmaceutically acceptable salt thereof, as well as to medicament combinations containing one or more of said compounds or a pharmaceutically acceptable salt thereof.

主权项

1. A compound of formula 1, wherein R1 is selected from methyl, HO(O)C—CH2—, C1-4-alkyl-O(O)C—CH2—, Cl(C1-4-alkyl)3N—CH2—CH2—HN(O)C—CH2— or aryl; R6 is selected from H or C1-4-alkyl; R2 is selected from C1-4-alkyl; R3 is selected from C1-4-alkyl, optionally substituted with one or two groups selected from C5-6-cycloalkyl, indolyl, HO(O)C—, C1-4-alkyl-O(O)C—, C5-6-cycloalkyl-O(O)C—, aryl-O— optionally substituted with C1-4-alkyl-O—,
aryl-C1-4-alkyl optionally substituted with C1-4-alkyl-O—, oraryl optionally substituted with one or two R3.1—, R3.1—O—, R3.1—CH2—, R3.1—CH2—O—, halogen or NC—, whereinR3.1 is selected independently from H, C1-4-alkyl, benzyl, HO(O)C—, C1-4-alkyl-O(O)C—, HO—CH2—, C1-4-alkyl-O—CH2—, (C1-4-alkyl)2N—CH2—, C1-4-alkyl-(O)2S, H—[O—CH2—CH2]—, R3.1.1HN(O)C—, (R3.1.1)2N(O)C—, R3.1.2HN(O)C— or (R3.1.2)2N(O)C—, whereinn is 3, 4 or 5,R3.1.1 is selected independently from H, H—[O—CH2—CH2]2—, H—[O—CH2—CH2]3— or a five-, six- or nine-membered heterocyclyl, wherein one, two or three elements are replaced by an element independently selected from N, O or S; each five-, six- or nine-membered heterocyclyl optionally substituted with one or two substituents independently selected from C1-4-alkyl-, HO—, HO—C1-4-alkyl- or O═ ortwo substituents R3.1.1 together with the nitrogen atom they are bound to form a five-, six- or nine-membered heterocyclyl, wherein one or two further elements are replaced by an element independently selected from N, O or S; each five-, six- or nine-membered heterocyclyl is optionally substituted with one or two substituents independently selected from C1-4-alkyl, C1-4-alkyl-O— or O═, andR3.1.2 is independently branched or unbranched C1-4-alkyl, optionally substituted with one or two substituents selected independently from O═, NC—, HO—, C1-4-alkyl-O—, (C1-4-alkyl)2N—, Cl(C1-4-alkyl)3N—, HO(O)C—, C1-4-alkyl-O(O)C—, HO(O)2S—, C1-4-alkyl-(O)2S—, C1-4-alkyl-(O)2S—, (C1-4-alkyl)2OP— or a five- or six-membered heterocyclyl or heteroaryl, wherein one or two elements are replaced by an element independently selected from N or O; each five- or six-membered heterocyclyl or heteroaryl being optionally substituted with one or two substituents independently selected from C1-4-alkyl or O═; R4 is selected from C1-4-alkyl, optionally substituted with one or two groups selected from C5-6-cycloalkyl, indolyl, HO(O)C—, C1-4-alkyl-O(O)C—, C5-6-cycloalkyl-O(O)C—, aryl-O— optionally substituted with C1-4-alkyl-O—, aryl-C1-4-alkyl optionally substituted with C1-4-alkyl-O—, or aryl optionally substituted with one or two R4.1—, R4.1—O—, R4.1—CH2—, R4.1—CH2—O—, halogen or NC—, wherein R4.1 is selected independently from H, C1-4-alkyl, benzyl, HO(O)C—, C1-4-alkyl-O(O)C—, HO—CH2—, C1-4-alkyl-O—CH2—, (C1-4-alkyl)2N—CH2—, C1-4-alkyl-(O)2S, H—[O—CH2—CH2]n—, R4.1.1HN(O)C—, (R4.1.1)2N(O)C—, R4.1.2HN(O)C— or (R4.1.2)2N(O)C—, wherein
n is n is 3, 4 or 5,R4.1.1 is selected independently from H, H—[O—CH2—CH2]2—, H—[O—CH2—CH2]3— or a five-, six- or nine-membered heterocyclyl, wherein one, two or three elements are replaced by an element independently selected from N, O or S; each five-, six- or nine-membered heterocyclyl being optionally substituted with one or two substituents independently selected from C1-4-alkyl-, HO—,HO—C1-4-alkyl-, O═ ortwo substituents R4.1.1 together with the nitrogen atom they are bound to form a five-, six- or nine-membered heterocyclyl, wherein one or two further elements are replaced by an element independently selected from N, O or S; each five-, six- or nine-membered heterocyclyl being optionally substituted with one or two substituents independently selected from C1-4-alkyl-, O═, andR4.1.2 is branched or unbranched C1-4-alkyl, optionally substituted with one or two substituents selected independently from O═, NC—, HO—, C1-4-alkyl-O—, (C1-4-alkyl)2N—, Cl(C1-4-alkyl)3N—, HO(O)C—, C1-4-alkyl-O(O)C—, HO(O)2S—, C1-4-alkyl-(O)2S—, C1-4-alkyl-(O)2S—, (C1-4-alkyl)2OP— or a five- or six-membered heterocyclyl or heteroaryl, wherein one or two elements are replaced by an element independently selected from N or O; each five- or six-membered heterocyclyl or heteroaryl being optionally substituted with one or two substituents independently selected from C1-4-alkyl or O═; R5 is H; or R1 and R2 are together R12, wherein R12 is selected from C2-4-alkylene each optionally partially or fully substituted with R12.1, wherein R12.1 is selected from phenyl, optionally substituted with C1-4-alkyl; or R1, R2 and R4 together with the atoms connecting them form an aza-bicyclo[2.2.2]octane; or R1 and R5 are together —CH2—; and X− is selected from chloride, bromide, iodide, hydroxide, hydrogensulfate, nitrate, formiate, acetate, trifluoroacetate, methanesulfonate or p-toluenesulfonate; or a pharmaceutically acceptable salt thereof.