PYRIDINE AND PYRIDIMINE COMPOUNDS AS PI3K-GAMMA INHIBITORS
The present disclosure provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that modulate the activity of phosphoinositide 3-kinases-gamma (PI3Kγ) and are useful in the treatment of diseases related to the activity of PI3Kγ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
1 . A compound of Formula I:
or a pharmaceutically acceptable salt or tautomer thereof, wherein:
W is CH and V is CH; or
W is N and V is CH; or
W is CH and V is N;
X is CH, Y is N, and Z is N or CR 4 ; or
X is N, Y is N or CR 3 , and Z is N or CR 4 ;
provided that no more than two of X, Y and Z are N;
ring A is a monocyclic 4-6 membered azaheterocycloalkyl ring or a monocyclic 5-6 membered azaheteroaryl ring, each of which has 1, 2, or 3 nitrogen atoms as ring members;
n is 0 or 1;
R 1 is independently selected from halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1a , —C 1-4 alkylene-Cy, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c OR d , NR c C(O)R b , NR c C(O)OR b , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R 11 groups;
R 2 is halo, OH, CN, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, cyano-C 1-4 alkyl, HO—C 1-4 alkyl, C 1-3 alkoxy-C 1-4 alkyl, C 1-6 alkylsulfonyl, or phenylsulfonyl, wherein the phenyl is optionally substituted with 1, 2, or 3 independently selected R g groups;
R 3 and R 4 are each independently selected from H, halo, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1 , —C 1-4 alkylene-Cy, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 OR d1 , NR c1 C(O)R b1 , NR c1 C(O)OR b1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R 13 groups;
provided that when both R 3 and R 4 are present, then one of R 3 and R 4 is selected from H, halo, OH, CN, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, cyano-C 1-4 alkyl, HO—C 1-4 alkyl, and C 1-3 alkoxy-C 1-4 alkyl;
alternatively R 3 and R 4 , taken together with the carbon atoms to which they are attached form a monocyclic 4-7 membered cycloalkyl ring, a phenyl ring, a monocyclic 4-6 membered heterocycloalkyl ring, or a monocyclic 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2 or 3 independently selected R 13 groups;
each R 11 is independently selected from halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 2 , —C 1-4 alkylene-Cy 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 OR d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R 13 is independently selected from halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 3 , —C 1-4 alkylene-Cy 3 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 OR d3 , NR c3 C(O)R b3 , NR 3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
Cy 1a is selected from 3-10 membered cycloalkyl and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 11 groups;
each Cy is independently selected from 3-10 membered cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 11 groups;
each Cy 1 is independently selected from 3-10 membered cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 13 groups;
each Cy 2 is independently selected from 3-10 membered cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R g groups;
each Cy 3 is independently selected from 3-10 membered cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R g groups;
R a , R c , and R d are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy, and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 11 groups;
R b is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy, and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 11 groups;
alternatively, any R c and R d attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group or a 5-6 membered heteroaryl group, each optionally substituted with 1, 2, or 3 independently selected R 11 groups;
R a1 , R 1 , and R d1 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups;
R b1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups; or
alternatively, any R c1 and R d1 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R 13 groups;
each R a2 , R c2 , and R d2 are independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 2 , and —C 1-4 alkylene-Cy 2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R b2 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 2 , and —C 1-4 alkylene-Cy 2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups; or
alternatively, any R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R g groups;
each R a3 , R c3 , and R d3 are independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 3 , and —C 1-4 alkylene-Cy 3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 3 , and —C 1-4 alkylene-Cy 3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R groups; or
alternatively, any R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R g groups; and
each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, cyano-C 1-3 alkyl, HO—C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein R 1 is selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1a , —C 1-4 alkylene-Cy, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c OR d , NR c C(O)R b , NR c (O)OR b , NR c (O)NR c R d , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R 11 groups.
3 - 4 . (canceled)
5 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein R a , R c , and R d are each independently selected from H, C 1-6 alkyl, Cy, and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R 11 groups; R b is independently selected from C 1-6 alkyl, Cy, and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R 11 groups; alternatively, any R c and R d attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1 or 2 independently selected R 11 groups.
6 . (canceled)
7 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each Cy is independently 3-7 membered cycloalkyl, 4-6 membered heterocycloalkyl, phenyl or 5-6 membered heteroaryl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 11 groups.
8 . (canceled)
9 . The compound of claim 1 , a pharmaceutically acceptable salt or tautomer thereof, wherein each Cy is independently cyclopropyl, cyclobutyl, cyclopentyl,
tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, or phenyl, each of which is optionally substituted by 1 or 2 independently selected R 11 groups.
10 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein Cy 1a is 4-10 membered heterocycloalkyl, which is optionally substituted by 1, 2, 3, or 4 independently selected R 11 groups.
11 - 12 . (canceled)
13 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each R 11 is independently selected from halo, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 2 , —C 1-4 alkylene-Cy 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 OR d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups.
14 - 15 . (canceled)
16 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each R a2 , R c2 , and R d2 are independently selected from H, C 1-6 alkyl, Cy 2 ; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R g groups; each R b2 is independently selected from C 1-6 alkyl and Cy 2 ; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R g groups; alternatively, any R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heterocycloalkyl group optionally substituted with 1 or 2 independently selected R g groups.
17 . (canceled)
18 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each Cy 2 is independently selected from 3-10 membered cycloalkyl, 6-10 membered aryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R g groups.
19 - 22 . (canceled)
23 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein R 2 is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, HO—C 1-4 alkyl, or C 1-3 alkoxy-C 1-4 alkyl.
24 - 29 . (canceled)
30 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein R 3 is selected from H, C 1-6 alkyl, C 1-4 haloalkyl, Cy 1 , C(O)NR c1 R d1 , and C(O)OR a1 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R 13 groups.
31 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein R 4 is selected from H, C 1-6 alkyl, C 1-4 haloalkyl, Cy 1 , —C 1-4 alkylene-Cy 1 , NR c1 R d1 , and NR c1 C(O)R b1 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R 13 groups.
32 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein R a1 , R d , and R d1 are each independently selected from H, C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups; R b1 are each independently selected from C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups; alternatively, any R c1 and R d1 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R 13 groups.
33 . (canceled)
34 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each Cy 1 is independently selected from 3-10 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, and phenyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 13 groups.
35 . (canceled)
36 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each R 13 is independently selected from halo, CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 3 , —C 1-4 alkylene-Cy 3 , OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR 3 OR d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R g groups.
37 - 38 . (canceled)
39 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each R a3 , R c3 , and R d3 are independently selected from H and C 1-6 alkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups; each R b3 is independently selected from C 1-6 alkyl, which is optionally substituted with 1, 2, 3, or 4 independently selected R g groups; alternatively, any R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 independently selected R g groups.
40 . (canceled)
41 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each Cy 3 is independently selected from 3-7 membered cycloalkyl and 4-6 membered heterocycloalkyl, each of which is optionally substituted by 1 or 2 independently selected R g groups.
42 . (canceled)
43 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein each R g is independently selected from OH, CN, halo, C 1-6 alkyl, C 1-4 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, cyano-C 1-3 alkyl, HO—C 1-3 alkyl, amino, C 1-6 alkylamino, and di(C 1-6 alkyl)amino.
44 . (canceled)
45 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein
46 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein
47 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein
48 - 50 . (canceled)
51 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein ring A is a monocyclic 5-6 membered azaheterocycloalkyl ring or a 5-6 membered azaheteroaryl ring.
52 . (canceled)
53 . The compound of claim 51 , or a pharmaceutically acceptable salt or tautomer thereof, wherein ring A is a pyrazole ring, a pyridine ring, an imidazole ring, a tetrahydropyridine ring, a dihydropyrrolyl ring, or a pyrrole ring.
54 . (canceled)
55 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein
ring A is a monocyclic 5-6 membered azaheterocycloalkyl ring or a 5-6 membered azaheteroaryl ring;
R 1 is selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1a , —C 1-4 alkylene-Cy, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c OR d , NR c C(O)R b , NR c C(O)OR b , NR c C(O)NR c R d , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R 11 groups;
R 2 is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, HO—C 1-4 alkyl, or C 1-3 alkoxy-C 1-4 alkyl;
R 3 and R 4 are independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1 , —C 1-4 alkylene-Cy 1 , OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 OR d1 , NR c1 C(O)R b1 , NR c1 C(O)OR b1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R 13 groups;
provided that when both R 3 and R 4 are present, then one of R 3 and R 4 is selected from H, halo, OH, CN, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, cyano-C 1-4 alkyl, HO—C 1-4 alkyl, and C 1-3 alkoxy-C 1-4 alkyl; and
alternatively, R 3 and R 4 , taken together with the carbon atoms to which they are attached form a monocyclic 4-7 membered cycloalkyl ring, a phenyl ring, a monocyclic 4-6 membered heterocycloalkyl ring, or a monocyclic 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2 or 3 independently selected R 13 groups.
56 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein
ring A is a monocyclic 5-6 membered azaheterocycloalkyl ring or a 5-6 membered azaheteroaryl ring;
R 1 is selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1a , —C 1-4 alkylene-Cy, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c OR d , NR c C(O)R b , NR c C(O)OR b , NR c C(O)NR c R d , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R 11 groups;
R 2 is halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, or C 1-3 alkoxy-C 1-4 alkyl;
R 3 and R 4 are independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, Cy 1 , —C 1-4 alkylene-Cy 1 , OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 NR c1 (O)R b1 , NR c1 C(O)OR b1 , NR c1 (O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-4 haloalkyl are each optionally substituted with 1, 2, or 3 independently selected R 13 groups;
provided that when both R 3 and R 4 are present, then one of R 3 and R 4 is selected from H, halo, OH, CN, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamine, di(C 1-4 alkyl)amino, cyano-C 1-4 alkyl, HO—C 1-4 alkyl, and C 1-3 alkoxy-C 1-4 alkyl; and
alternatively, R 3 and R 4 , taken together with the carbon atoms to which they are attached form a monocyclic 4-7 membered cycloalkyl ring, a phenyl ring, a monocyclic 4-6 membered heterocycloalkyl ring, or a monocyclic 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2 or 3 independently selected R 13 groups.
57 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein:
W is CH and V is CH; or
W is N and V is CH; or
W is CH and V is N;
ring A is a pyrazole ring, a pyridine ring, an imidazole ring, a tetrahydropyridine ring, or a dihydropyrrolyl ring;
R 1 is selected from halo, C 1-6 alkyl, C 1-4 haloalkyl, Cy 1a , —C 1-4 alkylene-Cy, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O)R b , NR c C(O)OR b , NR c C(O)NR c R d , NR c S(O) 2 R b , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl and C 1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R 11 groups;
R 2 is C 1-4 alkyl;
R 3 and R 4 are each independently selected from H, CN, C 1-6 alkyl, C 1-4 haloalkyl, Cy 1 , —C 1-4 alkylene-Cy 1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , and NR c1 C(O)R b1 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R 13 groups;
provided that when both R 3 and R 4 are present, then one of R 3 and R 4 is selected from H, C 1-4 alkyl, and C 1-4 haloalkyl;
or alternatively, R 3 and R 4 , taken together with the carbon atoms to which they are attached form a monocyclic 4-7 membered cycloalkyl ring, and a phenyl ring
each R 11 is independently selected from halo, CN, C 1-6 alkyl, C 1-4 haloalkyl, Cy 2 , —C 1-4 alkylene-Cy 2 , OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , and S(O) 2 R b2 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R 13 is selected from halo, CN, C 1-6 alkyl, C 1-4 haloalkyl, —C 1-4 alkylene-Cy 3 , OR a3 , NR c3 R d3 , C(O)R b3 , NR c3 C(O)OR a3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl is optionally substituted by 1 or 2 independently selected R g groups;
R a , R c , and R d are each independently selected from H, C 1-6 alkyl, Cy, and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R 11 groups;
R b is independently selected from C 1-6 alkyl, Cy, and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R 11 groups;
or alternatively, any R c and R d attached to the same N atom, together with the N atom to which they are attached, form an azetidine ring, a pyrrolidine ring, an azabiyclo[2.2.1]-heptane ring, a a piperidine ring, a piperazine ring, a morpholine ring, an azepane ring, a decahydroisoquinoline ring, a 2,8-diazaspiro[4.5]decan-1-one ring, a 3-oxa-9-azaspiro[5.5]undecane ring, a 2-oxa-7-azaspiro[3.5]nonane ring, or a 5-azaspiro[2.4]heptane ring, each of which is optionally substituted with 1 or 2 independently selected R 11 groups;
R a1 , R c1 , and R d1 are each independently selected from H, C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups;
R b1 are each independently selected from C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups;
or alternatively, any R c1 and R d1 attached to the same N atom, together with the N atom to which they are attached, form an azetidine ring, a pyrrolidine ring, or a morpholine ring, each of which is optionally substituted with 1, 2 or 3 independently selected R 13 groups;
each R a3 , R c3 , and R d3 are independently selected from H, C 1-6 alkyl, and phenyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R b3 is independently selected from C 1-6 alkyl and phenyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
or alternatively, any R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a morpholine ring;
each Cy is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, or phenyl, each of which is optionally substituted by 1 or 2 independently selected R 11 groups;
Cy 1a is a pyrrolidine ring, a dihydropyrrole ring, a morpholine ring, a piperidine ring, a piperazine ring, a tetrahydrofuran ring, or a tetrahydropyran ring, each of which is optionally substituted by 1 or 2 independently selected R 11 groups;
each Cy 1 is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, admantyl, indenyl, phenyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl, and pyridyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 13 groups;
each Cy 3 is independently cyclopentyl, tetrahydrofuranyl, or tetrahydropyranyl, or phenyl;
n is 0 or 1; and
each R g is independently selected from OH, methoxy, and methyl.
58 - 59 . (canceled)
60 . The compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, wherein:
W is CH and V is CH; or
W is N and V is CH; or
W is CH and V is N;
ring A is a pyrazole ring, a pyridine ring, an imidazole ring, a tetrahydropyridine ring, or a dihydropyrrolyl ring;
R 1 is selected from halo, C 1-6 alkyl, C 1-4 haloalkyl, Cy 1a , —C 1-4 alkylene-Cy, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O)R b , NR c C(O)OR b , NR c C(O)NR c R d , NR c S(O) 2 R b , and S(O) 2 R b ; wherein said C 1-6 alkyl and C 1-4 haloalkyl are optionally substituted with 1, 2, or 3 independently selected R 11 groups;
R 2 is C 1-4 alkyl;
R 3 and R 4 are each independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, Cy 1 , —C 1-4 alkylene-Cy 1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , and NR c1 C(O)R b1 wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R 13 groups;
provided that when both R 3 and R 4 are present, then one of R 3 and R 4 is selected from H, C 1-4 alkyl, and C 1-4 haloalkyl;
alternatively, R 3 and R 4 , taken together with the carbon atoms to which they are attached form a monocyclic 4-7 membered cycloalkyl ring, and a phenyl ring
each R 11 is independently selected from halo, CN, C 1-6 alkyl, C 1-4 haloalkyl, Cy 2 , —C 1-4 alkylene-Cy 2 , OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , and S(O) 2 R b2 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R 13 is selected from halo, CN, C 1-6 alkyl, C 1-4 haloalkyl, —C 1-4 alkylene-Cy 3 , OR a3 , NR c3 R d3 , NR c3 C(O)OR a3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl is optionally substituted by 1 or 2 independently selected R g groups;
R a , R c , and R d are each independently selected from H, C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R 11 groups;
R b is independently selected from C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 independently selected R 11 groups;
alternatively, any R c and R d attached to the same N atom, together with the N atom to which they are attached, form an azetidine ring, a pyrrolidine ring, an azabiyclo[2.2.1]-heptane ring, a a piperidine ring, a piperazine ring, a morpholine ring, an azepane ring, a decahydroisoquinoline ring, a 2,8-diazaspiro[4.5]decan-1-one ring, a 3-oxa-9-azaspiro[5.5]undecane ring, a 2-oxa-7-azaspiro[3.5]nonane ring, or a 5-azaspiro[2.4]heptane ring, each of which is optionally substituted with 1 or 2 independently selected R 11 groups;
R a1 , R c1 , and R d1 are each independently selected from H, C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups;
R b i are each independently selected from C 1-6 alkyl, Cy 1 , and —C 1-4 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 13 groups;
alternatively, any R c1 and R d1 attached to the same N atom, together with the N atom to which they are attached, form an azetidine ring, a pyrrolidine ring, or a morpholine ring, each of which is optionally substituted with 1, 2 or 3 independently selected R 13 groups;
each R a3 , R 3 , and R d3 are independently selected from H and C 1-6 alkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
each R b3 is independently selected from C 1-6 alkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R g groups;
alternatively, any R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a morpholine ring;
each Cy is independently cyclopropyl, cyclobutyl, cyclopentyl,
tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, or phenyl, each of which is optionally substituted by 1 or 2 independently selected R 11 groups;
Cy 1a is a pyrrolidine ring, a dihydropyrrole ring, a morpholine ring, a piperidine ring, a piperazine ring, a tetrahydrofuran ring, or a tetrahydropyran ring, each of which is optionally substituted by 1 or 2 independently selected R 11 groups;
each Cy 1 is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, admantyl, indenyl, phenyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, thiomorpholinyl, and pyridyl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R 13 groups;
each Cy 3 is independently cyclopentyl, tetrahydrofuranyl, or tetrahydropyranyl, or phenyl;
n is 0 or 1; and
each R g is independently selected from OH, methoxy, and methyl.
61 . The compound of claim 1 , having Formula II:
or a pharmaceutically acceptable salt or tautomer thereof.
62 . The compound of claim 1 , having Formula III:
or a pharmaceutically acceptable salt or tautomer thereof.
63 . The compound of claim 1 , having Formula IV:
or a pharmaceutically acceptable salt or tautomer thereof.
64 . The compound of claim 1 , having Formula V:
or a pharmaceutically acceptable salt or tautomer thereof.
65 - 67 . (canceled)
68 . The compound of claim 1 , wherein the compound is selected from:
4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-Benzyl-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
2-((4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzonitrile;
4-(1-(2-Chlorobenzyl)-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-Methyl-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(3-Methyl-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-Ethyl-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(3,5-Dimethyl-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
2-(5-Phenyl-1H-imidazol-2-yl)-4-(1-propyl-1H-pyrazol-4-yl)pyridine;
4-(1-Methyl-1H-pyrazol-5-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-Methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-Methyl-1H-imidazol-2-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
N-(2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)acetamide;
4-(2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
5-Methoxy-2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridine;
3-((4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzonitrile;
4-(1-(3-Chlorobenzyl)-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
2-(5-Phenyl-1H-imidazol-2-yl)-4-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridine;
4-(2-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)ethyl)morpholine;
Methyl 2-((4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzoate;
Methyl 3-((4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzoate;
Methyl 4-((4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzoate;
2-((4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzoic acid;
3-((4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzoic acid;
4-((4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzoic acid;
5-(4-Methylpiperazin-1-yl)-2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridine;
5-(Methylsulfonyl)-2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridine;
4-(2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-6-yl)morpholine;
4-((4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)methyl)benzonitrile;
4-(1-(Methylsulfonyl)-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-(Ethylsulfonyl)-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
4-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
2-(5-Phenyl-1H-imidazol-2-yl)-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridine;
2-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)acetamide;
N,N-Dimethyl-2-(4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)acetamide;
2-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)-1-(pyrrolidin-1-yl)ethanone;
1-Morpholino-2-(4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)ethanone;
3-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)propanenitrile;
3-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)propanamide;
4-(1-(Cyclopentylsulfonyl)-1H-pyrazol-4-yl)-2-(5-phenyl-1H-imidazol-2-yl)pyridine;
Ethyl 3-(4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)propanoate;
2-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)acetonitrile;
3-(4-(2-(5-Phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)propanoic acid;
N-Methyl-3-(4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)propanamide;
N-cyclopentyl-3-(4-(2-(5-phenyl-1H-imidazol-2-yl)pyridin-4-yl)-1H-pyrazol-1-yl)propanamide;
2-(5-Phenyl-1H-imidazol-2-yl)-4-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridine;
5-(5-Methoxy-3,4′-bipyridin-2′-yl)-1H-imidazol-2-amine;
N-Ethyl-5-(5-methoxy-3,4′-bipyridin-2′-yl)-1H-imidazol-2-amine;
5-(5-Methoxy-3,4′-bipyridin-2′-yl)-N-pentyl-1H-imidazol-2-amine;
N-Isobutyl-5-(5-methoxy-3,4′-bipyridin-2′-yl)-1H-imidazol-2-amine;
N-(Cyclobutylmethyl)-5-(5-methoxy-3,4′-bipyridin-2′-yl)-1H-imidazol-2-amine;
N-Butyl-5-(5-methoxy-3,4′-bipyridin-2′-yl)-4H-1,2,4-triazol-3-amine;
N-Isopropyl-5-(5-methoxy-3,4′-bipyridin-2′-yl)-4H-1,2,4-triazol-3-amine;
5-(5-Methoxy-3,4′-bipyridin-2′-yl)-N-methyl-4H-1,2,4-triazol-3-amine;
5-(5-Methoxy-3,4′-bipyridin-2′-yl)-N-phenyl-4H-1,2,4-triazol-3-amine;
5-Methoxy-2′-(5-phenyl-4H-1,2,4-triazol-3-yl)-3,4′-bipyridine;
5-Methoxy-2′-(4H-1,2,4-triazol-3-yl)-3,4′-bipyridine;
5-Methoxy-2′-(5-methyl-4H-1,2,4-triazol-3-yl)-3,4′-bipyridine;
5-Methoxy-2′-(2-phenyl-1H-imidazol-5-yl)-3,4′-bipyridine;
N-[2-(5-Methoxy-3,4′-bipyridin-2′-yl)-4-methyl-1H-imidazol-5-yl] acetamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-methoxy-3,4′-bipyridine;
5-Methoxy-2′-(5-methyl-1H-imidazol-2-yl)-3,4′-bipyridine;
2-(5-Methoxy-3,4′-bipyridin-2′-yl)-1,4,5,6-tetrahydrocyclopenta[d]imidazole;
5-Methoxy-2′-(5-(trifluoromethyl)-1H-imidazol-2-yl)-3,4′-bipyridine;
Ethyl 2-(5-methoxy-3,4′-bipyridin-2′-yl)-5-(trifluoromethyl)-1H-imidazole-4-carboxylate;
2-(5-Methoxy-3,4′-bipyridin-2′-yl)-5-(trifluoromethyl)-1H-imidazole-4-carboxylic acid;
5-Methoxy-2′-(4-methyl-5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridine;
4-(2-(5-Methoxy-3,4′-bipyridin-2′-yl)-1H-imidazol-5-yl)-N,N-dimethylbenzenesulfonamide;
2′-(5-Isopropyl-1H-imidazol-2-yl)-5-methoxy-3,4′-bipyridine;
2′-(5-Ethyl-1H-imidazol-2-yl)-5-methoxy-3,4′-bipyridine;
2′-(5-Cyclopropyl-1H-imidazol-2-yl)-5-methoxy-3,4′-bipyridine;
5-Methoxy-2′-(5-(pyridin-2-yl)-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(5-tert-Butyl-1H-imidazol-2-yl)-5-methoxy-3,4′-bipyridine;
2-[4-(5-Methoxypyridin-3-yl)pyrimidin-2-yl]-1H-benzimidazole;
2-[6-(5-Methoxypyridin-3-yl)pyrimidin-4-yl]-1H-benzimidazole;
2′-(5-Methyl-1H-imidazol-2-yl)-5-morpholin-4-yl-3,4′-bipyridine;
4-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-(Trifluoromethyl)-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-Ethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-Isopropyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-Cyclopropyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-Cyclobutyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-Cyclopropyl-4-methyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
4-(2′-(5-Ethyl-4-methyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)morpholine;
2′-(5-Cyclohexyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Methyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
5-(Methylsulfonyl)-2′-(5-(trifluoromethyl)-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(5-Ethyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Isopropyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Cyclopropyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Cyclobutyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Cyclopentyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Benzyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Cyclopropyl-4-methyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
2′-(5-Ethyl-4-methyl-1H-imidazol-2-yl)-5-(methylsulfonyl)-3,4′-bipyridine;
5-(Methylsulfonyl)-2′-(5-(pyridin-2-yl)-1H-imidazol-2-yl)-3,4′-bipyridine;
5-Methyl-2-(5-(methylsulfonyl)-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxylic acid;
4-Cyclohexyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazol-5-amine;
2′-[4-(Difluoromethyl)-5-methyl-1H-imidazol-2-yl]-5-(methylsulfonyl)-3,4′-bipyridine;
[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl] methanol;
2-[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]ethanol;
1-[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]ethanol;
Methyl 5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxylate;
tert-Butyl [2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbamate;
2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-amine;
tert-Butyl [2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbamate;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-amine;
N-[2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl] ethanesulfonamide;
2-Methoxy-N-[2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]acetamide;
N-(2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)benzamide;
2-Chloro-N-(2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)benzamide;
3-Chloro-N-(2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)benzamide;
4-Chloro-N-(2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)benzamide;
3-Cyano-N-(2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)benzamide;
4-Cyano-N-(2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)benzamide;
N-(2′-(5-Phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)cyclopentanecarboxamide;
N-Ethyl-N-[2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]urea;
Ethyl 2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-ylcarbamate;
2′-(5-Phenyl-1H-imidazol-2-yl)-N-(tetrahydro-2H-pyran-4-ylmethyl)-3,4′-bipyridin-5-amine;
2′-(5-Phenyl-1H-imidazol-2-yl)-N-(tetrahydro-2H-pyran-4-yl)-3,4′-bipyridin-5-amine;
N-(1-Methylpiperidin-4-yl)-2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-amine;
N-((1-Methylpiperidin-4-yl)methyl)-2′-(5-phenyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-amine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(tetrahydro-2H-pyran-4-ylmethyl)-3,4′-bipyridin-5-amine;
(S)-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-hydroxypyrrolidin-1-yl)methanone;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(4-methylpiperazin-1-yl)methanone;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(morpholino)methanone;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(3-(dimethylamino)propyl)-3,4′-bipyridine-5-carboxamide;
4-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carbonyl)piperazine-1-carboxamide;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(pyrrolidin-1-yl)methanone;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-hydroxyazetidin-1-yl)methanone;
1-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carbonyl)azetidine-3-carbonitrile;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-hydroxypiperidin-1-yl)methanone;
(R)-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-fluoropyrrolidin-1-yl)methanone;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-oxa-9-azaspiro[5.5]undecan-9-yl)methanone;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-isopropyl-3,4′-bipyridine-5-carboxamide;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(4-(1-methylpiperidin-4-yl)piperazin-1-yl)methanone;
1-(4-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carbonyl)piperazin-1-yl)ethanone;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(tetrahydro-2H-pyran-4-yl)-3,4′-bipyridine-5-carboxamide;
(R)-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-(dimethylamino)pyrrolidin-1-yl)methanone;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-3,4′-bipyridine-5-carboxamide;
(R)-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-hydroxypyrrolidin-1-yl)methanone;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4′-bipyridine-5-carboxamide;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(2-oxa-7-azaspiro[3,5]nonan-7-yl)methanone;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(2-methoxyethyl)-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-((tetrahydrofuran-2-yl)methyl)-3,4′-bipyridine-5-carboxamide;
1-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carbonyl)pyrrolidin-3-one;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-(2-hydroxyethyl)pyrrolidin-1-yl)methanone;
(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)(3-(pyridin-2-yl)pyrrolidin-1-yl)methanone;
2-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carbonyl)-6-methyl-2,6-diazaspiro[3.4]octan-5-one;
((3R,4R)-1-{[2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbonyl}-4-methylpyrrolidin-3-yl)methanol;
5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-methoxypyrrolidin-1-yl)carbonyl]-3,4′-bipyridine;
Methyl 1-{[2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbonyl}pyrrolidine-3-carboxylate;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-[(3R)-tetrahydrofuran-3-yl]-3,4′-bipyridine-5-carboxamide;
1-{[2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbonyl}piperidin-4-ol;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-{[3-(trifluoromethyl)pyrrolidin-1-yl]carbonyl}-3,4′-bipyridine;
5-(7-Azabicyclo[2.2.1]hept-7-ylcarbonyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
1-{[2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbonyl}-3-methylpyrrolidin-3-ol;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-phenylpyrrolidin-1-yl)carbonyl]-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-pyridin-4-ylpyrrolidin-1-yl)carbonyl]-3,4′-bipyridine;
1-{[2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbonyl}pyrrolidine-3-carbonitrile;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-{[2-(trifluoromethyl)azetidin-1-yl]carbonyl}-3,4′-bipyridine;
5-[(3,3-Dimethylazetidin-1-yl)carbonyl]-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(4-phenylpiperidin-1-yl)carbonyl]-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(4aR,8aS)-octahydroisoquinolin-2(1H)-ylcarbonyl]-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-phenylpiperidin-1-yl)carbonyl]-3,4′-bipyridine;
5-[(4-Benzylpiperidin-1-yl)carbonyl]-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(2-methylpiperidin-1-yl)carbonyl]-3,4′-bipyridine;
5-(Azetidin-1-ylcarbonyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
N-Benzyl-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carboxamide;
N-Benzyl-2′-(4,5-dimethyl-1H-imidazol-2-yl)-N-methyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-methyl-N-phenyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-[(1S)-1-phenylethyl]-3,4′-bipyridine-5-carboxamide;
4-Benzyl-1-{[2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]carbonyl}piperidin-4-ol;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-pyrazin-2-ylpyrrolidin-1-yl)carbonyl]-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-ethyl-N-methyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-methoxyazetidin-1-yl)carbonyl]-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(4-methyl-1,4-diazepan-1-yl)carbonyl]-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(2-hydroxyethyl)-N-methyl-3,4′-bipyridine-5-carboxamide;
N-(Cyclopropylmethyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carboxamide;
N-(Cyanomethyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-N-methyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(2-methoxyethyl)-N-methyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-{[1-(hydroxymethyl)cyclopropyl]methyl}-N-methyl-3,4′-bipyridine-5-carboxamide;
N-(Cyclobutylmethyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carboxamide;
N-(Cyclopentylmethyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carboxamide;
N-(tert-Butyl)-2-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(3-hydroxypropyl)-N-methyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-methyl-N-propyl-3,4′-bipyridine-5-carboxamide;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[(3-ethylpyrrolidin-1-yl)carbonyl]-3,4′-bipyridine;
5-(5-Azaspiro[2.4]hept-5-ylcarbonyl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-1-(phenylsulfonyl)-1,2,5,6-tetrahydro-3,4′-bipyridine;
2-(4,5-Dimethyl-1H-imidazol-2-yl)-4-[1-(phenylsulfonyl)piperidin-3-yl]pyridine;
1-(4-(2-(4,5-Dimethyl-1H-imidazol-2-yl)pyridin-4-yl)-5, 6-dihydropyridin-1(2H)-yl)ethanone;
1-(3-(2-(4,5-Dimethyl-1H-imidazol-2-yl)pyridin-4-yl)-5, 6-dihydropyridin-1 (2H)-yl)ethanone;
2-(4,5-Dimethyl-1H-imidazol-2-yl)-4-(1-(methylsulfonyl)-1,2,5,6-tetrahydropyridin-3-yl)pyridine;
4-(1-(4-Chlorophenylsulfonyl)-1,2,5,6-tetrahydropyridin-3-yl)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine;
(3-(2-(4,5-Dimethyl-1H-imidazol-2-yl)pyridin-4-yl)-5,6-dihydropyridin-1(2H)-yl)(phenyl)methanone;
4-(1-Benzyl-1,2,5,6-tetrahydropyridin-3-yl)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine;
4-(1-(4-Chlorobenzyl)-1,2,5,6-tetrahydropyridin-3-yl)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine;
2-(4,5-Dimethyl-1H-imidazol-2-yl)-4-(1-((tetrahydro-2H-pyran-4-yl)methyl)-1,2, 5,6-tetrahydropyridin-3-yl)pyridine;
1-(3-(2-(4,5-Dimethyl-1H-imidazol-2-yl)pyridin-4-yl)-2,5-dihydro-1H-pyrrol-1-yl)ethanone;
2-(4,5-Dimethyl-1H-imidazol-2-yl)-4-(1-(methylsulfonyl)-2,5-dihydro-1H-pyrrol-3-yl)pyridine;
4-(1-Benzyl-2,5-dihydro-1H-pyrrol-3-yl)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine;
4-(1-(4-Chlorobenzyl)-2,5-dihydro-1H-pyrrol-3-yl)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine;
2-(4,5-Dimethyl-1H-imidazol-2-yl)-4-(1-((tetrahydro-2H-pyran-4-yl)methyl)-2,5-dihydro-1H-pyrrol-3-yl)pyridine;
(3R)-1-[2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]pyrrolidin-3-ol;
(3S)-1-[2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]pyrrolidin-3-ol;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-phenyl-3,4′-bipyridin-5-amine;
5-Chloro-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
tert-Butyl 3-[2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]-2,5-dihydro-1H-pyrrole-1-carboxylate;
5-(2,5-Dihydro-1H-pyrrol-3-yl)-2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[1-(methylsulfonyl)-2,5-dihydro-1H-pyrrol-3-yl]-3,4′-bipyridine;
1-(3-(2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)-2,5-dihydro-1H-pyrrol-1-yl)ethanone;
Methyl 3-(2′-(4,5-dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-[1-(methylsulfonyl)pyrrolidin-3-yl]-3,4′-bipyridine;
Ethyl 5-methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxylate;
5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxylic acid;
N-Cyclopentyl-5-methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxamide;
2′-[5-Methyl-4-(morpholin-4-ylcarbonyl)-1H-imidazol-2-yl]-5-(methylsulfonyl)-3,4′-bipyridine;
(3R)-1-({5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazol-4-yl}carbonyl)pyrrolidin-3-ol;
(3S)-1-({5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazol-4-yl}carbonyl)pyrrolidin-3-ol;
1-({5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazol-4-yl}carbonyl)azetidin-3-ol;
1-({5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazol-4-yl}carbonyl)azetidine-3-carbonitrile;
5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxamide;
N,5-Dimethyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxamide;
N,N,5-Trimethyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxamide;
N-Ethyl-5-methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxamide;
N-Isopropyl-5-methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-1H-imidazole-4-carboxamide;
5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-N-(tetrahydro-2H-pyran-4-yl)-1H-imidazole-4-carboxamide;
5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-N-[(3S)-tetrahydrofuran-3-yl]-1H-imidazole-4-carboxamide;
5-Methyl-2-[5-(methylsulfonyl)-3,4′-bipyridin-2′-yl]-N-[(3R)-tetrahydrofuran-3-yl]-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxylic acid;
N-Cyclopentyl-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-Isopropyl-N,5-dimethyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-Ethyl-N,5-dimethyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N,5-Dimethyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-(tetrahydrofuran-3-yl)-1H-imidazole-4-carboxamide;
2′-(5-Methyl-4-{[3-(trifluoromethyl)azetidin-1-yl]carbonyl})-1H-imidazol-2-yl)-5-morpholin-4-yl-3,4′-bipyridine;
2′-{4-[(3-Methoxyazetidin-1-yl)carbonyl]-5-methyl-1H-imidazol-2-yl}-5-morpholin-4-yl-3,4′-bipyridine;
tert-Butyl (1-{[5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]carbonyl}azetidin-3-yl)carbamate;
N-Cyclohexyl-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-(tert-Butyl)-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
2′-{4-[(3,3-Dimethylazetidin-1-yl)carbonyl]-5-methyl-1H-imidazol-2-yl}-5-morpholin-4-yl-3,4′-bipyridine;
N-Isopropyl-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-(tetrahydro-2H-pyran-4-yl)-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-[(3R)-tetrahydrofuran-3-yl]-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-[(3S)-tetrahydrofuran-3-yl]-1H-imidazole-4-carboxamide;
N-Benzyl-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-[(1S)-1-phenylethyl]-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-[(1R)-1-phenylethyl]-1H-imidazole-4-carboxamide;
N-[(1R)-2-Methoxy-1-phenylethyl]-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-[(1 S)-2-Methoxy-1-phenyl ethyl]-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-[1-(3-Fluorophenyl)ethyl]-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-2-Adamantyl-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-[(3S)-1-Benzylpyrrolidin-3-yl]-S -methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-[(3R)-1-Benzylpyrrolidin-3-yl]-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-N-(tetrahydro-2H-thiopyran-4-yl)-1H-imidazole-4-carboxamide;
N-(2,3-Dihydro-1H-inden-2-yl)-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazole-4-carboxamide;
N-{[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methyl}tetrahydro-2H-pyran-4-amine;
N-{[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl] methyl}cyclopentanamine;
N-{[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl] methyl}propan-2-amine;
(3S)—N-{[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methyl}tetrahydrofuran-3-amine;
(3R)—N-{[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methyl}tetrahydrofuran-3-amine;
N-Methyl-1-[5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methanamine;
N,N-Dimethyl-1-[5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methanamine;
2-Methoxy-N-{[5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methyl}ethanamine;
3-Methoxy-N-{[5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]methyl}propan-1-amine;
2′-[5-Methyl-4-(morpholin-4-ylmethyl)-1H-imidazol-2-yl]-5-morpholin-4-yl-3,4′-bipyridine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-3,4′-bipyridin-5-yl]methanol;
4-(1-(4-Chlorobenzyl)-1H-pyrazol-4-yl)-2-(4,5-dimethyl-1H-imidazol-2-yl)pyridine; and
(2-{4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]pyridin-2-yl}-5-methyl-N-[(3S)-tetrahydrofuran-3-yl]-1H-imidazole-4-carboxamide;
or a pharmaceutically acceptable salt or tautomer of any of the aforementioned.
69 . The compound of claim 1 , wherein the compound is selected from:
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(tetrahydrofuran-3-ylmethyl)-3,4′-bipyridin-5-amine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-N-(1-phenylethyl)-3,4′-bipyridin-5-amine;
2′-(4,5-Dimethyl-1H-imidazol-2-yl)-5-{[(3S)-3-methoxypyrrolidin-1-yl]carbonyl}-3,4′-bipyridine;
2-{4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]pyridin-2-yl}-N,5-dimethyl-1H-imidazole-4-carboxamide;
2-{4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]pyridin-2-yl}-5-methyl-1H-imidazole-4-carbonitrile;
N-((1r,4r)-4-Hydroxy-4-methylcyclohexyl)-2′-(4-methyl-1H-imidazol-2-yl)-[3,4′-bipyridine]-5-sulfonamide;
N-((1r,4r)-4-Hydroxycyclohexyl)-2′-(4-methyl-1H-imidazol-2-yl)-[3,4′-bipyridine]-5-sulfonamide;
4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]-2-{4-[1-(methylsulfonyl)pyrrolidin-3-yl]-1H-imidazol-2-yl}pyridine;
2-[4-(1-Acetylpyrrolidin-3-yl)-1H-imidazol-2-yl]-4-[1-(4-chlorobenzyl)-1H-pyrazol-4-yl]pyridine;
4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]-2-{4-[1-(phenylsulfonyl)pyrrolidin-3-yl]-1H-imidazol-2-yl}pyridine;
4-[1-(4-Chlorobenzyl)-1H-pyrazol-4-yl]-2-(4-pyrrolidin-3-yl-1H-imidazol-2-yl)pyridine;
N-(2-Methoxyphenyl)-5-methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-amine; and
N-[5-Methyl-2-(5-morpholin-4-yl-3,4′-bipyridin-2′-yl)-1H-imidazol-4-yl]pyridazin-4-amine;
or a pharmaceutically acceptable salt or tautomer of any of the aforementioned.
70 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, and a pharmaceutically acceptable excipient or carrier.
71 . A method of inhibiting the activity of PI3Kγ kinase, comprising contacting the PI3Kγ kinase with a compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof.
72 - 73 . (canceled)
74 . A method of treating a disease or disorder in a patient, wherein said disease or disorder is associated with abnormal expression or activity of PI3Kγ kinase, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof.
75 . (canceled)
76 . The method of claim 74 , wherein disease or disorder is lung cancer, melanoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, color cancer, endometrial cancer, bladder cancer, skin cancer, cancer of the uterus, renal cancer, gastric cancer, or sarcoma.
77 . The method of claim 76 , wherein the sarcoma is Askin's tumor, sarcoma botryoides, chondrosarcoma, Ewing's sarcoma, malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, alveolar soft part sarcoma, angiosarcoma, cystosarcoma phyllodes, dermatofibrosarcoma protuberans, desmoid tumor, desmoplastic small round cell tumor, epithelioid sarcoma, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, gastrointestinal stromal tumor (GIST), hemangiopericytoma, hemangiosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphosarcoma, malignant peripheral nerve sheath tumor (MPNST), neurofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, or undifferentiated pleomorphic sarcoma.
78 . The method of claim 74 , wherein the disease or disorder is acute myeloid leukemia, acute monocytic leukemia, small lymphocyctic lymphoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma, T-cell actute lymphoblasic leukemia (T-ALL), cutaneous T-cell lymphoma, large granular lymphocytic leukemia, mature (peripheral) t-cell neoplasm (PTCL), anaplastic large cell lymphoma (ALCL), or lymphoblastic lymphoma.
79 . The method of claim 78 , wherein the mature (peripheral) t-cell neoplasm (PTCL) is T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia, mycosis fungoides/Sezary syndrome, naplastic large cell lymphoma (T-cell type), enteropathy type T-cell lymphoma, adult T-cell leukemia/lymphoma, or angioimmunoblastic T-cell lymphoma.
80 . The method of claim 78 , wherein the anaplastic large cell lymphoma (ALCL) is systemic ALCL or primary cutaneous ALCL.
81 . The method of claim 74 , wherein the disease or disorder is Burkitt's lymphoma, acute myeloblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, hairy cell leukemia, Mantle cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, extranodal marginal zone lymphoma, Waldenstrom's macroglobulinemia, prolymphocytic leukemia, acute lymphoblastic leukemia, myelofibrosis, mucosa-associated lymphatic tissue (MALT) lymphoma, mediastinal (thymic) large B-cell lymphoma, lymphomatoid granulomatosis, splenic marginal zone lymphoma, primary effusion lymphoma, intravascular large B-cell lymphoma, plasma cell leukemia, extramedullary plasmacytoma, smouldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), or diffuse large B cell lymphoma.
82 . The method of claim 81 , wherein non-Hodgkin's lymphoma (NHL) is relapsed NHL, refractory NHL, recucurrent follicular NHL, indolent NHL (iNHL), or aggressive NHL (aNHL).
83 . The method of claim 81 , wherein the diffuse large B cell lymphoma is activated B-cell like (ABC) diffuse large B cell lymphoma, or germinal center B cell (GCB) diffuse large B cell lymphoma.
84 . The method of claim 81 , wherein the Burkitt's lymphoma is endemic Burkitt's lymphoma, sporadic Burkitt's lymphoma, or Burkitt's-like lymphoma.
85 . The method of claim 74 , wherein the disease or disorder is rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, asthma, allergy, pancreatitis, psoriasis, anaphylaxis, glomerulonephritis, inflammatory bowel disease, thrombosis, meningitis, encephalitis, diabetic retinopathy, benign prostatic hypertrophy, myasthenia gravis, Sjögren's syndrome, osteoarthritis, restenosis, or atherosclerosis.
86 . The method of claim 74 , wherein the disease or disorder is heart hypertropy, cardiac myocyte dysfunction, chronic obstructive pulmonary disease (COPD), elevated blood pressure, ischemia, ischemia-reperfusion, vasoconstriction, anemia, bacterial infection, viral infection, graft rejection, kidney disease, anaphylactic shock fibrosis, skeletal muscle atrophy, skeletal muscle hypertrophy, angiogenesis, sepsis, graft rejection, glomerulosclerosis, progressive renal fibrosis, idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, vasculitis, systemic lupus erythematosus, lupus nephritis, pemphigus, or membranous nephropathy.
87 . The method of claim 86 , wherein the idiopathic thrombocytopenic purpura (ITP) is relapsed ITP or refractory ITP.
88 . The method of claim 86 , wherein the vasculitis is Behçet's disease, Cogan's syndrome, giant cell arteritis, polymyalgia rheumatica (PMR), Takayasu's arteritis, Buerger's disease, central nervous system vasculitis, Kawasaki disease, polyarteritis nodosa, Churg-Strauss syndrome, mixed cryoglobulinemia vasculitis, Henoch-Schönlein purpura (HSP), hypersensitivity vasculitis, microscopic polyangiitis, Wegener's granulomatosis, or anti-neutrophil cytoplasm antibody associated (ANCA) systemic vasculitis (AASV).
89 . The method of claim 74 , wherein the disease or disorder is Alzheimer's disease, central nervous system trauma, or stroke.