Triazolone compounds

Abstract

Described herein are triazalone compounds of formula (I): JPEG2023519361000182.jpg3243 and pharmaceutically acceptable salts thereof. Methods for preparing and using the compounds of formula (I) are also described. The compounds of formula (I) and their pharmaceutically acceptable salts may be useful as adenosine receptor antagonists in the treatment of diseases or conditions mediated by adenosine receptors, such as cancer, movement disorders, or attention disorders.

Description

[Background technology]

[0001] background Adenosine regulates several physiological functions. Intracellularly, adenosine is involved in energy metabolism, nucleic acid metabolism, and the methionine cycle; extracellular adenosine is involved in intercellular signaling. For example, extracellular adenosine is a potent immunosuppressant that prevents excessive immune responses during inflammation and infection. Adenosine also acts on other systems, including the cardiovascular and central nervous systems.

[0002] The actions of adenosine are mediated by a family of G protein-coupled receptors. At least four subtypes of adenosine receptors have been identified: A1R, A2aR, A2bR, and A3R. The A1R and A3 subtypes inhibit the activity of the enzyme adenylate cyclase, while the A2a and A2b subtypes stimulate its activity, thereby regulating intracellular cyclic AMP levels.

[0003] In the immune system, engagement of the A2a and A2b adenosine receptors is a critical regulatory mechanism protecting tissues against excessive immune responses. In tumors, this pathway is hijacked, disrupting antitumor immunity and promoting cancer progression. Furthermore, the tumor microenvironment often contains high levels of extracellular adenosine. Therefore, adenosine receptors, particularly the A2aR and A2bR, have been identified as targets for cancer therapy.

[0004] Numerous adenosine receptor antagonists have been reported. For example, International Application WO2006 / 138734 discloses triazolopyrimidine cannabinoid receptor 1 (CB-1) antagonists. WO2008 / 002596 and WO2009 / 111449 disclose adenosine A2a receptor antagonists containing a triazolone moiety. WO2012 / 038980 discloses fused tricyclic compounds as adenosine receptor antagonists. WO2016 / 161282 discloses heterocyclic compounds as LSD1 inhibitors. WO2018 / 166493 discloses heteroaryl[4,3-c]pyrimidin-5-amine derivatives for use as A2a receptor antagonists. Summary of the Invention [Problem to be solved by the invention]

[0005] There remains a need for highly soluble, highly selective and highly potent adenosine receptor antagonists. [Means for solving the problem]

[0006] overview In some embodiments, a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring A is: [ka] It could be; Each R 1 and each R 2 independently halo, C 1-3 Alkyl, -OC 1-3 Alkyl, -CO2R a or -NR 7 R 8 It could be; wherein alkyl is optionally —OR aand substituted with one or more substituents independently selected from halo; R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, aryl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a It could be; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and where R 3 is optionally halo, cyano, -R a AND -OR a substituted with 1 to 3 substituents selected from: R 4 is not present or -(CHR c ) i -(NR a ) j -R 5 It could be; R 5 teeth: (1)C 3-8 cycloalkyl, aryl, 3-, 4-, 6-, or 7-membered heterocyclyl or 3-, 4-, 6-, or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and where R 5 wherein one or two ring atoms are optionally replaced by -C(=O)-; (2) polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring systems; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and where R 5 wherein one or two ring atoms are optionally replaced by -C(=O)-; or (3) C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b can be; and where R 5 optionally 1 to 4 groups -XR 6 may be substituted with; Each X independently represents a bond, -O-, or -NR a -, -S(O) k -, -(CH2) m - or -C(O)-; Each R 6 are independently H, halo, -OR a , C 1-6 Alkyl, C 3-8 Cycloalkyl, heterocyclyl, heteroaryl, aryl, -CO2R a , -C(O)NR a R b , -(CH2) n -NR a R b Or it can be cyano; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and containing 1 to 4 heteroatoms independently selected from: Here, each C 3-8one or two ring atoms of the cycloalkyl, heterocyclyl, heteroaryl, or aryl are independently optionally substituted with -C(=O)-; wherein each of alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl is optionally —R a , -OR a , -(CH2) n -NR a R b and substituted with one or more substituents independently selected from halo; Each R 7 and each R 8 is independently R a It could be; or R 7 and R 8 together with the atoms to which they are attached, possibly -OR a and halo; Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 It can be cycloalkylalkyl; Here, each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo; Each R c are independently H, halo, and C 1-3 Alkyl or -(CH2) n -NR a R b It could be; wherein alkyl is optionally —OR a and substituted with one or more substituents independently selected from halo; a can be 0 or 1; i can be 0, 1, 2 or 3; j can be 0 or 1; Each k may independently be 0, 1, or 2; each m may independently be 1 or 2; and Each n can independently be 0 or 1.

[0007] The compounds of formula (I) may be selective adenosine receptor antagonists for CB-1. The compounds may have a K of 100 nM or less for at least one of A2aR and A2bR. i and K of 10,000 nM or greater for CB-1. i may have:

[0008] In some embodiments, R 5 is C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b It could be.

[0009] In some embodiments, R 5 can be aryl, 6-membered heterocyclyl or 6-membered heteroaryl.

[0010] In some embodiments, R 5 can be a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system.

[0011] In some embodiments, R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR aC(O)-R a OR-NHC(O)-OR a It could be.

[0012] In some embodiments, i can be 1 and R c is H or C 1-3 or i can be 2 and each R c can be H.

[0013] In other embodiments, a compound of formula (II): [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 1 and each R 2 independently halo, C 1-3 Alkyl or -OC 1-3 It can be alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Ring B is C 3-8 may be cycloalkyl, aryl, 6- or 7-membered heterocyclyl or 6- or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl independently contain 1 to 4 heteroatoms independently selected from N and O; Each R 9 are independently halo, -R a -OR a It could be; Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 It can be cycloalkylalkyl; Here, each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo; L is -(CHR c )e -can be; Each R c are independently H, halo, and C 1-3 Alkyl or -(CH2) n -NR a R b It could be; wherein alkyl is optionally —OR a and substituted with one or more substituents independently selected from halo; R d can be H or halo; a can be 0 or 1; b can be 0, 1 or 2; d can be 0, 1, 2, 3 or 4; e can be 1 or 2; and n can be 0 or 1.

[0014] In other embodiments, a compound of formula (III): [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 1 and each R 2 independently halo, C 1-3 Alkyl, -OC 1-3 Alkyl, -CO2R a or -NR 7 R 8 It could be; wherein alkyl is optionally —OR a and substituted with one or more substituents independently selected from halo; R 4 Ha-(CHR c )2-R 5 It could be; R 5 H, halo, C 1-3 Alkyl, -OR e , -COR e , -COOR e , -OS(O)2R e , -OCO-NR e R for -CO-NR e R f It could be; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 It can be cycloalkylalkyl; Here, each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo; Each R c are independently H, halo, and C 1-3 Alkyl or -(CH2) n -NR a R b It could be; wherein alkyl is optionally —OR a and substituted with one or more substituents independently selected from halo; R d can be H or halo; Each R e and each R f are independently H or C 1-6 It can be alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; a can be 0 or 1; and Each n can independently be 0 or 1.

[0015] In some embodiments, R 5 can be H, —CH 3 , —CH 2 F, —CHF 2 , or —CF 3 .

[0016] In other embodiments, there is provided a compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluorophenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-hydroxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-1-methyl-6-oxo-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-pyridylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isothiochroman-4-yl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(7-fluorotetralin-1-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,5-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(difluoromethylsulfanyl)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(o-tolylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluoro-2-methyl-phenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[(2-pyrazol-1-yl-3-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2-chloro-3-fluoro-phenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(cyclopropylmethoxy)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2,6-difluorophenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-[(dimethylamino)methyl]phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(4-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(3-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxy-6-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-phenyl-2-(2,2,2-trifluoroethylamino)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidylmethyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(2-amino-1-(2,6-difluorophenyl)ethyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoropyrimidin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-hydroxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[1-(5-fluoro-2-pyridyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-2-[1-(5-fluoro-2-pyridyl)propyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-2-[(3-fluoro-5-methoxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-6-hydroxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-bromo-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 6-[[5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 6-[[5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(dimethylamino)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-hydroxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-methoxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(trifluoromethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-2-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-hydroxyphenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-fluorophenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoate; 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoic acid; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-2-chloro-N-methyl-benzamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-[1-([1,2,4]triazolo[4,3-a]pyrimidin-3-yl)ethylamino]ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[methyl-(1-phenyl-4-piperidyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[(1S)-1-(6-methyl-2-pyridyl)ethyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[1-(3-methyl-1H-pyrazol-5-yl)-4-piperidyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[2-(1-methylpyrrol-2-yl)azepan-1-yl]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[4-[(5-methyl-2-pyridyl)amino]-1-piperidyl]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[3-(3-methyl-5-oxo-4H-pyrazol-1-yl)anilino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[2-(hydroxymethyl)tetralin-2-yl]-methyl-amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(aminomethyl)-2-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[(3R)-4-benzylmorpholin-3-yl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-benzyl-4-piperidyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholin-3-yl-1-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(5-aminoindan-2-yl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2H-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-methyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-ethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopropyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopentyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(3-fluoropropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl methanesulfonate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-methoxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanenitrile; Ethyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]carbamate; Ethyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-N-methyl-carbamate; tert-Butyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]carbamate; Methyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanoate; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl N-ethylcarbamate; 5-amino-2-(3,3-difluoropropyl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[ethyl(methyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-[cyclopropyl(methyl)amino]ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]acetamide; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[3-hydroxy-2-(hydroxymethyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-acetamide; 5-amino-2-[(3,3-difluorocyclopentyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethyl-2-methyl-cyclopropyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N-cyclopropyl-N-methyl-acetamide; Methyl 1-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]cyclopentanecarboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(trifluoromethoxy)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2,3,4,5,6-pentadeuteriophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(2,4-difluorophenyl)-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methoxyphenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 4-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl]benzonitrile; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(3-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(5-fluoro-2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylpyrazol-1-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-furyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(5-methyl-2-furyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylthiazol-2-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-methyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[5-amino-3-oxo-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-pyridine-2-carboxylate; 5-amino-8-[2-(hydroxymethyl)-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3-piperidyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-fluorocuban-1-yl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(cuban-1-ylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(3-bicyclo[1.1.1]pentanylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-butyl (R)-2-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)morpholine-4-carboxylate; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; tert-Butyl 4-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-piperidylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl (2S)-2-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]morpholine-4-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-3-piperidyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-4-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl (3S)-3-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]morpholine-4-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-morpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1-methyl-4-piperidyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-3-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3R)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -Amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; t ert-butyl (S)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate; tert-butyl (R)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate; (R)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1,1-dioxothiazol-2-yl)methyl] hmm -3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1,1-dioxothietan-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -Amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,4,5,6-tetrahydropyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(azetidin-1-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-(2-(2-azabicyclo[3.1.0]hexan-2-yl)ethyl)-5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(1-methyl-4-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(3-methyl-1-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholinoethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-((cis)-2,6-dimethylmorpholin-4-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(4,4-difluoro-1-piperidyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-methylpiperazin-1-yl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(8-azabicyclo[3.2.1]octan-8-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 3-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[2-(4-hydroxy-1-piperidyl)-2-oxo-ethyl]-methyl-amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-N-cyclopropyl-cyclohexanecarboxamide; Methyl 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoate; 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoic acid; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[3-(1-piperidyl)propyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(3-(2-oxopyridin-1(2H)-yl)propyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)-N-methylpropanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-morpholino-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(1-piperidyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-ethoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[ethyl(methyl)amino]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-chloro-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidine-7-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-prop-1-ynyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-methoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(Z)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; and 5-Amino-8-(2,6-dimethyl-4-pyridyl)-7-[(E)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one.

[0017] In another embodiment, there is provided a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or excipient.

[0018] In another embodiment, there is provided the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the treatment of a disease or condition mediated by an adenosine receptor.

[0019] In some embodiments, the disease or condition mediated by adenosine receptors is lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, gastric cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma, or other solid tumors.

[0020] Other features, objects, and advantages will be apparent from the description and claims. DETAILED DESCRIPTION OF THE INVENTION

[0021] explanation The compounds of formula (I), formula (II) and formula (III) are useful as adenosine receptor antagonists.

[0022] Formula (I): [ka] or a pharmaceutically acceptable salt thereof is described herein.

[0023] Ring A is: [ka] is.

[0024] Each R 1 and each R 2 independently, halo, C 1-3 Alkyl, -OC 1-3 Alkyl, -CO2R a or -NR 7 R 8 wherein alkyl is optionally -OR a and halo.

[0025] R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, aryl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 3 is optionally halo, cyano, -R a AND -OR a It is substituted with 1 to 3 substituents selected from:

[0026] R 4 is absent or -(CHR c ) i -(NR a ) j -R 5 is.

[0027] R 5 (1)C 3-8 cycloalkyl, aryl, 3-, 4-, 6-, or 7-membered heterocyclyl, or 3-, 4-, 6-, or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl are independently N, O, and S(O)k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced by -C(=O)-; (2) a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced by -C(=O)-; or (3) C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b is.

[0028] R 5 optionally 1 to 4 groups -XR 6 is replaced by .

[0029] Each X is independently a bond, —O—, or —NR a -, -S(O) k -, -(CH2) m - or -C(O)-.

[0030] Each R 6 are independently H, halo, -OR a , C 1-6 Alkyl, C 3-8 Cycloalkyl, heterocyclyl, heteroaryl, aryl, -CO2R a , -C(O)NR a R b , -(CH2) n -NR a R bor cyano; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 3-8 one or two ring atoms of the cycloalkyl, heterocyclyl, heteroaryl, or aryl are independently optionally substituted with —C(═O)—; and wherein each of the alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl is optionally substituted with —R a , -OR a , -(CH2) n -NR a R b and halo.

[0031] Each R 7 and each R 8 are independently a is.

[0032] or R 7 and R 8 together with the atoms to which they are attached, possibly -OR a and halo, forming a 3- to 8-membered heterocyclyl substituted with one or more substituents independently selected from:

[0033] Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 cycloalkylalkyl; where each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo.

[0034] Each R c are independently H, halo, and C 1-3 Alkyl or -(CH2) n -NR a R b wherein alkyl is optionally -ORa and halo.

[0035] a is 0 or 1.

[0036] i is 0, 1, 2 or 3.

[0037] j is 0 or 1.

[0038] Each k is independently 0, 1, or 2.

[0039] Each m is independently 1 or 2.

[0040] Each n is independently 0 or 1.

[0041] In some embodiments, R 5 is C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b is.

[0042] In some embodiments, R 5 is aryl, 6-membered heterocyclyl or 6-membered heteroaryl.

[0043] In some embodiments, R 5 is a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system.

[0044] In some embodiments, R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a is.

[0045] In some embodiments, i is 1 and R c is H or C 1-3 alkyl; or i is 2 and each R c is H.

[0046] In some embodiments, R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a i is 1 or 2; and each R c are independently H or C 1-3 It is alkyl.

[0047] In some embodiments, R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR awhere i is 1 or 2; and each R c are independently H or C 1-3 alkyl; and R 5 is C 3-8 cycloalkyl, aryl, 3-, 4-, 6-, or 7-membered heterocyclyl, or 3-, 4-, 6-, or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced by -C(=O)-.

[0048] In some embodiments, R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a where i is 1 or 2; and each R c are independently H or C 1-3 alkyl; and R 5 is a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced by -C(=O)-.

[0049] In some embodiments, R 5 is a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; wherein heterocyclyl and heteroaryl are independently N, O, and S(O)k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced by -C(=O)-.

[0050] In some embodiments, R 5 is a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced with -C(=O)-; i is 0; and j is 0.

[0051] In some embodiments, R 5 is a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced with -C(=O)-; i is 1 or 2; and j is 0.

[0052] In some embodiments, j is 1.

[0053] In some embodiments, j is 1; and i is 1 or 2.

[0054] In some embodiments, j is 1; i is 1 or 2; and R 5 is C 3-8 cycloalkyl, aryl, 3-, 4-, 6-, or 7-membered heterocyclyl, or 3-, 4-, 6-, or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5wherein one or two ring atoms are optionally replaced by -C(=O)-.

[0055] In some embodiments, j is 1; i is 1 or 2; and R 5 is a polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; wherein heterocyclyl and heteroaryl are independently N, O, and S(O) k and 1 to 4 heteroatoms independently selected from: 5 wherein one or two ring atoms are optionally replaced by -C(=O)-.

[0056] In some embodiments, R 5 is C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b is.

[0057] In some embodiments, R 5 is C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b and j is 0.

[0058] Formula (II): [ka] or a pharmaceutically acceptable salt thereof is described herein.

[0059] Each R 1 and each R 2 independently, halo, C 1-3 Alkyl or -OC 1-3 alkyl; wherein the alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Ring B is C 3-8 cycloalkyl, aryl, 6- or 7-membered heterocyclyl, or 6- or 7-membered heteroaryl; wherein the heterocyclyl and heteroaryl independently contain 1 to 4 heteroatoms independently selected from N and O.

[0060] Each R 9 independently, halo, -R a -OR a is.

[0061] Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 cycloalkylalkyl; where each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo.

[0062] L is -(CHR c ) e -It is.

[0063] Each R c are independently H, halo, and C 1-3 Alkyl or -(CH2) n -NR a R b wherein alkyl is optionally -OR a and halo.

[0064] R d is H or halo.

[0065] a is 0 or 1.

[0066] b is 0, 1 or 2.

[0067] d is 0, 1, 2, 3 or 4.

[0068] e is 1 or 2.

[0069] n is 0 or 1.

[0070] The compounds of formula (II) are included within the broad formula (I).

[0071] In certain embodiments, Ring B is phenyl, pyridyl, 2-oxo-pyridyl, pyrimidyl, or pyridazinyl.

[0072] In certain embodiments, Ring B is phenyl.

[0073] In some embodiments, e is 1; and Ring B is phenyl.

[0074] In some embodiments, e is 2; and Ring B is phenyl.

[0075] In some embodiments, Ring B is phenyl, pyridyl, 2-oxo-pyridyl, pyrimidyl, or pyridazinyl; and each R 9 independently, C 1-3 alkyl, wherein the alkyl is optionally substituted with one or more substituents independently selected from —OH and halo.

[0076] In some embodiments, e is 2; and Ring B is phenyl, pyridyl, 2-oxo-pyridyl, pyrimidyl, or pyridazinyl.

[0077] Formula (III): [ka] or a pharmaceutically acceptable salt thereof is described herein.

[0078] Each R 1 and each R 2 independently, halo, C 1-3 Alkyl, -OC 1-3 Alkyl, -CO2R a or -NR 7 R 8 wherein alkyl is optionally -OR a and halo.

[0079] R 4 Ha-(CHR c )2-R 5 is.

[0080] R 5 H, halo, C 1-3 Alkyl, -OR e , -COR e , -COOR e , -OS(O)2R e , -OCO-NR e R f or -CO-NR e R f wherein the alkyl is optionally substituted with one or more substituents independently selected from —OH and halo.

[0081] Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 cycloalkylalkyl; where each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo.

[0082] Each R care independently H, halo, and C 1-3 Alkyl or -(CH2) n -NR a R b wherein alkyl is optionally -OR a and halo.

[0083] R d is H or halo.

[0084] Each R e and each R f are independently H or C 1-6 alkyl; wherein the alkyl is optionally substituted with one or more substituents independently selected from -OH and halo.

[0085] a is 0 or 1.

[0086] Each n is independently 0 or 1.

[0087] Compounds of formula (III) are included within the broad formula (I).

[0088] In some embodiments, R 5 is H, -CH3, -CH2F, -CHF2, or -CF3.

[0089] The term "halo" refers to fluoro, chloro, bromo and iodo.

[0090] The term "alkyl," if specified, refers to a fully saturated straight-chain or branched aliphatic group having the specified number of carbon atoms (e.g., C 1-10 (Alkyl refers to alkyl groups having 1 to 10 carbons.) Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. Unless a size is specified, "alkyl" refers to groups having 1 to 10 carbon atoms.

[0091] The term "alkenyl" refers to an unsaturated, straight-chain or branched aliphatic group containing at least one carbon-carbon double bond and, if specified, having a specific number of carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, 1-propenyl, 2-butenyl, 3-butenyl, 3-methylbut-1-enyl, 1-pentenyl, and 4-hexenyl. Unless a size is specified, "alkenyl" refers to a group having 2 to 10 carbon atoms.

[0092] The term "alkynyl" refers to an unsaturated, straight-chain or branched aliphatic group containing at least one carbon-carbon triple bond and, if specified, having a specific number of carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl, propargyl, and but-2-ynyl. If no size is specified, "alkynyl" refers to a group having 2 to 10 carbon atoms.

[0093] Alkenyl and alkynyl groups can contain more than one unsaturated bond or a mixture of double and triple bonds.

[0094] The term "cycloalkyl" refers to a saturated or unsaturated aliphatic ring containing 3 to 10 carbon ring atoms, wherein one or more carbon ring atoms may optionally be replaced with -C(=O)-. Cycloalkyl groups can include fused and / or bridged rings, where the fused or bridged rings are cycloalkyl. Suitable examples of "cycloalkyl" include, but are not limited to, cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, cyclohexenyl, cyclohexynyl, cycloheptyl, norbornyl, 4-oxocyclohex-1-yl, and 3-oxocyclohept-5-en-1-yl.

[0095] The term "heterocyclyl" refers to a saturated or unsaturated heterocyclic ring containing 3 to 10 ring atoms, 1 to 4 ring atoms being independently N, O, or S, and in which one or more carbon ring atoms may optionally be replaced by -C(=O)-. Ring nitrogen or ring sulfur atoms may optionally be oxidized, including, for example, -N(O)-, -S(O)-, or -S(O)2-. Ring nitrogen atoms of a heterocyclyl group may optionally be quaternized, for example, -N + (CH3)2-. Heterocyclyl groups can contain fused and / or bridged rings, where the fused or bridged ring is a cycloalkyl or heterocyclyl group. Examples of heterocyclic groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, morpholinyl, thiomorpholinyl, dihydropyranyl, dihydropyridinyl, tetrahydropyranyl, octahydroquinolinyl, octahydroindolizinyl, and decahydroquinolinyl.

[0096] The term "aryl" refers to a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group containing 6 to 14 ring atoms. Aryl can contain fused rings, including an aryl ring fused to a cycloalkyl, heterocyclyl, or aryl ring. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, tetrahydronaphthyl, and dihydro-1H-indenyl.

[0097] The term "heteroaryl" refers to a monocyclic, bicyclic, or tricyclic aromatic group containing 6 to 14 ring atoms, wherein 1 to 4 ring atoms are independently N, O, or S. The ring nitrogen or sulfur atoms may be optionally oxidized, including, for example, -N(O)-, -S(O)-, or -S(O)-. Heteroaryl groups can contain fused and / or bridged rings, wherein the fused or bridged rings are cycloalkyl, heterocyclyl, aryl, or heteroaryl groups. Examples of heteroaryl groups include, but are not limited to, pyrrolyl, furanyl, pyridyl, imidazolyl, oxazolyl, thiazolyl, pyrimidinyl, 5,6,7,8-tetrahydroquinolinyl, benzofuranyl, pyrrolopyridinyl, pyrrolopyrimidinyl, triazinyl, and tetrazolyl.

[0098] The term "polycyclic ring system" refers to a cycloalkyl, heterocyclyl, aryl, or heteroaryl group that contains two or more fused and / or bridged rings.

[0099] Some compounds described herein can exist in more than one stereoisomeric form. Recitation of such compounds is intended to include all geometric and optical isomers, including racemates, unless otherwise specified.

[0100] Some compounds described herein may exhibit tautomerism. A structural depiction herein typically represents only one of the possible tautomeric forms of such a compound. It should be understood that a structural depiction is intended to encompass all tautomeric forms of such a compound.

[0101] The term "pharmaceutically acceptable salt" refers to a salt of a compound of Formula (I) that retains the biological activity of the free compound and can be administered to humans and / or animals as a pharmaceutical. The desired salt of a basic functional group of a compound can be prepared by treating the compound with an acid. Some examples of suitable inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Some examples of suitable organic acids include, but are not limited to, formic acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, sulfonic acid, and salicylic acid. The desired salt of an acidic functional group of a compound can be prepared by treating the compound with a base. Some examples of suitable inorganic salts of acid compounds include, but are not limited to, alkali metal and alkaline earth salts, such as sodium salts, potassium salts, magnesium salts, and calcium salts; ammonium salts; and aluminum salts. Some examples of suitable organic salts of acid compounds include, but are not limited to, procaine, dibenzylamine, N-ethylpiperidine, N,N'-dibenzylethylenediamine, and triethylamine salts.

[0102] The compounds of formula (I) may include the specified atoms in any of their isotopic forms. In this regard, particular embodiments of the invention include those in which (a) the compounds of formula (I) are not isotopically enriched or labeled with respect to any atom of the compound; and (b) the compounds of formula (I) are isotopically enriched or labeled with respect to one or more atoms of the compound.

[0103] In this formula, [ka] The use of indicates the point of attachment between different groups.

[0104] Exemplary compounds of formula (I) or pharmaceutically acceptable salts thereof include: 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluorophenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-hydroxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-1-methyl-6-oxo-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-pyridylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isothiochroman-4-yl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(7-fluorotetralin-1-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,5-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(difluoromethylsulfanyl)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(o-tolylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluoro-2-methyl-phenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[(2-pyrazol-1-yl-3-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2-chloro-3-fluoro-phenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(cyclopropylmethoxy)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2,6-difluorophenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-[(dimethylamino)methyl]phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(4-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(3-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxy-6-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-phenyl-2-(2,2,2-trifluoroethylamino)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidylmethyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(2-amino-1-(2,6-difluorophenyl)ethyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoropyrimidin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-hydroxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[1-(5-fluoro-2-pyridyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-2-[1-(5-fluoro-2-pyridyl)propyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-2-[(3-fluoro-5-methoxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-6-hydroxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-bromo-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 6-[[5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 6-[[5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(dimethylamino)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-hydroxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-methoxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(trifluoromethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-2-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-hydroxyphenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-fluorophenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoate; 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoic acid; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-2-chloro-N-methyl-benzamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-[1-([1,2,4]triazolo[4,3-a]pyrimidin-3-yl)ethylamino]ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[methyl-(1-phenyl-4-piperidyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[(1S)-1-(6-methyl-2-pyridyl)ethyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[1-(3-methyl-1H-pyrazol-5-yl)-4-piperidyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[2-(1-methylpyrrol-2-yl)azepan-1-yl]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[4-[(5-methyl-2-pyridyl)amino]-1-piperidyl]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[3-(3-methyl-5-oxo-4H-pyrazol-1-yl)anilino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[2-(hydroxymethyl)tetralin-2-yl]-methyl-amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(aminomethyl)-2-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[(3R)-4-benzylmorpholin-3-yl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-benzyl-4-piperidyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholin-3-yl-1-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(5-aminoindan-2-yl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2H-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-methyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-ethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopropyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopentyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(3-fluoropropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl methanesulfonate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-methoxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanenitrile; Ethyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]carbamate; Ethyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-N-methyl-carbamate; tert-Butyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]carbamate; Methyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanoate; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl N-ethylcarbamate; 5-amino-2-(3,3-difluoropropyl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[ethyl(methyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-[cyclopropyl(methyl)amino]ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]acetamide; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[3-hydroxy-2-(hydroxymethyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-acetamide; 5-amino-2-[(3,3-difluorocyclopentyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethyl-2-methyl-cyclopropyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N-cyclopropyl-N-methyl-acetamide; Methyl 1-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]cyclopentanecarboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(trifluoromethoxy)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2,3,4,5,6-pentadeuteriophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(2,4-difluorophenyl)-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methoxyphenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 4-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl]benzonitrile; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(3-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(5-fluoro-2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylpyrazol-1-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-furyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(5-methyl-2-furyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylthiazol-2-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-methyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[5-amino-3-oxo-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-pyridine-2-carboxylate; 5-amino-8-[2-(hydroxymethyl)-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3-piperidyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-fluorocuban-1-yl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(cuban-1-ylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(3-bicyclo[1.1.1]pentanylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-butyl (R)-2-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)morpholine-4-carboxylate; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; tert-Butyl 4-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-piperidylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl (2S)-2-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]morpholine-4-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-3-piperidyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-4-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl (3S)-3-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]morpholine-4-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-morpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1-methyl-4-piperidyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-3-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3R)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -Amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; t ert-butyl (S)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate; tert-butyl (R)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate; (R)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1,1-dioxothiazol-2-yl)methyl] hmm -3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1,1-dioxothietan-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5-Amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,4,5,6-tetrahydropyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(azetidin-1-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-(2-(2-azabicyclo[3.1.0]hexan-2-yl)ethyl)-5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(1-methyl-4-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(3-methyl-1-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholinoethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-((cis)-2,6-dimethylmorpholin-4-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(4,4-difluoro-1-piperidyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-methylpiperazin-1-yl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(8-azabicyclo[3.2.1]octan-8-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 3-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[2-(4-hydroxy-1-piperidyl)-2-oxo-ethyl]-methyl-amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-N-cyclopropyl-cyclohexanecarboxamide; Methyl 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoate; 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoic acid; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[3-(1-piperidyl)propyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(3-(2-oxopyridin-1(2H)-yl)propyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)-N-methylpropanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-morpholino-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(1-piperidyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-ethoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[ethyl(methyl)amino]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-chloro-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidine-7-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-prop-1-ynyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-methoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(Z)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; and 5-Amino-8-(2,6-dimethyl-4-pyridyl)-7-[(E)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one.

[0105] The compounds of formula (I) can be adenosine receptor antagonists, i.e., antagonists of one or more of the A1R, A2aR, A2bR, and A3R. The term "adenosine receptor antagonist" refers to a compound, e.g., a compound of formula (I), that binds to and antagonizes the activity of an adenosine receptor.

[0106] In some cases, the compound of formula (I) is a selective adenosine receptor antagonist. The term "selective" refers to the property of the compound of formula (I) to be an adenosine receptor antagonist but to be substantially inactive against other biological targets. As used herein, the term "substantially inactive" refers to a compound that (i) has significantly lower affinity for a given receptor compared to its affinity for adenosine receptors; (ii) does not exhibit substantial agonist or antagonist activity against a given receptor; or (i) and (ii) both.

[0107] The term "selective adenosine receptor antagonist" refers to a compound that exhibits a binding affinity for one or more adenosine receptor subtypes that is at least 100-fold greater, at least 1,000-fold greater, or at least 10,000-fold greater than its affinity for a given receptor. i The value ratio (one receptor:adenosine receptor) can be at least 100, at least 1,000, or at least 10,000.

[0108] In particular, selective adenosine receptor antagonists may be substantially inactive at other G protein-coupled receptors, such as the cannabinoid receptors designated CB-1 and CB-2.

[0109] The compounds of formula (I) have a binding affinity K for A2aR of, for example, 100 nM or less, 10 nM or less, or 1 nM or less. i may have:

[0110] The compounds of formula (I) have a binding affinity K for A2bR of, for example, 100 nM or less, 10 nM or less, or 1 nM or less. i may have:

[0111] The compound of formula (I) has a binding affinity K for CB-1 of, for example, 1,000 nM or more, 10,000 nM or more, or 13,000 nM or more. i may have:

[0112] The compounds of formula (I) may be selective adenosine receptor antagonists for CB-1.

[0113] Compounds of formula (I) may be active as adenosine receptor antagonists but substantially inactive at CB-1.

[0114] The compounds of Formula (I) may also be selective between various adenosine receptor subtypes. In certain embodiments, the compounds of Formula (I) are A2aR selective; A2bR selective; or dual A2aR / A2bR selective.

[0115] An A2aR selective compound exhibits a binding affinity for A2aR that is at least 100-fold stronger, at least 1,000-fold stronger, or at least 10,000-fold stronger than its binding affinity for each of the A1R, A2bR, and A3R.

[0116] An A2bR selective compound has a binding affinity that is at least 100-fold stronger, at least 1,000-fold stronger, or at least 10,000-fold stronger than its binding affinity to each of the A1R, A2aR, and A3R.

[0117] A dual A2aR / A2bR selective compound exhibits a binding affinity for A2aR that is at least 100-fold stronger, at least 1,000-fold stronger, or at least 10,000-fold stronger than its binding affinity for each of the A1R and A3R. A dual A2aR / A2bR selective compound also exhibits a binding affinity for A2bR that is at least 100-fold stronger, at least 1,000-fold stronger, or at least 10,000-fold stronger than its binding affinity for each of the A1R and A3R. Furthermore, for a dual A2aR / A2bR selective compound, the ratio of the binding affinity for A2aR to the binding affinity for A2bR is less than 100.

[0118] In certain embodiments, a pharmaceutical composition is provided comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent, or excipient.

[0119] Compositions of the invention may be in a form suitable for oral use (e.g., as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), topical use (e.g., as creams, ointments, gels, or aqueous or oily solutions or suspensions), administration by inhalation (e.g., as a finely divided powder or liquid aerosol), administration by insufflation (e.g., as a finely divided powder) or parenteral administration (e.g., as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular or intramuscular administration or as a suppository for rectal administration).

[0120] Pharmaceutically acceptable additives suitable for tablet formulations include, for example, inert diluents such as lactose, sodium carbonate, calcium phosphate, or calcium carbonate; granulating and disintegrating agents such as corn starch or alginic acid; binders such as starches; lubricants such as magnesium stearate, stearic acid, or talc; preservatives such as ethyl or propyl p-hydroxybenzoate; and antioxidants such as ascorbic acid. Tablet formulations may be uncoated or coated to modify disintegration in the gastrointestinal tract and subsequent release of the active ingredient or to improve stability and / or appearance, in either case using conventional coating agents and methods well known in the art.

[0121] Compositions for oral use may be in the form of hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, or kaolin, or soft gelatin capsules in which the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin, or olive oil.

[0122] The compound of formula (I) is useful for treating adenosine receptor-mediated diseases or conditions.In some embodiments, the compound of formula (I) or its pharmaceutically acceptable salt is provided for use in treating adenosine receptor-mediated diseases or conditions.In some embodiments, the disease or condition is mediated by A2aR; in other embodiments, A2bR; in still other embodiments, both A2aR and A2bR.

[0123] Some examples of diseases or conditions mediated by adenosine receptors include cancer, including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors; movement disorders, including Parkinson's disease and Huntington's disease; and attention disorders, including attention deficit disorder and attention deficit hyperactivity disorder. Other diseases and conditions mediated by adenosine receptors are known.

[0124] In certain embodiments, there is provided a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of a disease or condition mediated by an adenosine receptor.

[0125] In certain embodiments, there is provided a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of cancer (including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors).

[0126] In certain embodiments, there is provided a compound of Formula (I) or a pharmaceutically acceptable salt thereof, for use in treating a disease or condition mediated by an adenosine receptor, wherein the compound is a CB-1 selective adenosine receptor antagonist.

[0127] In certain embodiments, there is provided a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of cancer (including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, gastric cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors), wherein the compound is a CB-1 selective adenosine receptor antagonist.

[0128] In certain embodiments, methods are provided for treating a disease or condition mediated by an adenosine receptor, comprising administering to a subject in need of such treatment an effective amount of a disease or condition mediated by an adenosine receptor.

[0129] In certain embodiments, methods are provided for treating cancer (including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors), comprising administering to a subject in need of such treatment an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

[0130] In certain embodiments, methods are provided for treating a disease or condition mediated by an adenosine receptor, comprising administering to a subject in need of such treatment an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound is a selective adenosine receptor antagonist for CB-1.

[0131] In certain embodiments, provided is a method for treating cancer (including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors), comprising administering to a subject in need of such treatment an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound is a selective adenosine receptor antagonist for CB-1.

[0132] In certain embodiments, there is provided a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for use in the treatment of a disease or condition mediated by an adenosine receptor.

[0133] In certain embodiments, there is provided a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for use in the treatment of cancer (including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors).

[0134] In certain embodiments, provided is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for use in the treatment of a disease or condition mediated by an adenosine receptor, wherein the compound is a selective adenosine receptor antagonist for CB-1.

[0135] In certain embodiments, provided is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound is a selective adenosine receptor antagonist for CB-1, for use in the manufacture of a medicament for use in the treatment of cancer (including lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, gastric cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma or other solid tumors).

[0136] Compounds of formula (I) may be prepared according to the following general scheme.

[0137] Schemes 1a and 1b describe the preparation of intermediate 6-substituted-4-hydrazino-2-aminopyrimidine compounds of formula (IV). [ka] [ka]

[0138] Scheme 2 describes the conversion of a compound of formula (IV) to an intermediate 7-substituted-5-amino-8-bromo-[1,2,4]triazolo[4,3-c]pyrimidin-3-one compound of formula (V). Briefly, a compound of formula (IV) is treated with triphosgene to close the triazolone ring, followed by (CH)PhN + Br3 - Brominate with. Scheme 2 [ka]

[0139] Scheme 3a describes the conversion of a compound of formula (V) to a compound of formula (I). 4 Alkylation of a compound of formula (V) with may be carried out using a variety of methods, such as the Mitsunobu reaction; alcohol mesylation followed by an alkylation reaction; alcohol tosylation followed by an alkylation reaction; or alcohol chlorination followed by an alkylation reaction. [ka]

[0140] Alternatively, R 4 Compounds such as -Br may be used to directly alkylate compounds of formula (V).

[0141] In some cases, R 4 may be further modified after alkylation of the compound of formula (V).

[0142] Scheme 3b describes an alternative route for the conversion of compounds of formula (V) to compounds of formula (I). In Scheme 3b, [Pg] represents a reagent suitable for introducing the protecting group shown as Pg. R 4 Alkylation of a compound of formula (Va) with may be carried out using a variety of methods, for example, Mitsunobu reaction; alcohol mesylation followed by alkylation reaction; alcohol tosylation followed by alkylation reaction; alcohol chlorination followed by alkylation reaction. [ka]

[0143] Alternatively, R 4 Compounds such as -Br may be used to directly alkylate compounds of formula (Va).

[0144] In some cases, R 4 may be further modified after alkylation of the compound of formula (V).

[0145] Optionally, the compound of formula (I) may be further modified, for example, to form a different compound of formula (I). [Example]

[0146] general technology LCMS method A Instrument: Agilent Technologies 1200 Series, Agilent LC / MSD SL. Column: Waters XBridge C8 3.5 μm, 4.6 × 50 mm. Gradient [time (min) / % Solvent B]: 0.0 / 5, 8.0 / 100, 8.1 / 100, 8.5 / 5, 10.0 / 5. (Solvent A = 1 mL TFA in 1000 mL Milli-Q water; Solvent B = 1 mL TFA in 1000 mL MeCN); Injection volume 1 μL (variable); UV detection 220-400 nm; Column temperature 25 °C; 2.0 mL / min. For UV-inactive compounds, an ELSD detector (Polymer Laboratories PL-ELS 2100 ICE) is connected to the instrument.

[0147] LCMS method B Instrument: Agilent Technologies 1200 Series, Agilent LC / MSD SL; Column: Atlantis dC18 5 μm, 4.6 × 50 mm. Gradient [time (min) / % Solvent B]: 0.0 / 10, 2.5 / 95, 4.5 / 95, 4.6 / 10, 6.0 / 10. (Solvent A = 1 mL TFA in 1000 mL Milli-Q water; Solvent B = 1 mL TFA in 1000 mL MeCN); Injection volume 1 μL (variable); UV detection 210–400 nm; Column temperature 25 °C; 1.5 mL / min.

[0148] LCMS method C Instrument: Agilent Technologies 1200 Series, Agilent 6130 Quadrupole LC / MS, Column: Zorbax C18 5 μm, 4.6 × 50 mm. Gradient [time (min) / % Solvent B]: 0.0 / 10, 2.5 / 95, 4.5 / 95, 4.6 / 10, 6.0 / 10. (Solvent A = 1 mL formic acid in 1000 mL Milli-Q water; Solvent B = MeCN); Injection volume 1 μL (variable); UV detection 210–400 nm; Column temperature 25 °C; 1.5 mL / min.

[0149] LCMS method D Instrument: Agilent Technologies 1200 Series, Agilent 6130 Quadrupole LC / MS, Column: Zorbax C18 5 μm, 4.6 × 50 mm. Gradient [time (min) / % Solvent B]: 0.0 / 10, 4.0 / 95, 5.0 / 95, 5.5 / 10, 7.0 / 10. (Solvent A = 770.08 mg ammonium acetate in 1000 mL of Milli-Q water; Solvent B = MeCN); Injection volume 1 μL (variable); UV detection 210–400 nm; Column temperature 25 °C; 1.2 mL / min.

[0150] LCMS method E Instrument: Agilent Technologies 1200 Series, Agilent 6130 Quadrupole LC / MS; Column: XBridge C8 3.5 μm, 4.6 × 50 mm; Gradient [Time (min) / Solvent B (%)]: 0.0 / 5, 8.0 / 100, 8.1 / 100, 8.5 / 5, 10.0 / 5 (Solvent A = 790.06 mg ammonium bicarbonate added to 1000 mL Milli-Q water; Solvent B = MeCN); Injection volume 1 μL (variable); UV detection 210–400 nm; Column temperature 25°C; 1.0 mL / min.

[0151] LCMS method F Instrument: Agilent 1100 Series LC / MSD. Column: Zorbax SB-C18 1.8 μm 4.6 × 15 mm. Gradient [time (min) / solvent A (%)]: 0.0 / 100; 0.01 / 100; 1.5 / 0; 1.8 / 0; 1.81 / 100. (Solvent A = H2O; Solvent B = MeCN, both modified with 0.1% formic acid). Injection volume 1 μL (variable). UV detection 215 nm. Column temperature 60 °C.

[0152] Preparative HPLC method A Instrument: Agilent Technologies 1260 Infinity II Series LC. Solvent: A - 0.1% TFA in H2O, B - MeOH. Column: YMC Actus Triart C18 (30 mm x 250 mm) 5 μm. Gradient [time (min) / solvent B (%)]: 0.0 / 10, 20 / 95, 23 / 95, 24 / 10, 26 / 10.

[0153] Preparative HPLC method B Instrument: Agilent Technologies 1260 Infinity II Series LC. Solvents: A - 0.1% HCOOH in H2O, B - MeCN. Column: YMC Actus Triart C8 (20 mm x 250 mm) 5 μm. Gradient [time (min) / solvent B (%)]: 0.0 / 10, 20 / 95, 23 / 95, 24 / 10, 26 / 10.

[0154] Preparative HPLC method C Instrument: Agilent Technologies 1260 Infinity II Series LC. Solvent: A - 10 mM NH4HCO3B-MeOH or MeCN in H2O. Column: XBridge C8 (19 mm x 150 mm), 5 μm or YMC Actus Triart C18 (30 mm x 250 mm), 5 μm. Gradient [time (min) / solvent B (%)]: 0.0 / 10, 15 / 95, 18 / 95, 19 / 10, 21 / 10.

[0155] Preparative HPLC method D Apparatus: Agilent Technologies 1260 Infinity II Series LC. Mobile phase: Hexane B:IPA (60:40). Column: YMC silica (19 x 150) mm, 5 μm. Flow rate: 15 mL / min. Note: The gradient may vary from sample to sample based on sample separation and polarity.

[0156] Preparative HPLC method E Instrument: Agilent Technologies 1260 Infinity II Series LC. Solvent: A - H2O, B - MeOH or MeCN. Column: Waters Sunfire C18 OBD Prep Column, 100Å, 5 μm, 19 mm x 100 mm. Gradient [time (min) / solvent B (%)]: 0.0 / 10, 20 / 95, 23 / 95, 24 / 10, 26 / 10.

[0157] MD automatic preparative separation method A Instrument: Agilent Technologies 1260 Infinity II Series LC / 6125 Quadrupole MSD. Solvent: A - 0.1% TFA in H2O, B - MeOH. Column: X Bridge C8 (19 mm x 150 mm), 5 μm. Gradient: [time (min) / solvent B (%)]: 0.0 / 10, 15 / 95, 18 / 95, 19 / 10, 21 / 10.

[0158] Chiral SFC Method A Equipment: SFC Investigator-Waters. Solvent: A - CO2, B - MeOH. Column: 20 mM ammonia 5 μm in LUX C2 (cellulose) (250 × 4.6) mm. Isocratic 40%. Exhaust pressure: 100 bar. Column temperature: 25 °C; 1.6 mL / min.

[0159] Chiral SFC Method B Apparatus: SFC Investigator-Waters. Solvent: A-CO2, Bn-Hexane:EtOH: 0.1% DEA in 70:30. Column: Chiralcel C4 (cellulose) (250 x 4.6) mm, 5 μm. Exhaust pressure: 100 bar. Column temperature: 25°C; 1.0 mL / min.

[0160] Chiral SFC Method C Apparatus: SFC Investigator-Waters. Solvents: A - CO2, B - 20 mM ammonia in MeOH. Column: Lux A1 (amylose); (250 x 4.6) mm, 5 μm. 30% isocratic. Exhaust pressure: 100 bar. Column temperature: 35 °C; 3.0 mL / min.

[0161] Chiral SFC Method D Apparatus: SFC Investigator-Waters. Solvents: A - CO2, B - 20 mM ammonia in MeOH. Column: Chiralcel ODH (cellulose); (250 x 4.6) mm, 5 μm. Isocratic 40%. Exhaust pressure: 100 bar. Column temperature: 35 °C; 4.0 mL / min.

[0162] Chiral SFC Method E Apparatus: SFC Investigator-Waters. Solvents: A - CO2, B - 20 mM ammonia in MeOH. Column: Lux A1 (amylose); (250 x 4.6) mm, 5 μm. 30% isocratic. Exhaust pressure: 100 bar. Column temperature: 35 °C; 3.0 mL / min.

[0163] Synthetic route for intermediates Synthetic Routes 1-10 used to prepare the intermediates used in the synthesis of compounds of formula (I) are set out below. Details of Synthetic Routes 1-10 are examples of techniques used in the synthesis of other intermediates, as detailed in Table 2 below.

[0164] Synthetic Route 1: Method for Producing Intermediate 1 Intermediate 1, 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one [ka] Step 1: This reaction was carried out in two 250 g batches. To a degassed suspension of phenylboronic acid (250 g, 2.05 mol), 4,6-dichloro-2-aminopyrimidine (672 g, 4.10 mol), and K2CO3 (848 g, 6.15 mol) in CH3CN (15 L) and HO (2 L) was added Pd(PPh3)4 (118 g, 0.10 mol) at room temperature, and the resulting reaction mixture was heated at 90 °C for 6 h. The reaction mixture was concentrated under reduced pressure. The resulting residue was vigorously stirred with HO (4 L) and DCM (10 L), and the insoluble solid was filtered off using a Buchner funnel and rinsed with DCM (3 L). The filtrate was poured into a separatory funnel, and the organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by flash chromatography using 230-400 silica mesh, eluting with 0-15% EtOAc in petroleum ether to give 4-chloro-6-phenylpyrimidin-2-amine (350 g, 41%) as an off-white solid. LCMS (Method A): m / z 206 (M+H) + (ES + ), 2.53 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.05 - 8.03 (m, 2H), 7.52 - 7.47 (m, 3H), 7.21 (s, 1H). No exchangeable -NH2 protons were observed.

[0165] Step 2: To a stirred suspension of 4-chloro-6-phenylpyrimidin-2-amine (350 g, 1.70 mol) in EtOH (4.0 L) was added hydrazine hydrate (255 g, 5.1 mol), and the mixture was heated at 90° C. for 15 h. The reaction was concentrated under reduced pressure. The resulting residue was triturated with diethyl ether (1 L) and 10% sodium bicarbonate solution (1 L). The resulting solid was collected by filtration through a Buchner funnel, rinsed with diethyl ether (200 mL), and dried under reduced pressure to give 4-hydrazinyl-6-phenylpyrimidin-2-amine (250 g, 73%) as an off-white solid. LCMS (Method C): m / z 202 (M+H) + (ES +), 0.69 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.94 - 7.91 (m, 2H), 7.84 (s, 1H), 7.48 - 7.42 (m, 3H), 6.47 (s, 1H), 6.00 (s, 2H), 4.25 (s, 2H)

[0166] Step 3: A solution of 4-hydrazinyl-6-phenylpyrimidin-2-amine (250 g, 1.24 mol) in dry THF (3.0 L) was cooled to -30 °C under N2, and triphosgene (735 g, 2.48 mol) was added portionwise, and the mixture was stirred at the same temperature for 45 min. The reaction was carefully quenched with ice-cold water (10 L) with vigorous stirring. Once effervescence had ceased, the reaction was concentrated under reduced pressure. The resulting solid was collected by filtration through a Buchner funnel, rinsed with water (1 L), and dried under reduced pressure to give 5-amino-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (200 g, 70%) as a yellow solid. LCMS (Method C): m / z 228 (M+H) + (ES + ), 1.64 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 12.46 (s, 1H), 8.05 - 7.98 (m, 3H), 7.65 (s, 1H), 7.50 - 7.44 (m, 3H), 6.93 (s, 1H)

[0167] Step 4: To a suspension of 5-amino-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (200 g, 0.88 mol) in DCM / MeOH 1:1 (2 L) under N atmosphere was added CaCO (88 g, 0.88 mol), followed by (CH)PhN + Br3 -(331 g, 0.88 mol) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered through a Buchner funnel, rinsed with a small amount of MeOH / DCM (1:1), and dried under reduced pressure to give intermediate 1, 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (160 g, 59%) as a light brown solid. Data for the title compound are in Table 2.

[0168] Synthetic Route 2: Method for preparing intermediate 7 Intermediate 7: 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one [ka] Step 1: To a suspension of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (16.2 g, 53 mmol) in THF (200 mL) was added TEA (19 mL, 136.3 mmol) at 0 °C, followed by the dropwise addition of (2-(chloromethoxy)ethyl)trimethylsilane (11.3 g, 67.8 mmol). The reaction was stirred at 0 °C for 1 h and then partitioned between EtOAc (250 mL) and HO (200 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 100 g silica snap eluted with a gradient of 0 to 30% EtOAc in hexanes to give 5-amino-8-bromo-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (12 g, 52%) as an off-white solid. Data for the title compound are in Table 2.

[0169] Step 2: To a degassed suspension of 5-amino-8-bromo-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (11 g, 25 mmol), 2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (6.5 g, 28 mmol), and K2CO3 (8.6 g, 62.5 mmol) in 1,4-dioxane (150 mL) and HO (30 mL) was added Pd(PPh3)4 (1.44 g, 1.25 mmol) at room temperature, and the reaction mixture was heated at 120 °C for 5 h. The reaction mixture was partitioned between EtOAc (300 mL) and water (200 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 100 g silica snap eluting with a gradient of 0 to 80% EtOAc in hexanes to give 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (7.5 g, 64%) as a yellow solid. LCMS (Method B): m / z 462 (M+H) + (ES + ), 2.55 minutes, UV active 1 H NMR: (400 MHz, DMSO-d6) δ: 7.30 - 7.26 (m, 5H), 6.82 (s, 2H), 5.13 (s, 2H), 3.63 (t, J=7.4 Hz, 2H), 2.29 (s, 6H), 0.88 (t, J=7.4 Hz, 2H), 0.06 (s, 9H). No exchangeable -NH2 protons were observed.

[0170] Step 3: 5-Amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (7 g, 15 mmol) was dissolved in TFA (40 mL) and stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and dried under high vacuum. The resulting residue was dissolved in EtOH (30 mL), aqueous NH4OH (50 mL) was carefully added, and the reaction mixture was heated at 60°C for 2 hours. The solid was collected by filtration through a Buchner funnel, washed with water (10 mL) and EtOH (10 mol), and dried under reduced pressure to give 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (4.5 g, 89%) as a yellow solid. Data for the title compound are in Table 2.

[0171] Synthetic Route 3: Method for preparing intermediate 11 Intermediate 11: 6-(bromomethyl)-3-fluoro-2-methoxypyridine [ka] To a stirring solution of 3-fluoro-2-methoxy-6-methylpyridine (500 mg, 3.54 mmol) in CCl (10 mL) at 0 °C was added N-bromosuccinamide (700 mg, 3.89 mmol) and AIBN (57 mg, 0.35 mmol). The reaction mixture was heated at 80 °C for 16 h. The reaction mixture was partitioned between DCM (20 mL) and HO (20 mL), and the organic layer was separated and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap column, eluting with petroleum ether to give 6-(bromomethyl)-3-fluoro-2-methoxypyridine (720 mg, 89%) as a pale yellow gum. Data for the title compound are in Table 2.

[0172] Synthetic Route 4: Method for preparing intermediate 38 Intermediate 38: N,N-ditert-butoxycarbonyl(6-(bromomethyl)-3-fluoropyridin-2-yl)-amine [ka] Step 1: To a stirring solution of 3-fluoro-6-methylpyridin-2-amine (100 mg, 0.79 mmol) in DCM (10 mL) was added TEA (240 mg, 2.37 mmol), DMAP (9 mg, 0.08 mmol), and Boc-anhydride (432 mg, 1.98 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was partitioned between DCM (20 mL) and water (20 mL), and the organic layer was separated and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap column eluting with a gradient of 0 to 10% EtOAc in petroleum ether to give N,N-di-tert-butoxycarbonyl(3-fluoro-6-methylpyridin-2-yl)amine as a white liquid. LCMS (Method B): m / z 327 (M+H) + (ES + ), 2.82 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.79 - 7.73 (m, 1H), 7.38 - 7.34 (m, 1H), 2.44 (s, 3H), 1.38 (s, 18H)

[0173] Step 2: To a stirring solution of N,N-di-tert-butoxycarbonyl(3-fluoro-6-methylpyridin-2-yl)amine (160 mg, 0.49 mmol) in CCl4 (10 mL) was added N-bromosuccinamide (174 mg, 0.98 mmol) and AIBN (16 mg, 0.10 mmol). The reaction mixture was heated at 80°C for 16 hours. The reaction mixture was partitioned between DCM (20 mL) and water (20 mL), and the organic layer was separated and concentrated under reduced pressure to give N,N-di-tert-butoxycarbonyl(6-(bromomethyl)-3-fluoropyridin-2-yl)-amine (crude) as a brown gummy solid, which was used in the next step without purification. Data for the title compound are in Table 2.

[0174] Synthetic Route 5: Method for preparing intermediate 41 Intermediate 41: 5-amino-8-bromo-7-(4-fluorophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one [ka] Step 1: To a stirring suspension of 4,6-dichloropyrimidin-2-amine (400 g, 2.43 mol) in EtOH (5 L) was added hydrazine hydrate (365 g, 7.31 mol), and the mixture was heated at 90° C. for 15 h. The reaction was concentrated under reduced pressure. The resulting residue was triturated with diethyl ether (1 L) and 10% sodium bicarbonate solution (1 L). The resulting solid was collected by filtration through a Buchner funnel, rinsed with diethyl ether (200 mL), and dried under reduced pressure to give 4-chloro-6-hydrazinylpyrimidin-2-amine (300 g, 77%) as an off-white solid. LCMS (Method C): m / z 160 (M+H) + (ES + ), 0.37 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.10 (s, 1H), 6.36 (s, 2H), 5.97 (s, 1H), 4.26 (s, 2H)

[0175] Step 2: To a degassed suspension of 4-chloro-6-hydrazinylpyrimidin-2-amine (300 g, 1.87 mol), 4-fluorophenylboronic acid (313 g, 2.24 mol), and K2CO3 (774 g, 5.61 mol) in 1,4-dioxane (6 L) and HO (1 L) was added Pd(PPh3)4 (107 g, 0.093 mol) at room temperature, and the resulting reaction mixture was heated at 110 °C for 15 h. The reaction mixture was concentrated under reduced pressure to remove 1,4-dioxane. The resulting residue was vigorously stirred with HO (4 L) to give a solid, which was filtered through a Buchner funnel and rinsed with MeOH (1 L). The solid was dried under reduced pressure to give 4-(4-fluorophenyl)-6-hydrazinylpyrimidin-2-amine (200 g, 49%) as a green solid. LCMS (Method C): m / z 220 (M+H) + (ES+ ), 0.76 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.00 - 7.96 (m, 2H), 7.854 (s,1H), 7.29 - 7.24 (m, 2H), 6.45 (s, 1H), 6.01 (s, 2H), 4.24 (s, 2H)

[0176] Step 3: A solution of 4-(4-fluorophenyl)-6-hydrazinylpyrimidin-2-amine (200 g, 0.91 mol) in dry THF (3.0 L) was cooled to -30 °C under N2, and triphosgene (538 g, 1.82 mol) was added portionwise, and the mixture was stirred at the same temperature for 1 h. The reaction was carefully quenched with ice-cold water (10 L) with vigorous stirring. Once effervescence had ceased, the reaction was concentrated under reduced pressure. The resulting solid was collected by filtration through a Buchner funnel, rinsed with water (1 L), and dried under reduced pressure to give 5-amino-7-(4-fluorophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (150 g, 67%) as a yellow solid. LCMS (Method C): m / z 246 (M+H) + (ES + ), 1.77 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 12.43 (s, 1H), 8.19 - 8.01 (m, 2H), 7.95 - 7.52 (m, 2H), 7.50 - 7.27 (m, 2H), 6.92 (s, 1H)

[0177] Step 4: This reaction was carried out in 2 x 75 g batches. To a suspension of 5-amino-7-(4-fluorophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (150 g, 0.66 mol) in 1:1 DCM / MeOH (2 L) was added CaCO (66 g, 0.66 mol) followed by (CH)PhN under a N atmosphere. + Br3 -(250 g, 0.66 mol) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered through a Buchner funnel, rinsed with a small amount of MeOH / DCM (1:1), and dried under reduced pressure to give 5-amino-8-bromo-7-(4-fluorophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (120 g, 60%) as a light brown solid. Data for the title compound are in Table 2.

[0178] Synthetic Route 6: Method for preparing intermediate 42 Intermediate 42: Methyl-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate [ka] A degassed hexane solution of (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (51 mg, 0.33 mmol), 4,4'-di-tert-butyl-2,2'-dipyridyl (41 mg, 0.155 mmol), and bis-pinacolatodiborane (600 mg, 2.48 mmol) was heated at 55 °C for 10 min. Methyl 6-methylpyridine-2-carboxylate (500 mg, 3.1 mmol) was added to the mixture via syringe and heated at 60 °C for 14 h. The reaction was concentrated under reduced pressure to give methyl 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate as a brown gum, which was used crude without purification. Data for the title compound are in Table 2.

[0179] Synthetic Route 7: Typical Preparation of Triazolopyrimidine Analogues via Suzuki Coupling Using SEM Protection Intermediate 45: Methyl 4-(5-amino-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate [ka] Step 1: To a suspension of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (16.2 g, 53 mmol) in THF (200 mL) was added TEA (19 mL, 136.3 mmol) at 0 °C, followed by the dropwise addition of (2-(chloromethoxy)ethyl)trimethylsilane (11.3 g, 67.8 mmol). The reaction was stirred at 0 °C for 1 h and then partitioned between EtOAc (250 mL) and water (200 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 100 g silica snap eluted with a gradient of 0 to 30% EtOAc in hexanes to give 5-amino-8-bromo-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (12 g, 52%) as an off-white solid. LCMS (Method B): m / z 436 (M+H)+ (ES + ), 3.25 minutes, UV active 1 H NMR: (400 MHz, DMSO-d6) δ: 8.56 (s, 2H), 7.62 (d, J=7.1 Hz, 2H), 7.45 (d, J=6.6 Hz, 3H), 5.18 (s, 2H), 3.66 (t, J=8.2 Hz, 2H), 0.91 (t, J=8.2 Hz, 2H), 0.04 (s, 9H)

[0180] Step 2: Prepared in a manner analogous to Route a, Step 2, using Intermediate 34 to give methyl 4-(5-amino-3-oxo-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (6 g, 64%) as a yellow solid. Data for the title compound are in Table 2.

[0181] Step 3: A solution of methyl 4-(5-amino-3-oxo-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (1 g, 1.9 mmol) in TFA (15 mL) was stirred at room temperature for 30 minutes. After completion of the starting material as monitored by TLC, the reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in MeOH (20 mL), DIPEA (1.7 mL, 9.8 mmol) was added, and the resulting reaction mixture was heated at 60° C. for 4 hours. The precipitate was collected by filtration, washed with MeOH (2 x 2 mL), and dried under reduced pressure to give methyl 4-(5-amino-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (0.55 g, 67%) as a yellow solid. Data for the title compound are in Table 2.

[0182] Synthetic Route 8: Typical Preparation of Triazolopyrimidine Analogues Using an SEM Protection Strategy Intermediate 53: 5-amino-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one [ka] Step 1: To a solution of methyl 4-(5-amino-3-oxo-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (3.5 g, 6.90 mmol) in THF (30 mL) was added dropwise lithium triethylborohydride (1 M in THF, 13.8 mL, 13.81 mmol) at 0° C., and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was partitioned between EtOAc (50 mL) and HO (50 mL). The organic layer was separated, washed with brine solution (20 mL), dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was purified by flash column chromatography using silica (230-400) mesh eluting with a 0-3% MeOH in DCM gradient to give 5-amino-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (2.2 g, 66%) as a yellow solid. LCMS (Method C): m / z 479 (M+H) + (ES + ), 1.82 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ : 8.42 - 8.26 (m, 2H), 7.29 - 7.25 (m, 5H), 7.09 (s, 1H), 6.88 (s, 1H), 5.25 (t, J=5.7 Hz, 1H), 5.12 (s, 2H), 4.42 (d, J=5.7 Hz, 2H), 3.65- 3.61 (m, 2H), 2.31 (s, 3H), 0.88 (t, J=8.0 Hz, 2H), 0.01 (s, 9H)

[0183] Step 2: A suspension of 5-amino-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-2-((2-(trimethylsilyl)ethoxy)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (1.1 g, 2.29 mmol) in TFA (10 mL) was heated at 60° C. for 1 h. The reaction mixture was concentrated under reduced pressure. The crude product was diluted with EtOH, cooled to 0° C., and ammonium hydroxide solution (50 mL) was added dropwise and heated at 60° C. for 1 h. The reaction mixture was concentrated under reduced pressure to reduce the volume to approximately half. The precipitate was filtered, washed with EtOH, and dried to give 5-amino-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (450 mg, 56%) as a yellow solid. Data for the title compound are in Table 2.

[0184] Synthetic Route 9: Method for preparing intermediate 83 Intermediate 83: 2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl methanesulfonate [ka] To a suspension of 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (4 g, 0.01 mol) and TEA (4 mL, 0.03 mol) in THF (60 mL) was added methanesulfonyl chloride (1 mL, 0.012 mol) dropwise over 10 min at 0 °C. The reaction mixture was partitioned between EtOAc (50 mL) and brine solution (50 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was triturated with n-hexane (2 x 20 mL), decanted, and dried to give 2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl methanesulfonate (3.4 g, 70%) as a yellow solid. Data for the title compound are in Table 2.

[0185] Synthetic Route 10: Method for Preparation of Intermediate 138 Intermediate 138: 4-Methyl-2-(trimethylstannyl)thiazole [ka] To a solution of 4-methylthiazole (150 mg, 1.51 mmol) in diethyl ether (20 mL) was added dropwise methyllithium (470 mg, 2.25 mmol) at −78° C., and the reaction was stirred at the same temperature for 1 hour. Tributyltin chloride (180 mg, 1.65 mmol) was added at −78° C., and the reaction was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure to give 4-methyl-2-(trimethylstannyl)thiazole, which was used in the next step without further purification.

[0186] Synthesis route of example compounds Route a: Typical preparation of alkylated triazolopyrimidinones by alkylation reaction followed by Suzuki coupling Example 1-1, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluorophenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a suspension of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (0.3 g, 0.98 mmol) and K2CO3 (0.4 g, 2.94 mmol) in MeCN, 1-(bromomethyl)-4-fluorobenzene (0.18 g, 1.18 mol) was added at room temperature, and the reaction mixture was heated at 50 °C for 5 h. (In some analogs, a MeCN / DMSO mixture was used as the solvent.) The reaction mixture was partitioned between EtOAc (15 mL) and H2O (15 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap and a gradient of 0 to 20% EtOAc in hexanes to give 5-amino-8-bromo-2-(4-fluorobenzyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 24%) as a white solid. LCMS (Method C): m / z 413 (M+H) + (ES + ), 2.85 minutes, UV active 1 H NMR: (400 MHz, DMSO-d6) δ: 7.61 (d, J=6.0 Hz, 2H), 7.46 - 7.38 (m, 5H), 7.23 - 7.18 (m, 2H), 5.05 (s, 2H). No exchangeable -NH2 protons observed.

[0187] Step 2: A mixture of 5-amino-8-bromo-2-(4-fluorobenzyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.38 mmol), 2,6-dimethylpyridine-4-boronic acid pinacol ester (108 mg, 0.46 mmol), and KCO (104 mg, 0.76 mmol) in 1,4-dioxane (4 mL) and HO (1 mL) was degassed for several minutes, Pd(PPh) (22 mg, 0.02 mmol) was added, the vessel was sealed, and heated at 120 °C for 6 h. After cooling to room temperature, the reaction mixture was partitioned between HO (25 mL) and EtOAc (50 mL). The organic layer was separated, dried over anhydrous NaSO, concentrated under reduced pressure, and purified by Biotage-Isolera using a 10 g silica snap, eluting with hexane / EtOAc (50:50) to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluorophenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (46 mg, 43%) as a yellow solid. Data for the title compound are in Table 3.

[0188] Route b: Typical preparation of alkylated triazolopyrimidinones via alcohol mesylation and substitution reaction followed by Suzuki coupling Example 1-2, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of (5-fluoropyridin-2-yl)methanol (150 mg, 1.18 mmol) and TEA (395 mg, 3.92 mmol) in DCM (20 mL) was added mesyl chloride (135 mg, 1.18 mmol) at 0 °C, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was partitioned between DCM (20 mL) and HO (20 mL). The organic layer was separated and concentrated under reduced pressure to give the mesylated intermediate. This intermediate was dissolved in MeCN (20 mL) and 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (300 mg, 0.98 mmol) and KCO (405 mg, 2.94 mmol) were added. The mixture was heated at 70 °C in a sealed tube for 16 hours. (For other analogs, DMSO or a MeCN / DMSO mixture was used as the solvent.) The reaction mixture was partitioned between EtOAc (20 mL) and HO (20 mL), and the organic layer was separated and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 25 g silica snap, eluting with a gradient of 0 to 100% EtOAc in petroleum ether to give 5-amino-8-bromo-2-((5-fluoropyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one as an off-white solid. Data for the title compound are in Table 2.

[0189] Step 2: A mixture of 5-amino-8-bromo-2-((5-fluoropyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (0.17 g, 0.41 mmol), 2,6-dimethylpyridine-4-boronic acid pinacol ester (113 mg, 0.49 mmol), and KCO (169 mg, 1.22 mmol) in 1,4-dioxane (15 mL) and HO (5 mL) was degassed for several minutes, Pd(PPh) (46 mg, 0.04 mmol) was added, the vessel was sealed, and heated at 120 °C for 5 h. The reaction mixture was partitioned between HO (25 mL) and EtOAc (50 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated. The crude product was purified by Biotage-Isolera using a 10 g silica snap eluted with a gradient of 0 to 100% EtOAc in petroleum ether to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (82 mg, 44%) as a yellow solid. Data for the title compound are in Table 3.

[0190] Route C Example 1-3, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a suspension of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (300 mg, 0.98 mmol), (4-methoxyphenyl)methanol (162 mg, 1.1 mmol) and triphenylphosphine (385 mg, 1.4 mmol) in THF (10 mL) was added di-tert-butyl azodicarboxylate (332 mg, 1.4 mmol) at room temperature, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and purified on a Biotage-Isolera column using a 10 g silica snap sieve, eluting with a gradient of 30–100% EtOAc in petroleum ether to give 5-amino-8-bromo-2-(4-methoxybenzyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (180 mg, 44%) as an off-white solid. LCMS (Method B): m / z 426 (M+H) + (ES + ), 2.93 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.60 - 7.44 (m, 5H), 7.29 (d, J=10.8 Hz, 2H), 6.93 (d, J=10.8 Hz, 2H), 4.98 (s, 2H), 3.75 (s, 3H). No exchangeable -NH2 protons were observed.

[0191] Step 2: Route a, prepared in a manner similar to Step 2 to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (70 mg, 37%) as a yellow solid. Data for the title compound are in Table 3.

[0192] Route d: A typical preparation of alkylated triazolopyrimidinones via alcohol mesylation and substitution reactions Example 1-5, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a solution of pyridazin-3-ylmethanol (40 mg, 0.36 mmol) and TEA (90 mg, 0.90 mmol) in DCM (10 mL) was added mesyl chloride (45 mg, 0.39 mmol) at 0 °C, and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was partitioned between DCM (20 mL) and HO (20 mL), and the organic layer was separated and concentrated under reduced pressure to give the mesylated intermediate. This intermediate was dissolved in MeCN (20 mL), and 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.30 mmol) and KCO (124 mg, 0.90 mmol) were added. The mixture was heated at 80 °C in a sealed tube for 6 h. (In other examples, the reaction can be carried out in a MeCN / DMSO mixture or in DMSO alone.) The reaction mixture was partitioned between EtOAc (20 mL) and HO (20 mL), and the organic layer was separated and concentrated under reduced pressure. The crude product was purified on a Biotage-Isolera column using a 10 g silica snap column, eluting with a gradient of 0 to 100% EtOAc in petroleum ether to afford 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (33 mg, 26%) as a yellow solid. Data for the title compound are in Table 3.

[0193] Route e: A typical method for the preparation of triazolopyrimidinones via demethylation reaction Example 1-8, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A mixture of 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-((5-fluoro-6-methoxypyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (200 mg, 0.42 mmol) in MeCN (10 mL) was cooled to 0 °C, and iodotrimethylsilane (212 mg, 1.06 mmol) was added and stirred for 2 h at room temperature. The reaction mixture was partitioned between EtOAc (20 mL) and saturated NaHCO (20 mL), and the organic layer was separated, washed with saturated sodium hydrogen sulfate solution (20 mL), dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was triturated with MeOH to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (130 mg, 67%) as a yellow solid. Data for the title compound are in Table 3.

[0194] Route f Examples 1-10, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-1-methyl-6-oxo-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a solution of 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (40 mg, 0.08 mmol) in MeCN (5 mL) was added KCO (33.1 mg, 0.24 mmol) and methyl iodide (14.8 mg, 0.10 mmol), and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL), and the organic layer was separated and concentrated under reduced pressure. The crude product was purified on a Biotage isolecra using a 10 g silica snap column, eluting with 0 to 100% EtOAc in petroleum ether to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-1-methyl-6-oxo-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (9 mg, 25%) as a yellow solid. Data for the title compound are in Table 3.

[0195] Route g: A typical method for the preparation of alkylated triazolopyrimidinones via the Mitsunobu reaction Examples 1-11, 5-amino-2-[1-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a mixture of 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (56 mg, 0.19 mmol), 1-(2,4-difluorophenyl)ethan-1-ol (38 mg, 0.24 mmol), and PPh3 (62 mg, 0.24 mmol) in THF (3 mL) was added di-tert-butyl azodicarboxylate (55 mg, 0.24 mmol). The reaction mixture was stirred at room temperature for 16–18 h. The mixture was concentrated and the product was purified by preparative HPLC (Method E) to give 5-amino-2-[1-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (16 mg, 20%). Data for the title compound are in Table 3.

[0196] Route h: A typical method for the preparation of alkylated triazolopyrimidinones via Mitsunobu reaction and utilizing a Boc protection strategy Example 1-30, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] BocO (229 mg, 1.05 mmol) was added to a solution of [2-(piperidin-4-yl)phenyl]methanol (191 mg, 1 mmol) in MeOH (2 mL) at 0° C. The reaction mixture was stirred for 2 h at room temperature. The mixture was concentrated under reduced pressure, and the residue was crystallized from an i-propanol / hexane mixture to give the Boc-protected amine. Di-tert-butyl-azodicarboxylate (51 mg, 0.22 mmol) was added to a mixture of 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (66 mg, 0.20 mmol), Boc-protected amine (42 mg, 0.22 mol), and PPh3 (68 mg, 0.26 mmol) in THF (3 mL). The reaction was stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure, the residue was dissolved in DCM (3 mL), TFA (0.5 mL) was added, and the reaction was sonicated for 2 hours at room temperature. The mixture was concentrated under reduced pressure and the product was purified by preparative HPLC (Method E) to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (51 mg, 50%). Data for the title compound are in Table 3.

[0197] Route I Example 1-36, 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route a, carried out in a manner similar to step 1, except that the reaction was heated at 80° C. for 16 hours to afford N,N-di-tert-butoxycarbonyl(6-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-3-fluoropyridin-2-yl)amine (30 mg, 15%) as a pale yellow solid. LCMS (Method B): m / z 657 (M+H) + (ES + ), 2.57 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 7.92 - 7.86 (m, 1H), 7.52 - 7.49 (m, 1H), 7.26 - 7.25 (m, 5H), 6.76 (s, 2H), 5.11 (s, 2H), 2.25 (s, 6H), 1.29 (s, 18H). No exchangeable -NH2 protons were observed.

[0198] Step 2: To a stirred solution of N,N-di-tert-butoxycarbonyl(6-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-3-fluoropyridin-2-yl)amine (30 mg, 0.04 mmol) in diethyl ether (3 mL) was added 2M HCl in diethyl ether (2 mL) and stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. The crude product was loaded onto an SCX column and purified by elution with 20% ammonia in MeOH to give 5-amino-2-((6-amino-5-fluoropyridin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (5 mg, 27%) as a pale yellow solid. Data for the title compound are in Table 3.

[0199] Route j Example 1-38, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[1-(5-fluoro-2-pyridyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one and its chiral resolution into enantiomers 1-38 iso-1 and 1-38 iso-2 [ka] Step 1: To a suspension of 2-bromo-5-fluoropyridine (5 g, 28.4 mmol) in THF (100 mL) was added n-butyllithium (2 M in THF, 17 mL, 34.09 mmol) at -78 °C, and the reaction was stirred at -78 °C for 1 h. Propionaldehyde (2.5 mL, 34.09 mmol) was added dropwise at the same temperature, and the mixture was stirred at room temperature for 2 h. The reaction was quenched by the dropwise addition of NH₄Cl solution (100 mL) and extracted with EtOAc (100 mL). The organic layer was separated, dried over Na₂SO₄, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 50 g silica snapper with a petroleum ether gradient (0–100%) eluting with EtOAc to give 1-(5-fluoropyridin-2-yl)propan-1-ol (1.5 g, 39%) as a brown liquid. LCMS (Method A): m / z 156 (M+H) + (ES + ), 0.86 minutes, UV activity

[0200] Step 2: To a suspension of tosyl chloride (2.78 g, 14.61 mmol) and a catalytic amount of DMAP in THF (30 mL) was added NaH (60% dispersion in mineral oil, 280 mg, 11.68 mmol) portionwise at 0 °C, followed by a solution of 1-(5-fluoropyridin-2-yl)propan-1-ol (1.5 g, 9.67 mmol) in THF (10 mL) at 0 °C, followed by stirring at room temperature for 1 h. The reaction mixture was quenched with NH4Cl solution (100 mL) and extracted with EtOAc (100 mL). The organic layer was separated, dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 25 g silica snap eluted with a gradient of 0-100% EtOAc in petroleum ether to give 1-(5-fluoropyridin-2-yl)propyl 4-methylbenzenesulfonate (1.5 g, 34%) as an off-white solid. Data are in Table 2.

[0201] Step 3: To a suspension of 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (250 mg, 0.75 mmol) in MeCN (10 mL) and DMSO (2 mL) was added 1-(5-fluoropyridin-2-yl)propyl 4-methylbenzenesulfonate (232 mg, 0.75 mmol) and K2CO3 (311 mg, 0.22 mmol). The reaction was heated at 80 °C for 2 h. The reaction mixture was partitioned between EtOAc (20 mL) and H2O (10 mL). The organic layer was separated, dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap with a petroleum ether gradient of 0-100% EtOAc to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[1-(5-fluoro-2-pyridyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (110 mg, 29%) as a yellow solid. Data for the title compound are in Table 3.

[0202] The racemate was purified by chiral SFC (Method A) to give 1-38 iso-1 as the first eluting peak and 1-38 iso-2 as the second eluting peak. Data for the title compounds are in Table 3.

[0203] Route k: Typical preparation of pyridine N-oxide via oxidation using mCPBA Example 1-42, 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a solution of 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (100 mg, 0.22 mmol) in DCM (10 mL) was added 3-chlorobenzoperoxyacid (50 mg, 0.18 mmol), and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with 10% sodium bicarbonate solution (10 mL) and extracted with EtOAc (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap column eluting with a 0-100% EtOAc in hexanes gradient to give 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (28 mg, 27%) as a yellow solid. Data for the title compound are in Table 3.

[0204] Route Example 1-44, 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route a, carried out in a manner similar to step 2 to obtain methyl 4-(5-amino-2-((5-fluoropyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (70 mg, 19%) as a yellow solid. LCMS (Method B): m / z 485 (M+H) + (ES + ), 2.38 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 8.54 - 8.52 (m, 1H), 7.77 - 7.75 (m, 1H), 7.73 - 7.71 (m, 1H), 7.47 - 7.42 (m, 1H), 7.31 - 7.21 (m, 6H), 5.16 - 5.13 (m, 2H), 3.81 (s, 3H), 2.01 (s, 3H). No exchangeable -NH2 protons were observed.

[0205] Step 2: To a degassed solution of methyl 4-(5-amino-2-((5-fluoropyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (70 mg, 0.14 mmol) in MeOH, NaBH (24 mg, 0.9 mmol) was added portionwise at room temperature and stirred for 15 hours. The reaction mixture was partitioned between DCM (20 mL) and saturated NaHCO solution (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 230-400 silica snap column eluting with a 0-100% EtOAc in hexanes gradient to give 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (10 mg, 15%) as a yellow solid. Data for the title compound are in Table 3.

[0206] Route m Example 1-45, 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one Example 1-48, 5-amino-2-[(5-fluoro-6-hydroxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (350 mg, 1.143 mmol) and N,N-di-tert-butoxycarbonyl(6-(bromomethyl)-3-fluoropyridin-2-yl)-amine (507 mg, 1.258 mmol) in DMSO (10 mL) was added KCO (473 mg, 3.430 mmol) and the reaction was heated at 80° C. for 2 h. The reaction mixture was quenched with ice-cold water. The precipitate was filtered and dried under reduced pressure to give 5-amino-2-((6-di-Boc-protected amino-5-fluoropyridin-2-yl)methyl)-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (600 mg, 83%) as a yellow solid. LCMS (Method A): m / z 431 (M+H-2xBoc) + (ES + ), 3.02 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.92 (s, 2H), 7.61-7.56 (m, 3H), 7.46-7.45 (m, 4H), 5.15 (s, 2H), 1.37 (s, 18H)

[0207] Step 2; Route a, prepared in a manner similar to step 2 to give methyl 4-(5-amino-2-((6-di-Boc-protected amino-5-fluoropyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (250 mg, 37%) as a yellow solid. LCMS (Method A): m / z 701 (M+H) + (ES + ), 2.76 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 7.91-7.87 (m, 2H), 7.65-7.56 (m, 3H), 7.32-7.20 (m, 5H), 5.12 (s, 2H), 3.78 (s, 3H), 2.36 (s, 3H), 1.29 (s, 18H). No exchangeable -NH2 protons were observed.

[0208] Step 3: To a solution of methyl 4-(5-amino-2-((6-di-Boc-protected amino-5-fluoropyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (250 mg, 0.357 mmol) in THF (10 mL) at 0° C. was added lithium triethylborohydride (1 M solution in THF, 75.7 mg, 0.714 mmol) dropwise. The reaction was stirred at room temperature for 2 hours. The reaction mixture was partitioned between EtOAc (20 mL) and HO (10 mL). The organic layer was separated, washed with brine (10 mL), dried over NaSO, and concentrated under reduced pressure to give 5-amino-2-((6-di-Boc-protected amino-5-fluoropyridin-2-yl)methyl)-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 41%) as a yellow solid. The crude product was used in the next step without purification. LCMS (Method A): m / z 673 (M+H) + (ES + ), 4.09 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.91-7.87 (m, 2H), 7.66-7.50 (m, 3H), 7.25-7.13 (m, 5H), 5.15 (s, 2H), 4.85 (s, 2H), 2.19 (s, 3H), 1.24 (s, 18H). No exchangeable -NH2 protons were observed.

[0209] Step 4: To a solution of 5-amino-2-((6-di-Boc-protected amino-5-fluoropyridin-2-yl)methyl)-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.14 mmol) in 1,4-dioxane (2 mL) was added 4.0 M HCl in dioxane (3 mL) at room temperature at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. The crude product was purified by preparative HPLC (Method A), and two peaks were observed. The collected fractions were concentrated, and the residue was partitioned between EtOAc (10 mL) and 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated to dryness to give 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (30 mg, 45%) as an off-white solid and 5-amino-2-[(5-fluoro-6-hydroxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (1.5 mg, 2%) as an off-white solid. Data for the title compounds are in Table 3.

[0210] Route n Examples 1-46 Isomers 1 and 2, 5-amino-2-[1-(5-fluoro-2-pyridyl)propyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a stirred solution of 1-(6-fluoropyridin-2-yl)propyl 4-methylbenzenesulfonate (506 mg, 1.63 mmol) in DMSO (5 mL), 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (500 mg, 1.63 mmol) and K2CO3 (674 mg, 4.89 mmol) were added, and the resulting reaction mixture was heated at 80 ° C. for 2 hours. The reaction mixture was poured into ice, and the precipitate was filtered and dried to give 5-amino-8-bromo-2-(1-(6-fluoropyridin-3-yl)propyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one as a brown solid. LCMS (Method A): m / z 442 (M+H) + (ES + ), 2.69 minutes, UV activity

[0211] Step 2; Route a, prepared in a manner similar to step 2 to obtain methyl 4-(5-amino-2-(1-(6-fluoropyridin-3-yl)propyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (300 mg, 41%) as a yellow solid. LCMS (Method A): m / z 514 (M+H) + (ES + ), 3.32 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.47 (d, J=6.4 Hz, 2H), 7.61-7.60 (m, 3H), 7.58-7.45 (m, 3H), 7.32 (d, J=2.4 Hz, 2H), 5.50 (s, 1H), 4.04-4.03 (m, 2H), 3.93 (s, 3H), 2.38 (s, 3H), 0.91 (t, J=7.2 Hz, 3H). No exchangeable -NH2 protons were observed.

[0212] Step 3: To a solution of methyl 4-(5-amino-2-(1-(6-fluoropyridin-3-yl)propyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (300 mg, 0.58 mmol) in THF (20 mL) was added lithium triethylborohydride (1 M in THF, 1.16 mL, 1.16 mmol) at 0° C., and the resulting reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by dropwise addition of water (20 mL) and extracted with EtOAc (10 mL). The organic layer was separated and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using 25 g silica gel snap sieve eluting with a petroleum ether gradient of 0 to 100% EtOAc to give 5-amino-2-[1-(5-fluoro-2-pyridyl)propyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one as a yellow solid. The racemate was purified by chiral SFC (Method B) to give 1-46 iso-1 as the first eluting peak and 1-46 iso-2 as the second eluting peak. Data for the title compounds are in Table 3.

[0213] Route o: Typical preparation of alkylated triazolopyrimidinones via alcohol tosylation and substitution followed by ester reduction Example 1-47, 5-amino-2-[(3-fluoro-5-methoxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of tosyl chloride (120 mg, 0.63 mmol), TEA (0.2 mL, 1.7 mmol), and a catalytic amount of DMAP in DCM (5 mL) was added (3-fluoro-5-methoxypyridin-2-yl)methanol (90 mg, 0.57 mmol) at 0° C. The resulting reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was partitioned between DCM (10 mL) and HO (10 mL). The organic layer was separated and concentrated under reduced pressure to give the tosylated intermediate. The tosylated intermediate was dissolved in DMSO (2 mL), methyl 4-(5-amino-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (192 mg, 0.51 mmol), and K2CO3 (235 mg, 1.71 mmol) were added, and the resulting reaction mixture was heated at 80 °C for 2 h in a sealed tube. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was separated and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap eluted with a gradient of 0 to 100% EtOAc in petroleum ether to give methyl 4-(5-amino-2-((3-fluoro-5-methoxypyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (60 mg, 23%) as a yellow solid. LCMS (Method A): m / z 516 (M+H) + (ES + ), 2.56 minutes, UV activity

[0214] Step 2, Route m, was carried out in a similar manner to Step 3 and purified by preparative HPLC (Method A). The fractions were concentrated, and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated to give 5-amino-2-[(3-fluoro-5-methoxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (10 mg, 18%) as a yellow solid. Data for the title compound are in Table 3.

[0215] Route p: A typical method for the preparation of alkylated triazolopyrimidinones via alcohol mesylation and substitution reaction followed by Suzuki coupling and ester reduction Example 1-49, 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route b, carried out in a manner analogous to step 1 using intermediates 47 and 4 to give 5-amino-8-bromo-2-((5-fluoropyridin-2-yl)methyl)-7-(phenyl-d5)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (450 mg, 83%) as a brown solid. LCMS (Method C): m / z 421 (M+H) + (ES + ), 2.06 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d) δ: 8.55 (d, J=3.2 Hz, 1H), 7.76 (d, J=2.8 Hz, 1H), 7.50 (d, J=4.4 Hz, 1H), 5.17 (s, 2H). No exchangeable -NH protons were observed.

[0216] Step 2; Route a, carried out in a manner similar to step 2 to obtain methyl 4-(5-amino-2-((5-fluoropyridin-2-yl)methyl)-3-oxo-7-(phenyl-d5)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (160 mg, 30%) as a yellow solid. LCMS (Method C): m / z 491 (M+H) + (ES + ), 2.06 minutes, UV activity

[0217] Step 3: Route m. A procedure similar to Step 3 was carried out and purified by preparative HPLC (Method A). The fractions were concentrated, and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated to give 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (40 mg, 26%) as a yellow solid. Data for the title compound are in Table 3.

[0218] Route q: Typical preparation of alkylated triazolopyrimidinones via Mitsunobu reaction followed by ester reduction Example 1-50, 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route c. Carried out in a manner analogous to Step 1 using intermediates 45 and 39, methyl 4-(5-amino-2-((3-chloro-5-fluoropyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (25 mg, 14%) was obtained as a yellow solid. LCMS (Method C): m / z 520 (M+H)+ (ES + ), 2.01 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.56 (d, J=2.8 Hz, 1H), 8.19-8.16 (m, 1H), 7.64 (s, 1H), 7.32-7.20 (m, 5H), 7.20 (s, 1H), 5.25 (s, 2H), 3.79 (s, 3H), 2.35 (s, 3H). No exchangeable -NH2 protons were observed.

[0219] Step 2, Route m, was carried out in a similar manner to Step 3 and purified by preparative HPLC (Method A). The fractions were concentrated, and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated to give 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (4 mg, 17%) as a yellow solid. Data for the title compound are in Table 3.

[0220] Route r: Typical preparation of alkylated triazolopyrimidinones via alkylation reaction followed by ester reduction and Boc deprotection Example 1-51, 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route m, carried out in a manner analogous to step 1 using intermediates 49 and 38 to give methyl 4-(5-amino-2-((6-di-bocamino-5-fluoropyridin-2-yl)methyl)-3-oxo-7-(phenyl-d5)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (80 mg, 57%) as a yellow solid. LCMS (Method C): m / z 706 (M+H) + (ES + ), 2.44 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.90-7.85 (m, 1H), 7.60 (s, 1H), 7.51 (s, 1H), 7.18 (s, 1H), 5.10 (s, 2H), 3.77 (s, 3H), 2.34 (s, 3H), 1.27 (s, 18H). No exchangeable -NH2 protons were observed.

[0221] Step 2, Route m, carried out in a manner similar to Step 3, to afford 5-amino-2-((6-diboc-amino-5-fluoropyridin-2-yl)methyl)-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-(phenyl-d5)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (70 mg, 92%) as a yellow solid. LCMS (Method C): m / z 578 (M+H-Boc) + (ES + ), 1.43 minutes, UV activity

[0222] Step 3, Route m, was carried out in a manner similar to Step 4 to give 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (10 g, 20%) as a yellow solid. Data for the title compound are in Table 3.

[0223] Route s: A typical preparation of alkylated triazolopyrimidinones via alcohol mesylation and substitution reaction followed by ester reduction Example 1-53, 5-amino-2-[(5-bromo-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route b, carried out in a manner similar to step 1, afforded methyl 4-(5-amino-2-((5-bromopyridin-2-yl)methyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (120 mg, 36%) as a pale yellow solid. LCMS (Method C): m / z 547 (M+H) + (ES + ), 2.16 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.64 (s, 1H), 7.99 (s, 1H), 7.49 (s, 1H), 7.32-7.26 (m, 7H), 5.18-5.14 (m, 2H), 3.86 (s, 3H), 2.42 (s, 3H). No exchangeable -NH2 protons were observed.

[0224] Step 2: Route o, carried out in a manner similar to Step 2, afforded 5-amino-2-[(5-bromo-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (12 mg, 10%) as a yellow solid. Data for the title compound are in Table 3.

[0225] Route t: A typical method for the preparation of alkylated triazolopyrimidinones via alkylation reactions. Example 1-54, 6-[[5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile [ka] To a stirring solution of 5-amino-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (450 mg, 1.29 mmol) in DMSO (10 mL) was added 6-(bromomethyl)nicotinonitrile (254 mg, 1.29 mmol) and KCO (535 mg, 3.87 mmol), and the reaction mixture was heated at 70 °C for 1 h. The reaction mixture was partitioned between EtOAc (20 mL) and HO (20 mL). The organic layer was separated and concentrated under reduced pressure. The crude product was purified by flash column chromatography using silica (230-400) mesh and eluting with a 0-3% MeOH in DCM gradient to give 6-[[5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile (290 mg, 48%) as a yellow solid. Data for the title compound are in Table 3.

[0226] Route u: Typical preparation of alkylated triazolopyrimidinones via ester reduction followed by alkylation reaction Example 1-63, 6-[[5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile [ka] Step 1, Route o, was carried out in a manner similar to Step 2 to give 5-amino-7-(4-fluorophenyl)-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (460 mg, 48%) as a yellow solid. LCMS (Method C): m / z 367 (M+H) + (ES + ), 2.16 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 12.42 (s, 1H), 7.33 - 7.29 (m, 2H), 7.12 - 7.08 (m, 3H), 6.87 (s, 1H), 5.26 (t, J=5.8 Hz, 1H), 4.43 (d, J=5.8 Hz, 2H), 2.32 (s, 3H). No exchangeable -NH2 protons were observed.

[0227] Step 2 was carried out in a manner similar to Route t to give 6-[[5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile (250 g, 41%) as a yellow solid. Data for the title compound are in Table 3.

[0228] Route v: Suzuki coupling and S N A typical method for the preparation of alkylated triazolopyrimidinones via Ar substitution. Example 1-71, 5-amino-8-[2-(dimethylamino)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route a, carried out in a manner similar to step 2 to obtain 5-amino-8-(2-fluoro-6-methylpyridin-4-yl)-2-((5-fluoropyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (700 mg, 33%) as a yellow solid. LCMS (Method C): m / z 446 (M+H) + (ES + ), 1.93 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 8.55-8.02 (m, 1H), 8.00 (s, 1H), 7.77-7.72 (m, 2H), 7.29-6.93 (m, 5H), 6.68 (s, 1H), 5.15-5.11 (m, 2H), 2.26 (s, 3H). No exchangeable -NH2 protons were observed.

[0229] Step 2: To a solution of 5-amino-8-(2-fluoro-6-methylpyridin-4-yl)-2-((5-fluoropyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (350 mg, 0.78 mmol) in NMP (5 mL) was added TEA (0.3 mL, 2.34 mmol) and N,N-dimethylamine hydrochloride (130 mg, 0.56 mmol), and the resulting reaction mixture was heated at 120 °C for 16 h. (For other analogs, TEA can be omitted and an excess of the amine (free base) can be used.) The reaction mixture was partitioned between HO (20 mL) and EtOAc (40 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated. The crude product was purified by preparative HPLC (Method A). The collected fractions were concentrated under reduced pressure, and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated to give 5-amino-8-(2-(dimethylamino)-6-methylpyridin-4-yl)-2-((5-fluoropyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (45 mg, 12%) as a yellow solid. Data for the title compound are in Table 3.

[0230] Route w Example 1-77, 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a stirring solution of 5-amino-8-(2-chloro-6-methylpyridin-4-yl)-2-((5-fluoropyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.2 mmol) in DMSO (1 mL) was added NaOMe (35 mg, 0.6 mmol) and the reaction was heated at 120 °C for 5 h. The reaction mixture was partitioned between HO (10 mL) and EtOAc (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated. The crude product was purified by preparative HPLC (Method A). The fractions were concentrated and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated to give 5-amino-8-(2-chloro-6-methylpyridin-4-yl)-2-((5-methoxypyridin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (12 mg, 12%) as an off-white solid. Data for the title compound are in Table 3.

[0231] Route x: A typical method for the preparation of alkylated triazolopyrimidinones via aldehyde condensation reaction Example 1-80, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of 4-hydrazinyl-6-phenylpyrimidin-2-amine (0.6 g, 2.98 mmol) in MeOH (5 mL) was added phenylacetaldehyde (0.357 g, 2.98 mmol) at room temperature, and the resulting reaction was stirred for 3 hours. The mixture was concentrated under reduced pressure and dried under reduced pressure. The resulting residue was triturated with petroleum ether (3 × 3 mL), decanted, and dried under high vacuum to give (£)-4-phenyl-6-(2-(2-phenylethylidene)hydrazinyl)pyrimidin-2-amine (0.62 g, 68%) as an off-white solid. LCMS (Method D): m / z 304 (M+H) +(ES + ), 3.86 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 10.55 (br s, 1H), 7.98 - 7.96 (m, 2H), 7.49 - 7.46 (m, 4H), 7.37 - 7.32 (m, 2H), 7.30 - 7.23 (m, 3H), 6.76 (s, 1H), 6.20 (br s, 2H), 3.61 (d, J=5.8 Hz, 2H)

[0232] Step 2: To a solution of 4-phenyl-6-(2-(2-phenylethylidene)hydrazinyl)pyrimidin-2-amine (0.6 g, 1.98 mmol) in THF (20 mL) at −30° C. was added lithium aluminum hydride (1 M in THF, 9.9 mL, 9.9 mmol) dropwise over 2 minutes. The reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched with saturated NaSO solution (20 mL) and extracted with EtOAc (2×15 mL). The combined organic layers were dried over anhydrous NaSO and concentrated to give 4-(2-phenethylhydrazinyl)-6-phenylpyrimidin-2-amine as a brown gum, which was used directly in the next step without purification.

[0233] Step 3: To a solution of 4-(2-phenethylhydrazinyl)-6-phenylpyrimidin-2-amine (600 mg, 1.96 mmol) in dry THF (10 mL) cooled to −20° C. under N was added triphosgene (1152 mg, 3.92 mmol) and the mixture was stirred for 45 min. The reaction was concentrated and purified by gradient flash chromatography eluting with CHCl / MeOH 95:5 to give 5-amino-2-phenethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (350 mg, 53%) as a pale yellow solid. LCMS (Method D): m / z 332 (M+H) + (ES + ), 3.86 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 7.91 (d, J=9.6 Hz, 2H), 7.49 - 7.46 (m, 3H), 7.35 - 7.31 (m, 2H), 7.27 - 7.24 (m, 3H), 6.70 (s, 1H), 4.17 - 4.13 (m, 2H), 3.18 - 3.15 (m, 2H). No exchangeable -NH2 protons were observed.

[0234] Step 4: To a suspension of 5-amino-2-phenethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (350 mg, 1.05) in 1:1 CHCl / MeOH (10 mL) was added CaCO (105 mg, 1.05 mmol) and (CH)PhN under N. + Br3 - (392 mg, 1.05 mmol) was added and the mixture was stirred at room temperature for 1 h. The reaction was quenched with HO and extracted with CHCl. ​​The organic layer was dried over NaSO and concentrated. The crude product was purified by gradient flash chromatography eluting with CHCl / MeOH 95:5 to give 5-amino-8-bromo-2-phenethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (140 mg, 30%) as a yellow solid. LCMS (Method D): m / z 409 (M+H) + (ES + ), 4.19 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.64 - 7.61 (m, 2H), 7.49 - 7.44 (m, 3H), 7.33 - 7.21 (m, 5H), 4.06 (t, J=14.4 Hz, 2H), 3.06 (t, J=14.4 Hz, 2H). No exchangeable -NH2 protons were observed.

[0235] Step 5, Route a, was carried out in a manner similar to Step 2 to give 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-phenethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (68 mg, 45%) as a pale yellow solid. Data for the title compound are in Table 3.

[0236] Route y Example 1-85, 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoic acid [ka] To a solution of methyl 4-(2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl)benzoate (50 mg, 0.1 mmol) in THF (2 mL) and HO (1 mL) was added LiOH.HO (9 mg, 0.20 mmol) and the reaction was stirred at room temperature for 6 h. The reaction mixture was acidified to pH ∼6 and concentrated. The crude product was purified through an SCX cartridge (SolE×SCX, 6 mL, 500 mg) eluting with methanolic ammonia and dried to give 4-(2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl)benzoic acid (12 mg, 25%) as a yellow solid. Data for the title compound are in Table 3.

[0237] Route z Example 1-90, 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A solution of 5-amino-8-(2-chloro-6-methylpyridin-4-yl)-2-phenethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (60 mg, 0.13 mmol) and azetidine (12 mg, 0.19 mmol) in NMP (2 mL) was heated at 150° C. for 16 h. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude compound was purified by Biotage-Isolera using a 10 g silica snap and a gradient of EtOAc in hexane to give 5-amino-8-(2-(azetidin-1-yl)-6-methylpyridin-4-yl)-2-phenethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (7 mg, 10%) as a pale yellow solid. Data for the title compound are in Table 3.

[0238] Route aa: A typical method for the preparation of alkylated triazolopyrimidinones via substitution reactions. Example 1-91, 5-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-2-chloro-N-methyl-benzamide [ka] To a suspension of 2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl methanesulfonate 1 (73 mg, 0.16 mmol) in MeCN (2 mL) was added KCO (66 mg, 0.48 mmol) and 5-amino-2-chloro-N-methylbenzamide hydrochloride (42 mg, 0.19 mmol). The reaction mixture was heated at 100 °C for 15 h. The mixture was partitioned between EtOAc (5 mL) and HO (5 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was purified by preparative HPLC (Method E) to give 5-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-2-chloro-N-methyl-benzamide (7 mg, 8%). Data for the title compound are in Table 3.

[0239] Route ab Example 2-16, 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl N-ethylcarbamate [ka] Step 1: To a suspension of 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (50 mg, 0.13 mmol), di-tert-butyl-dicarbonate (31 mg, 0.014 mmol), and TEA (0.69 mL, 0.52 mmol) in THF (5 mL) was added DMAP (8 mg, 0.006 mmol) at room temperature. The reaction mixture was stirred for 48 hours at room temperature. The reaction mixture was partitioned between EtOAc (20 mL) and sodium bicarbonate (10 mL). The organic layer was dried over anhydrous NaSO and concentrated under reduced pressure to give tert-butyl (2-(2-((tert-butoxycarbonyl)oxy)ethyl)-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)carbamate (80 mg, crude) as a yellow solid, which was used without purification. LCMS (Method B): m / z 677 (M+H) + (ES + ), 2.89 minutes, UV activity

[0240] Step 2: To a suspension of tert-butyl (2-(2-((tert-butoxycarbonyl)oxy)ethyl)-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)carbamate (80 mg, 0.118) in 1,4-dioxane (2 mL) was added 2N aqueous NaOH solution (3 mL). The reaction mixture was stirred for 48 hours at room temperature and then partitioned between EtOAc (10 mL) and water (10 mL). The organic layer was dried over anhydrous NaSO, concentrated under reduced pressure, and purified by Biotage-Isolera using a 10 g silica snap eluting with a gradient of 10% MeOH in DCM to give tert-butyl (8-(2,6-dimethylpyridin-4-yl)-2-(2-hydroxyethyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)carbamate (40 mg, 21%) as a yellow solid. LCMS (Method B): m / z 477 (M+H) + (ES + ), 2.32 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 10.24 (s, 1H), 7.38 - 7.27 (m, 5H), 6.91 (s, 2H), 4.89 (s, 1H), 3.87 (t, J=7.6 Hz, 2H), 3.63 (t, J=7.6 Hz, 2H), 2.35 (s, 6H), 1.51 - 1.49 (m, 9H)

[0241] Step 3: To a suspension of tert-butyl (8-(2,6-dimethylpyridin-4-yl)-2-(2-hydroxyethyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)carbamate (35 mg, 0.073 mmol) and TEA (0.02 mL, 0.014 mmol) in THF (5 mL) was added ethyl isocyanate (5 mg, 0.066 mmol) at room temperature. The reaction mixture was heated at 60° C. for 12 hours. The reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was dried over anhydrous NaSO, concentrated under reduced pressure, and purified by Biotage-Isolera using a 10 g silica snap eluting with a gradient of 10% MeOH in DCM to give tert-butyl (tert-butoxycarbonyl)(8-(2,6-dimethylpyridin-4-yl)-2-(2-((ethylcarbamoyl)oxy)ethyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)carbamate (30 mg, 74%) as a yellow solid. LCMS (Method B): m / z 547 (M+H) + (ES + ), 2.50 minutes, UV activated

[0242] Step 4: To a suspension of tert-butyl (tert-butoxycarbonyl) (8-(2,6-dimethylpyridin-4-yl)-2-(2-((ethylcarbamoyl)oxy)ethyl)-3-oxo-7-phenyl-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)carbamate (30 mg, 0.054 mmol) in DCM, 5 mL of 20% TFA in DCM was added. The reaction mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, loaded onto an SCX cartridge, and eluted with 2 M methanolic ammonia to give 2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl ethylcarbamate (4 mg, 7%) as a yellow solid. Data for the title compounds are in Table 3.

[0243] Route AC Example 2-17, 5-amino-2-(3,3-difluoropropyl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Prepared analogously to Step 1, Route a, Step 1 and purified by trituration with diethyl ether to give 5-amino-8-bromo-2-(3,3-dimethoxypropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (1.2 g, 45%) as an off-white solid. LCMS (Method B): m / z 408 (M+H) + (ES + ), 2.68 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 7.62 - 7.61 (m, 2H), 7.48 - 7.43 (m, 3H), 4.47 (t, J=5.6 Hz, 1H), 3.85 (t, J=7.2 Hz, 2H), 3.26 (s, 6H), 1.99 - 1.94 (m, 2H). No exchangeable -NH2 protons were observed.

[0244] Step 2: To a solution of 5-amino-8-bromo-2-(3,3-dimethoxypropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (1.2 g, 2.94 mmol) in 1,4-dioxane (10 mL) was added 2N HCl (30 mL) at room temperature, and the reaction was stirred for 2 hours. The reaction was concentrated under reduced pressure and partitioned between EtOAc (30 mL) and saturated NaHCO solution (20 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure to give 3-(5-amino-8-bromo-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)propanal (0.6 g) as a brown gum, which was used immediately in the next step. LCMS (Method B): m / z 362 (M+H) + (ES + ), 2.32 minutes, UV activity

[0245] Step 3: To a solution of 3-(5-amino-8-bromo-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)propanal (0.6 g, 1.65 mmol) in DCM (15 mL) was added DAST (0.58 g, 3.63 mmol) at −78° C. and stirred at room temperature for 15 hours. The reaction was quenched by careful dropwise addition of saturated sodium bicarbonate solution (40 mL) and extracted with DCM (2×30 mL). The combined organic layer was dried over anhydrous NaSO and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 25 g silica snap eluted with a gradient of 0 to 40% EtOAc in hexanes to give 5-amino-8-bromo-2-(3,3-difluoropropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (0.2 g, 31%) as an off-white solid. LCMS (Method B): m / z 384 (M+H) + (ES + ), 2.80 minutes, UV active 1 H NMR: (400 MHz, DMSO-d6) δ: 7.63 - 7.61 (m, 2H), 7.48 - 7.45 (m, 3H), 6.35 - 6.05 (m, 1H), 3.99 (t, J=6.8 Hz, 2H), 2.39 - 2.22 (m, 2H). No exchangeable -NH2 protons were observed.

[0246] Step 4, Route a, was carried out in a manner similar to Step 2 to give 5-amino-2-(3,3-difluoropropyl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (100 mg, 47%) as a yellow solid. Data for the title compound are in Table 3.

[0247] Route ad: A typical method for the preparation of alkylated triazolopyrimidinones via alkylation reactions. Example 2-20, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A procedure similar to Route a, step 1 was carried out to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (45 mg, 40%) as a yellow solid. Data for the title compound are in Table 3.

[0248] Route ae: Typical preparation of amides Example 2-23, 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-propanamide [ka] Step 1: Route a, carried out in a manner similar to Step 1 using ethyl 3-bromopropanoate and Intermediate 7 to give ethyl 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)propanoate (180 mg, 69%) as a yellow solid. Data for this compound are in Table 2.

[0249] Step 2: To a suspension of ethyl 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)propanoate (90 mg, 0.20 mmol) in THF (5 mL), HO (5 mL), and MeOH (1 mL) was added lithium hydroxide monohydrate (43 mg, 1.04 mmol), and the reaction mixture was stirred at room temperature for 45 minutes. The reaction mixture was partitioned between EtOAc (5 mL) and HO (5 mL). The aqueous layer was separated, acidified with 6N HCl (2 mL), and extracted with EtOAc (10 mL). The organic layer was dried over anhydrous NaSO and concentrated under reduced pressure to give 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)propanoic acid (80 mg, 84%) as a yellow solid. LCMS (Method A): m / z 405 (M+H) + (ES + ), 2.11 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.26 - 7.23 (m, 5H), 6.82 (s, 2H), 3.98 (t, J=8.0 Hz, 2H), 2.74 (t, J=8.0 Hz, 2H), 2.30 (s, 6H). No exchangeable protons were observed.

[0250] Step 3: To a suspension of 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)propanoic acid (80 mg, 0.19 mmol) in THF (10 mL), DIPEA (196 mg, 1.5 mmol), dimethylamine hydrochloride (100 mg, 1.14 mmol), and HATU (108 mg, 0.28 mmol) were added and stirred at room temperature for 1 hour. The reaction mixture was partitioned between EtOAc (10 mL) and HO (5 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was dissolved in MeOH (5 mL), passed through an SCX column, eluted with 2N methanolic ammonia (10 mL), and concentrated to give 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-propanamide (29 mg, 33%) as a yellow solid. Data for the title compound are in Table 3.

[0251] Route af Example 2-24, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[3-hydroxy-2-(hydroxymethyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1; Route b, carried out in a manner analogous to step 1 using (2,2-dimethyl-1,3-dioxan-5-yl)methanol and intermediate 7 to afford 5-amino-2-((2,2-dimethyl-1,3-dioxan-5-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (55 mg, 20%) as a white solid. LCMS (Method B): m / z 461 (M+H) + (ES + ), 2.08 minutes, UV activity 1H NMR: (400 MHz, DMSO-d6) δ: 7.26 - 7.24 (m, 5H), 6.82 (s, 2H), 3.90 - 3.85 (m, 4H), 3.65 - 3.63 (m, 2H), 2.30 (s, 6H), 2.00 - 1.88 (m, 1H), 1.33 (s, 6H). No exchangeable -NH2 protons were observed.

[0252] Step 2: To a solution of 5-amino-2-((2,2-dimethyl-1,3-dioxan-5-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (50 mg, 0.1 mmol) in 1,4-dioxane (5 mL) was added 6N HCl (2 mL) and the reaction was stirred at room temperature for 6 hours. The mixture was concentrated under reduced pressure and partitioned between 10% sodium bicarbonate (15 mL) and EtOAc (15 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated. The crude product was recrystallized from diethyl ether to give 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(3-hydroxy-2-(hydroxymethyl)propyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (40 mg, 88%) as a yellow solid. Data for the title compound are in Table 3.

[0253] Route Ag Example 2-31, 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanamide [ka] A suspension of ethyl 2-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)acetate (90 mg, 0.28 mmol) in 2N methanolic ammonia was heated at 100° C. for 16 hours. The reaction was concentrated, dissolved in MeOH (5 mL), passed through an SCX column, eluted with 2N methanolic ammonia (10 mL), and concentrated to give 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanamide (35 mg, 35%) as a yellow solid. Data for the title compound are in Table 3.

[0254] Route ah: A typical method for the preparation of alkylated triazolopyrimidinones via alkylation reactions Example 2-37, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a suspension of 5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.25 mmol) in THF (10 mL) was added TEA (0.07 mL, 0.77 mmol), Boc anhydride (218 mg, 0.77 mmol), and a catalytic amount of DMAP. The reaction was heated at 50° C. for 5 hours. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was separated, dried over anhydrous NaSO and concentrated under reduced pressure to give di-boc-protected-5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (200 mg, 14%), which was used in the next step without purification. LCMS (Method A): m / z 587 (M+H) + (ES +), 2.66 minutes, UV activity

[0255] Step 2: To a solution of di-boc-protected 5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.17 mmol) in 1,4-dioxane (20 mL) was added 2-(tributylstannyl)pyridine (75.3 mg, 0.20 mmol) and Pd(PPh) (19.6 mg, 0.01 mmol). The reaction was heated in a sealed vial at 120 °C for 4 h and then partitioned between EtOAc (20 mL) and HO (15 mL). The organic layer was separated, dried over NaSO, and concentrated under reduced pressure. The crude product was purified on Biotage-Isolera using a 10 g silica snap column eluting with a 0-100% EtOAc in hexanes gradient to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (20 mg, 27%) as a yellow solid. Data for the title compound are in Table 3.

[0256] Route AI Example 2-41, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylpyrazol-1-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A suspension of 5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.25 mmol), 4-methyl-1H-pyrazole (0.5 mL), and DIPEA (0.5 mL) was placed in a sealed vial and heated at 120 °C for 16 h. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was recrystallized from hexane to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylpyrazol-1-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (11 mg, 11%) as a yellow solid. Data for the title compound are in Table 3.

[0257] Route aj Example 2-51, 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of 3,3,3-trifluoropropan-1-ol (400 mg, 3.6 mmol) in DCM (10 mL) was added TEA (1.3 mL, 9.6 mmol) at 0 °C, followed by the dropwise addition of mesyl chloride (0.4 mL, 4.8 mmol). The reaction mixture was stirred at 0 °C for 1 hour and then partitioned between DCM (20 mL) and brine (20 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give 3,3,3-trifluoropropyl methanesulfonate. This intermediate was added to a suspension of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (1 g, 3.2 mmol) and K2CO3 (1.3 g, 9.6 mmol) in MeCN (20 mL), and the reaction mixture was stirred at 80 °C for 15 hours. The reaction was partitioned between EtOAc (50 mL) and HO (50 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was triturated with MeOH (5 mL), filtered through a Buchner funnel, and dried under reduced pressure to give 5-amino-8-bromo-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (700 mg, 53%) as an off-white solid. LCMS (Method B): m / z 402 (M+H) + (ES + ), 2.69 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 8.26 (s, 2H), 7.64 - 7.61 (m, 2H), 7.47 - 7.44 (m, 3H), 4.10 (t, J=8.8 Hz, 2H), 2.84 - 2.76 (m, 2H)

[0258] Step 2: A mixture of 5-amino-8-bromo-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (0.6 g, 1.49 mmol), methyl 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (1 g, 3.6 mmol), and KCO (0.61 g, 4.47 mmol) in 1,4-dioxane (20 mL) and HO (2 mL) was degassed for several minutes, Pd(PPh) (17 mg, 0.015 mmol) was added, the vessel was sealed, and heated at 120 °C for 5 h. The reaction mixture was partitioned between HO (20 mL) and EtOAc (30 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated. The crude product was purified by Biotage-Isolera using a 10 g silica snap eluted with a 0-80% EtOAc in hexanes gradient to give methyl 4-(5-amino-3-oxo-7-phenyl-2-(3,3,3-trifluoropropyl)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (150 mg, 22%) as a yellow solid. LCMS (Method A): m / z 472 (M+H) + (ES + ), 3.52 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.67 (s, 1H), 7.30 - 7.26 (m, 6H), 4.06 (t, J=6.5 Hz, 2H), 3.81 (s, 3H), 2.76 - 2.73 (m, 2H), 2.41 (s, 3H). No exchangeable -NH2 protons were observed.

[0259] Step 3: To a solution of methyl 4-(5-amino-3-oxo-7-phenyl-2-(3,3,3-trifluoropropyl)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)-6-methylpicolinate (120 mg, 0.25 mmol) in MeOH was added NaBH (48 mg, 1.27 mmol) in portions at room temperature, and the reaction was stirred for 15 hours. The reaction mixture was partitioned between DCM (20 mL) and saturated NaHCO solution (10 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 230-400 silica snap column eluting with a 0-100% EtOAc in hexanes gradient to give 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (63 mg, 55%) as a yellow solid. Data for the title compound are in Table 3.

[0260] Route ak: Typical Boc deprotection method using TFA Example 2-55, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3-piperidyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A solution of tert-butyl 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)piperidine-1-carboxylate (70 mg, 0.13 mmol) in 20% TFA (5 mL) of DCM was stirred at room temperature for 15 hours and then concentrated. The crude material was dissolved in MeOH (2 mL), passed through a DSC-SCX column (6 mL), washed with water (5 mL), and finally the compound was eluted with 2 M ammonia in MeOH (10 mL), concentrated, and lyophilized to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3-piperidyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (34 mg, 60%) as a yellow solid. Data for the title compounds are in Table 3.

[0261] Route 1: Typical preparation of pyridine N-oxide Example 2-56, 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a stirred solution of 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (60 mg, 0.14 mmol) in DCM was added m-CPBA (30 mg, 0.16 mmol) in portions at 0 °C and stirred at room temperature for 30 min. The reaction mixture was partitioned between EtOAc (20 mL) and HO (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was purified by preparative HPLC (Method A). The collected fractions were concentrated under reduced pressure, and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated to give 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (30 mg, 48%) as a yellow solid. Data for the title compound are in Table 3.

[0262] Route am: A typical method for alkylating amines via reductive amination Example 2-72, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a suspension of (S)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (80 mg, 0.185 mmol) in MeCN was added 35% aqueous formaldehyde solution (16 mg, 0.185 mmol) and stirred for 10 minutes. Sodium triacetoxyborohydride (76 mg, 0.36 mmol) was added to the reaction mixture and stirred at room temperature for 15 minutes. The reaction mixture was partitioned between HO (10 mL) and EtOAc (10 mL), and the organic layer was separated, dried over anhydrous NaSO, and concentrated. The crude product was purified by Biotage-Isolera using a 10 g silica snap column eluting with a gradient of 0-20% EtOAc in MeOH to give (S)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-((4-methylmorpholin-2-yl)methyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (30 mg, 38%) as a yellow solid. Data for the title compound are in Table 3.

[0263] Route an Example 2-79, (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-3-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one [ka] Step 1; Route b, carried out in a manner similar to Step 1 and purified by preparative HPLC (Method-C) to give (R)-5-amino-2-((4-benzylmorpholin-3-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (320 mg, 40%) as a yellow solid. LCMS (Method A): m / z 522 (M+H) + (ES + ), 2.37 minutes, UV activity

[0264] Step 2: To a mixture of (R)-5-amino-2-((4-benzylmorpholin-3-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (300 mg, 0.57 mmol) in MeOH (10 mL), Pd(OH) was added, and the reaction mixture was stirred for 15 hours under a H atmosphere (balloon pressure). The reaction mixture was filtered through Celite and washed with MeOH. The filtrate was concentrated under reduced pressure. The crude product was purified on a Biotage isolecra using a 25 g silica snap column eluting with a gradient of 0-10% MeOH in EtOAc to give (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-3-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (120 mg, 48%) as a yellow solid. Data for the title compound are in Table 3.

[0265] Route ao: A typical preparation of alkylated triazolopyrimidinones via alcohol tosylation and substitution reactions. Example 2-81, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (followed by chiral resolution into enantiomers, 2-81 iso-1 and 2-81 iso-2) [ka] To a solution of tosyl chloride (189.4 mg, 0.99 mmol), DMAP (11 mg, 0.09 mmol), and TEA (0.4 mL, 2.71 mmol) in DCM (10 mL) was added dropwise a solution of (tetrahydro-2H-pyran-3-yl)methanol (126 mg, 1.08 mmol) in DCM (1 mL) at 0 °C, and the resulting reaction mixture was stirred at room temperature for 30 min. The reaction mixture was partitioned between DCM (20 mL) and HO (20 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure to give the tosylated intermediate. This tosylated intermediate was dissolved in MeCN (20 mL) and 5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (300 mg, 0.90 mmol), K2CO3 (374 mg, 2.71 mmol), and the resulting reaction mixture was heated at 50 °C for 6 h in a sealed vial. The reaction mixture was partitioned between EtOAc (20 mL) and HO (20 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica gel snap eluted with a petroleum ether gradient of 0 to 100% EtOAc to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one as a yellow solid.

[0266] The racemate was purified by chiral SFC (Method C) to give 2-81 iso-1 as the first eluting peak and 2-81 iso-2 as the second eluting peak. Data for the title compounds are in Table 3.

[0267] Route ap: Typical Boc deprotection method using HCl Example 2-86, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] To a solution of tert-butyl (R)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate (250 mg, 0.45 mmol) in 1,4-dioxane (10 mL) was added HCl in 1,4-dioxane (4N solution, 5 mL) at 0° C. and stirred at room temperature for 6 hours. The mixture was concentrated, and the residue was washed with diethyl ether (10 mL) and decanted. The crude product was purified by preparative HPLC (Method A), and the pure fractions were concentrated, and the residue was diluted with 10% MeOH in DCM (10 mL) and loaded onto an SCX cartridge. The cartridge was washed with HO and MeOH, and the product was eluted with 20% ammonia in MeOH (10 mL) and concentrated under reduced pressure to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (175 mg, 87%) as a yellow solid. Data for the title compound are in Table 3.

[0268] Route aq: A typical preparation of alkylated triazolopyrimidinones via alcohol tosylation and substitution reaction followed by Suzuki coupling and ester reduction Examples 2-91 ios-1 and 2-91 iso-2, 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of tetrahydro-2H-pyran-2-yl)methanol (500 mg, 4.30 mmol) in pyridine (5 mL) was added 4-toluenesulfonyl chloride (984 mg, 5.16 mmol) at 0 °C, and the resulting reaction mixture was stirred at room temperature for 16 h. The mixture was concentrated and diluted with HO (10 mL). The reaction mixture was extracted with EtOAc (2 × 10 mL), and the combined organic layers were washed with brine (20 mL), dried over NaSO, and concentrated to give the tosylated intermediate. The resulting tosylated intermediate was dissolved in DMSO, 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (770 mg, 2.52 mmol), and KCO (1.04 g, 7.57 mmol), and the resulting reaction mixture was heated at 70 °C for 7 h. The reaction mixture was partitioned between EtOAc (20 mL) and HO (20 mL). The organic layer was separated and concentrated under reduced pressure. The crude product was purified by Biotage Isolera column chromatography using silica (230-400) mesh eluting with a petroleum ether gradient of 0-100% EtOAc to give 5-amino-8-bromo-7-phenyl-2-((tetrahydro-2H-pyran-2-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (420 mg, 41%) as a white solid. LCMS (Method A): m / z 404 (M+H) + (ES + ), 2.26 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.63-7.61 (m, 2H), 7.48-7.44 (m, 3H), 3.92-3.83 (m, 2H), 3.76-3.69 (m, 2H), 3.34 (m, 1H), 1.79 (s, 1H), 1.67 (d, J=12.40 Hz, 1H), 1.47 (s, 3H), 1.27-1.18 (m, 1H). No exchangeable -NH2 protons were observed.

[0269] Step 2; Route a, carried out in a manner similar to Step 2 to obtain methyl 4-(5-amino-3-oxo-7-phenyl-2-((tetrahydro-2H-pyran-2-yl)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)picolinate (350 mg, 70%) as a yellow solid. LCMS (Method A): m / z 473 (MH) - (ES - ), 2.26 minutes, UV activity

[0270] Step 3, Route o, was carried out in a manner similar to Step 2 to give 5-amino-8-(2-(hydroxymethyl)-6-methylpyridin-4-yl)-7-phenyl-2-((tetrahydro-2H-pyran-2-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one as a yellow solid.

[0271] The racemate was purified by chiral SFC (Method D) to give 2-91 iso-1 as the first eluting peak and 2-91 iso-2 as the second eluting peak. Data for the title compounds are in Table 3.

[0272] Route ar: A typical method for the preparation of amine analogs via alcohol tosylation and substitution reaction followed by Suzuki coupling Example 2-98, 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(3-methyl-1-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a suspension of 5-amino-8-bromo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (2 g, 6.56 mmol) and K2CO3 (1.81 g, 13.12 mmol) in MeCN (40 mL) was added 2-bromoethan-1-ol (0.98 g, 7.87 mol) at room temperature, and the reaction mixture was heated at 80 °C for 15 h. The reaction mixture was partitioned between EtOAc (50 mL) and HO (30 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give 5-amino-8-bromo-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (1 g, 44%) as an off-white solid. LCMS (Method B): m / z 350 (M+H) + (ES + ), 2.26 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.62 - 7.60 (m, 2H), 7.46 - 7.44 (m, 3H), 4.83 (t, J=6.0 Hz, 1H), 3.86 (t, J=5.6 Hz, 2H), 3.72 - 3.68 (m, 2H). No exchangeable -NH2 protons were observed.

[0273] Step 2: To a suspension of 5-amino-8-bromo-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (0.3 g, 0.86 mmol) and TEA (0.17 g, 1.72 mmol) in THF (5 mL) was slowly added methanesulfonyl chloride (0.14 g, 1.03 mol) at 0 °C, and the reaction mixture was stirred at 0 °C for 20 minutes. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in MeCN (5 mL), and KCO (0.36 g, 2.58 mmol) and 3-methylpiperidine (0.11 g, 1.29 mmol) were added. The reaction mixture was heated at 100 °C for 15 hours. The reaction mixture was partitioned between EtOAc (15 mL) and HO (15 mL). The organic layer was separated, dried over anhydrous NaSO, concentrated, and then purified by Biotage-Isolera using a 10 g silica snap eluting with a gradient of 1 to 100% EtOAc in hexanes to give 5-amino-8-bromo-2-(2-(3-methylpiperidin-1-yl)ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (120 mg, 32%) as an off-white solid. LCMS (Method B): m / z 431 (M+H) + (ES + ), 2.26 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.62 - 7.60 (m, 2H), 7.45 - 7.44 (m, 3H), 3.92 (t, J=5.2 Hz, 2H), 2.78 (t, J=5.2 Hz, 2H), 2.66 - 2.60 (m, 4H), 1.62 - 1.52 (m, 4H), 1.41 - 1.38 (m, 1H), 0.81 (d, J=6.4 Hz, 3H). No exchangeable -NH2 protons were observed.

[0274] Step 3: Route a, prepared in a manner similar to Step 2 to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(3-methyl-1-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one as a yellow solid. Data for the title compound are in Table 3.

[0275] Route as Example 2-109, Methyl 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoate Example 2-110, 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoic acid [ka] A procedure similar to Step 1, Route b, Step 1 was carried out to give tert-butyl 4-(2-(5-amino-8-bromo-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl)piperidine-1-carboxylate (400 mg, 57%) as a yellow solid. LCMS (Method A): m / z 417 (M+H-Boc) + (ES + ), 3.23 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.62 - 7.61 (m, 2H), 7.46 - 7.44 (m, 3H), 3.88 - 3.86 (m, 4H), 2.51 (t, J=2.0 Hz, 2H), 1.72 - 1.68 (m, 4H), 1.66 (t, J=1.6 Hz, 1H), 1.65 (s, 9H), 1.39-1.38 (m, 2H). No exchangeable -NH2 protons were observed.

[0276] Step 2: To a solution of tert-butyl 4-(2-(5-amino-8-bromo-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl)piperidine-1-carboxylate (400 mg, 0.77 mmol) in DCM (10 mL) was added TFA (2 mL) and stirred for 2 hours at room temperature. The reaction mixture was partitioned between DCM (10 mL) and 1.5 N sodium bicarbonate solution (5 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated to give 5-amino-8-bromo-7-phenyl-2-(2-(piperidin-4-yl)ethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (300 mg, 90%) as a yellow solid. LCMS (Method A): m / z 417 (M+H) + (ES + ), 3.23 minutes, UV activity 1 H NMR: (400 MHz, DMSO-d6) δ: 7.62 - 7.61 (m, 2H), 7.46 - 7.44 (m, 3H), 3.88 - 3.86 (m, 4H), 2.51 (t, J=2.0 Hz, 2H), 1.72 - 1.68 (m, 4H), 1.66 (t, J=1.6 Hz, 2H), 1.39-1.38 (m, 2H). No exchangeable -NH2 protons were observed.

[0277] Step 3, Route a, was carried out in a manner similar to Step 1 to give methyl 3-(4-(2-(5-amino-8-bromo-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)ethyl)piperidin-1-yl)propanoate (200 mg, 45%) as a yellow solid. LCMS (Method A): m / z 503 (M+H) + (ES + ), 2.28 minutes, UV activity

[0278] Step 4: Route a, a method similar to Step 2 was carried out and purified by preparative HPLC (Method-A). The fractions were concentrated under reduced pressure, and the resulting residue was partitioned between 10% MeOH (15 mL) in DCM and 10% NaHCO3 solution (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give methyl 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoate as a yellow solid (22 mg, 21%). During the purification, 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoic acid (20 mg, 20%) was also isolated as a yellow solid. Data for the title compound are in Table 3.

[0279] Route at:S N Typical preparation of analogues via Ar reaction Example 3-1, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-morpholino-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A solution of 5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.25 mmol) in morpholine (2 mL) was placed in a sealed tube and heated to 120 °C in a preheated oil bath and stirred for 15 h. The reaction mixture was partitioned between HO (20 mL) and EtOAc (30 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated. The crude compound was purified by Biotage-Isolera using a 10 g silica snap column eluting with a 0-100% EtOAc in hexanes gradient to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-morpholino-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (55 mg, 45%) as a yellow solid. Data for the title compound are in Table 3.

[0280] Route au Examples 3-6, Methyl 5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidine-7-carboxylate [ka] To a suspension of 5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.25 mmol) in MeOH (10 mL) was added TEA (0.3 mL, 0.35 mmol) and PdCl(dppf).DCM (50 mg, 1.09 mmol). The reaction was heated to 100 °C and 5 kg / cm 2The mixture was stirred in an autoclave under carbon monoxide pressure for 16 hours. The reaction mixture was partitioned between EtOAc (10 mL) and HO (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated under reduced pressure. The crude product was purified by Biotage-Isolera using a 10 g silica snap elution column, eluting with a 0-100% EtOAc in hexane gradient, to give methyl 5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidine-7-carboxylate (14 mg, 14%) as a yellow solid. Data for the title compound are in Table 3.

[0281] Route av Example 3-8, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-methoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] A suspension of di-boc-protected 5-amino-7-chloro-8-(2,6-dimethylpyridin-4-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (100 mg, 0.25 mmol) in MeOH (10 mL) was cooled to -20 °C and purged with ammonia gas for 5 minutes in an autoclave vessel. The vessel was sealed and heated at 100 °C for 16 hours. The reaction mixture was concentrated under reduced pressure. The crude product was purified by preparative HPLC (Method A). The collected fractions were concentrated, and the resulting residue was diluted with EtOAc (10 mL) and washed with 10% sodium bicarbonate solution (10 mL). The organic layer was separated, dried over anhydrous NaSO, and concentrated to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-methoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (16 mg, 24%) as a yellow solid. Data for the title compound are in Table 3.

[0282] Route aw Examples 3-9, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(Z)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one Example 3-10, 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(E)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one [ka] Step 1: To a solution of 2-bromobut-2-ene (100 mg, 0.740 mmol) in THF (5 mL) was added t-BuLi (1.7 M in pentane, 0.43 mL, 1.629 mmol) dropwise at −78° C. The solution was stirred at −78° C. for 1 hour, and then tri-isopropylborate (0.26 mL, 1.111 mmol) was added. The reaction mixture was stirred at −78° C. for 4 hours. The reaction mixture was quenched with saturated NH4Cl (5 mL) and extracted with diethyl ether (10 mL). The organic layer was separated, dried over Na2SO4, and concentrated to give but-2-en-2-ylboronic acid as a white solid. The crude product was used in the next step without purification or analysis.

[0283] Step 2: Route a, a method similar to Step 2 was carried out to give a mixture of alkene regioisomers. These were separated by MD Auto-prep (Method A) to give 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(Z)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (50 mg, 13%) and 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(E)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one (16 mg, 4%). Data for the title compounds are listed in Table 3. Alkene geometry was assigned by NOE.

[0284] Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16

[0285] Intermediates used in the preparation of example compounds are listed in Table 2. Compounds were prepared by the method of the indicated synthetic route ("Rte."). When no route number or data is given, commercially available materials were used. LCMS and 1 H NMR data is shown for purified products (or as "used crude" when no purification was performed). In some cases, intermediates used in the preparation of other intermediates are indicated in parentheses; for example, intermediates 41 and 42 were used in the preparation of intermediate 56.

[0286] [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] [Table 2-12]

[0287] Table 3-1 Table 3-2 Table 3-3 Table 3-4 Table 3-5 Table 3-6 Table 3-7 Table 3-8 Table 3-9 Table 3-10 Table 3-11 Table 3-12 Table 3-13 Table 3-14 Table 3-15 Table 3-16 Table 3-17 Table 3-18 Table 3-19 Table 3-20 Table 3-21 Table 3-22 Table 3-23 Table 3-24 Table 3-25 Table 3-26 Table 3-27 Table 3-28 Table 3-29 Table 3-30 Table 3-31 Table 3-32 Table 3-33 Table 3-34 Table 3-35 Table 3-36 Table 3-37 Table 3-38 Table 3-39 Table 3-40 Table 3-41 Table 3-42 Table 3-43 Table 3-44 Table 3-45 Table 3-46 Table 3-47 Table 3-48 Table 3-49 Table 3-50 Table 3-51 Table 3-52 Table 3-53 Table 3-54 Table 3-55 Table 3-56 Table 3-57 Table 3-58 Table 3-59 Table 3-60 Table 3-61 Table 3-62 Table 3-63 Table 3-64 Table 3-65 Table 3-66 Table 3-67 Table 3-68 Table 3-69

[0288] Example 4: Adenosine receptor assay Inhibitory binding assays were performed using BacMam human adenosine A 2A The experiments were carried out using 0.2 μg of membranes prepared from HEK293 cells transfected with the receptor or 1.4 μg of membranes prepared from HEK293 cells transfected with the BacMam human adenosine A1 receptor. The membranes were incubated with various concentrations of compound and 1 nM [ 3 H]ZM241385(HEK293-hA 2A )or[ 3 H]DPCPX(CHO-hA1) at 25°C for 1 h in 50 mM Tris-HCl (HEK293-hA 2A Cells were incubated in 50 mM Tris-HCl, 100 mM NaCl, 10 mM MgCl (CHO-hA1; pH 7.4) or 50 mM Tris-HCl, 100 mM NaCl, 10 mM MgCl (CHO-hA1; pH 7.4). The assay was then terminated by rapid filtration through a GF / B grade Unifilter using a TomTec cell harvester, followed by 5 x 0.5 ml washes with ddH2O. Nonspecific binding was determined using 1 μM CGS15943 (HEK293-hA1). 2A ) or 1 μM DPCPX (CHO-hA1). Bound radioactivity was determined by liquid scintillation counting, and inhibition curves were analyzed using a four-parameter logistic equation. IC 50 value Wochi Using the KD value derived from saturation binding studies using the Weinstein-Prusoff equation, calculate the K i The results are summarized in Table 4.

[0289] [Table 4-1] [Table 4-75] [Table 4-75] [Table 4-75] [Table 4-75]

[0290] Example 5: CB1 Receptor Binding and Antagonism Receptor binding The affinity of compounds for the agonist site of the human CB-1 cannabinoid receptor in transfected CHO cells was determined by a radioligand binding assay: Cell membrane homogenates (20 μg protein) were incubated in a buffer containing 50 mM Tris-HCl (pH 7.4), 5 mM MgCl2, 2.5 mM EDTA, and 0.3% BSA with 0.5 nM [ 3 H]CP 55940 for 120 minutes at 37° C. Nonspecific binding is determined in the presence of 10 μM WIN 55212-2. After incubation, samples were rapidly filtered under vacuum through glass fiber filters (GF / B, Packard) presoaked in 0.3% PEI and rinsed several times with ice-cold buffer containing 50 mM Tris-HCl (pH 7.4) and 0.5% BSA using a 96-sample cell harvester (Unifilter, Packard). The filters were dried and then counted for radioactivity in a scintillation counter (Topcount, Packard) using a scintillation cocktail (Microscint 0, Packard). The standard reference compound was CP 55940, which was tested at several concentrations in each experiment to determine the IC 50 The competitive curve is calculated.

[0291] Receptor antagonism : Evaluation of the antagonist activity of compounds at human CB1 receptors expressed in transfected CHO cells, determined by measuring their effect on agonist-induced cAMP modulation by using the HTRF detection method. The cells were suspended in HBSS buffer (Invitrogen) supplemented with 20 mM HEPES (pH 7.4) and then incubated for 5.10 min.3 Cells are distributed into microplates at a density of 100 cells / well and pre-incubated for 5 minutes at room temperature in the presence of one of the following: HBSS (stimulation control), 3 μM or various concentrations (IC 50 determination) reference antagonist AM 281 (basal control) or test compound. The reference agonist CP 55940 and the adenylyl cyclase activator NKH 477 are then added to final concentrations of 3 nM and 3 μM, respectively. For basal control measurements, CP 55940 is omitted from wells containing 3 μM AM 281. After a 20 minute incubation at 37°C, the cells are lysed and a fluorescent acceptor (D2-labeled cAMP) and a fluorescent donor (anti-cAMP antibody labeled with europium cryptate) are added. After 60 min at room temperature, fluorescence transmission was measured using a microplate reader (Rubystar, BMG) at λ ex = 337 nm and λ em = 620 and 665 nm. The cAMP concentration is determined by dividing the signal measured at 665 nm by that measured at 620 nm (ratio). Results are expressed as percent inhibition of the control response to 3 nM CP 55940. The standard reference antagonist was AM 281, which was tested in each experiment at several concentrations to determine the IC 50 Concentration-response curves are constructed to calculate values. In Table 5, K i is blank because the observed binding is i indicates that the value was too weak to measure.

[0292] [Table 5]

[0293] Other embodiments are within the scope of the following claims. Furthermore, the present invention encompasses the following aspects. 1. Formula (I): [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring A is: [ka] and Each R 1 and each R 2 independently, halo, C 1-3 Alkyl, -OC 1-3 Alkyl, -CO2R a or -NR 7 R 8 and; wherein alkyl is optionally —OR a and substituted with one or more substituents independently selected from halo; R 3 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, aryl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a and; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and where R 3 is optionally halo, cyano, -R a AND -OR a substituted with 1 to 3 substituents selected from: R 4 is not present or -(CHR c ) i -(NR a ) j -R 5 and; R5 teeth: (1)C 3-8 cycloalkyl, aryl, 3-, 4-, 6-, or 7-membered heterocyclyl or 3-, 4-, 6-, or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and where R 5 wherein one or two ring atoms are optionally replaced by -C(=O)-; (2) polycyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring systems; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and where R 5 wherein one or two ring atoms are optionally replaced by -C(=O)-; or (3) C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b and where R 5 optionally 1 to 4 groups -XR 6 is replaced by; Each X is independently a bond, —O—, or —NR a -, -S(O) k -, -(CH2) m - or -C(O)-; Each R 6 are independently H, halo, -OR a , C 1-6 Alkyl, C3-8 Cycloalkyl, heterocyclyl, heteroaryl, aryl, -CO2R a , -C(O)NR a R b , -(CH2) n -NR a R b or cyano; wherein heterocyclyl and heteroaryl are independently N, O and S(O) k and containing 1 to 4 heteroatoms independently selected from: Here, each C 3-8 one or two ring atoms of the cycloalkyl, heterocyclyl, heteroaryl, or aryl are independently optionally substituted with -C(=O)-; wherein each of alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl is optionally —R a , -OR a , -(CH2) n -NR a R b and substituted with one or more substituents independently selected from halo; Each R 7 and each R 8 are independently a and; or R 7 and R 8 together with the atoms to which they are attached, possibly -OR a and forming a 3- to 8-membered heterocyclyl substituted with one or more substituents independently selected from halo; Each R a and each R b are independently H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 is cycloalkyl; Here, each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo; Each R c are independently H, halo, and C1-3 Alkyl or -(CH2) n -NR a R b and; wherein alkyl is optionally —OR a and substituted with one or more substituents independently selected from halo; a is 0 or 1; i is 0, 1, 2 or 3; j is 0 or 1; each k is independently 0, 1, or 2; each m is independently 1 or 2; and each n is independently 0 or 1; A compound or a pharmaceutically acceptable salt thereof. 2. The compound is a selective adenosine receptor antagonist for CB-1; term Compound 1. 3. The compound has a K of 100 nM or less for at least one of the A2aR and A2bR. i and has a K of 10,000 nM or more for CB-1 i having term Compound 2. 4. R 5 C 1-6 Alkyl, -OR a , -NR a R b , cyano, -OS(O)2-C 1-3 Alkyl, -CO2R a , -C(O)NR a R b , -NR a -C(O)-OR a or -OC(O)-NR a R b That is, term Any of compounds 1 to 3. 5. R 5 is aryl, 6-membered heterocyclyl or 6-membered heteroaryl; term Any of compounds 1 to 3. 6. R 5is a polycyclic, 6-11 membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system; term Any of compounds 1 to 3. 7. R 3 C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, heterocyclyl, heteroaryl, halo, -OR a , -NR a R b , -CO2R a , -CONR a R b , -NR a C(O)-R a OR-NHC(O)-OR a That is, term Any of compounds 1 to 6. 8. i is 1 and R c is H or C 1-3 alkyl; or i is 2 and each R c is H, term Any of compounds 1 to 7. 9. Formula (II): [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 1 and each R 2 independently, Halo, C 1-3 Alkyl or -OC 1-3 is alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Ring B is C 3-8 cycloalkyl, aryl, 6- or 7-membered heterocyclyl or 6- or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl independently contain 1 to 4 heteroatoms independently selected from N and O; Each R 9 independently, halo, -R a -OR a and; Each R a and each R b are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 is cycloalkyl; Here, each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo; L is -(CHR c ) e - and; Each R c are independent, H, halo, C 1-3 Alkyl or -(CH2) n -NR a R b and; wherein alkyl is optionally -OR a and substituted with one or more substituents independently selected from halo; R d is H or halo; a is 0 or 1; b is 0, 1 or 2; d is 0, 1, 2, 3 or 4; e is 1 or 2; and n is 0 or 1, A compound or a pharmaceutically acceptable salt thereof. 10. Formula (III): [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 1 and each R 2 independently, Halo, C 1-3 Alkyl, -OC 1-3 Alkyl, -CO2R a or -NR 7 R 8 and; wherein alkyl is optionally -OR aand substituted with one or more substituents independently selected from halo; R 4 Ga-(CHR c )2-R 5 and; R 5 H, halo, C 1-3 Alkyl, -OR e , -COR e , -COOR e , -OS(O)2R e , -OCO-NR e R f or -CO-NR e R f and; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Each R a and each R b are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl or C 4-9 is cycloalkyl; Here, each R a and each R b is independently optionally substituted with one or more substituents independently selected from —OH and halo; Each R c are independent, H, halo, C 1-3 Alkyl or -(CH2) n -NR a R b and; wherein alkyl is optionally -OR a and substituted with one or more substituents independently selected from halo; R d is H or halo; Each R e and each R f are independently H or C 1-6 is alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; a is 0 or 1; and each n is independently 0 or 1; A compound or a pharmaceutically acceptable salt thereof. 11. R 5 is H, -CH3, -CH2F, -CHF2 or -CF3; term 10 compounds. 12. A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of: 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluorophenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-hydroxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-1-methyl-6-oxo-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-pyridylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isothiochroman-4-yl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(7-fluorotetralin-1-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,5-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(difluoromethylsulfanyl)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(o-tolylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluoro-2-methyl-phenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[(2-pyrazol-1-yl-3-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2-chloro-3-fluoro-phenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(cyclopropylmethoxy)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2,6-difluorophenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-[(dimethylamino)methyl]phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(4-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(3-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxy-6-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-phenyl-2-(2,2,2-trifluoroethylamino)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[[2-(4-piperidylmethyl)phenyl]methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(2-amino-1-(2,6-difluorophenyl)ethyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoropyrimidin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-hydroxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[1-(5-fluoro-2-pyridyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-2-[1-(5-fluoro-2-pyridyl)propyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-2-[(3-fluoro-5-methoxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-6-hydroxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-bromo-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 6-[[5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 6-[[5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-3-oxo-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]pyridine-3-carbonitrile; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(dimethylamino)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-hydroxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-methoxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(trifluoromethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-2-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-hydroxyphenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-fluorophenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoate; 4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]benzoic acid; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(azetidin-1-yl)-6-methyl-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-2-chloro-N-methyl-benzamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-[1-([1,2,4]triazolo[4,3-a]pyrimidin-3-yl)ethylamino]ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[methyl-(1-phenyl-4-piperidyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[(1S)-1-(6-methyl-2-pyridyl)ethyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[1-(3-methyl-1H-pyrazol-5-yl)-4-piperidyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[2-(1-methylpyrrol-2-yl)azepan-1-yl]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[4-[(5-methyl-2-pyridyl)amino]-1-piperidyl]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[3-(3-methyl-5-oxo-4H-pyrazol-1-yl)anilino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[2-(hydroxymethyl)tetralin-2-yl]-methyl-amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(aminomethyl)-2-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[(3R)-4-benzylmorpholin-3-yl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-benzyl-4-piperidyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholin-3-yl-1-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(5-aminoindan-2-yl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2H-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-methyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-ethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopropyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopentyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(3-fluoropropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl methanesulfonate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-methoxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanenitrile; Ethyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]carbamate; Ethyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-N-methyl-carbamate; tert-Butyl N-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]carbamate; Methyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanoate; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl N-ethylcarbamate; 5-amino-2-(3,3-difluoropropyl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[ethyl(methyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-[cyclopropyl(methyl)amino]ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]acetamide; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[3-hydroxy-2-(hydroxymethyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-acetamide; 5-amino-2-[(3,3-difluorocyclopentyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethyl-2-methyl-cyclopropyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N-cyclopropyl-N-methyl-acetamide; Methyl 1-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]cyclopentanecarboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(trifluoromethoxy)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2,3,4,5,6-pentadeuteriophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(2,4-difluorophenyl)-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methoxyphenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 4-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-7-yl]benzonitrile; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(3-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(5-fluoro-2-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylpyrazol-1-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(2-furyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(5-methyl-2-furyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-methylthiazol-2-yl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-methyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[5-amino-3-oxo-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-pyridine-2-carboxylate; 5-amino-8-[2-(hydroxymethyl)-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3-piperidyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-fluorocuban-1-yl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-(2,3,4,5,6-pentadeuteriophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(cuban-1-ylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(3-bicyclo[1.1.1]pentanylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-butyl (R)-2-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)morpholine-4-carboxylate; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; tert-Butyl 4-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-piperidylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl (2S)-2-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]morpholine-4-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-3-piperidyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-4-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; tert-Butyl (3S)-3-[[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]methyl]morpholine-4-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-morpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1-methyl-4-piperidyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-3-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3R)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -Amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; t ert-butyl (S)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate; tert-butyl (R)-3-((5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)methyl)-4-methylpiperazine-1-carboxylate; (R)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1,1-dioxothiazol-2-yl)methyl] hmm -3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1,1-dioxothietan-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-Amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -Amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one ; 5 -amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,4,5,6-tetrahydropyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(azetidin-1-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-(2-(2-azabicyclo[3.1.0]hexan-2-yl)ethyl)-5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(1-methyl-4-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(3-methyl-1-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholinoethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-((cis)-2,6-dimethylmorpholin-4-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(4,4-difluoro-1-piperidyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-methylpiperazin-1-yl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(8-azabicyclo[3.2.1]octan-8-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 3-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]piperidine-1-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[2-(4-hydroxy-1-piperidyl)-2-oxo-ethyl]-methyl-amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethylamino]-N-cyclopropyl-cyclohexanecarboxamide; Methyl 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoate; 3-[4-[2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl]-1-piperidyl]propanoic acid; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[3-(1-piperidyl)propyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(3-(2-oxopyridin-1(2H)-yl)propyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)-N-methylpropanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-morpholino-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(1-piperidyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-ethoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[ethyl(methyl)amino]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-chloro-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidine-7-carboxylate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-prop-1-ynyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-methoxy-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-[(Z)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; and 5-Amino-8-(2,6-dimethyl-4-pyridyl)-7-[(E)-1-methylprop-1-enyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one. 13. term A pharmaceutical composition comprising any one of the compounds of 1 to 12 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or excipient. 14. For the treatment of diseases or conditions mediated by adenosine receptors, term Use of any of the compounds of 1 to 12 or a pharmaceutically acceptable salt thereof. 15. The disease or condition mediated by adenosine receptors is lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma, or other solid tumors; term 14 uses.

Claims

1. Formula (II): 【Chemistry 1】 or a pharmaceutically acceptable salt thereof, wherein: Each R １ and each R ２ became independent, Halo, C １－３ Alkyl or —O—C １－３ is alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Ring B is C ３－８ cycloalkyl, aryl, 6- or 7-membered heterocyclyl or 6- or 7-membered heteroaryl; wherein heterocyclyl and heteroaryl independently contain 1 to 4 heteroatoms independently selected from N and O; Each R ９ are independently halo, -R ａ or -OR ａ and Each R ａ and each R ｂ are independent, H, C １－６ Alkyl, C ３－８ Cycloalkyl or C ４－９ cycloalkylalkyl; Here, each R ａ and each R ｂ is independently optionally substituted with one or more substituents independently selected from —OH and halo; L is -(CHR ｃ ) ｅ - and; Each R ｃ are independent, H, halo, C １－３ Alkyl or -(CH ２ ) ｎ -NR ａ R ｂ and wherein alkyl is optionally —OR ａ and substituted with one or more substituents independently selected from halo; R ｄ is H or halo; a is 0 or 1; d is 0, 1, 2, 3 or 4; e is 1 or 2; and n is 0 or 1; A compound or a pharmaceutically acceptable salt thereof.

2. Formula (III): 【Chemistry 2】 or a pharmaceutically acceptable salt thereof, wherein: Each R １ and each R ２ became independent, Halo, C １－３ Alkyl, —O—C １－３ Alkyl, —CO ２ R ａ or -NR ７ R ８ and wherein alkyl is optionally —OR ａ and substituted with one or more substituents independently selected from halo; R ４ -(CHR ｃ ) ２ -R ５ and R ５ H, halo, C １－３ Alkyl, -OR ｅ , -COR ｅ , -COOR ｅ , -OS(O) ２ R ｅ , —OCO—NR ｅ R ｆ or —CO—NR ｅ R ｆ and wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; Each R ７ and R ８ is independently R ａ and or R ７ and R ８ may optionally be -OR together with the atom to which they are attached. ａ and halo; Each R ａ and each R ｂ are independent, H, C １－６ Alkyl, C ３－８ Cycloalkyl or C ４－９ cycloalkylalkyl; Here, each R ａ and each R ｂ is independently optionally substituted with one or more substituents independently selected from —OH and halo; Each R ｃ are independent, H, halo, C １－３ Alkyl or -(CH ２ ) ｎ -NR ａ R ｂ and wherein alkyl is optionally —OR ａ and substituted with one or more substituents independently selected from halo; R ｄ is H or halo; Each R ｅ and each R ｆ are independently H or C １－６ is alkyl; wherein alkyl is optionally substituted with one or more substituents independently selected from —OH and halo; a is 0 or 1; and each n is independently 0 or 1; A compound or a pharmaceutically acceptable salt thereof.

3. R ５ is H, -CH ３ , -CH ２ F, -CHF ２ or -CF ３ 3. The compound of claim 2, wherein:

4. A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of: 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluorophenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-hydroxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-oxo-1H-pyridin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-1-methyl-6-oxo-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-pyridylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(2,5-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(o-tolylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-fluoro-2-methyl-phenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2-chloro-3-fluoro-phenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[[2-(cyclopropylmethoxy)phenyl]methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(2,6-difluorophenyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethoxyphenyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(4-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-(3-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(4-methoxy-6-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[1-phenyl-2-(2,2,2-trifluoroethylamino)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-methoxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(2-amino-1-(2,6-difluorophenyl)ethyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoropyrimidin-2-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(6-hydroxypyridazin-3-yl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[1-(5-fluoro-2-pyridyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(5-fluoro-2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(5-fluoro-2-pyridyl)propyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-fluoro-5-methoxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-6-hydroxy-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-chloro-5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-bromo-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(2-methoxy-3-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(pyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(6-amino-5-fluoro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-[(5-methyl-2-pyridyl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-chloro-2-pyridyl)methyl]-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-hydroxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-2-[(5-methoxy-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(5-fluoro-2-pyridyl)methyl]-8-(2-methoxy-6-methyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(trifluoromethyl)-4-pyridyl]-2-[(5-fluoro-2-pyridyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(1-methyl-2-phenyl-ethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-hydroxyphenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-fluorophenyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(2-pyridyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-methyl-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(2-phenylethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[[(1S)-1-(6-methyl-2-pyridyl)ethyl]amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[1-(aminomethyl)-2-(2,4-difluorophenyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-ethyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopropyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isopentyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-hydroxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(3-fluoropropyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl methanesulfonate; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-methoxyethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanoate; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]ethyl N-ethylcarbamate; 5-amino-2-(3,3-difluoropropyl)-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-[ethyl(methyl)amino]ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-[cyclopropyl(methyl)amino]ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-propyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[3-hydroxy-2-(hydroxymethyl)propyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]-N,N-dimethyl-acetamide; 5-amino-2-[(3,3-difluorocyclopentyl)methyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(2-ethyl-2-methyl-cyclopropyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(trifluoromethoxy)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-[5-amino-8-(2,6-dimethyl-4-pyridyl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2-yl]propanamide; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(2,4-difluorophenyl)-8-(2,6-dimethyl-4-pyridyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-chloro-6-(hydroxymethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methoxy-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; Methyl 4-[5-amino-3-oxo-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-pyridine-2-carboxylate; 5-amino-8-[2-(hydroxymethyl)-6-(trifluoromethyl)-4-pyridyl]-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-phenyl-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-2-isobutyl-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-1-oxide-pyridin-1-ium-4-yl)-7-(4-fluorophenyl)-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[(4-fluorocuban-1-yl)methyl]-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(cuban-1-ylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-(3-bicyclo[1.1.1]pentanylmethyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(4-piperidylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-2-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-4-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-4-methylmorpholin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-morpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3S)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[(1-methyl-4-piperidyl)methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-8-(2,6-dimethylpyridin-4-yl)-2-(morpholin-3-ylmethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(3R)-4-methylmorpholin-3-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (R)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2R)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; (S)-5-amino-2-((1,4-dimethylpiperazin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[[(2S)-1-methylpiperazin-2-yl]methyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-7-phenyl-2-(tetrahydropyran-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-7-(4-fluorophenyl)-8-[2-(hydroxymethyl)-6-methyl-4-pyridyl]-2-(3,4,5,6-tetrahydropyridazin-3-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 2-(2-(2-azabicyclo[3.1.0]hexan-2-yl)ethyl)-5-amino-8-(2,6-dimethylpyridin-4-yl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(1-methyl-4-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(3-methyl-1-piperidyl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-(2-morpholinoethyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-((cis)-2,6-dimethylmorpholin-4-yl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-2-[2-(4,4-difluoro-1-piperidyl)ethyl]-8-(2,6-dimethyl-4-pyridyl)-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-2-[2-(4-methylpiperazin-1-yl)ethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2,6-dimethyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 5-amino-8-(2-chloro-6-methyl-4-pyridyl)-7-(4-fluorophenyl)-2-[2-(1-piperidyl)ethyl]-[1,2,4]triazolo[4,3-c]pyrimidin-3-one; 3-(5-amino-8-(2,6-dimethylpyridin-4-yl)-3-oxo-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidin-2(3H)-yl)-N-methylpropanamide.

5. A pharmaceutical composition comprising a compound of any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or excipient.

6. 10. A therapeutic agent for a disease or condition mediated by an adenosine receptor, comprising the compound of any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof.

7. The method of claim 6, wherein the disease or condition mediated by adenosine receptors is lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, brain cancer, stomach cancer, liver cancer, kidney cancer, endometrial cancer, thyroid cancer, bladder cancer, glioma, melanoma, or other solid tumors.

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