TRICYCLIC INHIBITORS OF HIF-2-ALPHA AND USES THEREOF

摘要

Compounds comprising a fused tricylic core that modulate HIF-2α activity, pharmaceutical compositions containing these chemical entities, and methods of using these chemical entities for treating diseases associated with HIF-2α activity are described herein.

主权项

1. A compound of Formula I: or a salt thereof, wherein: X and Y are independently selected from C(R3) and N; Z is —O—, —S—, —S(O)—, —S(O)2—, —N(R4)—, C1-C3 alkylene, C1-C3 heteroalkylene, C1-C3 alkenylene, or absent; W1 and W2 are independently C(R5R6), wherein one C(R5R6) or two non-adjacent C(R5R6) may be replaced with a heteroatom independently selected from O, S, and N(R7); W3 is C(R8R9); T is O or N(R10); m is 1, 2, 3, or 4; n is 1, 2, 3, or 4; R1 is selected from alkyl, heteroalkyl, carbocycle, and heterocycle; R2 is selected from hydrogen, halogen, hydroxy, alkoxy, and amino; R3 is independently selected at each occurrence from hydrogen, halogen, hydroxy, cyano, alkyl, and alkoxy; R5, R6, R8, and R9 are independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, amido, carboxyl, nitro, phosphonoxy, phosphono, thioxo, formyl, cyano, heteroalkyl, alkyl, alkenyl, alkynyl, alkoxy, carbocycle, heterocycle, and an R5 and R6 attached to the same carbon atom may form ═O, ═CH2, or ═N(OH), and an R8 and R9 attached to the same carbon atom may form ═O, ═CH2, or ═N(OH); and R4, R7, and R10 are independently selected at each occurrence from hydrogen, hydroxy, alkyl, and cyano.