Heterocyclic inhibitors of histamine receptors for the treatment of disease

A method of treatment of an H4R-mediated disease comprising the administration, to a patient in need thereof, of a therapeutically effective amount of a compound having structural Formula (I):

• or a salt thereof, wherein:
• the ring comprising X1-X5 is aromatic;
• X1 and X5 are independently chosen from C, CH and N;
• X2 is chosen from [C(R6)(R7)]1, NR8, O and S;
• X3 is chosen from [C(R9)(R10)]m, NR11, O, and S;
• X4 is chosen from [C(R12)(R13)], NR14, O and S;
• X6 is chosen from [C(R18)(R19)], NR20, O and S;
• X7 is chosen from [C(R21)(R22)], NR23, O and S;
• X8 is chosen from [C(R24)(R25)], NR26, O and S;
• n and m are each an integer from 1 to 2;
• Y1 is chosen from a bond, lower alkyl, lower alkoxy, OR15, NR16R17, and lower aminoalkyl;
• R1 is chosen from:
• aryl, heterocycloalkyl, cycloalkyl, and heteroaryl, any of which may be optionally substituted, when Y1 is a bond;
• and
• null, when Y1 is chosen from OR15, NR16R17, lower alkyl, lower alkoxy, or lower aminoalkyl;
• R6, R7, R9, R10, R12, R13, R18, R19, R21, R22, R24, and R25 are independently chosen from null, hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, halogen, haloalkyl, perhaloalkyl, amino, aminoalkyl, amido, carboxyl, acyl, hydroxy, cyano, nitro, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be optionally substituted;
• R8, R11, R14, R20, R23, and R26 are independently chosen from null, hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, haloalkyl, perhaloalkyl, aminoalkyl, C-amido, carboxyl, acyl, hydroxy, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be optionally substituted;
• R15 and R16 are independently chosen from aminoalkyl, alkylaminoalkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, ether, heterocycloalkyl, lower alkylaminoheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be optionally substituted;
• and
• R17 is independently chosen from hydrogen, aminoalkyl, alkylaminoalkyl aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, ether, heterocycloalkyl, lower alkylaminoheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be optionally substituted.