LXR AGONISTS AND USES THEREOF

摘要

This invention features compounds that modulate the activity of liver X receptors, pharmaceutical compositions including the compounds of the invention, and methods of utilizing those compositions for modulating the activity of liver X receptors in the treatment of cancer.

主权项

1. A compound of Formula I: wherein A is: wherein e, f, g, h, and i are independently 0, 1, 2, 3, or 4; j is 0, 1, 2, or 3; k is 0, 1, 2, 3, 4, 5, 6, 7, or 8; l is 0, 1, or 2; RA, RC, RI, RL, RM, and RT are independently hydrogen, hydroxyl, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C4-C10 cycloalkenyl, optionally substituted C8-C12 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heteroaryl C1-C6 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl; RD, RE, RG, RO, RP, RQ, and RR are independently hydrogen, hydroxy, optionally substituted amino, azido, halo, thiol, optionally substituted amino acid, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C4-C10 cycloalkenyl, optionally substituted C8-C12 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-09 heteroaryl C2-C9 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl; each RB, RF, RH, RK, RN, and RS are independently hydroxyl, optionally substituted amino, halo, thiol, optionally substituted amino acid, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C8-C12 cycloalkenyl, optionally substituted C4-C10 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heteroaryl C1-C6 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl; RJ is hydrogen, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C4-C10 cycloalkenyl, optionally substituted C8-C12 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heteroaryl C1-C6 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl; or RI and combine to form an optionally substituted C2-C9 heterocyclyl or RJ and RK combine to form an optionally substituted C2-C9 heterocyclyl; RU is hydroxyl, oxo, optionally substituted amino, halo, thiol, optionally substituted amino acid, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C8-C12 cycloalkenyl, optionally substituted C4-C10 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heteroaryl C1-C6 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl;and L is absent, —O—, —S—, —N(R12)—, or —C(R4)(R6)—; a is 2, 3, 4, 5, 6, 7, or 8; b, c, and d are independently 0 or 1; each R1, R2, R6, R7, R8, and R9 are independently hydrogen, hydroxyl, halo, optionally substituted amino, thiol, optionally substituted amino acid, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C4-C10 cycloalkenyl, optionally substituted C4-C10 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heteroaryl Cl-C6 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl; or R1 and R2 combine to form an optionally substituted C3-C10 cycloalkyl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl; or R6 and R7 combine to form an optionally substituted C3-C10 cycloalkyl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl; or R6 and R9 combine to form an optionally substituted C3-C10 cycloalkyl, optionally substituted 02-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl; R3 is hydrogen, hydroxyl, optionally substituted amino, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl; R4 and R5 are independently hydrogen, hydroxyl, halo, optionally substituted amino, thiol, optionally substituted amino acid, optionally substituted C1-C6 acyl, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C4-C10 cycloalkenyl, optionally substituted C4-C10 cycloalkynyl, optionally substituted C6-C10 aryl, optionally substituted C6-C10 aryl C1-C6 alkyl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heteroaryl C1-C6 alkyl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C2-C9 heterocyclyl C1-C6 alkyl; and B is optionally substituted C3-C10 cycloalkyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl; or a pharmaceutically acceptable salt thereof and/or a prodrug thereof.