IP Library › Patent Application 14997248

Patent Application

App. No. 14/997,248

Purinone Derivatives as Tyrosine Kinase Inhibitors

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Patent No.: US None
App. No.: 14/997,248

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Abstract

The present disclosure provides compounds and pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as autoimmune diseases, cancer and inflammatory diseases. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof.

Claims (779)

1 . A compound of Formula (I):

wherein:

L is O, CO, CH 2 , S, SO, SO 2 , NR, NRCO, CONR, or NRCONR′, where (each R and R′ is independently hydrogen or alkyl);

Ar is aryl, heteroaryl, cycloalkyl or heterocyclyl;

R 1 is hydrogen, alkyl, cyclopropyl, hydroxy, alkoxy, cyano, halo, haloalkyl or haloalkoxy;

R 2 is hydrogen, alkyl, alkynyl, cyclopropyl, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, carboxy, alkoxycarbonyl, alkylaminosulfonyl, dialkylaminosulfonyl, —CONH 2 , alkylaminocarbonyl, dialkylaminocarbonyl, 3-, 4-, or 5-membered heterocylyl, hydroxy, alkoxy, cyano, halo, haloalkyl or haloalkoxy;

R 3 , R 4 , and R 5 are independently hydrogen, alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, alkoxycarbonyl, cyano, —CONH 2 , amino, or monosubstituted or disubstituted amino;

X is alkylene, -alkynylene-NR a —, cycloalkylene, -alkylene-O—, -cycloalkylene-NR a —, (alkylene)-NR a —, -phenylene-NR a — (where each R a is hydrogen, alkyl or cycloalkyl), or

(where Z is bond or alkylene, and ring A is heterocycloamino optionally substituted with one or two substituents independently selected from alkyl, hydroxy, alkoxy, or fluoro);

Y is —CO— or —SO 2 —;

R c is alkyl, haloalkoxy, substituted alkyl, cycloalkyl, 1-(alkyleneR b )-cycloalkan-1-yl (where R b is amino, alkylamino, dialkylamino, hydroxy, or monocyclic heteroaryl), 1-NR d R e cycloalkan-1-yl (where R d and R e are independently hydrogen, alkyl, or cycloalkyl), or 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents independently selected from hydroxy, alkoxy, alkyl, fluoro, aminoalkyl, hydroxyalkyl, or alkoxyalkyl;

or a pharmaceutically acceptable salt thereof.

2 . The compound or a pharmaceutically acceptable salt of claim 1 wherein:

L is O and is attached at the 4-position of the phenyl ring with the carbon atom of the phenyl ring attached to purinone nitrogen being position 1; and

R 1 and R 2 are independently hydrogen, alkyl, halo, haloalkyl, or alkoxy.

3 . The compound or a pharmaceutically acceptable salt of claim 2

wherein R 1 is hydrogen or halo; and

R 2 is hydrogen.

4 . The compound or a pharmaceutically acceptable salt of claim 2

wherein R 1 and R 2 are hydrogen.

5 . The compound or a pharmaceutically acceptable salt of claim 2 wherein

is a ring of formula:

6 . The compound or a pharmaceutically acceptable salt of claim 2 wherein

is phenyl.

7 . The compound or a pharmaceutically acceptable salt of claim 2 wherein —X— is -cycloalkylene-NR a —, -(alkynylene)-NR a —, -(alkylene)-NR a —, -phenylene-NR a — (where each R a is hydrogen, alkyl or cycloalkyl), or

Z is a bond or alkylene;

ring A is heterocycloamino optionally substituted with one or two substituents independently selected from alkyl, hydroxy, alkoxy, or fluoro; and

Y is CO.

8 . The compound or a pharmaceutically acceptable salt of claim 2 wherein —X—Y— is:

9 . The compound or a pharmaceutically acceptable salt of claim 2 wherein —X—Y— is:

where the stereochemistry at *C is R or S.

10 . The compound or a pharmaceutically acceptable salt of claim 9 wherein R c is cycloalkyl.

11 . The compound or a pharmaceutically acceptable salt of claim 9 wherein R c is alkyl.

12 . The compound or a pharmaceutically acceptable salt of claim 9 wherein R c is alkyl substituted with hydroxyl, alkoxy, —NRR′ (where R is hydrogen, alkyl, alkoxyalkyl, heterocyclyl or cycloalkyl and R′ is hydrogen or alkyl), or heterocycicyl which is optionally substituted with one or two groups independently selected from alkyl.

13 . The compound or a pharmaceutically acceptable salt of claim 9 wherein R c is 3- to 6-membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents selected from hydroxy, alkyl or fluoro.

14 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt of claim 1 , and a pharmaceutically acceptable excipient.

15 . A method of treating an autoimmune disease, inflammatory disease or cancer which method comprises administering to the patient in need thereof, a pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt of claim 1 optionally in combination with one or more anticancer or anti-inflammatory agents.

16 . The method of claim 15 wherein the disease is leukemia or lymphoma.

17 . The method of claim 15 wherein the leukemia is chosen from chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), multiple myeloma, mantle cell lymphoma, and B-cell non-Hodgkin lymphoma.

18 . The method of claim 15 wherein the disease is arthritis, lupus, Sjogren's dry eye, non-Sjogren's dry eye, or asthma.

19 . A compound selected from:

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-3-cyclopropylacrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-3-cyclopropylacrylonitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-3-cyclopropylacrylamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-3-cyclopropylacrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-cyclopropylacrylonitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-cyclopropylacrylonitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-3-cyclopropylacrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-3-cyclopropylacrylonitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-3-cyclopropylacrylamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

3-cyclopropylacrylamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

3-cyclopropyl-N-methylacrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4,4-dimethylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4,4-dimethylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4,4-dimethylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-cyano-dimethylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4,4-dimethylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4,4-trimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methylpent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methylpent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-4-amino-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)methyl)pyrrolidine-1-carbonyl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-4-amino-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)piperidine-1-carbonyl)-4-methylpent-2-enenitrile;

4-amino-2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-4-amino-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)propan-2-yl)-2-cyano-4-methylpent-2-enamide;

4-amino-N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)cyclohexyl)-2-cyano-4-methylpent-2-enamide;

(RS), (R), or (S)-4-amino-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)methyl)azetidine-1-carbonyl)-4-methylpent-2-enenitrile;

4-amino-2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methylpent-2-enenitrile;

4-amino-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)azetidine-1-carbonyl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-4-amino-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)pyrrolidine-1-carbonyl)-4-methylpent-2-enenitrile;

4-amino-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methylpent-2-enamide;

4-amino-N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)ethyl)-2-cyano-4-methylpent-2-enamide;

4-amino-N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)ethyl)-2-cyano-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-ethoxy-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-ethoxy-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-ethoxy-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-ethoxy-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-ethoxy-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-ethoxy-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(dimethylamino)-4-methylpent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(dimethylamino)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(dimethylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(dimethylamino)-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(dimethylamino)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(dimethylamino)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(dimethylamino)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(dimethylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(dimethylamino)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(dimethylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(dimethylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(dimethylamino)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-morpholinopent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-morpholinopent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-morpholinopent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-morpholinopent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-morpholinopent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-morpholinopent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(methylamino)pent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(methylamino)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(methylamino)pent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(methylamino)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(methylamino)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(methylamino)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(ethylamino)-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(ethylamino)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(ethylamino)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(ethylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(ethylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(ethylamino)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(methyl(oxetan-3-

yl)amino)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-

enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-

enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-

2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-

2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

(carbonyl)-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-

enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-

enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(methyl(oxetan-3-yl)amino)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(methyl(oxetan-3-yl)amino)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-

enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-

enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-

enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(4-methylpiperazin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-

2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-

enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-

enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-

enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-

enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(ethyl(oxetan-3-yl)amino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(ethyl(oxetan-3-yl)amino)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-

6-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-

2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-

2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)pent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)pent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-

yl)pent-2-enenitrile;;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-

2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(oxetan-3-ylamino)pent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(oxetan-3-ylamino)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(oxetan-3-ylamino)pent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(oxetan-3-ylamino)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(oxetan-3-ylamino)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(oxetan-3-ylamino)pent-2-enamide;

2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(piperazin-1-yl)pent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(piperazin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(piperazin-1-yl)pent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(piperazin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(piperazin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(piperazin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-3-(3-methyloxetan-3-yl)acrylamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-3-(3-methyloxetan-3-yl)acrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-3-(3-methyloxetan-3-yl)acrylonitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-3-(3-methyloxetan-3-yl)acrylamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

3-(3-methyloxetan-3-yl)acrylamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N-methyl-3-(3-methyloxetan-3-yl)acrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(piperidin-1-yl)pent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(piperidin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(piperidin-1-yl)pent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(piperidin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(piperidin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(piperidin-1-yl)pent-2-enamide;

(R,S), (R,R), (S,R)or (S,S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)methyl)pyrrolidine-1-carbonyl)-3-(pyrrolldin-2-yl)acrylonitrile;

(R,S), (R,R), (S,R)or (S,S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)piperidine-1-carbonyl)-3-(pyrrolidin-2-yl)acrylonitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-3-(pyrrolidin-2-yl)acrylonitrile;

(R,S), (R,R), (S,R)or (S,S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)propan-2-yl)-2-cyano-3-(pyrrolidin-2-yl)acrylamide;

(RS), (R), or (S)-N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)cyclohexyl)-2-cyano-3-(pyrrolidin-2-yl)acrylamide;

(R,S), (R,R), (S,R)or (S,S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)methyl)azetidine-1-carbonyl)-3-(pyrrolidin-2-yl)acrylonitrile;

(RS), (R), or (S)-2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-(pyrrolidin-2-yl)acrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)azetidine-1-carbonyl)-3-(pyrrolidin-2-yl)acrylonitrile;

(R,S), (R,R), (S,R)or (S,S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-

purin-9(8H)-yl)pyrrolidine-1-carbonyl)-3-(pyrrolidin-2-yl)acrylonitrile;

(RS), (R), or (S)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)-2,2-dimethylpropyl)-2-cyano-3-(pyrrolidin-2-yl)acrylamide;

(RS), (R), or (S)-N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)ethyl)-2-cyano-3-(pyrrolidin-2-yl)acrylamide;

(RS), (R), or (S)-N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)ethyl)-2-cyano-N-methyl-3-(pyrrolidin-2-yl)acrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(cyclopropylamino)-4-methylpent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(cyclopropylamino)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(cyclopropylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(cyclopropylamino)-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(cyclopropylamino)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(cyclopropylamino)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(cyclopropylamino)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(cyclopropylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(cyclopropylamino)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(cyclopropylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(cyclopropylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(cyclopropylamino)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-3-(1-aminocyclopropyl)-2-cyanoacrylamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-3-

(1-aminocyclopropyl)-2-cyanoacrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-3-(1-aminocyclopropyl)acrylonitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-3-(1-aminocyclopropyl)-2-cyanoacrylamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-3-(1-

aminocyclopropyl)-2-cyanoacrylamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-3-(1-

aminocyclopropyl)-2-cyano-N-methylacrylamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-4-(azetidin-1-yl)-2-cyano-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-4-

(azetidin-1-yl)-2-cyano-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(azetidin-1-yl)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-4-(azetidin-1-yl)-2-cyano-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-4-

(azetidin-1-yl)-2-cyano-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-4-

(azetidin-1-yl)-2-cyano-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-methyl-4-(pyrrolidin-1-yl)pent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-methyl-4-(pyrrolidin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-methyl-4-(pyrrolidin-1-yl)pent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-methyl-4-(pyrrolidin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-methyl-4-(pyrrolidin-1-yl)pent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

N,4-dimethyl-4-(pyrrolidin-1-yl)pent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-

enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-

enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-

enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(3-hydroxyazetidin-1-yl)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-

enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(4-hydroxypiperidin-1-yl)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-5-hydroxy-4,4-dimethylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-5-hydroxy-4,4-dimethylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-5-hydroxy-4,4-dimethylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-5-hydroxy-4,4-dimethylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-5-hydroxy-4,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-5-hydroxy-4,4-dimethylpent-2-enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-5-hydroxy-4-dimethylpent-2-enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-5-hydroxy-4,4-dimethylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-5-hydroxy-4,4-dimethylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-5-hydroxy-4,4-dimethylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

5-hydroxy-4,4-dimethylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

5-hydroxy-4,4-trimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(isopropylamino)-4-methylpent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(isopropylamino)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(isopropylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(isopropylamino)-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(isopropylamino)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(isopropylamino)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(isopropylamino)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(isopropylamino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(isopropylamino)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(isopropylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(isopropylamino)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(isopropylamino)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-

enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-(4-ethylpiperazin-1-yl)-N,4-dimethylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)pyrrolidine-1-carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-

2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)piperidine-1-carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-2-

enenitrile;

2-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)piperidine-1-

carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-N-(1-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)propan-2-yl)-2-cyano-4-((2-methoxyethyl)amino)-4-methylpent-2-

enamide;

N-(4-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)cyclohexyl)-2-

cyano-4-((2-methoxyethyl)amino)-4-methylpent-2-enamide;

(RS), (R), or (S)-2-(2-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-2-

enenitrile;

2-(3-((6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)methyl)azetidine-1-carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-2-

enenitrile;

2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)azetidine-1-

carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-2-enenitrile;

(RS), (R), or (S)-2-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-

yl)pyrrolidine-1-carbonyl)-4-((2-methoxyethyl)amino)-4-methylpent-2-

enenitrile;

N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)-2,2-

dimethylpropyl)-2-cyano-4-((2-methoxyethyl)amino)-4-methylpent-2-

enamide;

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-((2-methoxyethyl)amino)-4-methylpent-2-enamide; and

N-(2-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)ethyl)-2-cyano-

4-((2-methoxyethyl)amino)-N,4-dimethylpent-2-enamide;

or a pharmaceutically acceptable salt thereof;

or an (E) or (Z) isomer or a mixture of (E) and (Z) isomer of any of the above compounds.

Assignments (2)

ASSIGNEE CHANGE OF ADDRESS Recorded Mar 22, 2019

From: PRINCIPIA BIOPHARMA INC.

To: PRINCIPIA BIOPHARMA INC.

Reel/Frame 048675/0297 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2019

From: OWENS, TIMOTHY D.

To: PRINCIPIA BIOPHARMA INC.

Reel/Frame 048616/0474 →