2,3-DIHYDROBENZO[b]THIOPHENE DERIVATIVES AS HYPOXIA INDUCIBLE FACTOR-2(ALPHA) INHIBITORS

A compound of Formula (I):

• wherein:
• m is 0 or 1;
• n is 0 or 1, provided that at least one of m and n is 1;
• X is O or NR8 where R8 is hydrogen, alkyl, cycloalkyl, cyano, haloalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylcarbonyl, heteroaryl, or heterocyclyl;
• R1 is hydrogen, alkyl, or halo;
• R2 is hydrogen, alkyl, cycloalkyl, halo, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl;
• or
• R1 and R2 together with the carbon to which they are attached form oxo, cycloalkylene, or 4 to 6 membered heterocyclylene;
• R3 is hydrogen, alkyl, halo, haloalkyl, hydroxy, amino, monosubstituted amino, or disubstituted amino, or alkoxy;
• R4 is hydrogen, deuterium, alkyl, or halo;
• or
• R3 and R4 together with the carbon to which they are attached form oxo, cycloalkylene, or 4 to 6 membered heterocyclylene;
• R5 is hydrogen, alkyl, alkoxy, cyano, halo, haloalkyl, or haloalkoxy;
• R6 is -L-R10 where L is a bond, S, O or NH, and where R10 is cycloalkyl, bicyclic cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclylalkyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl wherein aryl and heteroaryl, each by itself or as part of aralkyl or heteroaralkyl, and heterocyclyl are 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;
• X1 is N or CR11, where R11 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, or aminoalkyl;
• and
• R7 is alkyl, cycloalkyl, alkoxy, cyano, halo, haloalkyl, haloalkoxy, alkylsulfoxide, alkylsulfonyl, —SO2NR13R14 (where R13 and R14 are independently hydrogen or alkyl), —S(O)R14(═NHR15) (where R14 is alkyl or haloalkyl and R15 is hydrogen or cyano), or heteroaryl optionally substituted with Rg, Rh, and/or Ri independently selected from hydrogen, alkyl, haloalkyl, haloalkoxy, alkoxy, hydroxy, halo, and cyano;
• or
• a pharmaceutically acceptable salt thereof.

The compound of claim 1, selected from the group consisting of:

• 3-((7-(difluoromethyl)-2,2,3-trifluoro-1-oxido-2,3-dihydrobenzo[b]thiophen-6-yl)oxy)-5-fluorobenzonitrile;
• 3-chloro-5-((7-(difluoromethyl)-2,2,3-trifluoro-1-oxido-2,3-dihydrobenzo-[b]thiophen-6-yl)oxy)benzonitrile;
• 7-(difluoromethyl)-6-(3,5-difluorophenoxy)-2,2,3-trifluoro-2,3-dihydrobenzo[b]-thiophene 1-oxide;
• 6-(3-chloro-5-fluorophenoxy)-7-(difluoromethyl)-2,2,3-trifluoro-2,3-dihydrobenzo[b]-thiophene 1-oxide;
• 3-fluoro-5-((2,2,3-trifluoro-7-(methylsulfonyl)-1-oxido-2,3-dihydrobenzo[b]-thiophen-4-yl)oxy)benzonitrile;
• 3-fluoro-5-((2,2,3-trifluoro-1-oxido-7-(trifluoromethyl)-2,3-dihydrobenzo-[b]thiophen-4-yl)oxy)benzonitrile;
• 3-((7-(difluoromethyl)-2,2,3,3-tetrafluoro-1-oxido-2,3-dihydrobenzo[b]thiophen-6-yl)-oxy)-5-fluorobenzonitrile;
• 7-(difluoromethyl)-6-(3,5-difluorophenoxy)-2,2,3,3-tetrafluoro-2,3-dihydrobenzo-[b]-thiophene 1-oxide;
• 3-((7-chloro-2,2,3,3-tetrafluoro-1-oxido-2,3-dihydrobenzo[b]thiophen-6-yl)oxy)-5-fluorobenzonitrile;
• 3-((7-bromo-2,2,3,3-tetrafluoro-1-oxido-2,3-dihydrobenzo[b]thiophen-6-yl)oxy)-5-fluorobenzonitrile;
• 6-(3-cyano-5-fluorophenoxy)-2,2,3,3-tetrafluoro-2,3-dihydrobenzo[b]thiophene-7-carbonitrile 1-oxide;
• 3-((7-(difluoromethyl)-2,2,3,3-tetrafluoro-1,1-dioxido-2,3-dihydrobenzo[b]-thiophen-6-yl)oxy)-5-fluorobenzonitrile;
• and
• 3-((7-chloro-2,2,3,3-tetrafluoro-1,1-dioxido-2,3-dihydrobenzo[b]thiophen-6-yl)-oxy)-5-fluorobenzonitrile;
• or
• a pharmaceutically acceptable salt thereof.