Patent NZ-506614-A (NZ)
Title: Compounds for treating diseases associated with tryptase activity
Inventor: DENER JEFFREY MARK
IPC: A61K31/495
Filed: 1997-07-30
Abstract: Compound of Formula I where: X4-X5-X6  together are (C2-12)alkylene or hetero(C3-12)alkylene; X1 and X9 are independently a covalent bond, -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(R3)-, -N(R3)C(O)-, -S(O)2N(R3)-, -N(R3)S(O)2-, -OC(O)N(R3)-, -N(R3)C(O)O-, -N(R3)C(O)N(R3)- or -OC(O)O-, wherein each R3 is independently hydrogen, (C1-3)alkyl or (C3-8)cycloalkyl, with the proviso that X1 and X9 are not both covalent bonds; X3 and X7 are independently -C(O)-, -C(O)O-, -OC(O)-, -C(O)N(R3)-, -N(R3)C(O)-, -S(O)2N(R3)-, -N(R3)S(O)2-, -OC(O)N(R3)-, -N(R3)C(O)O-, -N(R3)C(O)N(R3) or-OC(O)O-, wherein R3 is as defined above; X2 and X8 are independently (C1-8)alkylene, hetero(C1-8)alkylene, -X10-X11- or - X11-X10-, wherein X10 is (C0-4)alkylene or hetero(C3-4)alkylene and X11 is (C3-8)cycloalkylene or hetero(C3-8)cycloalkylene; R1 is R4-X12- or R5-X13-, wherein: R4 is amino, amidino, guanidino, l-iminoethyl or methylamino, X12 is (C4-6)alkylene, hetero(C4-6)alkylene, heterooxo(C4-6)alkylene, oxo(C4-6)alkylene or -X14-X15-X16-, wherein X15 is (C3-6)cycloalkylene, hetero(C5-6)arylene, hetero(C3-6)cycloalkylene or phenylene, X14 is (Cn14)alkylene and X16 is (Cn16)alkylene, wherein the sum of n14 and n16 is 0, 1, 2, 3 or 4, R5 is a group selected from azetidin-3-yl, benzoimidazol-4-yl, benzoimidazol-5-yl imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, 2-imidazolin-2-yl, 2-imidazolin-3-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, 1-methylpiperid-3-yl, 1-methylpiperid-4-yl, piperid-3-yl, piperid-4-yl, piperazin-1-yl, piperazin-2-yl, pyrid-3-yl, pyrid-4-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrrolidin-3-yl, 1,4,5,6-tetrahydropyrimidin-2-yl, 1,4,5,6-tetrahydropyrimidin-4-yl and 1,4,5,6-tetrahydropyrimidin-5-yl and any carbocyclic ketone or thioketone derivative thereof, which group is optionally substituted with one or more radicals selected from halo, hydroxy, mercapto, (C1-8)alkyl, (C3-14)cycloalkyl, (C6-1 4)aryl, (C6-14)aryl(C1-4)alkyl, C1-8)alkanoyl, (C1-8)alkyloxy, (C6-14)aryloxy, (C3-14)cycloalkyloxy, (C1-4)alkyloxy, (C1-8)alkylthio, (C3-14)cycloalkylthio, (C6-14)arylthio and -NR6R7, wherein R6 and R7 are independently selected from hydrogen, (C1-8)alkyl, (C1-8)alkanoyl, (C3-14)cycloalkyl or (C6-14)aryl and X13 is (C0-6)alkylene, hetero(C2-6)alkylene, heterooxo(C3-6)alkylene, oxo(C2-6) alkylene or -X17-X18-X19-, wherein X18 is as defined above for X15, X17 is (Cn17)alkylene and X18 is (Cn18)alkylene, wherein the sum of n17 and n18 is 0, 1 or 2; and R2 is R8-X20- or R9-X21-, wherein: R8 is as defined above for R4, X20 is (C4-6)alkylene, hetero(C4-6)alkylene, heterooxo(C4-6)alkylene, oxo(C4-6)alkylene or -X22-X23-X24-, wherein X23 is as defined above for X15, X22 is (Cn22)alkylene and X24 is (Cn24)alkylene, wherein the sum of n22 and n24 is 0, 1, 2, 3 or 4, R9 is as defined above for R5 and X21 is (C0-6)alkylene, hetero(C2-6)alkylene, heterooxo(C3-6)alkylene, oxo(C2-6)alkylene or -X25-X26-X27-, wherein X26 is as defined above for X15, X25 is (Cn25)alkylene and X27 is (Cn27) alkylene, wherein the sum of n25 and n27 is 0, 1 or 2; wherein each alkylene, cycloalkylene, heteroalkylene, heterocycloalkylene, phenylene, arylene and heteroarylene, as defined above, are optionally substituted with one or more radicals selected from halo, hydroxy, mercapto, (C1-8)alkyl, (C3-14)cycloalkyl, (C6-14)aryl, (C6-14)aryl(C1-4)alkyl, (C1-8)alkanoyl, (C1-8)alkyloxy, (C6-14)aryloxy, (C3-14)cycloalkyloxy, (C1-4)alkyloxy, (C1-8)alkylthio, (C3-14)cycloalkylthio, (C6-14)arylthio and -NR6R7, wherein R6 and R7 are as defined above; with the proviso that covalent bonds do not occur between heteroatoms contained within R', X2, X4, X6, X8 and R2 and any heteroatoms contained with X3, X5, X7 and X9; and the pharmaceutically acceptable salts, N-oxides, prodrug derivatives and protected derivatives thereof.