# US 10,766,902 B2 · Wee-1 inhibiting pyrazolopyrimidinone compounds

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- Number: US 10,766,902 B2
- Document ID: US10766902B2
- Status: Granted
- Kind: B2
- Application number: 16/317,342
- Filed: 2017-07-12
- Published: 2019-08-15
- Granted: 2020-09-08
- Earliest claimed: 2016-07-12
- Assignees: Almac Discovery Limited
- Applicants: Almac Discovery Limited
- Inventors: Frank Burkamp; James Samuel Shane Rountree; Adam Piotr Treder
- Web page: https://patentgrep.com/patent/US10766902B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to pyrazolopyrimidinone derivatives, such as those of Formula (I), that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer

## Claims

### Claim 1

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R1 is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
R2 is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group,
or R1, R2 and the sulphur atom to which they are both attached, as taken together, form an optionally substituted heterocyclyl group;
R4 is an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, or an optionally substituted aryl group;
R5 is an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted cycloalkyl group;
R6 is a hydrogen atom or an optionally substituted aryl group;
Y is a phenyl group or a five- or six-membered heteroaryl group.

### Claim 2

A compound of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
R2 is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group;
R3 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, a cyano group, an optionally substituted alkanoyl group, an optionally substituted aroyl group, an optionally substituted heteroaroyl group, an optionally substituted alkoxy-carbonyl group, or an optionally substituted alkylamino-carbonyl group;
R4 is an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, or an optionally substituted aryl group;
R5 is an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted cycloalkyl group;
R6 is a hydrogen atom or an optionally substituted aryl group;
Y is a phenyl group or a five- or six-membered heteroaryl group.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 and/or R2 are optionally substituted C1-C3 alkyl groups, or R1, R2 and the sulphur atom to which they are both attached, as taken together, form an optionally substituted heterocyclyl group.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is a methyl group.

### Claim 5 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R3 is a hydrogen atom, an optionally substituted alkyl group, a cyano group, or an optionally substituted alkoxy-carbonyl group.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is an optionally substituted alkyl group or an optionally substituted cycloalkyl group.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is a methyl group.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 is an optionally substituted alkyl group or an optionally substituted alkenyl group.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 is a 2-propyl group or an allyl group.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is group or an optionally substituted heteroaryl group.

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is not a bridged cycloalkyl group.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is not an unsubstituted pyridyl group.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is an optionally substituted six-membered aryl group or an optionally substituted five- to seven-membered heteroaryl group.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is a group represented by the formula (d):
R5a and R5b are independently selected from the group consisting of a hydrogen atom, a halo group, an optionally substituted C1-C6 alkyl group, an optionally substituted C1-C6 nitrile group, an optionally substituted amino group, an optionally substituted C1-C6 alkoxy group, an optionally substituted sulfanyl group, an optionally substituted sulfonyl group, an optionally substituted sulfoximinyl group, and an optionally substituted four- to seven-membered nitrogen-containing heterocyclyl group;
wherein the optionally substituted four- to seven-membered nitrogen-containing heterocyclyl group is optionally substituted with one or more substituents selected from the group consisting of a halo group, an optionally substituted C1-C6 alkyl or cycloalkyl group, an oxo group, a hydroxyl group, an optionally substituted amino group, and a group of ═N—R5c;
or, in formula (d), R5a and R5b exist on adjacent ring atoms and R5a and R5b and the ring atoms to which they are attached may form, as taken together, a three- to seven-membered cycloalkyl group, or three- to seven-membered heterocyclyl group, wherein one or two of the ring atoms constituting the three- to seven-membered heterocyclyl group is independently an oxygen atom, a nitrogen atom, a group of —N(R5d)—, a sulfinyl group, a sulfonyl group, or a sulfoximinyl group, wherein the three- to seven-membered cycloalkyl or three- to seven-membered heterocyclyl group may be substituted with one or more substituents selected from the group consisting of a halo group and a C1-C6 alkyl or cycloalkyl group;
or R5a and R5b and the ring atoms to which they are attached may form, as taken together, a spirocyclic group or a bicyclic group formed of a five- to seven-membered aliphatic ring and any other three- to seven-membered aliphatic ring, in which one or two or more methylene groups constituting the spirocyclic group or the bicyclic group may be each independently replaced by an oxygen atom, a sulphur atom, a sulfinyl group, a sulfonyl, a sulfoximinyl group, an oxo group or a group of —N(R5e)—, and the spirocyclic group or the bicyclic group may be each independently substituted with a substituent selected from the group consisting of a halo group, a hydroxyl group, or a C1-C6 alkyl group; wherein
R5c, R5d and R5e are each independently a hydrogen atom or a C1-C6 alkyl or cycloalkyl group optionally substituted with a substituent selected from the group consisting of a halo group, a hydroxyl group, a cyano group, an oxo group, a C1-C6 alkyl group, a C1-C6 alkoxy group, an amino group, a substituted amino group, and a nitrogen-containing heterocyclyl group.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R6 is a hydrogen atom.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is a methyl group; R2 is a methyl group; R4 is an allyl group; R5 is a group represented by the formula (d) as defined above; R6 is a hydrogen atom; and Y is a pyridyl, phenyl or pyrazinyl group.

### Claim 17 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R2 is a methyl group or a cyclopropyl group; R3 is a hydrogen atom, a methyl group, a cyano group, or an alkoxy-carbonyl group; R4 is an allyl group; and R5 is a group represented by the formula (d) as defined above; R6 is a hydrogen atom; and Y is a pyridyl or phenyl group.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the following:
(5) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(6) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-{[4-(piperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(7: 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-2-(prop-2-en-1-yl)-6-({4-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(8) 6-{[4-(4-Cyclopropylpiperazin-1-yl)phenyl]amino}-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(9) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-({4-[(3R)-3-methylpiperazin-1-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(10) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-{[4-(4-ethylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(11) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-propyl-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(12) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(13) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-{[4-(piperidin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(14) 6-{[3-Chloro-4-(piperazin-1-yl)phenyl]amino}-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(15) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridine-2-yl)-6-({2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinoline]-7′-yl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(16) 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(17) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(18) 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-{[4-(piperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(19) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-(phenylamino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(20) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(21) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[3-methyl-4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(22) 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-({3-[(methylamino)methyl]-4-(morpholin-4-yl)phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(23) 2-Allyl-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1-(6-((1-oxidotetrahydrothiophen-1-ylidene)amino)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one;
(24) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[3-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one (25) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[3-methoxy-4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(26) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[3-methyl-4-(piperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(27): 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-({4-[2-(methylamino)ethoxy]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(28) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[3-methyl-4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(29) 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-{[3-(hydroxymethyl)-4-(piperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(30) 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-{[3-(hydroxymethyl)-4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(31) 1-(3-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(32) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{4-([(2S,6R)-2,6-dimethylmorpholin-4-yl]phenyl)amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one
(33) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[5-(morpholin-4-yl)pyridin-3-yl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(34) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(4,4-difluoropiperidin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(35) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[3-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(36) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(37) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(1-methyl-1H-pyrazol-4-yl)amino]-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(38) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-propyl-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(39) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[6-(morpholin-4-yl)pyridin-3-yl]amino}-2-propyl-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(40) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(4-fluorophenyl)amino]-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(41) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(4-fluorophenyl)amino]-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(42) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(4-methoxyphenyl)amino]-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(43) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(44) 1-(5-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-3-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(45) rac-1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-6-({4-[3-(trifluoromethyl)piperazin-1-yl]phenyl}amino)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(46) 6-{[4-(1,4-Diazepan-1-yl)phenyl]amino}-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(47) 6-(Cyclobutylamino)-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(48) 4-(4-{[1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-3-oxo-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-6-yl]amino}phenyl)piperazin-2-one;
(49) 4-(4-{[1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-3-oxo-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-6-yl]amino}phenyl)morpholin-3-one;
(50) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-6-({4-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]phenyl}amino)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(51) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyrazin-2-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(52) 1-(4-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyrimidin-2-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(53) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({4-[(2S)-2-(methoxymethyl)morpholin-4-yl]phenyl}amino)-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(54) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({4-[(2S)-2-(methoxymethyl)morpholin-4-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(55) 6-[(4-Fluorophenyl)amino]-1-{6-[(1-oxo-1λ6-thiolan-1-ylidene)amino]pyridin-2-yl}-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(56) 6-[(1-Methyl-1H-pyrazol-4-yl)amino]-1-{6-[(1-oxo-1λ6-thiolan-1-ylidene)amino]pyridin-2-yl}-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(57) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(dimethylamino)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(58) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(dimethylamino)phenyl]amino}-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(59) 1-{6-[(1-Oxo-1λ6-thiolan-1-ylidene)amino]pyridin-2-yl}-6-{[4-(piperazin-1-yl)phenyl]amino}-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(60) 4-[(4-Cyanophenyl)[1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-3-oxo-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-6-yl]amino]benzonitrile;
(61) 6-[(4-Chlorophenyl)amino]-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(62) 6-[(4-Chlorophenyl)amino]-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(63) 6-({Bicyclo[1.1.1]pentan-1-yl}amino)-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(64) 6-[(4-tert-Butylphenyl)amino]-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(65) 6-[(2,4-Difluorophenyl)amino]-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(66) 6-[(3,4-Difluorophenyl)amino]-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(67) 6-({4-[(3aR,6aS)-Hexahydro-1H-furo[3,4-c]pyrrol-5-yl]phenyl}amino)-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(68) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(69) rac-1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-6-({4-[3-(trifluoromethyl)piperazin-1-yl]phenyl}amino)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(70) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(6-fluoropyridin-3-yl)amino]-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(71) 4-{[1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-3-oxo-2-(propan-2-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-6-yl]amino}benzonitrile;
(72) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-6-{[4-(trifluoromethyl)phenyl]amino}-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(73) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(propan-2-yl)-6-{[3-(trifluoromethyl)phenyl]amino}-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(74) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyrazin-2-yl)-6-({4-[(2S)-2-(methoxymethyl)morpholin-4-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(75) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyrazin-2-yl)-6-[(4-fluorophenyl)amino]-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(76) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({4-[(3S)-3-(methoxymethyl)piperazin-1-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(77) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-6-[(pyridin-3-yl)amino]-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(78) 6-[(1-Methyl-1H-pyrazol-4-yl)amino]-1-{6-[(1-oxo-1λ6-thiolan-1-ylidene)amino]pyridin-2-yl}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(79) 1-(6-{[(S)-Methyl(oxo)phenyl-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(1-methyl-1H-pyrazol-4-yl)amino]-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(80) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-6-{[1-(propan-2-yl)-1H-pyrazol-4-yl]amino}-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(81) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-6-{[6-(trifluoromethyl)pyridin-3-yl]amino}-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(82) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-[(4-fluoro-3-methoxyphenyl)amino]-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(83) rac-1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(dimethylamino)-3-(2,2,2-trifluoro-1-hydroxyethyl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(84) 6-[(3,5-Difluorophenyl)amino]-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(85) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-6-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]amino}-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(86) rac-1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({3-methoxy-4-[3-(trifluoromethyl)piperazin-1-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(87) rac-1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({3-methoxy-4-[4-methyl-3-(trifluoromethyl)piperazin-1-yl]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(88) 6-{[4-(1-Cyclobutylpiperidin-4-yl)-3-methylphenyl]amino}-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(89) 1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-({4-[(2-methoxyethyl)(methyl)amino]phenyl}amino)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(91) 1-[6-({[Dimethyl(oxo)-λ6-sulfanylidene]amino}methyl)pyridin-2-yl]-6-{[4-(morpholin-4-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(92) 2-(Cyclopropylmethyl)-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-6-{[4-(morpholin-4-yl)phenyl]amino}-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(93) rac-1-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]amino}pyrazin-2-yl)-2-(prop-2-en-1-yl)-6-({4-[3-(trifluoromethyl)piperazin-1-yl]phenyl}amino)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one; and
(94) 1-(6-((Dimethyl(oxo)-λ6-sulfaneylidene)amino)pyridin-2-yl)-6-((1-isopropyl-1H-pyrazol-4-yl)amino)-2-(prop-2-yn-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the following:
(95) 2-Allyl-6-((1-allyl-1H-pyrazol-4-yl)amino)-1-(6-((dimethyl(oxo)-λ6-sulfaneylidene)amino) pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one;
(96) 2-Allyl-6-((1-cyclohexyl-1H-pyrazol-4-yl)amino)-1-(6-((dimethyl(oxo)-λ6-sulfaneylidene) amino)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one; and
(97) rac-2-Allyl-6-((1-cyclohexyl-1H-pyrazol-4-yl)amino)-1-(6-((dimethyl(oxo)-λ6-sulfaneylidene)amino)pyridin-2-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one.

### Claim 20 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the following:
(1) 1-{6-[(Cyanoimino)(methyl)oxo-λ6-sulfanyl]pyridin-2-yl}-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one;
(2) rac-Ethyl N-{methyl[6-(6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-3-oxo-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-1-yl)pyridine-2-yl]oxo-λ6-sulfanylidene}carbamate;
(3) rac-2-Allyl-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1-(6-(S-methylsulfonimidoyl)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one; and
(4) rac-2-Allyl-1-(6-(N,S-dimethylsulfonimidoyl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

### Claim 22 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

### Claim 23 (depends on 22)

The pharmaceutical composition of claim 22 comprising one or more further pharmaceutically active agents.

### Claim 24 (depends on 1)

A method of treating cancer in a human or animal patient comprising administering to a patient in need thereof an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said cancer is selected from the group consisting of lung cancer, gastrointestinal cancer, bone cancer, nervous system cancer, skin cancer, adrenal gland cancer, connective tissue cancer, brain cancer, breast cancer, cervical cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, leukemia, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer and sarcoma.

### Claim 25 (depends on 2)

A method of treating cancer in a human or animal patient comprising administering to a patient in need thereof an effective amount of a compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein said cancer is selected from the group consisting of lung cancer, gastrointestinal cancer, bone cancer, nervous system cancer, skin cancer, adrenal gland cancer, connective tissue cancer, brain cancer, breast cancer, cervical cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, leukemia, lymphoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer and sarcoma.

### Claim 26

A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is:
(90) 6-{[4-(Azetidin-1-yl)phenyl]amino}-1-(6-{[dimethyl(oxo)-λ6-sulfanylidene]amino}pyridin-2-yl)-2-(prop-2-en-1-yl)-1H,2H,3H-pyrazolo[3,4-d]pyrimidin-3-one.