US 12,077,506 B2
Indane derivatives as hypoxia inducible factor-2(α) inhibitors
Jiping Fu, Danville, CA (US); Yan Lou, Dallas, TX (US); and Yigang He, Newark, DE (US)
Assigned to NiKang Therapeutics, Inc., Wilmington, DE (US)
Appl. No. 17/286,818
Filed by NiKang Therapeutics, Inc., Wilmington, DE (US)
PCT Filed Oct. 16, 2019, PCT No. PCT/US2019/056555
§ 371(c)(1), (2) Date Apr. 19, 2021,
PCT Pub. No. WO2020/081695, PCT Pub. Date Apr. 23, 2020.
Prior Publication US 2021/0380536 A1, Dec. 9, 2021
Int. Cl. C07D 221/04 (2006.01); A61K 45/06 (2006.01); C07C 43/295 (2006.01); C07C 255/54 (2006.01); C07D 213/65 (2006.01); C07D 213/85 (2006.01)
CPC C07D 221/04 (2013.01) [A61K 45/06 (2013.01); C07C 43/295 (2013.01); C07C 255/54 (2013.01); C07D 213/65 (2013.01); C07D 213/85 (2013.01); C07B 2200/05 (2013.01)] 23 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
wherein:
X1 is CH or N;
R1 is hydroxy, amino, —OP(O)(OH)2, -OCH2OP(O)(OH)2, -OCOR10, -OCOOR11, -OCONR12R13, -OCHR14OCOR15 or -OCHR14OCOOR15 where R10, R11, and R15 are independently alkyl or alkyl substituted with amino, carboxy or hydroxy, R12 and R13 are independently alkyl or alkyl substituted with amino, carboxy or hydroxy or R12 and R13 together with the nitrogen atom to which they are attached form optionally substituted heterocyclyl, and R14 is hydrogen, alkyl, or haloalkyl;
R2 is hydrogen, deuterium, alkyl, haloalkyl, alkynyl, or alkenyl;
R3 and R4 are independently hydrogen, deuterium, alkyl, cycloalkyl, halo, haloalkyl, hydroxyalkyl, or alkoxyalkyl; provided that one of R3 and R4 is halo; or
R3 and R4 together with the carbon to which they are attached form oxo, cycloalkylene, or 4 to 6 membered optionally substituted heterocyclylene;
R5 is hydrogen, deuterium, alkyl, halo, haloalkyl, hydroxy, or alkoxy;
R6 is hydrogen, deuterium, alkyl, cycloalkyl, or halo; or
R5 and R6 together with the carbon to which they are attached form cycloalkylene or 4 to 6 membered optionally substituted heterocyclylene provided R1 and R2 and R3 and R4 together with the carbon to which they are attached do not form cycloalkylene or optionally substituted 4 to 6 membered heterocyclylene simultaneously;
R7 is hydrogen, deuterium, alkyl, alkoxy, cyano, halo, haloalkyl, or haloalkoxy;
L is a bond, S, SO, SO2, O, CO, or NR16 where R16 is hydrogen or alkyl;
R8 is cycloalkyl, cycloalkenyl, bicyclic cycloalkyl, oxocycloalkenyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl wherein aryl or heteroaryl, each by itself or as part of aralkyl or heteroaralkyl, or heterocyclyl by itself or as part of heterocyclylalkyl is substituted with Ra, Rb, and/or Rc independently selected from hydrogen, alkyl, haloalkyl, haloalkyloxy, alkoxy, hydroxy, halo, cyano, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, alkynyl, alkylidenyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted heterocyclyl; and
R9 is haloalkyl; or
a pharmaceutically acceptable salt thereof.