| CPC C07D 409/14 (2013.01) | 48 Claims |
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1. A compound of Formula I:
 or a pharmaceutically acceptable salt thereof wherein:
X, Y, and Z are independently selected from N and C(R5);
R1 is a 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 R6;
R2a and R2b are independently selected from
(1) hydrogen,
(2) halogen,
(3) hydroxy,
(4) (C1-6)alkyl,
(5) (C1-6)haloalkyl,
(6) R2a and R2b join to form spiro(C3-8)cycloalkyl wherein the spiro(C3-8)cycloalkyl is unsubstituted or mono or di-substituted with substituents independently selected from C1-3alkyl, halogen, and OH, and
(7) R2a and R2b join to form spiro 4- to 8-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 R7;
R3 is
(1) 4- to 7-membered heterocyclyl containing 1, 2 or 3 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) —(C1-6)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) —(C1-6)alkyl-aryl,
(5) —(C1-6)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) (C1-6)alkyl,
(7) (C3-6)cycloalkyl,
(8) (C1-6)hydroxyalkyl,
(9) —(C1-6)alkyl-S(O)2—NR8aR8b, or
(10) —(C1-6)alkyl-S(O)2—(C1-3)alkyl,
wherein each cycloalkyl, or heterocyclyl is unsubstituted or substituted with 1, 2, or 3 R9, and wherein each alkyl, aryl, or heteroaryl is unsubstituted or substituted with 1, 2, or 3 R10;
R4 is
(1) hydrogen, or
(2) (C1-3)alkyl,
or R3 and R4 combine together with the nitrogen atom to which they are attached to form a mono- or bicyclic heterocyclyl ring containing 1 or 2 heteroatoms independently selected from N, O and S, wherein the heterocyclyl ring is unsubstituted or substituted by 1, 2, or 3 R11,
when present, each R5 is independently selected from
(1) hydrogen,
(2) (C1-3)alkyl,
(3) (C1-3)haloalkyl,
(4) cyano, and
(5) halogen,
when present, each R6 is independently selected from
(1) cyano,
(2) halogen,
(3) —OC1-6alkyl
(4) (C3-6)cycloalkyl, unsubstituted or substituted with halogen, and OH,
(5) —(C═O)NH2,
(6) (C3-6)cycloalkyloxy wherein the cycloalkyl is unsubstituted or substituted with halogen or OH,
(7) hydroxy,
(8) —NR11R11,
(9) —NH(C═O)(C1-6)alkyl,
(10) (C2-6) cyclic amine, unsubstituted or substituted with one or two halogen substituents,
(11) —(C1-6)haloalkyl
(12) —O(C1-6)haloalkyl unsubstituted or substituted with OH,
(13) —O(C0-3)alkyl-(C3-6)cycloalkyl optionally unsubstituted or substituted with one or two halogen substituents,
(14) —SO2(C1-6)alkyl,
(15) —SO2NH(C1-6)alkyl,
(16) —SC1-6alkyl,
(17) —SC1-6haloalkyl, and
(18) (C1-6)alkyl,
when present, each R7 is independently selected from
(1) (C1-3)alkyl,
(2) halogen,
(3) (C1-3)alkoxy-,
(4) —(C1-3)haloalkyl, and
(5) hydroxy,
when present, R8a and R8b are independently selected from
(1) hydrogen,
(2) (C1-3)alkyl, and
(3) (C3-7)cycloalkyl;
when present, each R9 is independently selected from
(1) (C1-3)alkyl,
(2) —(C1-3)haloalkyl,
(3) OXO,
(4) (C3-6)cycloalkyl,
(5) —N(R11)2,
(6) hydroxy,
(7) (C1-3)alkoxyl,
(8) cyano,
(9) halogen,
(10) —SO2(C1-6)alkyl,
(11) —(C1-6)alkyl SO2(C1-6)alkyl,
(12) —C(O)(C1-3)alkyl, and
(13) —O(C1-3)alkyl,
when present, R10 is independently selected from
(1) hydrogen,
(2) (C1-3)alkyl,
(3) (C1-3)alkoxy-,
(4) hydroxy,
(5) halogen,
(6) (C1-3)alkyl-S—,
(7) —(C1-3)haloalkyl, and
(8) N(R11)2, and
R11, when present, is independently
(1) hydrogen, or
(2) (C1-3)alkyl.
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