IMIDAZOPYRAZINES AS LSD1 INHIBITORS

• US 20170369497A1
• Filed: 06/05/2017
• Published: 12/28/2017
• Est. Priority Date: 07/10/2014
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: Wu, Liangxing, Courter, Joel R., He, Chunhong, Li, Jingwei, Lu, Liang, Sun, Yaping, Wang, Xiaozhao, Yao, Wenqing, Zhang, Colin, Zhuo, Jincong
• Granted Patent: US 10,112,950 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention is directed to imidazo[1,2-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Claims

1-58. -58. (canceled)

59. A method of treating cancer comprising administering to a patient a therapeutically effective amount of a compound of Formula I:

60. The method of claim 59, wherein said cancer is a hematological cancer.

61. The method of claim 60, wherein said hematological cancer is selected from acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, Non-Hodgkin lymphoma, Hodgkin lymphoma, primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocytosis (ET), myelodysplasia syndrome (MDS), or multiple myeloma.

62. The method of claim 59, wherein said cancer is a sarcoma, lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, or skin cancer.

63. A method of treating a disease comprising administering to a patient a therapeutically effective amount of a compound of claim 59, or a pharmaceutically acceptable salt thereof, wherein said disease is a viral disease or a beta-globinopathy.

64. The method of claim 59, wherein:

Ring A is phenyl optionally substituted by 1, 2, or 3 substituents independently selected from R^A;

Ring B is phenyl or 5-6 membered heteroaryl comprising carbon and 1 or 2 heteroatoms selected from N;

wherein said phenyl or 5-6 membered heteroaryl is optionally substituted by 1, or 2 substituents independently selected from R^B;

R¹ is halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, Cy¹, CN, OR^a1, SR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, OC(O)R^b1, OC(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, NR^c1C(O)NR^c1R^d1, NR^c1S(O)R^b1, NR^c1S(O)₂R^b1, NR^c1S(O)₂NR^c1R^d1, S(O)R^b1, S(O)NR^c1R^d1, S(O)₂R^b1, or S(O)₂NR^c1R^d1;

wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy¹, halo, CN, OH, OR^a1, SR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, OC(O)R^b1, OC(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, NR^c1(O)NR^c1R^d1, NR^c1S(O)R^b1, NR^c1S(O)₂R^b1, NR^c1S(O)₂NR^c1R^d1, S(O)R^b1, S(O)NR^c1R^d1, S(O)₂R^b1, and S(O)₂NR^c1R^d1;

R² is H, halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, Cy², CN, OR^a2, SR^a2, C(O)R^b2, C(O)NR^c2R^d2, C(O)OR^a2, OC(O)R^b2, OC(O)NR^c2R^d2, NR^c2R^d2, NR^c2C(O)R^b2, NR^c2C(O)OR^a2;

NR^c2C(O)NR^c2R^d2, NR^c2S(O)R^b2, NR^c2S(O)₂R^b2, NR^c2S(O)₂NR^c2R^d, S(O)R^b2, S(O)NR^c2R^d2, S(O)₂R^b2, or S(O)₂NR^c2R^d2;

wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy², halo, CN, OR^a2, SR^a2, C(O)R^b2, C(O)NR^c2R^d2, C(O)OR^a2, OC(O)R^b2, OC(O)NR^c2R^d2, NR^c2R^d2, NR^c2C (O)R^b2, NR^c2C(O)OR^a2, NR^c2C(O)NR^c2R^d2, NR^c2S(O)R^b2, NR^c2S(O)₂R^b2, NR^c2S(O)₂NR^c2R^d2, S(O)R^b2, S(O)NR^c2R^d2, S(O)₂R^b2, and S(O)₂NR^c2R^d2;

R³ is H;

each R^A is independently selected from halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, CN, OR^a4, SR^a4, C(O)R^b4, C(O)NR^c4R^d4, NR^c4R^d4, NR^c4C(O)R^b4, NR^c4S(O)₂R^b4, S(O)R^b4, S(O)NR^c4R^d4, S(O)₂R^b4, and S(O)₂NR^c4R^d4, wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted by 1, 2, or 3, substituents independently selected from halo, C_1-6 haloalkyl, CN, OR^a4, SR^a4, C(O)R^b4, C(O)NR^c4R^d4, NR^c4R^d4, NR^c4C(O)R^b4, NR^c4S(O)₂R^b4, S(O)R^b4, S(O)NR^c4R^d4, S(O)₂R^b4, and S(O)₂NR^c4R^d4;

each R^B is independently selected from Cy³, halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, CN, OR^a5, SR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, OC(O)R^b5, OC(O)NR^c5R^d5, NR^c5R^d5, NR^c5C(O)R^b5, NR^c5C(O)OR^a5, NR^c5C(O)NR^c5R^d5, NR^c5S(O)R^b5, NR^c5S(O)₂R^b5, NR^c5S(O)₂NR^c5R^d5, S(O)R^b5, S(O)NR^c5R^d5, S(O)₂R^b5, and S(O)₂NR^c5R^d5, wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from Cy³, halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, CN, OR^a5, SR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, OC(O)R^b5, OC(O)NR^c5R^d5, NR^c5R^d5, NR^c5R^d5, NR^c5C(O)R^b5, NR^c5C(O)OR^a5, NR^c5C(O)NR^c5R^d5, NR^c5S(O)R^b5, NR^c5S(O)₂R^b5, NR^c5S(O)₂NR^c5R^d5, S(O)R^b5, S(O)NR^c5R^d5, S(O)₂R^b5, and S(O)₂NR^c5R^d5;

each Cy¹, Cy², Cy³, and Cy⁴ is independently selected from C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^Cy;

each R^Cy is selected from halo, C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, C_2-6 alkenyl, C_2-6 alkynyl, phenyl, C_3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C_1-4 alkyl-, C_3-7 cycloalkyl-C_1-4 alkyl-, (5-6 membered heteroaryl)-C_1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C_1-4 alkyl-, CN, NO₂, OR^a6, SR^a6, C(O)R^b6, C(O)NR^c6R^d6, C(O)OR^a6, OC(O)R^b6, OC(O)NR^c6R^d6, NR^c6R^d6, NR^c6C(O)R^b6, NR^c6C(O)OR^a6, NR^c6C(O)NR^c6R^d6, NR^c6S(O)R^b6, NR^c6S(O)₂R^b6, NR^c6S(O)₂NR^c6R^d6, S(O)R^b6, S(O)NR^c6R^d6, S(O)₂R^b6, and S(O)₂NR^c6R^d6, wherein said C_1-4 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, phenyl, C_3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C_1-4 alkyl-, C_3-7 cycloalkyl-C_1-4 alkyl-, (5-6 membered heteroaryl)-C_1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C_1-4 alkyl- are each optionally substituted by 1, 2, or 3 substituents independently selected from C_1-6 alkyl, C_1-4 haloalkyl, C_1-6 cyanoalkyl, halo, CN, NO₂, OR^a6, SR^a6, C(O)R^b6, C(O)NR^c6R^d6, C(O)OR^a6, OC(O)R^b6, OC(O)NR^c6R^d6, NR^c6R^d6, NR^c6C(O)R^b6, NR^c6C(O)OR^a6NR^c6C(O)NR^c6R^d6, NR^c6S(O)R^b6, NR^c6S(O)₂R^b6, NR^c6S(O)₂NR^c6R^d6, S(O)R^b6, S(O)NR^c6R^d6, S(O)₂R^b6, and S(O)₂NR^c6R^d6;

each R^a1 is independently selected from C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, and Cy⁴;

wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, OR^a3, SR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, OC(O)R^b3, OC(O)NR^c3R^d3, NR^c3R^d3, NR^c3C(O)R^b3, NR^c3C(O)OR^a3, NR^c3C(O)NR^c3R^d3, NR^c3S(O)R^b3, NR^c3S(O)₂R^b3, NR^c3S(O)₂NR^c3R^d3, S(O)NR^b3, S(O)NR^c3R^d3, S(O)₂R^b3, and S(O)₂NR^c3R^d3;

each R^b1, R^c1, and R^d1 is independently selected from H, C_1-6 alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10 membered heteroaryl)-C_1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C_1-4 alkyl-, wherein said C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10 membered heteroaryl)-C_1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C_1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, halo, CN, OR^a7, SR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, OC(O)R^b7, OC(O)NR^c7R^d7, NR^c7R^d7, NR^c7C(O)R^b7, NR^c7C(O)R^c7R^d7, NR^c7C(O)OR^a7, S(O)R^b7, S(O)NR^c7R^d7, S(O)₂R^b7, NR^c7S(O)₂R^b7, NR^c7S(O)₂NR^c7R^d7, and S(O)₂NR^c7R^d7;

or any R^c1 and R^d1 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 substituents independently selected from C_1-6 alkyl, C_3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-10 aryl, 5-6 membered heteroaryl, C_1-6 haloalkyl, halo, CN, OR^a7, SR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, OC(O)R^b7, OC(O)NR^c7R^d7, NR^c7R^d7, NR^c7C(O)R^b7, NR^c7C(O)NR^c7R^d7, NR^c7C(O)OR^a7, C(═

NR^c7)NR^c7R^d7, NR^c7C(═

NR^c7)NR^c7R^d7, S(O)R^b7, S(O)NR^c7R^d7, S(O)₂R^b7, NR^c7S(O)₂R^b7, NR^c7S(O)₂NR^c7R^d7, and S(O)₂NR^c7R^d7, wherein said C_1-6 alkyl, C_3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C_6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, CN, OR^a7, SR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, OC(O)R^b7, OC(O)NR^c7R^d7, NR^c7R^d7NR^c7C(O)R^b7, NR^c7C(O)NR^c7R^d7, NR^c7C (O)OR^a7, C(═

NR^e7)NR^c7R^d7, NR^c7C(═

NR^e7)NR^c7R^d7, S(O)R^b7, S(O)NR^c7R^d7, S(O)₂R^b7, NR^c7S(O)₂R^b7, NR^c7S(O)₂NR^c7R^d7, and S(O)₂NR^c7R^d7;

each R^a2, R^b2 and R^d2 is independently selected from H, C_1-6 alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10 membered heteroaryl)-C_1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C_1-4 alkyl-, wherein said C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10 membered heteroaryl)-C_1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C_1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, halo, CN, OR^a7, SR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, OC(O)R^b7, OC(O)NR^c7R^d7, NR^c7R^d7, NR^c7C(O)R^b7, NR^c7C(O)NR^c7R^d7, NR^c7C(O)OR^a7, S(O)R^b7, S(O)NR^c7R^d7, S(O)₂R^b7, NR^c7S(O)₂R^b7, NR^c7S(O)₂NR^c7R^d7, and S(O)₂NR^c7R^d7;

each R^a3, R^b3, R^c3, and R^d3 is independently selected from H, C_1-6 alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10 membered heteroaryl)-C_1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C_1-4 alkyl-, wherein said C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_6-10 aryl, C_3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10 membered heteroaryl)-C_1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C_1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, halo, CN, OR^a7, SR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, OC(O)R^b7, OC(O)NR^c7R^d7, NR^c7R^d7, NR^c7C(O)R^b7, NR^c7C(O)NR^c7R^d7, NR^c7C(O)OR^a7, S(O)R^b7, S(O)NR^c7R^d7, S(O)₂R^b7, NR^c7S(O)₂R^b7, NR^c7S(O)₂NR^c7R^d7, and S(O)₂NR^c7R^d7;

each R^a4, R^b4, R^c4, and R^d4 is independently selected from H and C_1-3 alkyl;

each R^a5, R^b5, R^c5, and R^d5 is independently selected from H or C_1-3 alkyl;

each R^a6, R^b6, R^c6 and R^d6 is independently selected from H or C_1-3 alkyl; and

each R^a7, R^b7, R^c7, and R^d7 is independently selected from H or C_1-3 alkyl.

65. The method of claim 59, wherein:

Ring A is phenyl optionally substituted by 1, 2, or 3 substituents independently selected from R^A;

Ring B is phenyl, pyridyl, or pyrimidinyl, each optionally substituted by 1 or 2 substituents independently selected from R^B;

R¹ is halo, C_1-3 alkyl, Cy¹, OR^a1, SR^a1, C(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, or NR^c1C(O)NR^c1R^d1;

wherein said C_1-3 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy¹, halo, CN, OH, OR^a1, C(O)NR^c1R^d1, NR^c1R^d1, and NR^c1C(O)R^b1;

R² is H, halo, C_1-3 alkyl, C_1-3 haloalkyl, Cy², C(O)NR^c2R^d2, NR^c2R^d2, or NR^c2C(O)R^b2;

wherein said C_1-3 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy², halo, CN, OR^a2, C(O)NR^c2R^d2, NR^c2R^d2, and NR^c2C(O)R^b2;

R³ is H;

each R^A is independently selected from halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, CN, OR^a4, SR^a4, C(O)R^b4, C(O)NR^c4R^d4, NR^c4R^d4NR^c4C(O)R^b4, NR^c4S(O)₂R^b4, S(O)R^b4, S(O)NR^c4R^d4, S(O)₂R^b4, and S(O)₂NR^c4R^d4, wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted by 1, 2, or 3, substituents independently selected from halo, C_1-6 haloalkyl, CN, OR^a4, SR^a4, C(O)R^b4, C(O)NR^c4R^d4, NR^c4R^d4, NR^c4C(O)R^b4, NR^c4S(O)₂R^b4, S(O)R^b4, S(O)NR^c4R^d4, S(O)₂R^b4, and S(O)₂NR^c4R^d4;

each R^B is independently selected from Cy³, halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, OR^a5, C(O)NR^c5R^d5, NR^c5R^d5, NR^c5C(O)R^b5, NR^c5C(O)OR^a5, NR^c5C(O)NR^c5R^d5, NR^c5S(O)R^b5, NR^c5S(O)₂R^b5, and NR^c5S(O)₂NR^c5R^d5, wherein said C_1-6 alkyl is optionally substituted by 1, 2, or 3 substituents independently selected from Cy³, halo, C_1-6 haloalkyl, CN, OR^a5, C(O)NR^c5R^d5, NR^c5R^d5, and NR^c5C(O)R^b5;

each Cy¹, Cy², Cy³, and Cy⁴ is independently selected from phenyl, cyclopropyl, azetidinyl, piperidinyl, pyrrolidinyl, diazapanyl, and diazaspirononanyl, each of which is optionally substituted with 1 or 2 substituents independently selected from R^Cy;

each R^Cy is independently selected from halo, C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, CN, OR^a6, and NR^c6R^d6;

each R^a1 is independently selected from C_1-3 alkyl and Cy⁴;

wherein said C_1-3 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, and OR^a3, and NR^c3R^d3;

each R^b1, R^c1, and R^d1 is independently selected from H, C_1-3 alkyl, C_1-3 haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyridinyl, pyrimidinyl, azetidinyl, piperidinyl, pyrrolidinyl, thiazolyl, phenyl-C_1-2 alkyl-, cyclopropyl-C_1-2 alkyl-, cyclobutyl-C_1-2 alkyl-, cyclopentyl-C_1-2 alkyl-, cyclohexyl-C_1-2 alkyl-, pyridinyl-C_1-2 alkyl-, pyrimidinyl-C_1-2 alkyl-, azetidinyl-C_1-2 alkyl-, piperidinyl-C_1-2 alkyl-, pyrrolidinyl-C_1-2 alkyl-, and thiazolyl-C_1-2 alkyl-, wherein said alkyl, C_1-3 haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyridinyl, pyrimidinyl, azetidinyl, piperidinyl, pyrrolidinyl, thiazolyl, phenyl-C_1-2 alkyl-, cyclopropyl-C_1-2 alkyl-, cyclobutyl-C_1-2 alkyl-, cyclopentyl-C_1-2 alkyl-, cyclohexyl-C_1-2 alkyl-, pyridinyl-C_1-2 alkyl-, pyrimidinyl-C_1-2 alkyl-, azetidinyl-C_1-2 alkyl-, piperidinyl-C_1-2 alkyl-, pyrrolidinyl-C_1-2 alkyl-, and thiazolyl-C_1-2 alkyl- are each optionally substituted with 1, 2, or 3 substituents independently selected from C_1-3 alkyl, C_1-3 haloalkyl, halo, CN, OR^a7, and NR^c7R^d7;

or any R^c1 and R^d1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with NR^c7R^d7;

each R^a2, R^b2, R^c2, and R^d2 is independently selected from H, C_1-3 alkyl, C_1-3 haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopropyl-C_1-2 alkyl-, cyclobutyl-C_1-2 alkyl-, pyridinyl, pyrimidinyl, isoxazolyl, azetidinyl, piperidinyl, and pyrrolidinyl, wherein said C_1-3 alkyl, C_1-3 haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopropyl-C_1-2 alkyl-, cyclobutyl-C_1-2 alkyl-, pyridinyl, pyrimidinyl, isoxazolyl, azetidinyl, piperidinyl, and pyrrolidinyl are each optionally substituted with 1 or 2 substituents independently selected from C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, halo, CN, OR^a7, and NR^c7R^d7;

each R^a1, R^b3, R^c3, and R^d3 is independently selected from H, C_1-3 alkyl, C_1-3 haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopropyl-C_1-2 alkyl-, cyclobutyl-C_1-2 alkyl-, pyridinyl, pyrimidinyl, isoxazolyl, azetidinyl, piperidinyl, and pyrrolidinyl, wherein said C_1-3 alkyl, C_1-3 haloalkyl, phenyl, cyclopropyl, cyclobutyl, cyclopropyl-C_1-2 alkyl-, cyclobutyl-C_1-2 alkyl-, pyridinyl, pyrimidinyl, isoxazolyl, azetidinyl, piperidinyl, and pyrrolidinyl are each optionally substituted with 1 or 2 substituents independently selected from C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, halo, CN, OR^a7, and NR^c7R^d7;

each R^a4, R^b4, R^c4, and R^d4 is independently selected from H and C_1-3 alkyl;

each R^a5, R^b5, R^c5, and R^d5 is independently selected from H or C_1-3 alkyl;

each R^a6, R^b6, R^c6, and R^d6 is independently selected from H or alkyl; and

each R^a7, R^b7, R^c7, and R^d7 is independently selected from H or C_1-3 alkyl.

66. The method of claim 59, wherein Ring A is phenyl optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^A.

67. The method of claim 59, wherein Ring A is phenyl substituted by one R^A.

68. The method of claim 59, wherein Ring A is phenyl substituted by CN.

69. The method of claim 59, wherein Ring B is phenyl, C_3-10 cycloalkyl, 4-10 membered heterocycloalkyl, or 5-6 membered heteroaryl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^B.

70. The method of claim 59, wherein Ring B is phenyl or 5-6 membered heteroaryl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^B.

71. The method of claim 59, wherein Ring B is phenyl, pyridyl, 3-oxo-3,4-dihydro-2H-1,4-benzoxazinyl, 2,3-dihydro-1,4-benzodioxinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, 1,3-benzothiazolyl, 2-oxo-2,3-dihydro-1,3-benzoxazolyl, indazolyl, 2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridinyl, 2,3-dihydro-1H-indenyl, 2-oxo-2,3-dihydro-1H-indolyl, quinoxalinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, benzimidazolyl, 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, or pyrimidinyl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^B.

72. The method of claim 59, wherein Ring B is phenyl, pyridyl, or pyrimidinyl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^B.

73. The method of claim 59, wherein Ring B is phenyl, pyridyl, 3-oxo-3,4-dihydro-2H-1,4-benzoxazinyl, 2,3-dihydro-1,4-benzodioxinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, 1,3-benzothiazolyl, 2-oxo-2,3-dihydro-1,3-benzoxazolyl, indazolyl, 2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridinyl, 2,3-dihydro-1H-indenyl, 2-oxo-2,3-dihydro-1H-indolyl, quinoxalinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, benzimidazolyl, 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, or pyrimidinyl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from Cy³, halo, C_1-6 alkyl, C_1-6 haloalkyl, OR^a5, CN, NR^c5C(O)OR^a5, and NR^c5R^d5.

74. The method of claim 59, wherein Ring B is phenyl, pyridyl, or pyrimidinyl, each optionally substituted by one substituent selected from Cy³, halo, C_1-6 alkyl, C_1-6 haloalkyl, OR^a5, and NR^c5R^d5.

75. The method of claim 59, wherein Ring B is phenyl, pyridyl, 3-oxo-3,4-dihydro-2H-1,4-benzoxazinyl, 2,3-dihydro-1,4-benzodioxinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, 1,3-benzothiazolyl, 2-oxo-2,3-dihydro-1,3-benzoxazolyl, indazolyl, 2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridinyl, 2,3-dihydro-1H-indenyl, 2-oxo-2,3-dihydro-1H-indolyl, quinoxalinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, benzimidazolyl, 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, or pyrimidinyl, each optionally substituted by 1, 2, 3, or 4 substituents independently selected from chloro, methyl, trifluoromethyl, piperidinyl, methoxy, ethyl, 2-oxopyrrolidinyl, methyl(tetrahydrofuran-2-ylmethyl)amino, fluoro, 2-oxo-1,3-oxazolidinyl, amino, cyano, hydroxymethyl, (4-(methylsulfonyl)piperazin-1-yl)methyl, hydroxy, morpholin-4-ylmethyl, (CH₃O)(C═

O)N(CH₃), (CH₃O)(C═

O)N(CH₃)-methyl, 1-hydroxyethyl, cyanomethyl, 3-methyl-2-oxoimidazolidinyl or dimethylamino.

76. The method of claim 59, wherein Ring B is phenyl, pyridyl, or pyrimidinyl, each optionally substituted by chloro, methyl, trifluoromethyl, piperidinyl, methoxy, or dimethylamino.

77. The method of claim 59, wherein Ring B is phenyl substituted by methyl.

78. The method of claim 59, wherein R¹ is C_1-6 alkyl, Cy¹, OR^a1, SR^a1, C(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, or NR^c1C(O)NR^c1R^d1 wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy¹, halo, CN, OH, OR^a1, SR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, OC(O)R^b1, OC(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, NR^c1C(O)NR^c1R^d1, C(═

NR^e1)R^b1, C(═

NR^e1)NR^c1R^d1, NR^c1C(═

NR^e1)NR^c1R^d1NR^c1S(O)R^b1, NR^c1S(O)₂R^b1, NR^c1S(O)₂NR^c1R^d1, S(O)R^b1, S(O)NR^c1R^d1, S(O)₂R^b1, and S(O)₂NR^c1R^d1.

79. The method of claim 59, wherein R¹ is C_1-6 alkyl, Cy¹, OR^a1, SR^a1, C(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, or NR^c1C(O)NR^c1R^d1, wherein said C_1-6 alkyl is optionally substituted with Cy¹, OH, or OR^a1.

80. The method of claim 59, wherein R¹ is OR^a1.

81. The method of claim 59, wherein R¹ is C_1-6 alkyl substituted with 1 or 2 substituents independently selected from Cy¹ or OR^a1.

82. The method of claim 59, wherein R¹ is Cy¹ optionally substituted with 1 or 2 substituents independently selected from C_1-4 alkyl or NR^c6R^d6.

83. The method of claim 59, wherein R¹ is pyrrolidin-3-ylmethoxy, 2-pyrrolidin-3-ylethyl, [pyrrolidin-3-yloxy]methyl, [3-(dimethylamino)pyrrolidin-1-yl]methyl, [3-(dimethylamino)pyrrolidin-1-yl]ethyl, (1-methylpyrrolidin-3-yl)oxy, 3-(dimethylamino)propoxy, piperidin-3-ylmethoxy, [1, methylpyrrolidin-3-yl]methoxy, [1-methylpiperidin-3-yl]methoxy, [pyrrolidin-3-ylmethyl]thio, 4-(dimethylamino)piperidin-1-yl, 3-(dimethylamino)propyl](methyl)amino, [2-(1-methylpyrrolidin-2-yl)ethyl]amino, (1-methylpiperidin-4-yl)amino, 4-methyl-1,4-diazepan-1-yl, 2,7-diazaspiro[4.4]non-2-yl, 2,7-diazaspiro[3.5]non-7-yl, 3-(dimethylamino)-N-methylpyrrolidine, [2-(2-amino-1,3-thiazol-4-yl)ethyl]amino, azetidin-3-ylmethylaminocarbonyl, 3-(dimethylamino)piperidin-1-yl, [1-(2-hydroxyethyl)piperidin-3-yl]methoxy, [1-(2-cyanoethyl)piperidin-3-yl]methoxy, [1-ethylpiperidin-3-yl]methoxy, or 1-methylazetidin-3-ylaminocarbonyl.

84. The method of claim 59, wherein R¹ is pyrrolidin-3-ylmethoxy, 2-pyrrolidin-3-ylethyl, [pyrrolidin-3-yloxy]methyl, [3-(dimethylamino)pyrrolidin-1-yl]methyl, [3-(dimethylamino)pyrrolidin-1-yl]ethyl, (1-methylpyrrolidin-3-yl)oxy, 3-(dimethylamino)propoxy, piperidin-3-ylmethoxy, [1, methylpyrrolidin-3-yl]methoxy, [1-methylpiperidin-3-yl]methoxy, [pyrrolidin-3-ylmethyl]thio, 4-(dimethylamino)piperidin-1-yl, 3-(dimethylamino)propyl](methyl)amino, [2-(1-methylpyrrolidin-2-yl)ethyl]amino, (1-methylpiperidin-4-yl)amino, 4-methyl-1,4-diazepan-1-yl, 2,7-diazaspiro[4.4]non-2-yl, 2,7-diazaspiro [3.5]non-7-yl, 3-(dimethylamino)-N-methylpyrrolidine, [2-(2-amino-1,3-thiazol-4-yl)ethyl]amino, azetidin-3-ylmethylaminocarbonyl, or 1-methylazetidin-3-ylaminocarbonyl.

85. The method of claim 59, wherein each R^a1 is independently selected from C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, and Cy⁴;

wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, OR^a3, SR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, OC(O)R^b3, OC(O)NR^c3R^d3, NR^c3R^d3, NR^c3C(O)R^b3, NR^c3C(O)OR^a3, NR^c3C(O)NR^c3R^d3, C(═

NR^e3)R^b3, (═

NR^e3)NR^c3R^d3, NR^c3C(═

NR^e3)NR^c3R^d3, NR^c3S(O)R^b3, NR^c3S(O)₂R^b3, NR^c3S(O)₂NR^c3R^d3, S(O)R^b3, S(O)NR^c3R^d3, S(O)₂R^b3, and S(O)₂NR^c3R^d3.

86. The method of claim 59, wherein each R^a1 is C_1-6 alkyl optionally substituted with 1 or 2 substituents independently selected from Cy⁴ and NR^c3R^d3.

87. The method of claim 59, wherein each R^a1 is C_1-3 alkyl optionally substituted with pyrrolidinyl, piperidinyl, or dimethylamino, wherein said pyrrolidinyl and piperidinyl are each optionally substituted with 1, 2, or 3 substituents independently selected from methyl, ethyl, cyanoethyl, and hydroxyethyl.

88. The method of claim 59, wherein R² is H, C_1-6 alkyl, C_1-6 haloalkyl, Cy², or C(O)NR^c2R^d2, wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy², halo, CN, OR^a2, SR^a2, C(O)R^b2, C(O)NR^c2R^d2, C(O)OR^a2, OC(O)R^b2, OC(O)NR^c2R^d2, NR^c2R^d2, NR^c2C(O)R^b2, NR^c2C(O)OR^a2, NR^c2C (O)NR^c2R^d2, C(═

NR^e2)R^b2, (═

NR^e2)NR^c2R^d2, NR^c2C(═

NR^e2)NR^c2R^d2, NR^c2S(O)R^b2, NR^c2S(O)₂R^b2, NR^c2S(O)₂NR^c2R^d2, S(O)R^b2, S(O)NR^c2R^d2, S(O)₂R^b2, _and S(O)₂NR^c2R^d2.

89. The method of claim 59, wherein R² is H, C_1-6 alkyl, C_1-6 haloalkyl, Cy², or C(O)NR^c2R^d2, wherein said C_1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from Cy², CN, OR^a2, and NR^c2R^d2.

90. The method of claim 59, wherein R² is H, methyl, trifluoromethyl, 4-methylphenyl, cyanomethyl, methylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, 1-methylazetidin-3-ylaminocarbonyl, hydroxymethyl, azetidin-1-ylmethyl, cyclopropylmethylaminomethyl, (isoxazol-3-ylamino)methyl, dimethylaminomethyl, or dimethylaminoethyl.

91. The method of claim 59, wherein R² is H.

92. The method of claim 59, wherein R³ is H.

93. The method of claim 59, wherein R^A is CN.

94. The method of claim 59, wherein each R^B is independently selected from Cy³, halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, NR^c5C(O)OR^a5, NR^c5R^d5 and OR^a5.

95. The method of claim 59, wherein each R^B is independently selected from Cy³, halo, C_1-6 alkyl, C_1-6 haloalkyl, and OR^a5.

96. The method of claim 59, wherein R^B is C_1-6 alkyl.

97. The method of claim 59, wherein R^B is methyl, chloro, trifluoromethyl, piperidinyl, methoxy, ethyl, 2-oxopyrrolidinyl, methyl(tetrahydrofuran-2-ylmethyl)amino, fluoro, 2-oxo-1,3-oxazolidinyl, amino, cyano, hydroxymethyl, (4-(methylsulfonyl)piperazin-1-yl)methyl, hydroxy, morpholin-4-ylmethyl, (CH₃O)(C═

O)N(CH3), (CH₃O)(C═

O)N(CH₃)-methyl, 1-hydroxyethyl, cyanomethyl, 3-methyl-2-oxoimidazolidinyl or dimethylamino.

98. The method of claim 59, wherein R^B is methyl.

99. The method of claim 59, wherein each Cy¹ is independently selected from 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^Cy.

100. The method of claim 59, wherein each Cy¹ is independently selected from 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1 or 2 substituents independently selected from C_1-4 alkyl and NR^c6R^d6.

101. The method of claim 59, wherein Cy¹ is 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R.

102. The method of claim 59, wherein Cy¹ is azetidinyl, piperidinyl, pyrrolidinyl, diazapanyl, or diazaspirononanyl, each optionally substituted with 1 or 2 substituents independently selected from R^Cy.

103. The method of claim 59, wherein the compound is a compound having Formula II:

104. The method of claim 59, wherein the compound is a compound having Formula IIa:

105. The method of claim 59, wherein the compound is a compound wherein group:

106. The method of claim 59, wherein the compound is a compound Formula III:

107. The method of claim 59, wherein the compound is a compound Formula IV:

108. The method of claim 59, wherein the compound is a compound Formula V:

109. The method of claim 59, wherein the compound is a compound Formula VI:

110. The method of claim 59, wherein the compound is a compound Formula VII:

111. The method of claim 59, wherein the group:

112. The method of claim 59, wherein the compound is selected from:

4-{5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[5-(4-methylphenyl)-8-(2-pyrrolidin-3-ylethyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-(5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-yloxy]methyl imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-[8-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-{2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]ethyl}-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{5-(4-methylphenyl)-8-[(1-methylpyrrolidin-3-yl)oxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[8-[3-(dimethylamino)propoxy]-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{5-(4-methylphenyl)-8-[(3R)-piperidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{5-(4-methylphenyl)-8-[(3S)-piperidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-(5-(4-methylphenyl)-8-[(3R)-1-methylpyrrolidin-3-yl]methoxylimidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(4-methylphenyl)-8-[(3R)-1-methylpiperidin-3-yl]methoxylimidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(4-methylphenyl)-8-{[(3R)-pyrrolidin-3-ylmethyl]thio}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[[3-(dimethylamino)propyl](methypamino]-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-(5-(4-methylphenyl)-8-{[2-(1-methylpyrrolidin-2-yl)ethyl]amino}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-{5-(4-methylphenyl)-8-[(1-methylpiperidin-4-yl)amino]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[8-(4-methyl-1,4-diazepan-1-yl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-(2,7-diazaspiro[4.4]non-2-yl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-(2,7-diazaspiro[3.5]non-7-yl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

(3R)—

N-[6-(4-cyanophenyl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-8-yl]-3-(dimethylamino)-N-methylpyrrolidine-1-carboxamide;

(3S)—

N-[6-(4-cyanophenyl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-8-yl]-3-(dimethylamino)-N-methylpyrrolidine-1-carboxamide;

4-[8-[2-(2-amino-1,3-thiazol-4-yl)ethyl]amino-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

N-(azetidin-3-ylmethyl)-6-(4-cyanophenyl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazine-8-carboxamide;

6-(4-cyanophenyl)-N-(1-methylazetidin-3-yl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazine-8-carboxamide;

4-{(5-phenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{5-(4-chlorophenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[(3R)-pyrrolidin-3-ylmethoxy]-5-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{5-(4-piperidin-1-ylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{5-(4-methoxyphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{5-[2-(dimethylamino)pyrimidin-5-yl]-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-(5-[6-(dimethylamino)pyridin-3-yl]-8-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-{2-methyl-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]-2-(trifluoromethyl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{2,5-bis(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{2-(cyanomethyl)-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

6-(4-cyanophenyl)-N-methyl-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo-[1,2-a]pyrazine-2-carboxamide;

6-(4-cyanophenyl)-N,N-dimethyl-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazine-2-carboxamide;

6-(4-cyanophenyl)-N-cyclopropyl-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazine-2-carboxamide;

6-(4-cyanophenyl)-N-(1-methylazetidin-3-yl)-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazine-2-carboxamide;

4-{2-(hydroxymethyl)-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{2-[(dimethylamino)methyl]-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{2-(azetidin-1-ylmethyl)-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{2-{[(cyclopropylmethyl)amino]methyl}-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{2-[(isoxazol-3-ylamino)methyl]-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-(2-[(dimethylamino)methyl]-5-(4-methylphenyl)-8-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1, 2-a]pyrazin-6-yl)benzonitrile; and

4-{2-[2-(dimethylamino)ethyl]-5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy]imidazo[1,2-a]pyrazin-6-yl}benzonitrile,

or a pharmaceutically acceptable salt of any of the aforementioned.

113. The method of claim 59, wherein the compound is selected from:

4-{8-{[(3R)-1-methylpiperidin-3-yl]methoxy}-5-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-(5-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(2,3-dihydro-1,4-benzodioxin-6-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[6-(dimethylamino)pyridin-3-yl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(8-{[(3R)-1-methylpiperidin-3-yl]methoxy}-5-{6-[methyl(tetrahydrofuran-2-ylmethyl)amino]pyridin-3-yl}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-[8-{[(3R)-1-methylpiperidin-3-yl]methoxy}-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-{[(3R)-1-methylpiperidin-3-yl]methoxy}-5-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1, 2-a]pyrazin-6-yl]benzonitrile;

4-(5-(1,3-benzothiazol-5-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-{8-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-5-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1, 2-a]pyrazin-6-yl}benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)p iperidin-1-yl]-5-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)p iperidin-1-yl]-5-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)imidazo[1, 2-a]pyrazin-6-yl]benzonitrile;

4-[8-{[(3R)-1-ethylpiperidin-3-yl]methoxy}-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1, 2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)p iperidin-1-yl]-5-(5-fluoro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-{[(3R)-1-ethylpip eridin-3-yl]methoxy}-5-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-{[(3R)-1-(2-cyanoethyl)piperidin-3-yl]methoxy}-5-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1, 2-a]pyrazin-6-yl]benzonitrile;

4-[8-{[(3R)-1-(2-hydroxyethyl)p iperidin-3-yl]methoxy}-5-(1-methyl-1H-indazol-5-yl)imidazo[1, 2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(3-methyl-2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridin-6-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[6-(2-oxo-1,3-oxazolidin-3-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{5-(3-amino-1-methyl-1H-indazol-5-yl)-8-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

5-(6-(4-cyanophenyl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-5-yl)-2-methylbenzonitrile;

4-(5-[3-(hydroxymethyl)-4-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(4-methyl-3-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[4-(hydroxymethyl)-3-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(3-hydroxy-2,3-dihydro-1H-inden-5-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[4-(hydroxymethyl)phenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-{8-{[(3R)-1-methylpiperidin-3-yl]methoxy}-5-[4-(morpholin-4-ylmethyl)phenyl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

methyl [5-(6-(4-cyanophenyl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-5-yl)-2-methylphenyl]methylcarbamate;

methyl [4-(6-(4-cyanophenyl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-5-yl)phenyl]methylcarbamate;

4-(5-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(7-fluoro-3-hydroxy-2,3-dihydro-1H-inden-5-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(1-hydroxy-2,3-dihydro-1H-inden-5-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[3-fluoro-4-(hydroxymethyl)-5-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[3,5-difluoro-4-(hydroxymethyl)phenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(5-fluoro-6-methoxypyridin-3-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

methyl [4-(6-(4-cyanophenyl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-5-yl)-2-fluorobenzyl]methylcarbamate;

4-(5-[4-(1-hydroxyethyl)-3-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[3-(1-hydroxyethyl)-4-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-(7-fluoro-1-hydroxy-2,3-dihydro-1H-inden-5-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[2-fluoro-4-(morpholin-4-ylmethyl)phenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(5-[2-(hydroxymethyl)-4-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1 2-a]pyrazin-6-yl)benzonitrile;

4-(5-[3-(cyanomethyl)-4-methylphenyl]-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(5,6-dimethylpyridin-3-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(5-hydroxy-6-methylpyridin-3-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(3-hydroxy-2,3-dihydro-1H-inden-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[3-(hydroxymethyl)-4-methylphenyl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[3-fluoro-4-(hydroxymethyl)-5-methylphenyl]imidazo[1, 2-a]pyrazin-6-yl}benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{8-[3-(dimethylamino)piperidin-1-yl]-5-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[6-(3-methyl-2-oxoimidazolidin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-quinoxalin-6-ylimidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[2-(hydroxymethyl)-1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(3-ethyl-2-oxo-2,3-dihydro[1,3 ]oxazolo[4,5-b]pyridin-6-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-1H-benzimidazol-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(4-methyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-{8-[4-(dimethylamino)piperidin-1-yl]-5-[6-(4-methyl-3-oxopiperazin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-{8-[4-(dimethylamino)p ip eridin-1-yl]-5-[3-(hydroxymethyl)-1-methyl-1H-indazol-5-yl]imidazo[1,2-a]pyrazin-6-yl}benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-(8-[4-(dimethylamino)piperidin-1-yl]-5-{2-[(1R)-1-hydroxyethyl]-1-methyl-1H-benzimidazol-5-yl}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-(8-[4-(dimethylamino)piperidin-1-yl]-5-{2-[(1S)-1-hydroxyethyl]-1-methyl-1H-benzimidazol-5-yl}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(1,2-dimethyl-1H-benzimidazol-5-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(5-methoxy-6-methylpyridin-3-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile;

5-(6-(4-cyanophenyl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-5-yl)-2-methylnicotinonitrile;

4-[8-[4-(dimethylamino)piperidin-1-yl]-5-(5-hydroxy-6-methoxypyridin-3-yl)imidazo[1,2-a]pyrazin-6-yl]benzonitrile; and

4-(5-(5-hydroxy-6-methoxypyridin-3-yl)-8-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-a]pyrazin-6-yl)benzonitrile;

or a pharmaceutically acceptable salt thereof.