Preparation of tetrahydroindazole derivatives as novel diacylglyceride O-acyltransferase 2 inhibitors
Invented are compounds of formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.
1 . A compound of Formula I:
or pharmaceutically acceptable salts thereof wherein:
X and Y are independently selected from O or C(R 5 ) 2 ; wherein X and Y are both not O; and
R 1 is
(1) phenyl unsubstituted or substituted with 1, 2, or 3 R 6 ,
(2) 5- or 6-membered heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted with 1, 2, or 3 R 6 , or
(3) 8- to 10-membered fused heteroaryl containing 1, 2, 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted with 1, 2, or 3 R 6 ;
R 2 is
(1) aryl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(2) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted with 1, 2, or 3 R 7 ,
(3) C 1-6 alkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with halogen, OH, CF 3 , —CN, or (C 3-6 )cycloalkyl,
(4) (C 3-6 )cycloalkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with C 1-6 alkyl, halogen, OH, CF 3 , or —CN,
(5) —(C 3-6 )alkylC(O)NH 2 ,
(6) 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S wherein the heterocyclyl is unsubstituted or substituted by 1, 2, or 3 R 7 ,
(7) —CH 2 -aryl unsubstituted or substituted by 1, 2, or 3 R 7 ,
(8) —CH 2 -heterocyclyl unsubstituted or substituted by 1, 2, or 3 R 7 ,
(9) —C(═O) (C 1-6 )alkyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(10) —C(═O) (C 3-6 )cycloalkyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(11) —C(═O) (C 1-6 )heterocyclyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(12) —C(═O) aryl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(13) —SO 2 (C 1-6 )alkyl unsubstituted or substituted with 1, 2, or 3 R 7 , or
(14) —SO 2 -aryl unsubstituted or substituted with 1, 2, or 3 R 7 ;
R 3 is
(1) 4- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S,
(2) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S,
(3) —(C 1-6 )alkyl-heteroaryl, wherein the heteroaryl is a 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O and S,
(4) —(C 1-6 )alkyl-aryl,
(5) —(C 1-6 )alkyl-heterocyclyl, wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(6) —(C 1-6 )alkyl,
(7) —(C 3-6 )cycloalkyl,
(8) —(C 3-6 )cycloalkyl-heterocyclyl wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(9) —(C 1-6 )hydroxyalkyl,
(10) —(C 1-6 )alkyl-S(O) 2 —NR 8a R 8b ,
(11) —(C 1-6 )alkyl-S(O) 2 —(C 1-3 )alkyl,
(12) —(C 1-3 )alkyl-heteroaryl, wherein the heteroaryl is an 8- to 10-membered fused ring, and wherein the heteroaryl contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S,
(13) —(C 1-6 )alkyl-SONH—(C 1-3 )alkyl,
(14) —(C 1-6 )alkyl-(C 3-6 )cycloalkyl,
(15) fused aryl,
(16) —C( 1-6 )alkyl-N(R 11 ) 2 ,
(17) —C( 1-6 )alkyl-O—C 1-3 alkyl, or
(18) —C( 1-6 )alkyl-O—C 3-6 cycloalkyl,
wherein each aryl, fused aryl, heteroaryl, cycloalkyl, or heterocyclyl is unsubstituted or substituted with 1, 2, or 3 R 9 , and wherein each alkyl is unsubstituted or substituted with 1, 2, or 3 R 10 ;
R 4 is
(1) hydrogen,
(2) (C 1-3 )alkyl,
or R 3 and R 4 , together with the nitrogen atom to which they are attached, combine to form a mono- or bicyclic heterocyclyl ring containing 1 N and optionally containing 1 additional heteroatoms independently selected from N, O and S, wherein the heterocyclyl ring is unsubstituted or substituted by 1, 2, or 3 R 11 ;
when present, each R 5 is selected from
(1) hydrogen,
(2) halogen, or
(3) cyano;
when present, each R 6 is independently selected from
(1) cyano,
(2) halogen,
(3) (C 1-6 )alkyl or OC 1-6 alkyl wherein the alkyl moiety is optionally substituted with cyano,
(4) (C 3-6 )cycloalkyl, optionally substituted with halogen, C 1-6 alkyl, C 1-6 haloalkyl, cyano, OH or OC 1-6 alkyl,
(5) —C(O)N(R 11 ) 2 ,
(6) (C 3-6 )cycloalkyloxy wherein the cycloalkyl is optionally substituted with halogen, C 1-6 alkyl, C 1-6 haloalkyl, cyano, OH, or OC 1-6 alkyl,
(7) hydroxy,
(8) —NR 11 R 11 ,
(9) (C 1-6 )haloalkyl-,
(10) (C 1-6 )haloalkoxy-,
(11) —SO 2 (C 1-6 )alkyl,
(12) —SONH(C 1-6 )alkyl,
(13) C 1-6 alkyl-NR 11 R 11 , or
(14) 5 membered heteroaryl comprising 2 nitrogen atoms;
when present, each R 7 is independently selected from
(1) (C 1-6 )alkyl,
(2) halo,
(3) (C 1-6 )alkoxy-,
(4) (C 1-6 )haloalkyl-,
(5) (C 3-6 )cycloalkyl,
(6) C(O)H or —C(O)—OH,
(7) C(O)(C 1-6 )alkyl or —C(O)O—(C 1-6 )alkyl,
(8) hydroxy,
(9) CN,
(10) deuterium,
(11) OC 1-3 haloalkyl, or
(12) oxo;
when present, R 8a and R 8b are independently selected from
(1) hydrogen,
(2) (C 1-3 )alkyl,
(3) —(C 1-3 )alkyl-phenyl,
(4) 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, or
(5) phenyl;
when present, each R 9 is independently selected from
(1) (C 1-3 )alkyl,
(2) (C 1-3 ) haloalkyl-,
(3) oxo,
(4) (C 3-6 )cycloalkyl,
(5) —C(O)O—(C 1-4 )alkyl,
(6) —NR 11 R 11 ,
(7) hydroxy,
(8) phenyl, unsubstituted or substituted with halo,
(9) hydroxy(C 1-3 )alkyl-,
(10) cyano,
(11) halo,
(12) C(O)C 1-6 alkyl or C(O)C 3-6 cycloalkyl,
(13) C(O)NHC 1-3 alkyl, or
(14) 6 membered heterocycle containing one Oxygen and one Nitrogen;
when present, R 10 is
(1) (C 1-3 )alkyl,
(2) (C 1-3 )hydroxy alkyl-,
(3) (C 1-3 )alkoxy-,
(4) hydroxy,
(5) halogen,
(6) (C 1-3 )haloalkyl-,
(7) N(R 11 ) 2 ,
(8) (C 1-3 )alkyl-S—, or
(9) phenyl;
when present, R 11 is independently
(1) hydrogen, or
(2) (C 1-6 )alkyl;
when present, R 12 , R 12a and R 12b are independently
(1) hydrogen,
(2) (C 1-6 )alkyl,
(3) (C 3-6 )cycloalkyl, or
(4) (C 1-6 )haloalkyl.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
(a) phenyl substituted with one to three substituents independently selected from hydroxy, halogen, hydroxy, CN, C 1-3 alkyl, C 1-3 alkyl-CN, OC 1-3 alkyl-CN, C 1-3 haloalkyl, C 3-6 cycloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —OC 3-6 cycloalkyl, 5 membered heteroaryl containing 2 nitrogen atoms, S(O) 2 C 1-6 alkyl, S(O) 2 NHC 1-3 alkyl, or C 1-3 alkylNH 2 , and optionally further substituted with 1 or 2 substituents independently selected from halogen, C 1-3 alkyl, C 1-3 haloalkyl, CN, or OH;
(b) a 6 membered heteroaryl containing one or two nitrogen atoms substituted with one to two substituent selected from: halogen, hydroxy, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —O—C 3-6 cycloalkyl, C(O)NC 1-6 alkyl, or CN, and optionally further substituted with 1 or 2 fluoro atoms or C 1-3 alkyl;
(c) a 5 membered heteroaryl containing one to four nitrogen atoms or heteroatoms independently selected from N, O, and S optionally substituted with one to two substituents independently selected from with halogen, (C 1-3 )alkyl, (C 3-6 )cycloalkyl, (C 1-3 )haloalkyl-, OH or OC 1-3 alkyl; or
(d) 8- to 10-membered fused heteroaryl containing at least one nitrogen and optionally containing one oxygen optionally substituted with 1 or 2 substituents independently selected from halogen, C 1-3 alkyl, C 1-3 haloalkyl, OC 1-3 alkyl, or OC 1-3 haloalkyl.
3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
(a) phenyl substituted with a substituent selected from: hydroxy, halogen, CN, C 1-3 alkyl, C 1-3 alkyl-CN, OC 1-3 alkyl-CN, C 1-3 haloalkyl, C 3-6 cycloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —O-cyclopropyl, 5 membered heteroaryl containing 2 nitrogen atoms, S(O) 2 C 1-3 alkyl, S(O) 2 NHC 1-3 alkyl, or C 1-3 alkylNH 2 , and optionally further substituted with 1 or 2 substituents independently selected from F, CH 3 , CF 3 , CN, or OH;
(b) a 6 membered heteroaryl containing one or two nitrogen atoms substituted with one or two substituents selected from: halogen, hydroxy, C 1-3 alkyl, C 1-3 haloalkyl, —OC 1-3 alkyl, —OC 1-3 haloalkyl, —O-cyclopropyl, or C(O)NHC 1-6 alkyl, and optionally further substituted with 1 or 2 fluorine atoms or CH 3 ;
(c) 5 membered heteroaryl containing one to four nitrogen atoms or heteroatoms independently selected from N, O, and S optionally substituted with one to two substituents independently selected from with halogen, (C 1-3 )alkyl; or
(d) 9 or 10-membered fused heteroaryl containing one or two heteroatoms independently selected from nitrogen or oxygen optionally substituted with 1 or 2 methyl substituents.
4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is
(a) phenyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(b) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted with 1, 2, or 3 R 7 ,
(c) C 1-6 alkyl unsubstituted or mono-substituted, disubstituted, or trisubstituted with halogen, OH, CF 3 , —CN, deuterium, or (C 3-6 )cycloalkyl,
(d) (C 3-6 )cycloalkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with C 1-6 alkyl, halogen, OH, CF 3 , or —CN,
(e) —(C 3-6 )alkylC(O)NH 2 ,
(f) 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S wherein the heterocyclyl is unsubstituted or substituted by 1, 2, or 3 R 7 ,
(g) —CH 2 -heteroaryl unsubstituted or substituted by 1, 2, or 3 R 7 ,
(h) —CH 2 -aryl unsubstituted or substituted by 1, 2, or 3 R 7 ,
(i) —CH 2 -heterocyclyl unsubstituted or substituted by 1, 2, or 3 R 7 ,
(j) —C(═O) (C 1-6 )alkyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(k) —C(═O) (C 3-6 )cycloalkyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(l) —C(═O) (C 1-6 )heterocyclyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(m) —C(═O) aryl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(n) —SO 2 (C 1-6 )alkyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(o) − SO 2 (C 3-6 )cycloalkyl unsubstituted or substituted with 1, 2, or 3 R 7 , or
(p) —SO 2 -aryl unsubstituted or substituted with 1, 2, or 3 R 7 .
7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is
(a) phenyl unsubstituted or substituted with 1, 2, or 3 R 7 ,
(b) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N and S, wherein the heteroaryl is unsubstituted or substituted with 1 or 2 halogen, C 1-3 alkyl, or cyclopropyl,
(c) C 1-6 alkyl unsubstituted or mono-substituted, disubstituted, or trisubstituted with halogen, OH, CF 3 , —CN, deuterium, or (C 3-6 )cycloalkyl,
(d) (C 3-6 )cycloalkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with halogen, C 1-6 alkyl, OC 1-3 haloalkyl, OH, CF 3 , or —CN,
(e) —(C 3-6 )alkylC(O)NH 2 ,
(f) 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S wherein the heterocyclyl is unsubstituted or substituted with 1 or 2 substituents selected from CH 3 or oxo,
(g) —CH 2 -heteroaryl unsubstituted or substituted with 1 or 2 methyl substituents,
(h) —CH 2 -aryl,
(i) CH 2 -heterocyclyl,
(j) —C(═O) (C 1-6 )alkyl,
(k) —C(═O) (C 3-6 )cycloalkyl,
(l) —C(═O) (C 1-6 ) heterocyclyl,
(m) —C(═O) aryl,
(n) —SO 2 (C 1-6 )alkyl,
(o) —SO 2 (C 3-6 )cycloalkyl.
8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is
(a) phenyl unsubstituted or substituted with halogen or OCHF 2 ,
(b) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N and S, wherein the heteroaryl is unsubstituted or substituted with 1 or 2 halogen, C 1-3 alkyl, or cyclopropyl,
(c) C 1-6 alkyl unsubstituted or mono-substituted, disubstituted, or trisubstituted with halogen, OH, CF 3 , —CN, deuterium, or (C 3-6 )cycloalkyl,
(d) (C 3-6 )cycloalkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with halogen, C 1-6 alkyl, OC 1-3 haloalkyl, OH, CF 3 , or —CN,
(e) —(C 3-6 )alkylC(O)NH 2 ,
(f) 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S wherein the heterocyclyl is unsubstituted or substituted with 1 or 2 substituents selected from CH 3 or oxo,
(g) —CH 2 -heteroaryl unsubstituted or substituted with 1 or 2 methyl substituents,
(h) —CH 2 -aryl,
(i) —CH 2 -heterocyclyl,
(j) —C(═O) (C 1-6 )alkyl,
(k) —C(═O) (C 3-6 )cycloalkyl,
(l) —C(═O) (C 1-6 ) heterocyclyl,
(m) —C(═O) aryl,
(n) —SO 2 (C 1-6 )alkyl, or
(o) —SO 2 (C 3-6 )cycloalkyl.
9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is
10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is
(a) 4- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S,
(b) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S,
(c) —(C 1-6 )alkyl-heteroaryl, wherein the heteroaryl is a 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O and S,
(d) —(C 1-6 )alkyl-aryl,
(e) —(C 1-6 )alkyl-heterocyclyl, wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(f) —(C 1-6 )alkyl,
(g) —(C 3-6 )cycloalkyl,
(h) —(C 3-6 )cycloalkyl-heterocyclyl wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(i) —(C 1-6 )hydroxyalkyl,
(j) —(C 1-6 )alkyl-S(O) 2 —NR 8a R 8b ,
(k) —(C 1-6 )alkyl-S(O) 2 —(C 1-3 )alkyl,
(l) —(C 1-3 )alkyl-heteroaryl, wherein the heteroaryl is an 8- to 10-membered fused ring, and wherein the heteroaryl contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S,
(m) —(C 1-6 )alkyl-SONH—(C 1-3 )alkyl,
(n) —(C 1-6 )alkyl-(C 3-6 )cycloalkyl,
(o) fused aryl,
(p) —C( 1-6 )alkyl-N(R 11 ) 2 ,
(q) —C( 1-6 )alkyl-O—C 1-3 alkyl, or
(r) —C( 1-6 )alkyl-O—C 3-6 cycloalkyl,
wherein each aryl, fused aryl, heteroaryl, cycloalkyl, or heterocyclyl is unsubstituted or substituted with 1, 2, or 3 R 9 , and wherein each alkyl is unsubstituted or substituted with 1, 2, or 3 R 10 .
11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is
(a) 4- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S,
(b) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S,
(c) —(C 1-6 )alkyl-heteroaryl, wherein the heteroaryl is a 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O and S,
(d) —(C 1-6 )alkyl-aryl,
(e) —(C 1-6 )alkyl-heterocyclyl, wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(f) —(C 1-6 )alkyl,
(g) —(C 3-6 )cycloalkyl,
(h) —(C 3-6 )cycloalkyl-heterocyclyl wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S, or
(i) —(C 1-6 )alkyl-S(O) 2 —NR 8a R 8b ,
(j) —C( 1-6 )alkyl-O—C 1-3 alkyl, or
(k) —C( 1-6 )alkyl-O—C 3-6 cycloalkyl,
wherein each aryl, fused aryl, heteroaryl, cycloalkyl, or heterocyclyl is unsubstituted or substituted with 1, 2, or 3 R 9 , and wherein each alkyl is unsubstituted or substituted with 1, 2, or 3 R 10 .
12 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is
13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is H.
14 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, halogen, or CN.
15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, F, Cl, or CN.
16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is halogen, hydroxy, CN, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, OC 1-3 alkyl, OC 1-3 haloalkyl, OC 3-6 cycloalkyl, S(O) 2 C 1-3 alkyl, S(O) 2 NHC 1-3 alkyl, C(O)NHC 1-3 alkyl, C 1-6 alkylNR 11 R 11 , or 5 membered heteroaryl with 2 N atoms, and wherein the cycloalkyl is optionally substituted with halogen.
17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is C 1-3 alkyl, O—C 3-6 cycloalkyl, OC 1-3 alkyl, S(O) 2 C 1-3 alkyl, S(O) 2 NHC 1-3 alkyl, C(O)NHC 1-3 alkyl, C 1-6 alkylNR 11 R 11 , or 5 membered heteroaryl with 2 N atoms, and wherein the cycloalkyl is additionally optionally substituted with 1-3 F.
18 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is CH 3 , OCH 2 CH 3 , C(O)NHC(CH 3 ) 3 , C(CH 3 ) 2 NH 2 , S(O 2 )CH 3 , S(O 2 )NHCH 2 CH 3 , OCD 2 CD 3 , pyrazolidine, or O-cyclopropyl, and wherein the cyclopropyl is additionally optionally substituted with one to three halogen atoms: CN, CF 3 , or OH.
19 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is halogen, oxo, C 1-6 alkyl, OC 1-6 haloalkyl, CN, deuterium, or C 3-6 cycloalkyl.
20 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is F, Cl, oxo, OCHF 2 , CH 3 , CN, deuterium, or cyclopropyl.
21 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8a and R 8b are independently selected from hydrogen or (C 1-3 )alkyl.
22 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9 is ═O, halogen, OH, C 1-6 alkyl, C 1-6 haloalky, C 1-3 alkyl-CN, C(O)C 3-6 cycloalkyl, C(O)C 1-3 alkylOH, C(O)NHC 1-3 alkyl, or C 1-6 alkylOH, or a 6 membered heterocycle containing one Oxygen and one Nitrogen atom.
23 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9 is ═O, CH 3 , CH 2 CH 3 , F, CF 3 , CH 3 CN, C(O)cyclopropyl, C(O)EtO, CH(CH 3 ) 2 , or C(O)NHCH(CH 3 ) 2 , or a 6 membered heterocycle containing one Oxygen and one Nitrogen atom.
24 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 10 is ═O, halogen, OH, C 1-6 alkyl, C 1-6 haloalky, or C 1-6 alkylOH.
25 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 10 is OH, CH 3 , or OCH 3 .
26 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X and Y are C(R 5 ).
27 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is O, and Y is C(R 5 ).
28 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is C(R 5 ), and Y is O.
29 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is
3-(2-chlorophenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(S)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-(5-(difluoromethoxy)pyridin-3-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N—((R)-3-methyltetrahydrofuran-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N—((S)-3-methyltetrahydrofuran-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(3,3-difluoro-1-methylcyclobutyl)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N—((R)-3,3-difluoro-1-(hydroxymethyl)cyclopentyl)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N—((S)-3,3-difluoro-1-(hydroxymethyl)cyclopentyl)-3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(3,5-difluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
1-(5-chloropyrimidin-2-yl)-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
((R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-(3,5-difluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(3,3-difluorocyclobutyl)phenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N—((S)-3-cyanotetrahydrofuran-3-yl)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N—((R)-3-cyanotetrahydrofuran-3-yl)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-(5-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-((1R,2R)-2-morpholinocyclopentyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-(difluoromethoxy)-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-(tetrahydro-2H-pyran-4-yl)-N-(2-(6-(trifluoromethyl) pyridin-3-yl) propan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N—((R)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-cyclopropoxyphenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-ethoxyphenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(3-(2,2,2-trifluoroethoxy)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(3-(1,1,2,2-tetrafluoroethoxy)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-cyclopropoxy-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-isopropoxypyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-chloro-2-ethoxypyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-(2,2-difluoroethoxy)-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-(difluoromethoxy)-5-fluoropyridin-4-yl)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-(difluoromethyl) pyridin-3-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-(propan-2-yl-d 7 )-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-(propan-2-yl-d 7 )-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((R)-1,1-difluoropropan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((S)-1,1-difluoropropan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((R)-1,1-difluoropropan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((S)-1,1-difluoropropan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-(ethoxy-d 5 )-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-(propan-2-yl-d7)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-((R)-1,1,1-trifluoropropan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-((S)-1,1,1-trifluoropropan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-ethoxy-2-fluorophenyl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(3-(trifluoromethoxy)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-cyclobutyl-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-((R)-1-cyclopropylethyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-((S)-1-cyclopropylethyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
ethyl 3-((R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamido)-3-methylpyrrolidine-1-carboxylate,
(6R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(1-(isopropylcarbamoyl)-3-methylpyrrolidin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(6R)—N-(1-(cyclopropanecarbonyl)-3-methylpyrrolidin-3-yl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-fluoro-5-isopropoxyphenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-cyclopropyl-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-chloro-5-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-cyclopropoxy-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-methylpyridin-3-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-ethoxy-2,3-difluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-chloro-5-(trifluoromethoxy)pyridin-3-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(3,3-difluoro-1-methylcyclobutyl)-3-(5-(difluoromethoxy)-2-methylpyridin-3-yl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(5-(1,1,2,2-tetrafluoroethoxy)pyridin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(5-(1,1,2,2-tetrafluoroethoxy)pyridin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-(1,1,2,2-tetrafluoroethoxy)pyridin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-ethoxy-5-fluoropyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(4-cyano-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((R)-3-hydroxy-3-methylbutan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(4-cyano-1,1-dioxidotetrahydro-2/I-thiopyran-4-yl)-3-(5-fluoro-2-(2,2,2-trifluoroethoxy)pyridin-4-yl)-1-((S)-3-hydroxy-3-methylbutan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1R,2S)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1R,2R)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1S,2S)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-((1S,2R)-2-hydroxycyclopentyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1-(methylsulfonyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-(cyclopropylsulfonyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
3-(3-(difluoromethoxy)phenyl)-4,4-difluoro-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-4,4-difluoro-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(S)-3-(3-(difluoromethoxy)phenyl)-4,4-difluoro-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
(S)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N—((R)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
N-(3,3-difluoro-1-methylcyclobutyl)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
(S)-3-(3-cyclopropylphenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,5,6,7-tetrahydropyrano[3,2-c]pyrazole-6-carboxamide,
(R)-3-(3-(1-fluorocyclopropyl)phenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(2-aminopropan-2-yl)phenyl)-1-(4-fluorophenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(6-(difluoromethoxy) pyrazin-2-yl)-1-(5-fluoropyridin-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-(5-fluoropyridin-2-yl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(1-methyl-1H-pyrazol-5-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(pyridin-3-ylmethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(isoxazol-4-ylmethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(6R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(1-isopropyl-2-oxopyrrolidin-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N—((S)-1-hydroxypropan-2-yl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(1-methoxy-2-methylpropan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)pyridin-3-yl)-1-isopropyl-N—((S)-1-((R)-2-methylmorpholino) propan-2-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N-(3-ethyl-1,1-dioxidothietan-3-yl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N-(2-(1,1-dioxidothiomorpholino)ethyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(2-(N-methylsulfamoyl)ethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N—((R)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(1-methylpiperidin-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-acetyl-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-(cyclopropanecarbonyl)-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-4-carbonyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-benzoyl-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-benzyl-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-N—((S)-3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(6R)-1-(1-cyanoethyl)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(6R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-N-(3-methyl-1,1-dioxidothietan-3-yl)-1-(1-(thiazol-2-yl)ethyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(3-(1-(trifluoromethyl)cyclopropyl)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(1-cyanocyclopropyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(2-(1,1-difluoroethyl)-5-fluoropyridin-4-yl)-1-isopropyl-N-(4-methyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(2-methylbenzo[d]oxazol-4-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(cyanomethyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-(tert-butylcarbamoyl)pyridin-3-yl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(cyanomethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(1H-pyrazol-1-yl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-3-(3-(methylsulfonyl)phenyl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(N-ethylsulfamoyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-ethyl-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(5-cyano-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(1,1-difluoroethyl)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)—N-(3,3-difluoro-1-methylcyclobutyl)-3-(3-(1-hydroxycyclobutyl)phenyl)-1-isopropyl-4,5,6,7-tetrahydro-1H-indazole-6-carboxamide,
(R)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide,
(S)-3-(3-(difluoromethoxy)phenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide,
(R)-3-(5-(difluoromethoxy)-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide, or
(R)-3-(5-cyclopropyl-2-fluorophenyl)-1-isopropyl-N-(3-methyl-1,1-dioxidothietan-3-yl)-1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-6-carboxamide.
30 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is
31 . A composition for treating a condition selected from hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases and heart failure comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically carrier.
32 . A composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
33 . A method for treating a condition selected from hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases and heart failure comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.