Compositions and methods for treating toxoplasmosis, cryptosporidiosis and other apicomplexan protozoan related diseases

1. A compound of formula:

or a pharmaceutically acceptable salt thereof, wherein

X, Y, and Z are defined by either: (i) X is N, Y is C, and Z is N; or (ii) X is C, Y is N, and Z is C(H);

R 1 is C 2-6 alkyl, C 1-6 haloalkyl, —C 1-6 alkyl-R 12 , C 3-8 cycloalkyl, heterocyclyl, heteroaryl, or aryl,

wherein

the alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl groups are each optionally substituted with one or two R 11 groups;

each R 11 is independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —OR, —SR, —NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —S(O) 2 NR 2 , or —S(O) 2 R;

and

R 12 is —OR, —SR, —NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —S(O) 2 R, —OC(O)R, —OC(O)OR, —OC(O)NR 2 , —N(R)C(O)R, —N(R)C(O)OR, —N(R)C(O)NR 2 , aryl, heteroaryl, C 3-8 cycloalkyl, or heterocyclyl, wherein R 12 is optionally substituted by one, two, or three groups that are each independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydoxyalkyl, —OR, —SR, —NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —S(O) 2 R, —OC(O)R, —OC(O)OR, —OC(O)NR 2 , —N(R)C(O)R, —N(R)C(O)OR, or —N(R)C(O)NR 2 ;

R 3 is one of the formulas,

wherein

n is 0, 1, or 2;

Q is —O—, —S—, or —N(R Q )—, wherein R Q is hydrogen or C 1-6 alkyl; and

R 33 is C 1-6 haloalkyl, C 3-8 cycloalkyl, or heterocyclyl, wherein the cycloalkyl and heterocyclyl are optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —C(O)N(R 20 ) 2 , —S(O) 2 R 20 , —OC(O)R 20 , —OC(O)OR 20 , —OC(O)N(R 20 ) 2 , —N(R 20 )C(O)R 20 , —N(R 20 )C(O)OR 20 , or —N(R 20 )C(O)N(R 20 ) 2 , wherein each R 20 is independently hydrogen or C 1-6 alkyl,

each R 32 is independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —OR 34 , —SR 34 , —N(R 34 ) 2 , —C(O)R 34 , —C(O)OR 34 , —C(O)N(R 34 ) 2 , —S(O) 2 R 34 , —OC(O)R 34 , —OC(O)OR 34 , —OC(O)N(R 34 ) 2 , —N(R 34 )C(O)R 34 , —N(R 34 )C(O)OR 34 , or —N(R 34 )C(O)N(R 34 ) 2 , wherein each R 34 is independently hydrogen or C 1-6 alkyl; and

each R is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, heterocyclyl, aryl, arylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl wherein the alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl are optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —OR 0 , —SR 0 , —N(R 0 ) 2 , —C(O)R 0 , —C(O)OR 0 , —C(O)N(R 0 ) 2 , —S(O) 2 R 0 , —OC(O)R 0 , —OC(O)OR 0 , —OC(O)N(R 0 ) 2 , —N(R 0 )C(O)R 0 , —N(R 0 )C(O)OR 0 , or —N(R 0 )C(O)N(R 0 ) 2 , wherein each R 0 is independently hydrogen or C 1-6 alkyl;

provided the compound is not:

3-(6-cyclopropoxynaphthalen-2-yl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine.

2. The compound of claim 1 , which is of the formula

3. The compound of claim 1 , wherein R 3 is of the formula

4. The compound of claim 1 , wherein Q is —O—.

5. The compound of claim 4 , wherein R 33 is C 3-8 cycloalkyl, optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —C(O)N(R 20 ) 2 , —S(O) 2 R 20 , —OC(O)R 20 , —OC(O)OR 20 , —OC(O)N(R 20 ) 2 , —N(R 20 )C(O)R 20 , —N(R 20 )C(O)OR 20 , or —N(R 20 )C(O)N(R 20 ) 2 , wherein each R 20 is independently hydrogen or C 1-6 alkyl.

6. The compound of claim 4 , wherein R 33 is alkyl or C 3-6 cycloalkyl.

7. The compound of claim 1 , wherein R 3 is of the formula

8. The compound of claim 1 , wherein R 1 is C 2-6 alkyl or —C 1-4 alkyl-R 12 .

9. The compound of claim 8 , wherein R 12 is —OR or heterocyclyl, each optionally substituted.

10. The compound selected from the group consisting of:

3-(2-methoxyquinolin-6-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-(cyclopropylmethoxy)quinolin-6-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-(cyclopropylmethoxy)naphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-cyclobutoxynaphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-(oxetan-3-yloxy)naphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-cyclopropoxynaphthalen-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol;

3-(6-cyclopropoxynaphthalen-2-yl)-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropan-1-ol;

3-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropan-1-ol;

1-(6-(4-amino-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yloxy)-2-methylpropan-2-ol;

2-(6-(4-amino-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yloxy)ethanol;

1-isobutyl-3-(6-(oxetan-3-yloxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-isobutyl-3-(6-(2-methoxyethoxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol;

3-(2-(2-methoxyethoxy)quinolin-6-yl)-1-neopentyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(4-Amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropan-1-ol;

3-(2-cyclopropoxyquinolin-6-yl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-cyclopropoxyquinolin-6-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol;

3-(2-cyclopropoxyquinolin-6-yl)-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-cyclopropoxyquinolin-6-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(azetidin-3-ylmethyl)-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-cyclopropoxyquinolin-6-yl)-1-((1-methylazetidin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-(2-methoxyethoxy)quinolin-6-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(4-Amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol;

1-isobutyl-3-(2-(2,2,2-trifluoroethoxy)quinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(piperidin-4-ylmethyl)-3-(2-(2,2,2-trifluoroethoxy)quinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-((1-methylpiperidin-4-yl)methyl)-3-(2-(2,2,2-trifluoroethoxy)quinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-(3-(4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropoxy)ethanol;

1-(4-amino-3-(2-(2,2,2-trifluoroethoxy)quinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol;

3-(4-amino-3-(2-(2,2,2-trifluoroethoxy)quinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropan-1-ol;

3-(2-cyclopropoxyquinolin-6-yl)-1-(3-(dimethylamino)-2,2-dimethylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(7-ethoxynaphthalen-2-yl)-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(7-ethoxynaphthalen-2-yl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-cyclopropoxynaphthalen-2-yl)-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-ethoxynaphthalen-2-yl)-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-cyclopropoxyquinolin-6-yl)-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-(4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-morpholinoethanone;

2-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-morpholinoethanone;

2-((4-amino-3-(6-(methoxymethyl)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1,1,1,3,3,3-hexafluoropropan-2-ol;

2-((4-Amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1,1,1,3,3,3-hexafluoropropan-2-ol;

2-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1,1,1,3,3,3-hexafluoropropan-2-ol;

1-(3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrrolo[3,2-c]pyridin-1-yl)-2-methylpropan-2-ol;

1-(4-amino-5-(2-cyclopropoxyquinolin-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylpropan-2-ol;

4-(4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,3,3-trimethylbutan-2-ol;

1-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclobutanol;

1-(4-amino-5-(6-cyclopropoxynaphthalen-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylpropan-2-ol;

1-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclobutanol;

1-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclopentanol;

1-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclopentanol;

4-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-tetrahydro-2H-pyran-4-ol;

4-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-tetrahydro-2H-pyran-4-ol;

(3-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)oxetan-3-yl)methanol;

(3-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)oxetan-3-yl)methanol;

3-(6-cyclopropoxynaphthalen-2-yl)-1-(2-methoxy-2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(2-cyclopropoxyquinolin-6-yl)-1-(2-methoxy-2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

methyl 3-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropanoate;

methyl 3-(4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropanoate;

4-((4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidin-4-ol;

4-((4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidin-4-ol;

methyl 2-((6-(4-amino-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yl)oxy)acetate;

2-((6-(4-amino-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yl)oxy)acetonitrile;

4-((4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidine-4-carbonitrile;

4-((4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidine-4-carbonitrile;

3-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropanoic acid;

3-(6-cyclopropoxynaphthalen-2-yl)-1-(2-fluoro-2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

4-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidin-4-ol;

4-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidin-4-ol;

4-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidin-4-ol;

4-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidin-4-ol;

4-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidin-4-ol;

4-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidine-4-carbonitrile;

4-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidin-4-ol;

4-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidin-4-ol;

4-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidine-4-carbonitrile;

4-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidine-4-carbonitrile;

2-(6-(4-amino-1-(2-hydroxy-2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yloxy)acetonitrile;

methyl 2-(6-(4-amino-1-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)quinolin-2-yloxy)acetate;

3-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)azetidin-3-ol;

3-((4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylazetidin-3-ol;

4-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidine-4-carbonitrile;

3-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)azetidin-3-ol;

3-(6-(difluoromethoxy)naphthalen-2-yl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-(difluoromethoxy)naphthalen-2-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-((4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)azetidin-3-ol;

3-((4-amino-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylazetidin-3-ol;

4-((4-amino-3-(6-(difluoromethoxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidin-4-ol;

4-((4-amino-3-(6-(difluoromethoxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidin-4-ol;

4-((4-amino-3-(6-(difluoromethoxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)piperidine-4-carbonitrile;

3-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)azetidin-3-ol;

4-((4-amino-3-(6-(difluoromethoxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylpiperidine-4-carbonitrile;

3-((4-amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1-methylazetidin-3-ol;

1-(3-(6-ethoxynaphthalen-2-yl)-1-((1-(methylcarbamoyl)piperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-methylurea;

4-((4-amino-3-(2-ethoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-N-methylpiperidine-1-carboxamide;

3-(6-ethoxynaphthalen-2-yl)-1-(2-(1-ethylpiperidin-4-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-ethoxynaphthalen-2-yl)-1-(2-(1-propylpiperidin-4-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(2-(1-(3-aminopropyl)piperidin-4-yl)ethyl)-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-(1-(3-aminopropyl)piperidin-4-yl)-3-(6-ethoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-isopropyl-3-(6-(oxetan-3-yloxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-cyclopropoxynaphthalen-2-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-((6-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yl)oxy)-2-methylpropan-2-ol;

2-((6-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yl)oxy)ethan-1-ol;

3-(6-(cyclopropylmethoxy)naphthalen-2-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-cyclobutoxynaphthalen-2-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(6-(2-methoxyethoxy)naphthalen-2-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

1-((1-methylpiperidin-4-yl)methyl)-3-(6-(oxetan-3-yloxy)naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-(6-(4-amino-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yloxy)ethanol;

1-(6-(4-amino-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-yloxy)-2-methylpropan-2-ol; and

pharmaceutically acceptable salts thereof.

11. A method of treating an apicomplexan protozoan related disease comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 1 , wherein the apicomplexan protozoan related disease is selected from toxoplasmosis, cryptosporidiosis, coccidiosis, malaria, neosporosis, sarcocystosis, besnoitiosis, coccidiosis, cystoisoporosis, babesiosis, and theileriosis.

12. The method of claim 11 , wherein the apicomplexan protozoan related disease is selected from toxoplasmosis, cryptosporidiosis, and coccidiosis.

13. A method of treating malaria comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 1 .

14. A method of inhibiting apicomplexan calcium dependent protein kinase, comprising administering a therapeutically effective amount of a compound of claim 1 .

15. The method of claim 14 , wherein the apicomplexan calcium dependent protein kinases is selected from T. gondii calcium dependent protein kinases (TgCDPKs), C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs), and P. falciparum and P. berghei calcium dependent protein kinase 4 (PfCDPKs).

16. The method of claim 11 , wherein the compound is:

1-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol;

1-(4-amino-5-(6-cyclopropoxynaphthalen-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylpropan-2-ol;

3-(6-cyclopropoxynaphthalen-2-yl)-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-(4-Amino-3-(2-cyclopropoxyquinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2,2-dimethylpropan-1-ol;

3-(2-cyclopropoxyquinolin-6-yl)-1-isobutyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

or pharmaceutically acceptable salts thereof.

17. A method of treating neosporosis, sarcocystosis, besnoitiosis, coccidiosis, cystoisoporosis, babesiosis, or theileriosis, comprising administering to a patient in need of such treatment a therapeutically effective amount of (i) a compound, or (ii) a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient, carrier, or diluent, wherein the compound is 1-(4-amino-3-(6-cyclopropoxynaphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropan-2-ol, or 3-(2-ethoxyquinolin-6-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine.

18. A method of treating neosporosis, sarcocystosis, besnoitiosis, cystoisoporosis, or theileriosis, comprising administering to a patient in need of such treatment a therapeutically effective amount of (i) a compound, or (ii) a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient, carrier, or diluent, wherein the compound is:

3-(6-ethoxynaphthalen-2-yl)-1-((1-methylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine.

19. A method of treating an apicomplexan protozoan related disease comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 10 , wherein the apicomplexan protozoan related disease is selected from toxoplasmosis, cryptosporidiosis, coccidiosis, malaria, neosporosis, sarcocystosis, besnoitiosis, coccidiosis, cystoisoporosis, babesiosis, and theileriosis.

20. The method of claim 19 , wherein the apicomplexan protozoan related disease is selected from toxoplasmosis, cryptosporidiosis, and coccidiosis.

21. A method of treating malaria comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 10 .