N-heteroaryl compounds with cyclic bridging unit for the treatment of parasitic diseases

摘要

This invention relates to certain N-heteroaryl compounds that are generally useful as medicaments, more specifically as medicaments for animals. The medicament can preferably be used for the treatment of helminth infections and the treatment of parasitosis, such as caused by helminth infections. This invention also relates to uses of the compounds to make medicaments and treatments comprising the administration of the compounds to animals in need of the treatments. This invention also relates to the preparation of the N-heteroaryl compounds. Moreover this invention relates to pharmaceutical compositions and kits comprising the compounds.

主权项

1. A compound of the formula (I) and pharmaceutically acceptable, N-oxides, salts and prodrugs thereof,wherein
R1 is halogen, amino, C1-C6-alkylamino, di-(C1-C6-alkyl)amino, C1-C6-alkylamino-C1-C6-alkyl, di-(C1-C6-alkyl)amino-C1-C6-alkyl, C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkyloxy, C1-C6-alkylthio, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkyloxy C1-C6-alkyl, C1-C6-alkylthio C1-C6-alkyl, C1-C6-alkyl carbonyl, C1-C6-alkyloxy carbonyl, C2-C6-alkenyl carbonyl, SF5, C1-C6-alkyl sulfonyl wherein each of the carbon-containing radicals optionally is substituted by one or more halogen atoms, R2 is hydrogen, halogen, amino, C1-C6-alkylamino, di-(C1-C6-alkyl)amino, C1-C6-alkylamino-C1-C6-alkyl, di-(C1-C6-alkyl)amino-C1-C6-alkyl, C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkyloxy, C1-C6-alkylthio, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkyloxy C1-C6-alkyl, C1-C6-alkylthio C1-C6-alkyl, C1-C6-alkyl carbonyl, C1-C6-alkyloxy carbonyl, C2-C6-alkenyl carbonyl, wherein each of the carbon-containing radicals optionally is substituted by one or more halogen atoms, R3 is hydrogen, C1-C6-alkyl or cycloalkyl, R4 is hydrogen, C1-C6-alkyl or cycloalkyl, R5 is hydrogen, C1-C6-alkyl or cycloalkyl, R6 is hydrogen, C1-C6-alkyl, cycloalkyl, hydroxy, C1-C6-alkyloxy, phenyl C1-C6-alkyloxy, hydroxy C1-C6-alkyl, C1-C6-alkyloxy C1-C6-alkyl, phenyl C1-C6-alkyloxy C1-C6-alkyl, thiol C1-C6-alkyl, C1-C6-alkylthio C1-C6-alkyl, phenyl C1-C6-alkylthio C1-C6-alkyl, hydroxycarbonyl, hydroxycarbonyl C1-C6-alkyl, C1-C6-alkyloxycarbonyl, C1-C6-alkyloxycarbonyl C1-C6-alkyl, aminocarbonyl, aminocarbonyl C1-C6-alkyl, C1-C6-alkylaminocarbonyl, C1-C6-alkylaminocarbonyl (C1-C6-alkyl), di(C1-C6-alkyl)aminocarbonyl, di(C1-C6-alkyl)aminocarbonyl (C1-C6-alkyl), C1-C6-alkylamino C1-C6-alkyl, di(C1-C6-alkyl)amino C1-C6-alkyl, phenyl, phenyl C1-C6-alkyl, wherein each phenyl group is optionally substituted by hydroxy, C1-C6-alkyloxy or cycloalkyloxy, R7 is hydrogen, C1-C6-alkyl or cycloalkyl, or R6 and R7 together represent an oxo-group or a thioxo-group or R6 or R7 is joined together with R4 or R5 to form a C1-C3-alkylene group which is optionally substituted by one or more radicals selected from the group of C1-C6-alkyl, and cycloalkyl, m is 2, n is 2, X is a carbonyl, thiocarbonyl or sulfonyl group, A is a bond or NR8, wherein R8 is hydrogen or C1-C6-alkyl, E is a bond or NR9, wherein R9 is hydrogen or C1-C6-alkyl, B is N, D is N, Y1 is CR12 or N, wherein C is substituted by R12 which is hydrogen, halogen, C1-C6-alkyl, C1-C6-alkenyl, Cycloalkyl, C1-C6-haloalkyl, C1-C6-alkoxy, Cycloalkyloxy, C1-C6-haloalkoxy, nitrilo, nitro, amino, C1-C6-alkylamino, Cycloalkylamino, (C1-C6-alkyl)-(Cycloalkyl)amino, di(C1-C6-alkyl)amino, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, C1-C6-alkylthio, Cycloalkylthio, C1-C6-haloalkylthio, C1-C6-alkyl carbonyl, C1-C6-haloalkyl carbonyl, C1-C6-alkylcarbonylamino, aminocarbonyl, C1-C6-alkylaminocarbonyl, di(C1-C6-alkyl)aminocarbonyl, C1-C6-alkoxycarbonyl, phenyl, dioxolane, dioxane, or dioxepane, each said ring being unsubstituted or substituted by C1-C6-alkyl, Y2 is CR13 or N, wherein C is substituted by R13 which is hydrogen, halogen, C1-C6-alkyl, C1-C6-alkenyl, Cycloalkyl, Cycloalkyloxy, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, nitrilo, nitro, amino, C1-C6-alkylamino, Cycloalkylamino, (C1-C6-alkyl)-(Cycloalkyl)amino, di(C1-C6-alkyl)amino, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, thiol, hydroxy, C1-C6-alkylthio, Cycloalkylthio, C1-C6-haloalkylthio, C1-C6-alkyl carbonyl, C1-C6-haloalkyl carbonyl, aminocarbonyl, C1-C6-alkylaminocarbonyl, di(C1-C6-alkyl)aminocarbonyl, C1-C6-alkylcarbonylamino, C1-C6-alkoxycarbonyl, dioxolane, dioxane, or dioxepane, each said ring being unsubstituted or substituted by C1-C6-alkyl, Y3 is CR14 or N, wherein C is substituted by R14 which is hydrogen, halogen, C1-C6-alkyl, C1-C6-alkenyl, Cycloalkyl, Cycloalkyloxy, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, nitrilo, nitro, amino, C1-C6-alkylamino, Cycloalkylamino, (C1-C6-alkyl)-(Cycloalkyl)amino, di(C1-C6-alkyl)amino, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, thiol, hydroxy, C1-C6-alkylthio, Cycloalkylthio, C1-C6-haloalkylthio, C1-C6-alkyl carbonyl, C1-C6-haloalkyl carbonyl, C1-C6-alkylcarbonylamino, aminocarbonyl, C1-C6-alkylaminocarbonyl, di(C1-C6-alkyl)aminocarbonyl, C1-C6-alkoxycarbonyl, dioxolane, dioxane, or dioxepane, each said ring being unsubstituted or substituted by C1-C6-alkyl, Y4 is CR15 or N, wherein C is substituted by R15 which is hydrogen, halogen, C1-C6-alkyl, C1-C6-alkenyl, Cycloalkyl, Cycloalkyloxy, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, nitrilo, nitro, amino, C1-C6-alkylamino, Cycloalkylamino, (C1-C6-alkyl)-(Cycloalkyl)amino, di(C1-C6-alkyl)amino, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, C1-C6-alkylthio, Cycloalkylthio, C1-C6-haloalkylthio, C1-C6-alkyl carbonyl, C1-C6-haloalkyl carbonyl, C1-C6-alkylcarbonylamino, aminocarbonyl, C1-C6-alkylaminocarbonyl, di(C1-C6-alkyl)aminocarbonyl, C1-C6-alkoxycarbonyl, phenyl, dioxolane, dioxane, or dioxepane, each said ring being unsubstituted or substituted by C1-C6-alkyl, or Y1 and Y2 and/or Y3 and Y4 are joined together to form a ring system, and wherein R1 and R2 are both different from a perfluorinated methyl group if the group of the formula (A) represents a thienopyrimidine group substituted by C1-C6-alkyl.