Substituted [1,2,4]triazolo[1,5-a]pyridines and substituted [1,2,4]triazolo[1,5-a]pyrazines as LSD1 inhibitors

• US 10,125,133 B2
• Filed: 06/05/2017
• Issued: 11/13/2018
• 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, Wang, Xiaozhao, Yao, Wenqing, Zhang, Colin
• Primary Examiner(s): Willis, Douglas M
• Application Number:
  US15/613,379
• Publication Number:
  US 20170369488A1
• Time in Patent Office: 526 Days
• Field of Search: 544350, 546119
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention is directed to [1,2,4]triazolo[1,5-a]pyridine and [1,2,4]triazolo[1,5-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. A method for inhibiting lysine specific demethylase-1 activity in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula I:

2. The method of claim 1, wherein the patient has cancer.

3. The method of claim 2, wherein the cancer is a sarcoma, lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, or skin cancer.

4. The method of claim 2, wherein the cancer is lung cancer.

5. The method of claim 2, wherein the cancer is non-small cell lung cancer, bronchogenic carcinoma, alveolar carcinoma, bronchial carcinoma, chondromatous hamartoma, or mesothelioma.

6. The method of claim 2, wherein the cancer is a hematological cancer.

7. The method of claim 6, wherein the hematological cancer is selected from acute lymphoblastic leukemia, acute myelogenous leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, primary myelofibrosis, polycythemia vera, essential thrombocytosis, myelodysplasia syndrome, and multiple myeloma.

8. The method of claim 6, wherein the hematological cancer is relapsed or refractory non-Hodgkin lymphoma, or recurrent follicular non-Hodgkin lymphoma.

9. The method of claim 1, wherein X is N.

10. The method of claim 1, wherein X is CR^X.

11. The method of claim 1, wherein:

X is N or CR^X;

Ring A is phenyl or 5-10 membered heteroaryl comprising carbon and 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein said C_6-10 aryl and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^A;

Ring B is phenyl or 5-6 membered heteroaryl comprising carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S;

wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 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^a1C(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^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, 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^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;

wherein when X is CR^X, then R¹ is not CN;

R² is H, halo, C_1-6 alkyl, CN, OR^a2, C(O)R^b2, C(O)NR^c2R^d2, NR^c2R^d2, NR^c2C(O)R^b2, S(O)₂R^b2, or S(O)₂NR^c2R^d2;

wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, OR^a2, C(O)R^b2, C(O)NR^c2R^d2, NR^c2R^d2, NR^c2C(O)R^b2, S(O)₂R^b2, and S(O)₂NR^c2R^d2;

each R^A is independently selected from halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, OR^a4, C(O)R^b4, C(O)NR^c4R^d4, C(O)OR^a4, NR^c4R^d4, NR^c4C(O)R^b4, S(O)₂R^b4, and S(O)₂NR^c4R^d4, wherein said C_1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, OR^a4, C(O)R^b4, C(O)NR^c4R^d4, C(O)OR^a4, NR^c4R^d4, NR^c4C(O)R^b4, 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, NO₂, OR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, NR^c5R^d5, NR^c5C(O)R^b5, 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 haloalkyl, CN, NO₂, OR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, NR^c5R^d5, NR^c5C(O)R^b5, S(O)₂R^b5, and S(O)₂NR^c5R^d5;

R^X is independently selected from H, halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, OR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, NR^c7R^d7, NR^c7C(O)R^b7, S(O)₂R^b7, and S(O)₂NR^c7R^d7;

each Cy¹, 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 independently 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, C(═

NR^e6)NR^c6R^d6, NR^c6C(═

NR^e6)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_1-4 alkyl, C_1-4 haloalkyl, C_1-4 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, C(═

NR^e6)NR^c6R^d6, NR^c6C(═

NR^e6)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;

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

wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, OR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, NR^c3R^d3, NR^c3C(O)R^b3, 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)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;

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^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, 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^d7, NR^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, R^c2, 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, 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;

or any R^c2 and R^d2 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, phenyl, 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^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, wherein said C_1-6 alkyl, C_3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 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^d7, NR^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^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, 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;

or any R^c3 and R^d3 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, phenyl, 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^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, wherein said C_1-6 alkyl, C_3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 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^d7, NR^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^a4, R^b4, R^c4, and R^d4 is independently selected from H, C_1-6 alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, and C_2-6 alkynyl, wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl 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, 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;

or any R^c4 and R^d4 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_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^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^a5, R^b5, R^c5, and R^d5 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, 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;

or any R^c5 and R^d5 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^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, 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^d7, NR^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^a6, R^b6, R^c6, and R^d6 is independently selected from H, C_1-6 alkyl, C_1-4 haloalkyl, C_2-6 alkenyl, and C_2-6 alkynyl, wherein said C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl 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, 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;

or any R^c6 and R^d6 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_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^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^a7, R^b7, R^c7, and R^d7 is independently selected from H, C_1-4 alkyl, C_1-4 haloalkyl, C_2-4 alkenyl, and C_2-4 alkynyl, wherein said C_1-4 alkyl, C_2-4 alkenyl, and C_2-4 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C_1-4 alkyl, C_1-4 alkoxy, C_1-4 alkylthio, C_1-4 alkylamino, di(C_1-4 alkyl)amino, C_1-4 haloalkyl, and C_1-4 haloalkoxy; and

each R^e1, R^e6, and R^e7 is independently selected from H, C_1-4 alkyl, and CN.

12. The method of claim 1, wherein:

X is N or CR^X;

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

Ring B is phenyl 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, OR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, 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, OR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, NR^c1R^d1, NR^c1C(O)R^b1, S(O)₂R^b1, and S(O)₂NR^c1R^d1;

R² is H;

each R^A is independently selected from halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, and OR^a4, wherein said C_1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from CN and OR^a4;

each R^B is independently selected from halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, CN, and OR^a5;

R^X is H;

each Cy¹ and Cy⁴ is independently selected from phenyl, C_3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 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, C_2-6 alkenyl, C_2-6 alkynyl, 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, are each optionally substituted by 1, 2, or 3 substituents independently selected from C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 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^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;

each R^a1 is independently selected from H, C_1-6 alkyl, and 4-7 membered heterocycloalkyl;

wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, OR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, NR^c3R^d3, NR^c3C(O)R^b3, S(O)₂R^b3, and S(O)₂NR^c3R^d3, and wherein said 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, CN, NO₂, OR^a6, C(O)R^b6, C(O)NR^c6R^d6, C(O)OR^a6, NR^c6R^d6, NR^c6C(O)R^b6, S(O)₂R^b6, and S(O)₂NR^c6R^d6;

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, 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-, wherein said C_1-6 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 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;

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, 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^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 and C_1-6 alkyl;

each R^a4 is independently selected from H and C_1-6 alkyl;

each R^a5 is independently selected from H and C_1-6 alkyl;

each R^a6, R^b6, R^c6, and R^d6 is independently selected from H and C_1-6 alkyl; and

each R^a7, R^b7, R^c7, and R^d7 is independently selected from H and C_1-4 alkyl.

13. The method of claim 1, wherein Ring A is phenyl or 5-10 membered heteroaryl comprising carbon and 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein said phenyl and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^A.

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

15. The method of claim 1, wherein Ring A is phenyl substituted by 1 R^A.

16. The method of claim 1, wherein Ring A is phenyl substituted by CN.

17. The method of claim 1, wherein Ring B is phenyl or 5-6 membered heteroaryl comprising carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S;

wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R^B.

18. The method of claim 1, wherein Ring B is phenyl optionally substituted by 1 or 2 substituents independently selected from R^B.

19. The method of claim 1, wherein Ring B is phenyl substituted by 1 R^B.

20. The method of claim 1, wherein Ring B is phenyl substituted by CH₃.

21. The method of claim 1, wherein R¹ is halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, Cy¹, OR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, 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, OR^a1, C(O)R^b1, C(O)NR^c1R^d1, C(O)OR^a1, NR^c1R^d1, NR^c1C(O)R^b1, S(O)₂R^b1, and S(O)₂NR^c1R^d1.

22. The method of claim 1, wherein R¹ is C_1-6 alkyl, Cy¹, or OR^a1, wherein said C_1-6 alkyl is substituted by 1 Cy¹.

23. The method of claim 1, wherein R¹ is pyrrolidin-3-ylmethoxy, 2-pyrrolidin-3-ylethyl, (1-methylpyrrolidin-3-yl)ethyl, 3-[(methylamino)methyl]phenyl, 3-aminopyrrolidin-1-yl)methyl]phenyl, piperazin-1-ylmethyl, 4-methylpiperazin-1-yl)methyl, 3-(dimethylamino)pyrrolidin-1-yl, 3-(methylamino)pyrrolidin-1-yl, or (1-methylpyrrolidin-3-yl)methoxy.

24. The method of claim 1, wherein R² is H.

25. The method of claim 1, wherein each R^A is independently selected from halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, OR^a4, C(O)R^b4, C(O)NR^c4R^d4, C(O)OR^a4, NR^c4R^d4, NR^c4C(O)R^b4, S(O)₂R^b4, and S(O)₂NR^c4R^d4, wherein said C_1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, OR^a4, C(O)R^b4, C(O)NR^c4R^d4, C(O)OR^a4, NR^c4R^d4, NR^c4C(O)R^b4, S(O)₂R^b4, and S(O)₂NR^c4R^d4.

26. The method of claim 1, wherein each R^A is independently selected from halo, C_1-6 alkyl, C_1-6 haloalkyl, CN, and OR^a4, wherein said C_1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from CN and OR^a4.

27. The method of claim 1, wherein R^A is CN.

28. The method of claim 1, wherein 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, NO₂, OR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, NR^c5R^d5, NR^c5C(O)R^b5, 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 haloalkyl, CN, NO₂, OR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, NR^c5R^d5, NR^c5C(O)R^b5, S(O)₂R^b5, and S(O)₂NR^c5R^d5.

29. The method of claim 1, wherein each R^B is independently selected from halo, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 haloalkyl, CN, and OR^a5.

30. The method of claim 1, wherein R^B is C_1-6 alkyl.

31. The method of claim 1, wherein R^B is CH₃.

32. The method of claim 1, wherein R^Cy is C_1-4 alkyl and NR^c6R^d6, wherein said C_1-4 alkyl is optionally substituted with NR^c6R^d6.

33. The method of claim 1, wherein R^X is H.

34. The method of claim 1, wherein each R^a1 is independently selected from H, C_1-6 alkyl, and Cy⁴;

wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, OR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, NR^c3R^d3, NR^c3C(O)R^b3, S(O)₂R^b3, and S(O)₂NR^c3R^d3.

35. The method of claim 1, wherein each R^a1 is independently selected from H, C_1-6 alkyl, and 4-7 membered heterocycloalkyl;

wherein said C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy⁴, halo, CN, OR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, NR^c3R^d3, NR^c3C(O)R^b3, S(O)₂R^b3, and S(O)₂NR^c3R^d3, and wherein said 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, CN, NO₂, OR^a6, C(O)R^b6, C(O)NR^c6R^d6, C(O)OR^a6, NR^c6R^d6, NR^c6C(O)R^b6, S(O)₂R^b6, and S(O)₂NR^c6R^d6.

36. The method of claim 1, wherein each R^a1 is C_1-4 alkyl substituted by 4-7 membered heterocycloalkyl, wherein said 4-7 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from halo, C_1-4 alkyl, C_1-4 haloalkyl, C_1-4 cyanoalkyl, CN, NO₂, OR^a6, C(O)R^b6, C(O)NR^c6R^d6, C(O)OR^a6, NR^c6R^d6, NR^c6C(O)R^b6, S(O)₂R^b6, and S(O)₂NR^c6R^d6.

37. The method of claim 1, wherein each R^a1 is pyrrolidinylmethyl optionally substituted by 1 C_1-4 alkyl.

38. The method of claim 1, wherein each Cy¹ is independently selected from phenyl, C_3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^Cy.

39. The method of claim 1, wherein each Cy¹ is phenyl or 4-7 membered heterocycloalkyl, each optionally substituted with 1 or 2 substituents independently selected from R^Cy.

40. The method of claim 1, wherein each Cy¹ is phenyl, pyrrolidinyl, or piperazinyl, each optionally substituted with 1 or 2 substituents independently selected from R^Cy.

41. The method of claim 1, wherein each Cy¹ is phenyl, pyrrolidinyl, or piperazinyl, each optionally substituted with 1 or 2 substituents independently selected from C_1-4 alkyl and NR^c6R^d6, wherein said C_1-4 alkyl is optionally substituted with NR^c6R^d6.

42. The method of claim 1, wherein the compound is a compound having Formula IIa:

43. The method of claim 1, wherein the compound is a compound having Formula IIb:

44. The method of claim 1, wherein the compound is a compound having Formula IIIa:

45. The method of claim 1, wherein the compound is a compound having Formula IIIb:

46. The method of claim 1, wherein the compound is selected from:

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

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

4-{5-(4-methylphenyl)-8-[2-(1-methylpyrrolidin-3-yl)ethyl][1,2,4]triazolo[1,5-a]pyridin-6-yl}benzonitrile;

4-[8-{3-[(methylamino)methyl]phenyl}-5-(4-methylphenyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-[8-{3-[(3-aminopyrrolidin-1-yl)methyl]phenyl}-5-(4-methylphenyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-[5-(4-methylphenyl)-8-(piperazin-1-ylmethyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-{5-(4-methylphenyl)-8-[(4-methylpiperazin-1-yl)methyl][1,2,4]triazolo[1,5-a]pyridin-6-yl}benzonitrile;

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

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

4-[8-{[(3 S)-3-(methylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)-[1,2,4]triazolo[1, 5-a]pyridin-6-yl]benzonitrile;

4-[8-{[(3R)-3-(methylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)-[1,2,4]triazolo[1, 5-a]pyridin-6-yl]benzonitrile;

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

4-(5-(4-methylphenyl)-8-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile,

or a pharmaceutically acceptable salt of any of the aforementioned.