| CPC C07D 471/04 (2013.01) [C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 491/107 (2013.01); C07D 491/20 (2013.01); C07D 513/04 (2013.01)] | 21 Claims |
|
1. A compound having formula (I):
 or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide, optically enriched form, or rotamer thereof,
wherein
X is N or CH;
Z is O or —N(Rf)—, wherein Rf is selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, and C3-6 cycloalkyl;
Ring A is a benzene or pyridine ring;
Ar1 is a monocyclic 5- or 6-membered aromatic or heteroaromatic ring having 0 to 3 heteroatoms as ring vertices selected from N, O, and S, substituted with from 1 to 5 R1 substituents independently selected from the group consisting of halogen, CN, C1-8 alkyl, C3-8 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C1-8 hydroxyalkyl,
—ORa, and —NRaRb;
each Ra and Rb is independently selected from the group consisting of hydrogen, hydroxyl, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, and C3-6 cycloalkyl;
Y is selected from the group consisting of:
i) bicyclic 9- or 10-membered fused aromatic or heteroaromatic ring having 0 to 4 heteroatoms as ring vertices selected from N, O, S and S(O)2, and which is substituted with 0 to 5 R2;
ii) 4- to 7-membered monocyclic heterocyclic ring having 1 or 2 heteroatoms as ring vertices selected from N, O, S and S(O)2, and which is substituted with 0 to 5 R2;
iii) 6- to 12-membered fused or bridged heterocyclic ring having 1 to 4 heteroatoms as ring vertices selected from N, O, S and S(O)2, and which is substituted with 0 to 6 R2; and
iv) 7- to 12-membered spiroheterocyclic ring having 0 to 4 heteroatoms as ring vertices selected from N, O and S, and which is substituted with 0 to 6 R2;
each R2 is independently selected from the group consisting of halogen, CN, C1-8 alkyl, C3-8 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, haloalkyl, hydroxyalkyl, —ORc, —SRc, —OSi(Rc)3, —CORc, —CO2Rc, —NRcRd, —NRcRd, —CONRcRd, —(CO)2NRcRd, —NRcCO2Rd, —NRcCORd, —NRcCONRcRd, —NRCSO2Rd, —SO2Rd, —CO—C1-4 hydroxyalkyl, —SO2NRcRd, —X2—NRcRd, —X2—CONRcRd, —X2—NRcCONRcRd, —X2—NRcCO2Rd, —X2—NRcCORd, —X2—NRcSO2Rd, —CO—X2—NRcCORd, oxo, 4- to 7-membered heterocyclic ring having 1 or 2 heteroatoms as ring vertices selected from N, O, S and S(O)2, 5- or 6-membered heteroaryl, and —X2-5- or 6-membered heteroaryl; and wherein the 5- or 6-membered heteroaryl ring and the 4- to 7-membered heterocyclic ring of R2 have from 1 to 3 heteroatoms selected from N, O, and S, and are each unsubstituted or substituted with one or two members independently selected from the group consisting of halogen, hydroxyl, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, —CORc, —CO2Rc, and —CONRcRd; and wherein two R2 groups attached to the same carbon atom are optionally combined to form a 3- to 6-membered spirocyclic ring or a 3- to 6-membered spiroheterocyclic ring having 1 to 3 heteroatoms as ring vertices selected from N, O and S, and which is unsubstituted or substituted with 1 or 2 members independently selected from C1-4 alkyl, —CORc, —CO2Rc, and —CONRcRd;
each Rc and Rd is independently selected from the group consisting of hydrogen, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, and C3-6 cycloalkyl; or Rc and Rd, when attached to the same nitrogen atom are joined to form a 4- to 7-membered heterocyclic ring having from 0 to 2 additional heteroatoms as ring vertices selected from O, S, S(O), S(O)2, NH and N(C1-4 alkyl);
each Re is selected from the group consisting of phenyl;
X2 is C1-4 alkylene or cyclopropyl;
the subscript m is 0, 1 or 2;
each R3 is a member independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 alkoxy, C3-8 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkoxy, and C2-4 hydroxyalkyl; and
R4 is a member selected from the group consisting of H, C1-4 alkyl, C3-8 cycloalkyl, and C1-4 haloalkyl.
|