Substituted triazoles useful as Axl inhibitors

摘要

Substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

主权项

1. A compound of formula (Ia1): wherein: R1, R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, —C(O)R8 and —C(O)N(R6)R7; R2a is —R10a—N(R6a)R7a where R6a and R7a, together with the common nitrogen to which they are both attached, form an optionally substituted pyrrolidinyl or an optionally substituted piperidinyl, and R10a is an optionally substituted straight or branched alkylene chain; R2g is selected from the group consisting of hydrogen, halo, alkyl, haloalkyl, aryl, aralkyl, —R9g—C(O)R8g, —R9g—C(O)OR8g, —R9g—N(R6g)R7g and —R9g—C(O)N(R6g)R7g, where each R6g, R7g and R8g is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl and aralkyl, and each R9g is independently selected from the group consisting of a direct bond and an optionally substituted straight or branched alkylene chain; R3 is selected from the group consisting of aryl and heteroaryl, where the aryl and the heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of oxo, thioxo, cyano, nitro, halo, haloalkyl, alkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, —R9—OR8, —R9—O—R10—OR8, —R9—O—R10—O—R10—OR8, —R9—O—R10—C(O)OR8, —R9—O—R10—C(O)N(R6)R7, —R9—O—R10—S(O)pR8 (where p is 0, 1 or 2), —R9—O—R10—N(R6)R7, —R9—O—R10—C(NR11)N(R11)H, —R9—OC(O)—R8, —R9—N(R6)R7, —R9—C(O)R8, —R9—C(O)OR8, —R9—C(O)N(R6)R7, —R9—N(R6)C(O)OR8, —R9—N(R6)C(O)R8, —R9—N(R6)S(O)tR8 (where t is 1 or 2), —R9—S(O)tOR8 (where t is 1 or 2), —R9—S(O)pR8 (where p is 0, 1 or 2), and —R9—S(O)tN(R6)R7 (where t is 1 or 2); each R6 and R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, —R10—OR8, —R10—CN, —R10—NO2, —R10—N(R8)2, —R10—C(O)OR8 and —R10—C(O)N(R8)2, or any R6 and R7, together with the common nitrogen to which they are both attached, form an optionally substituted N-heteroaryl or an optionally substituted N-heterocyclyl; each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl; each R9 is independently selected from the group consisting of a direct bond, an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; each R10 is independently selected from the group consisting of an optionally substituted straight or branched alkylene chain, an optionally substituted straight or branched alkenylene chain and an optionally substituted straight or branched alkynylene chain; and each R11 is hydrogen, alkyl, cyano, nitro or —OR8; as an isolated stereoisomer or mixture thereof, or a pharmaceutically acceptable salt thereof.