Pyrazolo[4,3-D]pyrimidines as kinase inhibitors

Abstract

The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases. ##STR00001##

Claims

1. A compound of formula (I): ##STR00045## wherein R.sup.1 is an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; and R.sup.2 is an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group, wherein R.sup.2 is bound to the pyrimidine ring of formula (I) via a carbon-carbon bond; or a pharmaceutically acceptable salt, solvate or hydrate or a pharmaceutically acceptable formulation thereof.

2. The compound of claim 1, wherein R.sup.1 is an optionally substituted cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group.

3. The compound of claim 1, wherein R.sup.1 is an optionally substituted phenyl or naphthyl group or an optionally substituted heteroaryl group having one or two rings containing 5, 6, 7, 8, 9 or 10 ring atoms, or an optionally substituted arylheterocycloalkyl, heteroarylcycloalkyl or heteroaryl-heterocycloalkyl group containing two or three rings and 9 to 20 ring atoms.

4. The compound of claim 1, wherein R.sup.1 is a group of formula X.sup.1-L.sup.1-Y.sup.1 or a group of formula X.sup.1-L.sup.1-y.sup.1-L.sup.2-Z.sup.1 wherein X.sup.1 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.1 is a bond or a group of formula CH.sub.2, C(O), SO, SO.sub.2, NHC(O), C(O)NH; C(O)O, OC(O), NHC(O)O, OC(O)NH, NHSO.sub.2NH, CH.sub.2NHCH.sub.2, NHSO.sub.2, SO.sub.2NH or NHC(O)NH; Y.sup.1 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.2 is a bond or a group of formula CH.sub.2, C(O), SO, SO.sub.2, NHC(O), C(O)NH; C(O)O, OC(O), NHC(O)O, OC(O)NH, NHSO.sub.2NH, CH.sub.2NHCH.sub.2, NHSO.sub.2, SO.sub.2NH or NHC(O)NH; and Z.sup.1 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N.

5. The compound of claim 1, wherein R.sup.1 is selected from the following groups: ##STR00046## ##STR00047## ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053##

6. The compound according to claim 1, wherein R.sup.1 is selected from the following groups: ##STR00054## ##STR00055## ##STR00056## ##STR00057##

7. A compound according to claim 1, wherein R.sup.1 is selected from the following groups: ##STR00058##

8. A compound according to claim 1, wherein R.sup.1 is selected from the following groups: ##STR00059## ##STR00060## ##STR00061## ##STR00062## ##STR00063## ##STR00064## ##STR00065## ##STR00066## ##STR00067## ##STR00068## ##STR00069##

9. The compound according to claim 1, wherein R.sup.1 has the following structure: ##STR00070## wherein R.sup.3 is hydrogen or an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; R.sup.3a is hydrogen, halogen, OH, SH, NH.sub.2, or an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; R.sup.3b is hydrogen, halogen, OH, SH, NH.sub.2, or an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; and R.sup.3c is hydrogen, halogen, OH, SH, NH.sub.2, or an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group.

10. The compound of claim 9 wherein R.sup.3 is an optionally substituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl or heteroalkylcycloalkyl group and R.sup.3a and R.sup.3b are both hydrogen.

11. The compound of claim 9 wherein R.sup.3a and R.sup.3b are both hydrogen and R.sup.3 is selected from the following groups: ##STR00071##

12. The compound of claim 1, wherein R.sup.2 is an optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aralkyl or heteroaralkyl group.

13. The compound of claim 1, wherein R.sup.2 is an optionally substituted phenyl or naphthyl group or an optionally substituted heteroaryl group having one or two rings containing 5, 6, 7, 8, 9 or 10 ring atoms, or an optionally substituted arylheterocycloalkyl or heteroarylheterocycloalkyl group containing two or three rings and 9 to 20 ring atoms.

14. The compound of claim 1, wherein R.sup.2 is a group of formula X.sup.2-L.sup.3-Y.sup.2 or a group of formula X.sup.2-L.sup.3-Y.sup.2-L.sup.4-Z.sup.2wherein X.sup.2 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.3 is a bond or a group of formula CH.sub.2, C(O), SO, SO.sub.2, NHC(O), C(O)NH; C(O)O, OC(O), NHC(O)O, OC(O)NH, NHSO.sub.2NH, CH.sub.2NHCH.sub.2, NHSO.sub.2, SO.sub.2NH or NHC(O)NH; Y.sup.2 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.4 is a bond or a group of formula CH.sub.2, C(O), SO, SO.sub.2, NHC(O), C(O)NH; C(O)O, OC(O), NHC(O)O, OC(O)NH, NHSO.sub.2NH, CH.sub.2NHCH.sub.2, NHSO.sub.2, SO.sub.2NH or NHC(O)NH; and Z.sup.2 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N.

15. The compound of claim 1, wherein R.sup.2 is an optionally substituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl or heteroalkylcycloalkyl group.

16. The compound of claim 1, wherein R.sup.2 is a heteroalkyl group containing from 1 to 6 carbon atoms and 1, 2 or 3 heteroatoms selected from O, S and N, or an optionally substituted C.sub.3-C.sub.7 cycloalkyl group, or an optionally substituted heterocycloalkyl group containing from 2 to 6 carbon atoms and 1, 2 or 3 heteroatoms selected from O, S and N, or an optionally substituted C.sub.4-C.sub.10 alkylcycloalkyl group, or an optionally substituted heteroalkylcycloalkyl group containing from 3 to 10 carbon atoms and from 1 to 4 heteroatoms selected from O, S and N.

17. The compound of claim 1, wherein R.sup.2 is selected from the following groups: ##STR00072## ##STR00073## ##STR00074## ##STR00075##

18. The compound of claim 1, wherein R.sup.2 is selected from the following groups: ##STR00076##

19. The compound of claim 1, wherein R.sup.2 is selected from the following groups: ##STR00077##

20. The compound of claim 1, wherein R.sup.2 is selected from the following groups: ##STR00078## ##STR00079## ##STR00080##

21. The compound of claim 1 selected from the group consisting of: N-(2-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(2-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(2-(7-((3-(methylsulfonyl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(1H-indazol-6-yl)-5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(3-nitrophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(3-aminophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(5-methylthiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(5-methylthiophen-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N -(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N-(3-fluoro-4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N -(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 1-(4-(4-((5-(3-aminophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; methyl 3-(7-(benzo[d][1,3]dioxol-5-ylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; N-(benzo[d][1,3]dioxol-5-yl)-5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2,3-dihydrobenzo[b]thiophene 1,1-dioxide; 5-cyclopropyl-N -(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; 7-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-fluoro-4-morpholinophenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(3-methoxy-4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 2-(4-((5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)-2-methylpropanenitrile; 2-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)-2-methylpropanenitrile; N-(2-(7-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)-1H -pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N -(2-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(2-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 5-cyclopropyl-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-cyclopropyl-N-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(3-methoxy-4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(thiophen-2-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzo[b]thiophene 1,1-dioxide; N-(3-methoxy-4-morpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one; N-(3-(7-((4-(4-(tert -butyl)piperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((3-fluoro-4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((3-methoxy-4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((4-(2-oxooxazolidin-3-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(4-(4-(tert -butyl)piperazin-1-yl)phenyl)-5-(1H-indazol-6-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-fluoro-4-morpholinophenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-methoxy-4-morpholinophenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(3-methylthiophen-2yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methylthiophen-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone; 5-(1H-indazol-6-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(tetrahydrofuran-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-fluoro-4-morpholinophenyl)-5-(oxazol-4-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one; 5-(methoxymethyl)-N-(4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(methoxymethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(methoxymethyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(methoxymethyl)-N-(3-(methylsulfonyl)phenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(methoxymethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(1-methoxyethyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1-methoxyethyl)-1H -pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(1-methoxyethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(isoxazol-5-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N -(3-fluoro-4-morpholinophenyl)-5-(isoxazol-5-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 5-(isoxazol-5-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(isoxazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(isoxazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(isoxazol-3-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N -(3-fluoro-4-morpholinophenyl)-5-(isoxazol-3-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 5-(isoxazol-3-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(5-fluoro-1H-indazol-6-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(tetrahydrofuran-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(tetrahydrofuran-3-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(1,4-dioxan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1,4-dioxan-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-morpholinobenzonitrile; 5-(furan-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N -(3,4-dimethoxyphenyl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(4-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (4-methylpiperazin-1-yl)(4-((5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; 5-(1-methyl-1H-imidazol-2-yl)-N -(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1-methyl-1H-imidazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(morpholinomethyl)-N-(4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(morpholinomethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(furan-3-yl) -N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(furan-3-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one; 5-(1-methylcyclopropyl) -N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(2-methylcyclopropyl)-N-(4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(2-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(2-methylcyclopropyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H -pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-((dimethylamino)methyl)-N-(4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 5-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole-3-carboxylic acid; 5-(furan-3-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(furan-3-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H -benzo[b]azepin-2(3H)-one; 5-(furan-3-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H -pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(4-(4-(tert -butyl)piperazin-1-yl)phenyl)-5-(furan-2-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(furan-2-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H -benzo[b]azepin-2(3H)-one; 5-(furan-2-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one; 5-(furan-2-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(tetrahydro-2H -pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H -pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-pyrazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H -pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(pyridazin-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(pyridazin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(6-morpholinopyridin-3-yl)-5-(pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(oxazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 5-(1H-indazol-6-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; and 5-(1H-indazol-6-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; or a pharmaceutically acceptable salt, ester, solvate or hydrate or a pharmaceutically acceptable formulation thereof.

22. The compound of claim 1 selected from the group consisting of: 5-(1-methylcyclopropyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(2-methylcyclopropyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(2-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(2-methylcyclopropyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-((dimethylamino)methyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole-3-carboxylic acid; 5-(furan-3-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 5-(furan-3-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(4-(4-(tert-butyl) piperazin-1-yl)phenyl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 5-(furan-2-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one; 5-(furan-2-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-pyrazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(pyridazin-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(pyridazin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(oxazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 5-(1H-indazol-6-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 5-(1H-indazol-6-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(pyridazin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-1,2,4-triazol-3-yl)-N-(4-morpholinophenyl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-pyrazol-3-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methyl-1H-pyrazol-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile; 5-(1H-indazol-5-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-5-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-isopropyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-isopropyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (2-fluoro-4-((5-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone; 5-isopropyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-isopropyl-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 1-(4-(4-((5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 5-(1-methyl-1H-pyrazol-4-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; (4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-fluorophenyl)(morpholino)methanone; 5-cyclopropyl-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (2-fluoro-4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone; 5-(furan-2-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (2-fluoro-4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone; 5-(furan-3-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile; 1-(4-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 1-(4-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 5-cyclobutyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-fluorophenyl)(morpholino)methanone; 4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-methylpyridin-2 (1H)-one; 4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-methylpyridin-2(1H)-one; 2-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarbonitrile; 5-(furan-2-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; methyl 3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarbonitrile; 5-(furan-3-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile; 4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-(2-methoxyethyl)pyridin-2(1H)-one; (4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-1-amine; 5-cyclopropyl-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-(2-methoxyethyl)pyridin-2(1H)-one; (4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone; 5-cyclopropyl-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(5-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)pyridin-2-yl)piperazin-1-yl)ethan-1-one; 5-(furan-2-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; 5-(furan-3-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)acetonitrile; 2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isobutyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; (4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(oxazol-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isobutyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; 5-(oxazol-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; N-(3-(7-((1-(tert-butyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-isopropyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-isobutyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 5-cyclobutyl-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(tert-butyl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(tert-butyl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(tert-butyl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(tert-butyl)-N-(1,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(tert-butyl)-N-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(tert-butyl)-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(tert-butyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile; (4-((5-(tert-butyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone; 3-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-methylpyridin-2 (1H)-one; N-(1-(tert-butyl)-1H-pyrazol-3-yl)-5-(furan-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-bromo-1-methyl-1H-pyrazol-3-yl)-5-(furan-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1,5-dimethyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(furan-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(1-methoxy-2-methylpropan-2yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(2-methoxyethyl)-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(2-methoxyethyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(2-methoxyethyl)-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(2-methoxyethyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-cyclopropyl-4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)pyridin-2(1H)-one; N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(2-methoxyethyl)-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(2-methoxyethyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-3-methoxy-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-3-methoxy-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isopropyl-5-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-isopropyl-5-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-3-methoxy-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-5-methoxy-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-(4-(oxazol-5-yl)phenyl)benzamide; N-(4-(2H-1,2,3-triazol-2-yl)phenyl)-3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide; 3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-(4-(oxazol-2-yl)phenyl)benzamide; N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-5-(furan-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(furan-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)oxazolidin-2-one; 5-(furan-3-yl)-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(3-methoxy-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)oxazolidin-2-one; N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tert-butyl)-5-methyl-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)oxazolidin-2-one; 5-(furan-2-yl)-N-(3-methoxy-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tert-butyl)-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tert-butyl)-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-2yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione; N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone; 6-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione; N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-chloro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol; 5-cyclopropyl-N-(2-fluoro-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(2,3-dimethylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(2-methyl-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(2-methyl-4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(2-methyl-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(2-methyl-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(2-methyl-4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-isopropyl-1H-pyrazole-5-carbonitrile; 5-(furan-2-yl)-N-(1-(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-2-yl)-N-(1-(2-methoxyethyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-isobutyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (3-methoxy-4-((5-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone; N-(3,4-dimethoxyphenyl)-5-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (4-((5-cycloheptyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone; 5-cycloheptyl-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cycloheptyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(5-chloro-4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; 5-cyclopropyl-N-(1-(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(1-(2-methoxyethyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-isopropyl-1H-pyrazole-5-carbonitrile; 5-(furan-3-yl)-N-(1-(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(2-methoxyethyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-bromo-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-fluoro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(2-methyl-3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclopropyl-N-(5-ethynyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-bromo-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-fluoro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N4-(5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-1-(2-methoxyethyl)-N5,N5-dimethyl-1H-pyrazole-4,5-diamine; 5-(furan-2-yl)-N-(2-methyl-3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methoxyphenyl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methoxyphenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2-yl)-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2-yl)-N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile; N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isopropyl-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-isopropyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-ol; 5-(1H-indazol-6-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(7-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((1-isopropyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((1-isobutyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isopropyl-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isobutyl-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,5-dimethylisoxazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methylthiophen-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-isobutyl-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(trifluoromethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N4-(5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-1-(2-methoxyethyl)-N5,N5-dimethyl-1H-pyrazole-4,5-diamine; 2-(4-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-ol; 1-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol; 2-(4-((5-(benzo[d]oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; 5-(benzo[d]oxazol-2-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]oxazol-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol; 1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol; 1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol; 2-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-N,N-dimethylacetamide; tert-butyl 3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate; N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(benzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; 5-(benzo[d]thiazol-2-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol 4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-benzyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-N,N-dimethylacetamide; 5-cyclobutyl-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-cyclobutyl-N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-(pyridin-3-yl)phenyl)-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N,N-dimethyl-2-(4-((5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)acetamide; N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one; 6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-ethyl-2H-benzo[b][1,4]oxazin-3(4H)-one; 5-(1H-indazol-6-yl)-N-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(bicyclo[4.1.0]heptan-7-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(bicyclo[4.1.0]heptan-7-yl)-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-1-amine; 5-(bicycio[4.1.0]heptan-7-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol; 5-(1H-indazol-6-yl)-N-(1-(1-phenylethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-ethylphenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (7-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone; N-(3,4-dimethoxyphenyl)-5-(2-fluoro-6-methylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluoro-6-methylphenyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(furan-3-yl)-N-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-ethyl-6-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; 2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)propanoic acid; 5-(furan-3-yl)-N-(1-(1-phenylethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one; N-(3-ethylphenyl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; cyclopropyl(7-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)methanone; 5-(2,2-dimethylcyclopropyl)-N-(i-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,2-dimethylcyclopropyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)propanoic acid; 5-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazole-3-carboxylic acid; N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one; 5-cyclopropyl-N-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazole-3-carboxylic acid; (4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone; 2-(4-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-ol; 5-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-morpholinobenzonitrile; cyclopropyl(7-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)methanone; 2-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)propanoic acid; 5-(1H-indazol-6-yl)-N-(1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; N1-(5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-4,5-dimethoxybenzene-1,2-diamine; N-(3-methoxy-4-morpholinophenyl)-5-((1S,2S)-2-phenylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-((1S,2S)-2-phenylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-((1S,2S)-2-phenylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-methoxy-4-morpholinophenyl)-5-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-chloro-6-fluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-chloro-6-fluorophenyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(4-(phenylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 5-(1H-indazol-6-yl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol; 6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; 6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]thiazin-3(4H)-one; 8-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 1-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol; N-(5-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-methoxyphenyl)acetamide; 5-(2,6-difluorophenyl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 5-(2-(methylsulfonyl)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(2-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; N-(3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 5-(3-aminophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-aminophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-amino-6-fluorophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(2-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-(methylsulfonyl)phenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (5-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)methanol; N-(5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; N-(2-(4-acetylpiperazin-1-yl)-5-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)acetamide; N-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2,6-dichloro-4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; and 5-(2,6-difluorophenyl)-N-(3-ethoxy-4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine.

23. A pharmaceutical composition comprising a compound of claim 1, 21 or 22 or a pharmaceutically acceptable hydrate, solvate or salt thereof, optionally in combination with a pharmaceutically acceptable carrier.

24. A method of treatment of a disease mediated by kinase-activity comprising the administration, to a patient in need thereof, of a therapeutically effective amount of a compound of claim 1, 21 or 22 or a pharmaceutical composition according to claim 23, wherein the kinese is selected from SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2), and/or Myosin light chain kinase (MYLK or MLCK) or mutants thereof and wherein the disease is selected from the group consisting of pruritus, eczema, asthma, rhinitis, dry eye, ocular inflammation, allergic conjunctivitis, vernal conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, fungal keratitis and uveitis.

25. The method of claim 24, wherein said treatment is systemic or topical.

26. The method of claim 25, wherein said topical administration is to the skin, the eye, by intranasal administration or by inhalation.

Description

EXAMPLES

(1) Materials and Methods

(2) Biological AssaysProtein Kinase Assays

(3) SYK Assay

(4) In the assay OMNIA KINASE ASSAY by Invitrogen Corporation (Carlsbad) the effect of invention of a compound on the phosphorylation is determined by measurement of fluorescence intensity of a chelation-enhanced fluorophore called SOX. Upon phosphorylation of the peptide by the kinase of interest, Mg2+ is chelated to form a bridge between the SOX moiety and the phosphate group that is transferred to the specific tyrosine on the peptide. The fluorescence intensity is directly proportional to the amount of peptide phosphorylation.

(5) To the wells of an 384 well small volume plate (Greiner, Frickenhausen) are added (i) the compound under test in 5% DMSO/distilled water (2 l), (ii) 16 l of the master mix containing ATP, DTT, Kinase Reaction Buffer, Omina Peptide Substrate Tyr 7 resulting in a final concentration of 1 mM ATP, 0.2 mM DTT and 10 M Peptide Substrate. The Master Mix and the assay plate was incubated to reaction temperature before the measurement (30 C.). The reaction was started with addition of (iii) 2 l 4 g/ml SYK kinase (Invitrogen, Carlsbad). During measurement fluorescence intensitiy readings were collected using a TECAN M1000 at a wavelength of ex 360/em 485 nm every 30 s for 30 minutes. The reaction velocity was plotted versus the inhibitor concentration to determine the IC50 using XLFit 5.0 (IDBS, Guildford) to fit to a sigmoidal dose response curve.

(6) The ATP dependency was determined according to Lai C-J-, Wu J C A Simple Kinetic Method for Rapid Mechanistic Analysis of Reversible Enzyme Inhibitors. Assays and Drug Dev. Technologies. 2003; 1(4):527-535. To demonstrate a competition effect of the test compounds towards ATP the corresponding test compound was used at the 50% inhibitory concentration. Assay conditions as described previously were maintained. ATP concentrations used was 1000, 333, 100, 33.3, 10, 3.3, 1 M.

(7) LRRK2LRRK2 G2019SAssay

(8) In the assay LanthaScreen Eu Kinase Binding Assay by Invitrogen Corporation (Carlsbad) the effect of invention of a compound on the phosphorylation is determined by measurement of fluorescence intensity emission ratio based on the binding and displacement of a proprietary, Alexa Fluor 647-labeled, ATP-competitive kinase inhibitor scaffold (kinase tracer) to the kinase of interest. Binding of the tracer to the kinase is detected using a europium-labeled anti-tag antibody, which binds to the kinase of interest. Simultaneous binding of both the tracer and antibody to the kinase results in a high degree of FRET (fluorescence resonance energy transfer) from the europium (Eu) donor fluorophore to the Alexa Fluor 647 acceptor fluorophore on the kinase tracer. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET. The fluorescence intensity ratio is directly proportional to the amount of peptide phosphorylation. To the wells of an 384 well small volume plate (Greiner, Frickenhausen) are added (i) the compound under test in 5% DMSO/distilled water (5 l), (ii) 5 l of the kinase antibody mixture resulting in a final concentration 5 nM LRRK2 or their mutants, 2 nM EU-Anti-GST antibody in 1 kinase buffer A. The reaction was started with addition of (iii) 5 l resulting in a final concentration of 10 nM tracer 236. The assay plate was incubated at RT for 1 h and fluorescence intensitiy readings were collected using a TECAN M1000 at two wavelengthes of ex 340/em 615 nm and ex 340/em 665 nm with a delay time of 100 s and an integration time of 200 s after 60 minutes. The emission ratio was calculated by division of the acceptor/tracer emission (665 nM) by the antibody/donor emission (615 nM). The inhibitor concentration was plotted versus the emission ratio to determine the IC50 using XLFit 5.0 (IDBS, Guildford) to fit to a sigmoidal dose response curve with a variable slope.

(9) General Procedures for Synthesis of Compounds

(10) Chromatography

(11) The compound verification via analytical HPLC-MS was done after purification using the following instrumentation, column and method:

(12) Analytical Method for Compound Purity

(13) Instrumentation:

(14) Agilent MSD 1100
Analytical Methods:
Solvents: A: acetonitrile B: H2O C: 2% HCOOH in acetonitrile D: 0.1% NEt3 in acetonitrile

(15) The following analytical methods were used:

(16) Method A

(17) Column YMC TriArt C18 2.050 mm, 1.9 m, #TA12SP90502WT thermostated@40 C.
Gradient:

(18) TABLE-US-00001 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 0.45 0.5 90 5 0 0.45 4.5 10 5 0 0.45 5.5 10 5 0 0.45 5.6 90 5 0 0.45
Stoptime@10min MS:ESIpositive,Massscanfrom100to800 gradientfragmentation: 50to125V UV: detection @ 220 and 254 nm
Purification and Characterisation:

(19) The resulting crude reaction products were purified in an automatic process using a semi-preparative HPLC-MS with mass-triggered sampling of the desired peak:

(20) Purification Via Semi-preparative HPLC-MS

(21) Instrumentation:

(22) 2 Varian PrepStar SD-1 1 Dionex P580 Pump 1 Channel(MakeUP I) 1 Dionex AXP-MS (MakeUP II) 1 Dionex MSQ 1 Dionex UVD 340V Prep Flow Cell Gilson 215 Liquid Handler
Column: SunFire Prep C18 OBD 5 m 1950 mm
Method: Column Flow: 30 ml/min Solvent A: methanol, 0.3% acetic acid Solvent B: water, 0.3% acetic acid
Time Table for Gradient:

(23) TABLE-US-00002 Time (min) Solv. A Solv. B 0.0 30.00 70.00 10.0 100.00 0.00 14.0 100.00 0.00 14.4 30.00 70.00 16.4 30.00 70.00
Detection: UV 254 nm, Mass Spectrometer Detector (API-ES, positive)
Compound Preparation

(24) Where the preparation of starting materials is not described, these are commercially available, known in the literature, or readily obtainable by those skilled in the art using standard procedures. Where it is stated that compounds were prepared analogously to earlier examples or intermediates, it will be appreciated by the skilled person that the reaction time, number of equivalents of reagents and temperature can be modified for each specific reaction and that it may be necessary or desirable to employ different workup or purification techniques. Where reactions are carried out using microwave irradiation, the microwave used is an Initiator 60 supplied by Biotage. The actual power supplied varies during the course of the reaction in order to maintain a constant temperature.

(25) Abbreviations

(26) DCM=Dichloromethane DIPEA=N,N-Diisopropylethylamine DMF=N,N-Dimethylformamide DDQ=2,3-Dichloro-5,6-dicyano-1,4-benzoquinone THF=Tetrahydrofuran MeOH=Methanol tBuOH=2-Methyl-2-propanol tBuOK=Potassium tertiary butoxide T3P=Propane phosphonic acid anhydride TFA=Trifluoroacetic acid TEA=Triethylamine rm=Reaction mixture rt=Room temperature AcOH=Acetic acid MeCN=Acetonitrile EtOH=Ethanol EtOAc=Ethyl Acetate LCMS=Mass spectrometry directed high pressure liquid chromatography UV=Ultraviolet DMSO=Dimethylsulphoxide
Intermediates
Route A:

Preparation of 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine

(27) Step 1: 5-Phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one

(28) 4-Amino-2H-pyrazole-3-carboxylic acid amide (5 mmol) and benzaldehyde (5 mmol) were dissolved in acetic acid (14 ml). Subsequently DDQ (3.75 mmol) were added and the reaction mixture was heated in the microwave to 180 C. for 30 minutes. The precipitate was filtered and washed with Et2O.

(29) Step 2: Protection of Pyrazole with 1-Chloromethyl-4-methoxy-benzene

(30) 5-Phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (3.9 mmol) was dissolved in 14 ml acetonitrile. 1-Chloromethyl-4-methoxy-benzene (4.7 mmol), 1.2 eq triethylamine (4.7 mmol) and sodiumiodide (0.39 mmol) was added subsequently. The reaction mixture was heated in the microwave for 30 min at 160 C. After cooling down the reaction the resulting precipitate was filtered and washed with Et2O.

(31) The reaction is leading to two isomers (1-(4-Methoxy-benzyl)-5-phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one and 2-(4-Methoxy-benzyl)-5-phenyl-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one).

(32) Both isomers can be used for the next steps.

(33) Step 3: Chlorination

(34) The mixture of 1-(4-Methoxy-benzyl)-5-phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one and 2-(4-Methoxy-benzyl)-5-phenyl-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (0.18 mmol) was suspended in POCl3. The mixture was heated to 100 C. in a reaction vessel. After 0.5 h-24 h LC-MS showed reaction completion. The mixture was cooled to rt. The mixture was concentrated to dryness, cooled to 0 C., and quenched with ice/water. The mixture was extracted with DCM. The organic layer was washed with NaHCO3 sat. aq. and water, dried (Na2SO4) filtered and concentrated.

(35) The product was used without further purification.

(36) The product is an isomeric mixture of 7-Chloro-1-(4-methoxy-benzyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidine and 7-Chloro-2-(4-methoxy-benzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine

(37) Both isomers can be used for the next steps.

(38) The following Chlorides and Isomers were synthezised according to ROUTE A: N-(2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 7-chloro-2-(4-methoxybenzyl)-5-(3-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2,6-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 7-chloro-5-(1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole; 7-chloro-2-(4-methoxybenzyl)-5-(3-methylthiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole; 7-chloro-5-(5-fluoro-1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(furan-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-imidazol-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-imidazol-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(furan-3-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole-3-carboxylic acid ethyl ester; 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(pyridazin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(pyridazin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-pyrazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1H-indazol-5-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-(4-(oxazol-5-yl)phenyl)benzamide; N-(4-(2H-1,2,3-triazol-2-yl)phenyl)-3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-(4-(oxazol-2-yl)phenyl)benzamide; 7-chloro-2-(4-methoxybenzyl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]thiazole; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylisoxazole; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]oxazole; 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2-fluoro-6-methylphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2-chloro-6-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(2-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)aniline; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)aniline; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-fluoro aniline; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole

(39) Route B:

Preparation of 7-chloro-5-cyclopropyl-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine

(40) Step 1: 5-cyclopropyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 4-amino-2H-pyrazole-3-carboxylic acid amide (5 mmol) and DIPEA (7.5 mmol) were dissolved in DCM (30 mL). The solution was stirred at 0 C. followed by dropwise addition of cyclopropanecarbonyl chloride (10 mmol) in DCM (20 mL). After stirring over night at rt, the mixture was concentrated. After addition of water, the pH was adjusted to pH=6 and the product was extracted with DCM. The crude product2-cyclopropanecarbonyl-4-(cyclopropanecarbonyl-amino)-2H-pyrazole-3-carboxylic acid amidewas used directly without further purification.

(41) 2-cyclopropanecarbonyl-4-(cyclopropanecarbonyl-amino)-2H-pyrazole-3-carboxylic acid amide (3 mmol) was dissolved in tBuOH (20 mL). tBuOK (6eq.) in tBuOHA11 was added. the reaction mixture was heated in the microwave to 150 C. for 30 minutes. The reaction mixture was concentrated. After addition of cold water, the solution was adjusted to pH=5. The product was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and evaporated. The crude product5-cyclopropyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-onewas used directly without further purification

(42) Step 2 and Step 3, according to the steps described in ROUTE A, will result in the formation of the intermediate 7-chloro-5-cyclopropyl-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine

(43) Route C:

Preparation of 7-chloro-2-(4-methoxybenzyl)-5-(1-methylcyclopropyl)-2H-pyrazolo[4,3-d]pyrimidine

(44) Step 1: 5-(1-methylcyclopropyl)-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one

(45) 4-amino-2H-pyrazole-3-carboxylic acid amide (3.5 mmol), 1-methyl-cyclopropanecarboxylic acid (3.5 mmol) and TEA (21 mmol) were dissolved in DCM (30 mL). After addition of T3P (5.25 mmol) the reaction mixture was stirred at rt over night. After addition of 5 mL 0.5 N NaOG (aq.) and 75 mL water, the product was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and evaporated. The crude product4-[(1-methyl-cyclopropanecarbonyl)-amino]-2H-pyrazole-3-carboxylic acid amidewas used directly without further purification.

(46) 4-[(1-methyl-cyclopropanecarbonyl)-amino]-2H-pyrazole-3-carboxylic acid amide (3 mmol) was dissolved in tBuOH (20 mL). tBuOK (6eq.) in tBuOHA11 was added. the reaction mixture was heated in the microwave to 150 C. for 30 minutes. The reaction mixture was concentrated. After addition of cold water, the solution was adjusted to pH=5. The product was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and evaporated. The crude product5-cyclopropyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-onewas used directly without further purification

(47) Step 2 and Step 3, as described in ROUTE A, will result in the formation of the intermediate 7-chloro-2-(4-methoxybenzyl)-5-(1-methylcyclopropyl)-2H-pyrazolo[4,3-d]pyrimidine

(48) The following Chlorides and Isomers were synthezised according to ROUTE C: 7-chloro-2-(4-methoxybenzyl)-5-(tetrahydrofuran-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(methoxymethyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methoxyethyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(tetrahydrofuran-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(tetrahydro-2H-pyran-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1,4-dioxan-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 4-((7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)methyl)morpholine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methylcyclopropyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(2-methylcyclopropyl)-2H-pyrazolo[4,3-d]pyrimidine; 1-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-N,N-dimethylmethanamine; 7-chloro-5-cyclobutyl-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(5-methylthiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(3-methylthiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-isopropyl-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(tert-butyl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1-isobutyl-1H-pyrazol-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-propyl-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-cycloheptyl-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1-isopropyl-1H-pyrazol-4-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylisoxazole; 7-chloro-2-(4-methoxybenzyl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(1-benzyl-1H-pyrazol-4-yl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(bicyclo[4.1.0]heptan-7-yl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2,2-dimethylcyclopropyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-4,5,6,7-tetrahydrobenzo[d]thiazole; 7-chloro-2-(4-methoxybenzyl)-5-(2-phenylcyclopropyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidine;
Route D:

Preparation of 7-chloro-2-(4-methoxybenzyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine

(49) Step 1

(50) 4-Amino-1-(4-methoxy-benzyl)-1H-pyrazole-3-carboxylic acid methyl ester (0.3 mmol) and 1H-[1,2,4]triazole-3-carbonitrile (0.45 mmol) were dissolved in 2.5 mL 4N HCl in dioxane. The reaction mixture was heated in the microwave to 140 C. for 10 minutes. After completition the solvent was evaporated. The crude product2-(4-Methoxy-benzyl)-5-(1H-[1,2,4]triazol-3-yl)-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-onewas used directly without further purification.

(51) Step 3, as described in ROUTE A, will result the in the formation of the intermediate 7-chloro-2-(4-methoxybenzyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine

(52) The following Chlorides and Isomers were synthezised according to ROUTE D: 7-chloro-2-(4-methoxybenzyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine: 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine

(53) Products

Example 1

N-(2-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

(54) N-(2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide (0.16 mmol) and 4-morpholinoaniline (2 eq., 0.3 mmol) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(55) exact mass: 465.1913 g/mol

(56) HPLC-MS: analytical method A

(57) rt: 4.87 minfound mass: 466.2 (m/z+H)

(58) The following examples were synthesized according to the protocol of Example 1:

Example 2

N-(2-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 3

N-(2-(7-((3-(methylsulfonyl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 4

N-(1H-indazol-6-yl)-5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 5

N-(4-morpholinophenyl)-5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 6

1-(4-(4-((5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 8

N-(3,4-dimethoxyphenyl)-5-(5-methylthiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 9

5-(5-methylthiophen-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 10

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 11

5-(2,6-difluorophenyl)-N-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 12

5-(2,6-difluorophenyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 13

1-(4-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 15

methyl 3-(7-(benzo[d][1,3]dioxol-5-ylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

Example 16

N-(benzo[d][1,3]dioxol-5-yl)-5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 17

6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2,3-dihydrobenzo[b]thiophene 1,1-dioxide

Example 18

5-cyclopropyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 19

5-cyclopropyl-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 20

5-cyclopropyl-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 21

6-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 22

7-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

Example 23

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 24

N-(3-fluoro-4-morpholinophenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 25

5-(2-fluorophenyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 26

1-(4-(4-((5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 27

2-(4-((5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)-2-methylpropanenitrile

Example 28

2-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)-2-methylpropanenitrile

Example 29

N-(2-(7-((4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 30

N-(2-(7-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 31

N-(2-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 32

5-cyclopropyl-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 33

1-(4-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 34

5-cyclopropyl-N-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 35

5-cyclopropyl-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 36

6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzo[b]thiophene 1,1-dioxide

Example 37

N-(3-methoxy-4-morpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 38

3-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenypoxazolidin-2-one

Example 39

N-(3-(7-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 40

N-(3-(7-((3-fluoro-4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 41

N-(3-(7-((3-methoxy-4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 42

N-(3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 43

N-(3-(7-(4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 44

N-(3-(7-((4-(2-oxooxazolidin-3-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 45

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 46

N-(3-fluoro-4-morpholinophenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 47

N-(3-methoxy-4-morpholinophenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 48

N-(4-morpholinophenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 49

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 50

1-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 51

N-(3,4-dimethoxyphenyl)-5-(3-methylthiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 52

5-(3-methylthiophen-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 53

(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone

Example 54

5-(1H-indazol-6-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 55

5-cyclopropyl-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 56

N-(4-morpholinophenyl)-5-(tetrahydrofuran-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 57

N-(3-fluoro-4-morpholinophenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 58

3-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenypoxazolidin-2-one

Example 59

5-(methoxymethyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 60

N-(3,4-dimethoxyphenyl)-5-(methoxymethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 61

5-(methoxymethyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 62

5-(methoxymethyl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 63

1-(4-(4-((5-(methoxymethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 64

5-(1-methoxyethyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 65

1-(4-(4-((5-(1-methoxyethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 66

N-(3,4-dimethoxyphenyl)-5-(1-methoxyethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 67

1-(4-(4-((5-(isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 68

N-(3,4-dimethoxyphenyl)-5-(isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 69

5-(isoxazol-5-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 70

N-(3-fluoro-4-morpholinophenyl)-5-(isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 71

5-(isoxazol-5-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 72

1-(4-(4-((5-(isoxazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 73

N-(3,4-dimethoxyphenyl)-5-(isoxazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 74

5-(isoxazol-3-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 75

N-(3-fluoro-4-morpholinophenyl)-5-(isoxazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 76

5-(isoxazol-3-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 77

5-(5-fluoro-1H-indazol-6-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 78

N-(3,4-dimethoxyphenyl)-5-(tetrahydrofuran-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 79

N-(4-morpholinophenyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 80

N-(3,4-dimethoxyphenyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 81

N-(3,4-dimethoxyphenyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 82

N-(4-morpholinophenyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 83

N-(3,4-dimethoxyphenyl)-5-(1,4-dioxan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 84

5-(1,4-dioxan-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 85

5-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-morpholinobenzonitrile

Example 86

5-(furan-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 87

N-(3,4-dimethoxyphenyl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 88

5-(1H-indazol-6-yl)-N-(4-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 89

(4-methylpiperazin-1-yl)(4-((5-(3-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

Example 90

5-(1-methyl-1H-imidazol-2-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 91

1-(4-(4-((5-(1-methyl-1H-imidazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 92

5-(morpholinomethyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 93

1-(4-(4-((5-(morpholinomethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 94

5-(furan-3-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 95

N-(3,4-dimethoxyphenyl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 96

1-(4-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 97

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 98

3-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenypoxazolidin-2-one

Example 99

5-(1-methylcyclopropyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 100

1-(4-(4-((5-(1-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 101

5-(2-methylcyclopropyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 102

1-(4-(4-((5-(2-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 103

5-(2-methylcyclopropyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 104

5-((dimethylamino)methyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 106

5-(furan-3-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 107

8-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 108

5-(furan-3-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 109

5-(furan-3-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 110

5-(furan-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 111

1-(4-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 112

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 113

8-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 114

5-(furan-2-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 115

3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one

Example 116

5-(furan-2-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 117

5-(furan-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 118

5-cyclopropyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 119

5-cyclobutyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 120

5-cyclobutyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 121

5-(1-methyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 122

5-(1-methyl-1H-pyrazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 123

N-(4-morpholinophenyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 124

5-(pyridazin-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 125

N-(4-morpholinophenyl)-5-(pyridazin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 126

N-(6-morpholinopyridin-3-yl)-5-(pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 127

5-(oxazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 128

N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 129

N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 130

1-(4-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 131

5-(1H-indazol-6-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 132

5-(1H-indazol-6-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 133

1-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 134

5-(1H-indazol-6-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 135

5-(1-methylcyclopropyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 136

1-(4-(4-((5-(1-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 137

5-(2-methylcyclopropyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 138

1-(4-(4-((5-(2-methylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 139

5-(2-methylcyclopropyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 140

5-((dimethylamino)methyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 142

5-(furan-3-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 143

8-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 144

5-(furan-3-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 145

5-(furan-3-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 146

5-(furan-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 147

1-(4-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 148

N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 149

8-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 150

5-(furan-2-yl)-N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 151

3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)oxazolidin-2-one

Example 152

5-(furan-2-yl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 153

5-(furan-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 154

5-cyclopropyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 155

5-cyclobutyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 156

5-cyclobutyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 157

5-(1-methyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 158

5-(1-methyl-1H-pyrazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 159

N-(4-morpholinophenyl)-5-(1H-1,2,4-triazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 160

5-(pyridazin-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 161

N-(4-morpholinophenyl)-5-(pyridazin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 162

N-(4-morpholinophenyl)-5-(pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 163

5-(oxazol-4-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 164

N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 165

N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 166

1-(4-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 167

5-(1H-indazol-6-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 168

5-(1H-indazol-6-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 169

1-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 170

5-(1H-indazol-6-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 172

N-(4-morpholinophenyl)-5-(pyridazin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 173

5-(1-methyl-1H-1,2,4-triazol-3-yl)-N-(4-morpholinophenyl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 175

5-(1-methyl-1H-pyrazol-3-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 176

5-(1-methyl-1H-pyrazol-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 177

2-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile

Example 178

5-(1H-indazol-5-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 179

5-(1H-indazol-5-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 180

1-(4-(4-((5-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 181

5-isopropyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 182

5-isopropyl-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 183

(2-fluoro-4-((5-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone

Example 184

5-isopropyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 185

5-isopropyl-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 186

1-(4-(4-((5-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 187

1-(4-(4-((5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 188

N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 189

1-(4-(4-((5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 190

5-(1-methyl-1H-pyrazol-4-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 191

5-cyclobutyl-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 192

1-(4-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 193

(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-fluorophenyl)(morpholino)methanone

Example 194

5-cyclopropyl-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 195

5-(furan-2-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 196

1-(4-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 197

(2-fluoro-4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone

Example 198

5-(furan-2-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 199

5-(furan-3-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 200

1-(4-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 201

(2-fluoro-4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone

Example 202

5-(furan-3-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 203

2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile

Example 204

1-(4-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 205

1-(4-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 206

5-cyclobutyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 207

5-cyclopropyl-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 208

(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-fluorophenyl)(morpholino)methanone

Example 209

4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-methylpyridin-2(1H)-one

Example 210

4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-methylpyridin-2(1H)-one

Example 211

2-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile

Example 212

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 213

1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarbonitrile

Example 214

5-(furan-2-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 215

5-(furan-2-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 216

methyl 3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

Example 218

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 219

1-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)cyclohexanecarbonitrile

Example 220

5-(furan-3-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 221

5-(furan-3-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 222

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 223

5-cyclobutyl-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 224

5-cyclobutyl-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 225

2-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile

Example 226

4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-(2-methoxyethyl)pyridin-2(1H)-one

Example 227

(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone

Example 228

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 229

5-cyclopropyl-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 230

5-cyclopropyl-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 231

4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-(2-methoxyethyl)pyridin-2(1H)-one

Example 232

(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone

Example 233

5-cyclopropyl-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 234

5-cyclobutyl-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 235

5-cyclopropyl-N-(1,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 236

5-cyclopropyl-N-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 237

1-(4-(5-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)pyridin-2-yl)piperazin-1-yl)ethan-1-one

Example 238

5-(furan-2-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 239

2-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 240

5-(furan-3-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 241

2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)acetonitrile

Example 242

2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 243

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 244

N-(1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 245

N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 246

N-(1-isobutyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 247

2-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 248

(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone

Example 249

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 250

N-(1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 251

N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 252

N-(1-isobutyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 253

2-(4-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 254

5-(oxazol-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 255

N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 256

N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 257

1-(4-(4-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 258

N-(3-(7-((1-(tert-butyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 259

N-(3-(7-((1-isopropyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 260

N-(3-(7-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 261

N-(3-(7-((1-isobutyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 262

N-(3-(7-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 263

N-(3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 264

N-(3-(7-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 265

N-(3-(7-((1-(2-methoxyethyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 266

N-(3-(7-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 267

5-cyclobutyl-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 268

5-(tert-butyl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 269

5-(tert-butyl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 270

5-(tert-butyl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 271

5-(tert-butyl)-N-(1,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 272

5-(tert-butyl)-N-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 273

5-(tert-butyl)-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 274

2-(4-((5-(tert-butyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile

Example 275

(4-((5-(tert-butyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone

Example 276

3-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-methylpyridin-2(1H)-one

Example 277

N-(1-(tert-butyl)-1H-pyrazol-3-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 278

N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 279

N-(4-bromo-1-methyl-1H-pyrazol-3-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 280

N-(1,5-dimethyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 281

N-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 282

5-cyclopropyl-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 283

5-cyclopropyl-N-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 284

5-cyclopropyl-N-(1-(2-methoxyethyl)-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 285

5-cyclopropyl-N-(1-(2-methoxyethyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 286

5-cyclopropyl-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 287

5-cyclopropyl-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 288

5-(furan-3-yl)-N-(1-(2-methoxyethyl)-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 289

5-(furan-3-yl)-N-(1-(2-methoxyethyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 290

5-(furan-3-yl)-N-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 291

N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 292

5-(furan-3-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 293

5-(furan-3-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 294

5-(furan-3-yl)-N-(3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 295

5-(furan-3-yl)-N-(5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 296

1-cyclopropyl-4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)pyridin-2(1H)-one

Example 297

N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 298

5-(furan-2-yl)-N-(1-(2-methoxyethyl)-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 299

5-(furan-2-yl)-N-(1-(2-methoxyethyl)-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 300

5-(furan-2-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 301

5-(furan-2-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 302

5-(furan-2-yl)-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 303

5-(furan-2-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 304

5-(furan-2-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 305

N-(1-(1-(tert-butyl)piperidin-4-yl)-3-methoxy-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 306

5-(furan-3-yl)-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 307

5-(furan-3-yl)-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 308

5-(furan-3-yl)-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 309

N-(1-(1-(tert-butyl)piperidin-4-yl)-3-methoxy-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 310

5-cyclobutyl-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 311

5-cyclobutyl-N-(1-isopropyl-5-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 312

N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 313

5-cyclopropyl-N-(5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 314

5-cyclopropyl-N-(3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 315

5-cyclopropyl-N-(1-isopropyl-3-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 316

5-cyclopropyl-N-(1-isopropyl-5-methoxy-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 317

N-(1-(1-(tert-butyl)piperidin-4-yl)-3-methoxy-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 318

N-(1-(1-(tert-butyl)piperidin-4-yl)-5-methoxy-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 319

3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-(4-(oxazol-5-yl)phenyl)benzamide

Example 320

N-(4-(2H-1,2,3-triazol-2-yl)phenyl)-3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide

Example 321

3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-(4-(oxazol-2-yl)phenyl)benzamide

Example 322

N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 323

N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 324

5-cyclobutyl-N-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 325

5-cyclobutyl-N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 326

5-cyclobutyl-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 327

N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 328

N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 329

5-cyclopropyl-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 330

N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 331

5-cyclobutyl-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 332

5-(furan-2-yl)-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 333

N-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 334

N-(5-chloro-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 335

3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)oxazolidin-2-one

Example 336

5-(furan-3-yl)-N-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 337

N-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 338

5-(furan-3-yl)-N-(3-methoxy-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 339

5-(furan-3-yl)-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 340

3-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)oxazolidin-2-one

Example 341

N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 342

N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 343

N-(1-(tert-butyl)-5-methyl-1H-pyrazol-4-yl)-5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 344

5-cyclopropyl-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 345

3-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenypoxazolidin-2-one

Example 346

5-(furan-2-yl)-N-(3-methoxy-1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 347

N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 348

5-(furan-2-yl)-N-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 349

N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 350

6-((9-methoxy-3H-pyrazolo[3,4-c]quinolin-4-yl)amino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Example 351

N-(1-(tert-butyl)-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 352

N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 353

N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 354

N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 355

N-(1-(tert-butyl)-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 356

N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 357

N-(5-chloro-1-isopropyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 358

N-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 359

6-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Example 360

N-(5-chloro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 361

N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 362

5-cyclopropyl-N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 363

5-cyclobutyl-N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 364

N-(5-chloro-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 365

(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone

Example 366

6-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Example 367

N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 368

N-(5-chloro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 369

1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol

Example 370

5-cyclopropyl-N-(2-fluoro-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 371

5-cyclopropyl-N-(2,3-dimethylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 372

5-cyclopropyl-N-(2-methyl-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 373

5-cyclopropyl-N-(2-methyl-4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 374

5-cyclopropyl-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 375

5-(furan-3-yl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 376

5-(furan-3-yl)-N-(2-methyl-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 377

5-(furan-2-yl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 378

5-(furan-2-yl)-N-(2-methyl-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 379

5-(furan-2-yl)-N-(2-methyl-4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 380

4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-isopropyl-1H-pyrazole-5-carbonitrile

Example 381

5-(furan-2-yl)-N-(1-(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 382

5-(furan-2-yl)-N-(1-(2-methoxyethyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 383

5-(1-isobutyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 384

(3-methoxy-4-((5-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(morpholino)methanone

Example 385

N-(3,4-dimethoxyphenyl)-5-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 386

N-(4-morpholinophenyl)-5-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 387

(4-((5-cycloheptyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3-methoxyphenyl)(morpholino)methanone

Example 388

5-cycloheptyl-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 389

5-cycloheptyl-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 390

2-(5-chloro-4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 391

5-cyclopropyl-N-(1-(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 392

5-cyclopropyl-N-(1-(2-methoxyethyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 393

5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 394

N-(4-morpholinophenyl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 395

4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1-isopropyl-1H-pyrazole-5-carbonitrile

Example 396

5-(furan-3-yl)-N-(1-(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 397

5-(furan-3-yl)-N-(1-(2-methoxyethyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 398

N-(5-bromo-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 399

N-(5-fluoro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 400

5-cyclopropyl-N-(2-methyl-3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 401

5-cyclopropyl-N-(5-ethynyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 402

N-(5-bromo-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 403

N-(5-fluoro-1-(2-methoxyethyl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 404

N4-(5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-1-(2-methoxyethyl)-N5,N5-dimethyl-1H-pyrazole-4,5-diamine

Example 405

5-(furan-2-yl)-N-(2-methyl-3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 406

N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 407

N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 408

5-(3-methoxyphenyl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 409

5-(3-methoxyphenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 410

5-(benzo[d]thiazol-2-yl)-N-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 411

5-(benzo[d]thiazol-2-yl)-N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 412

5-(benzo[d]thiazol-2-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 413

5-(benzo[d]thiazol-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 414

5-(1H-indazol-6-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 415

N-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 416

2-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile

Example 417

N-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 418

N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 419

5-(1H-indazol-6-yl)-N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 420

N-(1-isopropyl-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 421

5-(1-isopropyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 422

2-(4-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-ol

Example 423

5-(1H-indazol-6-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 424

3-(7-((1-(3-methoxypropyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 425

3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 426

3-(7-((1-isopropyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 427

3-(7-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 428

3-(7-((1-isobutyl-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 429

N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 430

N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 431

N-(1-isopropyl-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 432

N-(1-isobutyl-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 433

N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 434

5-(3,5-dimethylisoxazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 435

5-(3-methylthiophen-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 436

N-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 437

N-(1-isobutyl-1H-pyrazol-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 438

N-(4-morpholinophenyl)-5-(trifluoromethyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 439

5-(2,6-difluorophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 440

5-(2,6-difluorophenyl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 441

N4-(5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-1-(2-methoxyethyl)-N5,N5-dimethyl-1H-pyrazole-4,5-diamine

Example 442

2-(4-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-ol

Example 443

1-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol

Example 444

2-(4-((5-(benzo[d]oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 445

5-(benzo[d]oxazol-2-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 446

5-(benzo[d]oxazol-2-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 447

5-(1H-indazol-6-yl)-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 448

N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 449

1-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol

Example 450

1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol

Example 451

1-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-2-ol

Example 452

2-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-N,N-dimethylacetamide

Example 453

tert-butyl 3-(4-((5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate

Example 454

N-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 455

N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-5-(furan-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 456

5-(benzo[d]thiazol-2-yl)-N-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 457

5-(benzo[d]thiazol-2-yl)-N-(1-isobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 458

1-(4-(4-((5-(benzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one

Example 459

5-(benzo[d]thiazol-2-yl)-N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 460

5-(1-benzyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 461

2-(4-((5-cyclobutyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)-N,N-dimethylacetamide

Example 462

5-cyclobutyl-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 463

5-cyclobutyl-N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 464

N-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 465

5-(3-(pyridin-3-yl)phenyl)-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 466

N,N-dimethyl-2-(4-((5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)acetamide

Example 467

N-(1-(1,3-dimethoxypropan-2-yl)-1H-pyrazol-4-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 468

N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 469

5-(1H-indazol-6-yl)-N-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 470

6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 471

6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-ethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 472

5-(1H-indazol-6-yl)-N-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 473

5-(bicyclo[4.1.0]heptan-7-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 474

5-(bicyclo[4.1.0]heptan-7-yl)-N-(1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 475

5-(bicyclo[4.1.0]heptan-7-yl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 476

2-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)ethan-1-ol

Example 477

5-(1H-indazol-6-yl)-N-(1-(1-phenylethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 478

N-(3-ethylphenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 479

(7-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

Example 480

N-(3,4-dimethoxyphenyl)-5-(2-fluoro-6-methylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 481

5-(2-fluoro-6-methylphenyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 482

5-(furan-3-yl)-N-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 483

5-(furan-3-yl)-N-(1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 484

5-(furan-3-yl)-N-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 485

4-ethyl-6-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 486

2-(4-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)propanoic acid

Example 487

5-(furan-3-yl)-N-(1-(1-phenylethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 488

6-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 489

N-(3-ethylphenyl)-5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 490

cyclopropyl(7-((5-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)methanone

Example 491

5-(2,2-dimethylcyclopropyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 492

5-(2,2-dimethylcyclopropyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 493

2-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)propanoic acid

Example 494

5-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazole-3-carboxylic acid

Example 495

N-(1-(1-(tert-butyl)piperidin-4-yl)-1H-pyrazol-4-yl)-5-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 496

N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 497

6-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 498

5-cyclopropyl-N-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 499

5-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazole-3-carboxylic acid

Example 500

(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone

Example 501

2-(4-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-ol

Example 502

5-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-morpholinobenzonitrile

Example 503

cyclopropyl(7-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)methanone

Example 504

2-(4-((5-cyclopropyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-1H-pyrazol-1-yl)propanoic acid

Example 505

5-(1H-indazol-6-yl)-N-(1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 506

2-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

Example 507

N1-(5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-4,5-dimethoxybenzene-1,2-diamine

Example 508

N-(3-methoxy-4-morpholinophenyl)-5-((1S,2S)-2-phenylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 509

N-(3,4-dimethoxyphenyl)-5-((1S,2S)-2-phenylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 510

N-(4-morpholinophenyl)-5-((1S,2S)-2-phenylcyclopropyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 511

N-(3,4-dimethoxyphenyl)-5-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 512

N-(3-methoxy-4-morpholinophenyl)-5-(1-(3-methylbutan-2-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 513

5-(2-chloro-6-fluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 514

5-(2-chloro-6-fluorophenyl)-N-(3-methoxy-4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 515

5-(1H-indazol-6-yl)-N-(4-(phenylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 516

8-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 517

5-(1H-indazol-6-yl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 518

1-(4-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol

Example 519

6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

Example 520

6-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]thiazin-3(4H)-one

Example 521

8-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 522

1-(4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperidin-4-ol

Example 523

N-(5-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-methoxyphenyl)acetamide

Example 524

5-(2,6-difluorophenyl)-N-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 525

3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 526

3-(7-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

Example 527

5-(2-(methylsulfonyl)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 528

8-((5-(2-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Example 529

N-(3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

Example 533

N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(2-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 534

5-(2-(methylsulfonyl)phenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 535

N-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 536

(5-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)methanol

Example 537

N-(5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

Example 538

N-(2-(4-acetylpiperazin-1-yl)-5-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)acetamide

Example 539

N-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 540

2,6-dichloro-4-((5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

Example 541

5-(2,6-difluorophenyl)-N-(3-ethoxy-4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 7

5-(3-aminophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(59) 7-chloro-2-(4-methoxybenzyl)-5-(3-nitrophenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (2 eq., 0.3 mmol) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was concentrated. The reaction mixture was dissolved in methanol (3 mL). Pd/C was added (20 mg) and the reaction was stirred overnight under N2 at room temperature. After filtration with celite the reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 362.1744 g/mol
HPLC-MS: analytical method A rt: 3.60 minfound mass: 363.2 (m/z+H)

(60) The following examples were synthesized according to the protocol of Example 7:

Example 14

1-(4-(4-((5-(3-aminophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

Example 530

5-(3-aminophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 531

5-(2-aminophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 532

5-(2-amino-6-fluorophenyl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Example 105

5-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole-3-carboxylic acid

(61) 5-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole-3-carboxylic acid ethyl ester (0.16 mmol) and 4-morpholinoaniline (2 eq., 0.3 mmol) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was evaporated and 2N NaOH (3 mL, aq.) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140 C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 407.1556 g/mol
HPLC-MS: analytical method A rt: 3.53 minfound mass: 408.2 (m/z+H)

(62) The following examples were synthesized according to the protocol of Example 105:

Example 141

5-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)isoxazole-3-carboxylic acid

Example 217

3-(7-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(63) Biological Data

(64) SYK Activities:

(65) IC50 lower than 10 nM: Example 12; Example 18; Example 22; Example 35; Example 45; Example 50; Example 54; Example 69; Example 106; Example 112; Example 120; Example 134; Example 1-(2; Example 146; Example 148; Example 156; Example 170; Example 189; Example 192; Example 196; Example 198; Example 200; Example 202; Example 204; Example 206; Example 214; Example 215; Example 220; Example 221; Example 223; Example 229; Example 239; Example 241; Example 242; Example 244; Example 245; Example 291; Example 328; Example 410; Example 411; Example 417; Example 418; Example 433; Example 447; Example 456; Example 458; Example 462; Example 468; Example 519; Example 536; Example 412; Example 413;
IC50 between 10 nM and 100 nM: Example 9; Example 10; Example 19; Example 21; Example 25; Example 29; Example 46; Example 49; Example 51; Example 52; Example 77; Example 85; Example 86; Example 87; Example 94; Example 96; Example 97; Example 101; Example 107; Example 110; Example 111; Example 113; Example 115; Example 117; Example 118; Example 119; Example 121; Example 122; Example 131; Example 132; Example 133; Example 137; Example 143; Example 147; Example 149; Example 151; Example 153; Example 154; Example 155; Example 157; Example 158; Example 167; Example 168; Example 169; Example 178; Example 179; Example 187; Example 190; Example 191; Example 195; Example 205; Example 207; Example 212; Example 216; Example 218; Example 222; Example 224; Example 228; Example 230; Example 233; Example 237; Example 238; Example 240; Example 243; Example 246; Example 247; Example 259; Example 260; Example 264; Example 267; Example 269; Example 278; Example 282; Example 283; Example 296; Example 361; Example 362; Example 363; Example 367; Example 374; Example 377; Example 394; Example 407; Example 408; Example 409; Example 414; Example 415; Example 416; Example 419; Example 420; Example 421; Example 422; Example 423; Example 425; Example 426; Example 428; Example 429; Example 430; Example 431; Example 432; Example 437; Example 442; Example 443; Example 445; Example 446; Example 448; Example 449; Example 450; Example 451; Example 454; Example 459; Example 460; Example 465; Example 466; Example 469; Example 476; Example 482; Example 483; Example 488; Example 495; Example 496; Example 498; Example 501; Example 502; Example 505; Example 514; Example 516; Example 517; Example 522; Example 525; Example 526; Example 530; Example 535; Example 537; Example 539; Example 540;
IC50 between 100 nM and 1000 nM: Example 2; Example 8; Example 11; Example 13; Example 14; Example 17; Example 23; Example 24; Example 26; Example 28; Example 33; Example 34; Example 37; Example 38; Example 39; Example 41; Example 48; Example 53; Example 55; Example 67; Example 68; Example 70; Example 71; Example 72; Example 73; Example 74; Example 75; Example 76; Example 80; Example 84; Example 95; Example 98; Example 99; Example 100; Example 102; Example 103; Example 108; Example 114; Example 126; Example 127; Example 128; Example 129; Example 130; Example 135; Example 136; Example 138; Example 139; Example 144; Example 150; Example 162; Example 163; Example 164; Example 165; Example 166; Example 175; Example 177; Example 180; Example 181; Example 182; Example 184; Example 185; Example 186; Example 188; Example 193; Example 194; Example 197; Example 199; Example 201; Example 203; Example 208; Example 211; Example 213; Example 217; Example 219; Example 225; Example 226; Example 231; Example 234; Example 249; Example 250; Example 251; Example 252; Example 253; Example 254; Example 255; Example 256; Example 257; Example 258; Example 261; Example 262; Example 263; Example 265; Example 266; Example 268; Example 270; Example 273; Example 287; Example 290; Example 292; Example 293; Example 294; Example 295; Example 297; Example 300; Example 301; Example 304; Example 308; Example 312; Example 319; Example 321; Example 325; Example 364; Example 369; Example 375; Example 383; Example 386; Example 388; Example 393; Example 403; Example 404; Example 406; Example 424; Example 427; Example 436; Example 439; Example 440; Example 444; Example 452; Example 453; Example 455; Example 461; Example 463; Example 467; Example 470; Example 472; Example 473; Example 474; Example 475; Example 477; Example 481; Example 484; Example 485; Example 486; Example 487; Example 493; Example 497; Example 500; Example 503; Example 504; Example 506; Example 508; Example 511; Example 513; Example 515; Example 520; Example 521; Example 523; Example 529; Example 531; Example 538;
LRRK2 Activities:
IC50 lower than 10 nM: Example 2; Example 50; Example 110; Example 118; Example 131; Example 133; Example 134; Example 146; Example 154; Example 167; Example 169; Example 170; Example 191; Example 196; Example 198; Example 200; Example 202; Example 204; Example 206; Example 212; Example 214; Example 218; Example 219; Example 220; Example 221; Example 222; Example 223; Example 224; Example 227; Example 228; Example 229; Example 232; Example 239; Example 241; Example 242; Example 267; Example 278; Example 282; Example 287; Example 291; Example 292; Example 293; Example 294; Example 295; Example 297; Example 300; Example 301; Example 304; Example 308; Example 312; Example 325; Example 347; Example 361; Example 362; Example 363; Example 367; Example 395; Example 410; Example 413; Example 505; Example 519; Example 525; Example 527;
IC50 between 10 nM and 100 nM: Example 1; Example 3; Example 12; Example 18; Example 19; Example 29; Example 30; Example 35; Example 45; Example 46; Example 53; Example 54; Example 85; Example 87; Example 94; Example 96; Example 99; Example 101; Example 102; Example 103; Example 106; Example 107; Example 111; Example 112; Example 113; Example 117; Example 119; Example 120; Example 122; Example 127; Example 132; Example 135; Example 137; Example 138; Example 139; Example 1-(2; Example 143; Example 147; Example 148; Example 149; Example 153; Example 155; Example 156; Example 158; Example 163; Example 168; Example 178; Example 179; Example 182; Example 185; Example 189; Example 192; Example 195; Example 197; Example 199; Example 201; Example 203; Example 205; Example 207; Example 208; Example 211; Example 213; Example 215; Example 216; Example 217; Example 225; Example 230; Example 233; Example 234; Example 235; Example 236; Example 237; Example 238; Example 240; Example 243; Example 244; Example 245; Example 246; Example 247; Example 248; Example 249; Example 250; Example 251; Example 252; Example 253; Example 254; Example 256; Example 257; Example 258; Example 259; Example 260; Example 261; Example 262; Example 263; Example 265; Example 268; Example 269; Example 270; Example 273; Example 274; Example 275; Example 280; Example 281; Example 283; Example 284; Example 285; Example 286; Example 288; Example 289; Example 290; Example 298; Example 299; Example 302; Example 303; Example 306; Example 307; Example 310; Example 311; Example 313; Example 314; Example 315; Example 316; Example 324; Example 327; Example 328; Example 330; Example 334; Example 338; Example 340; Example 341; Example 342; Example 343; Example 345; Example 346; Example 349; Example 353; Example 354; Example 358; Example 360; Example 364; Example 365; Example 368; Example 369; Example 374; Example 375; Example 377; Example 380; Example 386; Example 387; Example 388; Example 389; Example 393; Example 394; Example 398; Example 399; Example 401; Example 402; Example 406; Example 407; Example 408; Example 409; Example 411; Example 412; Example 416; Example 417; Example 418; Example 422; Example 423; Example 425; Example 426; Example 428; Example 429; Example 430; Example 431; Example 432; Example 433; Example 437; Example 442; Example 443; Example 446; Example 447; Example 448; Example 449; Example 451; Example 453; Example 454; Example 455; Example 456; Example 458; Example 460; Example 461; Example 462; Example 463; Example 468; Example 469; Example 470; Example 473; Example 475; Example 476; Example 477; Example 482; Example 483; Example 484; Example 493; Example 497; Example 498; Example 504; Example 514; Example 516; Example 517; Example 520; Example 522; Example 526; Example 530;
IC50 between 100 nM and 1000 nM: Example 8; Example 9; Example 10; Example 11; Example 13; Example 17; Example 20; Example 21; Example 22; Example 24; Example 25; Example 26; Example 28; Example 31; Example 33; Example 34; Example 37; Example 38; Example 48; Example 52; Example 55; Example 67; Example 68; Example 69; Example 70; Example 71; Example 72; Example 73; Example 74; Example 75; Example 76; Example 77; Example 80; Example 81; Example 82; Example 84; Example 89; Example 95; Example 97; Example 98; Example 100; Example 108; Example 109; Example 114; Example 115; Example 116; Example 121; Example 126; Example 128; Example 129; Example 130; Example 136; Example 144; Example 145; Example 150; Example 151; Example 152; Example 157; Example 162; Example 164; Example 165; Example 166; Example 175; Example 177; Example 180; Example 181; Example 183; Example 184; Example 186; Example 187; Example 188; Example 190; Example 193; Example 194; Example 209; Example 226; Example 231; Example 255; Example 264; Example 266; Example 271; Example 272; Example 296; Example 305; Example 309; Example 317; Example 318; Example 322; Example 323; Example 331; Example 332; Example 335; Example 336; Example 339; Example 352; Example 356; Example 357; Example 366; Example 371; Example 372; Example 381; Example 382; Example 383; Example 384; Example 385; Example 390; Example 391; Example 392; Example 396; Example 397; Example 400; Example 403; Example 404; Example 405; Example 421; Example 424; Example 427; Example 436; Example 439; Example 440; Example 441; Example 444; Example 445; Example 450; Example 452; Example 459; Example 465; Example 466; Example 467; Example 472; Example 474; Example 481; Example 485; Example 486; Example 487; Example 488; Example 489; Example 490; Example 495; Example 496; Example 500; Example 501; Example 503; Example 506; Example 508; Example 510; Example 511; Example 512; Example 513; Example 521; Example 523; Example 524; Example 529; Example 531; Example 532.