Substituted amino triazoles useful as human chitinase inhibitors

A method for the therapeutic treatment of a disease associated with aberrant expression or activity of chitotriosidase or acidic mammalian chitinase, comprising administering to a human in need thereof a therapeutically effective amount of a compound, wherein said compound is represented by formula (I):

• wherein:
• W is halo, (C1-C3)alkyl, (C1-C3)alkoxy-, or (C1-C3)alkylthio-;
• X is a single bond, —CH2—, —CH2CH2—, —CH═CH—, or —C(O)—;
• Y is a single bond, —CH—, —CHCH2—, —CH2CH—, —C═CH—, —CH═C—, —N—, —O—, —S(O)—, or —S(O)2—;
• if Y is a single bond, —O—, —S(O)—, or —S(O)2—, then R1 is absent;
• R1 is H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy(C1-C6)alkyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, —C(O)(C1-C6)alkyl, —C(O)aryl, —C(O)heteroaryl, —C(O)aryl(C1-C6)alkyl, —C(O)heteroaryl(C1-C6)alkyl, —S(O)2(C1-C6)alkyl, —S(O)2aryl, —S(O)2heteroaryl, —S(O)2aryl(C1-C6)alkyl, —S(O)2heteroaryl(C1-C6)alkyl, —CO2H, —C(O)O(C1-C6)alkyl, —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(aryl(C1-C6)alkyl), —C(O)O(heteroaryl(C1-C6)alkyl), —C(O)NH2, —C(O)NHOH, —C(O)NHCN, —C(O)NH((C1-C6)alkyl), —C(O)N((C1-C6)alkyl)2, —C(O)NH(aryl(C1-C6)alkyl), —C(O)N(aryl(C1-C6)alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)((C1-C6)alkyl), —C(O)N(aryl)2, —C(O)N(C1-C6)alkyl)(aryl(C1-C6)alkyl), —C(O)N(aryl)(aryl(C1-C6)alkyl), —C(O)NH((C1-C6)haloalkyl), —C(O)N((C1-C6)haloalkyl)2, —S(O)2NH2, —S(O)2NH((C1-C6)alkyl), —S(O)2NH((C1-C6)haloalkyl), —S(O)2NH(aryl), —S(O)2NH(heteroaryl(C1-C6)alkyl), —S(O)2NH(heteroaryl), —S(O)2N((C1-C6)alkyl)2, —S(O)2NHC(O)(C1-C6)alkyl, —S(O)2NHC(O)(C1-C6)haloalkyl, —S(O)2NHC(O)aryl, —S(O)2NHC(O)aryl(C1-C6)alkyl, —S(O)2NHC(O)heteroaryl, —S(O)2NHC(O)heteroaryl(C1-C6)alkyl, —NHS(O)2(C1-C6)alkyl, —NHS(O)2aryl, —NHS(O)2(C1-C6)haloalkyl, —NHS(O)2aryl(C1-C6)alkyl, —NHS(O)2heteroaryl, —NHS(O)2heteroaryl(C1-C6)alkyl, —NHC(O)((C1-C6)alkyl), —NHC(O)((C1-C6)haloalkyl), —NHC(O)(aryl), —NHC(O)(aryl(C1-C6)alkyl), —NHC(O)(heteroaryl), —NHC(O)(heteroaryl(C1-C6)alkyl), —NHC(O)NH(C1-C6)alkyl, —NHC(O)NH(aryl), —NHC(O)NH(aryl(C1-C6)alkyl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heteroaryl(C1-C6)alkyl), —C(O)NHS(O)2(C1-C6)alkyl, —C(O)NHS(O)2aryl, C(O)NHS(O)2((C1-C6)haloalkyl), —C(O)NHS(O)2(aryl(C1-C6)alkyl), —C(O)NHS(O)2heteroaryl, —C(O)NHS(O)2(heteroaryl(C1-C6)alkyl), —P(O)(OH)2, —((C1-C6)alkylene)C(O)OH, —((C1-C6)alkylene)C(O)O(C1-C6)alkyl, —NH2, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, —NC, —CN, —C(S)NH2, —NHC(O)NH2, —C≡CH, (C1-C6)alkylthio-, (C1-C6)mercaptoalkyl-, or —C(O)heterocyclyl;
• Z is —CH—, —C(O)—, or —C((C1-C3)alkyl)-;
• if Z is —C(O)—, then R2 is absent,
• R2 is H, halo, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy(C1-C6)alkyl, —CO2H, —C(O)O(C1-C6)alkyl, —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(aryl(C1-C6)alkyl), —C(O)O(heteroaryl(C1-C6)alkyl), —C(O)NHOH, —C(O)NHCN, —C(O)NH2, —C(O)NH((C1-C6)alkyl), —C(O)N((C1-C6)alkyl)2, —C(O)NH(aryl(C1-C6)alkyl), —C(O)N(aryl(C1-C6)alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)((C1-C6)alkyl), —C(O)N(aryl)2, —C(O)N(C1-C6)alkyl)(aryl(C1-C6)alkyl), —C(O)N(aryl)(aryl(C1-C6)alkyl), —C(O)NH((C1-C6)haloalkyl), —C(O)N((C1-C6)haloalkyl)2, —S(O)2NH2, —S(O)2NH((C1-C6)alkyl), —S(O)2NH((C1-C6)haloalkyl), —S(O)2NH(aryl), —S(O)2NH(heteroaryl(C1-C6)alkyl), —S(O)2NH(heteroaryl), —S(O)2NH(heteroaryl(C1-C6) alkyl), —S(O)2N((C1-C6)alkyl)2, —S(O)2NHC(O)(C1-C6)alkyl, —S(O)2NHC(O)(C1-C6)haloalkyl, -S(O)2NHC(O)aryl, —S(O)2NHC(O)aryl(C1-C6)alkyl, —S(O)2NHC(O)heteroaryl, —S(O)2NHC(O)heteroaryl(C1-C6)alkyl, —NHS(O)2(C1-C6)alkyl, —NHS(O)2aryl, NHS(O)2(C1-C6)haloalkyl, —NHS(O)2aryl(C1-C6)alkyl, -NHS(O)2heteroaryl, —NHS(O)2heteroaryl(C1-C6)alkyl, —NHC(O)((C1-C6)alkyl), —NHC(O)((C1-C6)haloalkyl), —NHC(O)(aryl), —NHC(O)(aryl(C1-C6)alkyl), —NHC(O)(heteroaryl), —NHC(O)(heteroaryl(C1-C6)alkyl), —NHC(O)NH(C1-C6)alkyl, —NHC(O)NHaryl, —NHC(O)NH(aryl(C1-C6)alkyl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heteroaryl(C1-C6)alkyl), —C(O)NHS(O)2(C1-C6)alkyl, —C(O)NHS(O)2aryl, C(O)NHS(O)2((C1-C6)haloalkyl), —C(O)NHS(O)2(aryl(C1-C6)alkyl), —C(O)NHS(O)2heteroaryl, —C(O)NHS(O)2(heteroaryl(C1-C6)alkyl), —P(O)(OH)2, aryl(C1-C6)alkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, —NC, —CN, —C(S)NH2, —NHC(O)NH2, —C≡CH, (C1-C6)alkylthio-, (C1-C6)mercaptoalkyl-, or —C(O)heterocyclyl;
• R3 is H, (C1-C3)alkyl, (C1-C3)alkoxy(C1-C3)alkyl, (C1-C3)alkylthio(C1-C3)alkyl, (C1-C6)haloalkyl, —NC, —CN, —C(S)NH2, —NHC(O)NH2, or —C≡CH;
• R4 is H, (C1-C3)alkyl, (C1-C3)alkylthio(C1-C3)alkyl, (C1-C6)haloalkyl, (C1-C3)alkoxy(C1-C3)alkyl-, or (C1-C4)hydroxyalkyl;
• R5 is H, halo, —NO2, —CN, (C1-C6)alkyl, (C1-C6)haloalkyl, —NH2, —NH((C1-C6)alkyl), —N((C1-C6)alkyl)2, —OH, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)haloalkoxy, —SH, (C1-C3)alkylthio(C1-C3)alkyl, —NC, —C(S)NH2, —NHC(O)NH2, or —C≡CH;
• and
• R6 is H, halo, —OH, —NH2, or —SH;
• or
• R6, taken together with the carbon atom bearing it, represents —C(O)—;
• wherein:
• any occurrence of alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkylene, heterocyclyl, cycloalkyl, alkoxy, alkylthio, haloalkyl, or hydroxyalkyl is optionally substituted with one or more substituents independently selected from the group consisting of —OH, halo, —NH2, —NH((C1-C6)alkyl), —N((C1-C6)alkyl)2, —CN, —NO2, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C7)cycloalkyl, heterocyclyl, —C(O)OH, —C(O)O(C1-C6)alkyl, —C(O)NH2, —C(O)NH(C1-C6)alkyl, and —C(O)N((C1-C6)alkyl)2;
• or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, or polymorph thereof;
• and
• the disease is selected from the group consisting of acute or chronic inflammatory diseases of the lungs, autoimmune diseases, liver diseases, kidney diseases, and storage diseases.