Heterocyclic compounds as kinase inhibitors for therapeutic uses
Heterocyclic compounds of formula I shown below and pharmaceutical compositions containing one of such compounds: Also disclosed is a method of treating a condition modulated by the colony-stimulating factor-1 receptor with one of the heterocyclic compounds.
1 . A compound of formula I:
wherein
A is H or C 1 -C 6 alkyl;
Y 1 is phenyl substituted with (R 1 ) n , in which R 1 in (R 1 ) n , n being 1-4, is, independently, F, Cl, Br, NO 2 , CN, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 5- to 15-membered heterocycloalkyl, carbonyl, thionyl, iminyl, or spiroamino, and at least one R 1 is amino or 5- to 15-membered heterocycloalkyl;
X 1 is N;
X 2 is O;
Y 2 is
in which each of Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , Q 6 , Q 7 , and Q 8 is, independently, N or CR 4 , R 4 being H, F, Cl, Br, CN, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 alkoxyl; Z 1 is O, S, or NRr, Rr being H or C 1 -C 6 alkyl; Z 2 is O, S, or NRr; and G and H are, respectively, C or N and N or C;
X 3 is deleted, CH 2 , (CH 2 ) 2 , or CH(C≡CH);
Y 3 is C 1 -C 6 alkyl, aryl, heteroaryl, C 3 -C 8 cycloalkyl, or C 5 -C 6 heterocycloalkyl having one heteroatom, in which the one heteroatom is O or N; and
X 4 in (X 4 ) m , m being 0-5, is, independently, F, Cl, Br, CN, SO 2 NH 2 , amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 alkoxyl.
2 . The compound of claim 1 , wherein Y 1 is phenyl substituted with R 1 selected from amino and 5- to 15-membered heterocycloalkyl.
3 . The compound of claim 2 , wherein Y 2 is
Y 3 is pyridyl, and R 1 is 5- to 15-membered heterocycloalkyl.
4 . The compound of claim 1 , wherein Y 2 is
in which Z 2 is O or NRr.
5 . The compound of claim 4 , wherein Y 2 is
Y 3 is pyridyl, and R 1 is amino.
6 . The compound of claim 1 , wherein the compound is of formula Ia:
in which R 1 is amino or 5- to 15-membered heterocycloalkyl.
7 . The compound of claim 6 , wherein Y 2 is
Y 3 is pyridyl; X 3 is CH 2 ; X 4 is CH 3 , CH 2 F, CHF 2 , CF 3 , or OCH 3 ; and m is 1.
8 . The compound of claim 6 , wherein Y 2 is
Y 3 is phenyl; X 3 is CH 2 ; each of X 4 is, independently, F, Cl, Br, CN, SO 2 NH 2 , CH 3 , CH 2 F, CHF 2 , CF 3 , OCF 3 , C 1 -C 6 alkoxyl, or amino; and m is 0-2.
9 . The compound of claim 6 , wherein Y 2 is
Y 3 is phenyl; X 3 is deleted; each of X 4 is, independently, F, Cl, Br, CN, SO 2 NH 2 , CH 3 , CH 2 F, CHF 2 , CF 3 , OCF 3 , C 1 -C 6 alkoxyl, or amino; and m is 0-2.
10 . The compound of claim 7 , wherein R 1 is amino.
11 . The compound of claim 6 , wherein Y 2 is
Y 3 is phenyl or pyridyl; and X 3 is CH 2 .
12 . The compound of claim 11 , wherein Y 2 is
13 . The compound of claim 6 , wherein Y 2 is
Y 3 is phenyl or pyridyl; and X 3 is CH 2 .
14 . The compound of claim 13 , wherein Y 2 is
15 . The compound of claim 1 , wherein the compound is of formula Ib:
16 . The compound of claim 15 , wherein Y 1 is
Y 3 is phenyl or pyridyl; and X 3 is deleted or CH 2 .
17 . The compound of claim 16 , wherein each of X 4 is, independently, CH 3 , CH 2 F, CHF 2 , CF 3 , or OCH 3 and m is 0-2.
18 . The compound of claim 1 , wherein the compound is one of the following compounds:
19 . The compound of claim 1 , wherein the compound is
20 . The compound of claim 1 , wherein the compound is