received by the International Bureau on 30 January 2020 (30.01.2020)

CLAIMS

1. A compound of formula (I):

or a tautomeric or a stereochemically isomeric form, a pharmaceutically acceptable salt or a solvate thereof, wherein:

R¹ represents Ci-e alkyl, halogen, haloCi-₆ alkyl, haloCi-₆ alkoxy, -S-haloCi-₆ alkyl, ethoxy, propoxy, isopropoxy, methoxyethoxy, methoxypropoxy, n-butoxy, i-butoxy, s-butoxy, -X-C3-8 cycloalkyl, -X-aryl, -X-heterocyclyl or -X-heteroaryl, wherein said cycloalkyl, heterocyclyl or heteroaryl groups of R¹ may be optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁴ groups;

R⁴ represents Ci-e alkyl, halogen, oxo, Ci-e alkoxy, -CO-C1 -6 alkyl, Ci-e alkanol or -CO-C2-6 alkenyl;

X represents a bond, -0-, -CH2-O- or -CH2-CH2-O-;

R² represents -(CH₂)₃0H, piperidinyl or heteroaryl, wherein said piperidinyl or heteroaryl groups of R² may be optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁵ groups;

R⁵ represents methyl, halogen, haloCi-₆ alkyl, Ci-e alkoxy, oxo or Ci-e alkylamino;

R³ represents Ci-e alkyl, halogen, haloCi-₆ alkyl, haloCi-₆ alkoxy, hydroxy, Ci-e alkoxy, cyano or amino; and

n represents an integer selected from 0 to 3.

2. The compound as defined in claim 1 , wherein R¹ represents:

C1 -6 alkyl (such as methyl, isopropyl, n-butyl or t-butyl);

halogen (such as bromine);

haloCi-₆ alkyl (such as trifluoromethyl);

haloCi-₆ alkoxy (such as trifluoromethoxy or 2,2,2-trifluoroethoxy);

-S-haloCi-e alkyl (such as trifluoromethylthio (-SCF₃));

ethoxy, propoxy, isopropoxy, methoxyethoxy, methoxypropoxy, n-butoxy, i-butoxy or s-butoxy;

-X-C3-8 cycloalkyl (such as -O-Chk-cyclobutyl or cyclohexyl);

-X-aryl (such as -O-Chk-phenyl);

-X-heterocyclyl (such as oxetanyl, -O-Chk-oxetanyl, -O-Chk-CI-k-oxetanyl, dihydrofuranyl, -O-ChMetrahydrofuranyl, -O-Chk-CI-Metrahydrofuranyl, -O- tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl, -O-ChMetrahydropyranyl, -O- tetrahydropyranyl, pyrrolidinyl, -O-pyrrolidinyl, -O-Chh-pyrrolidinyl, -O-Chh-CI-h-pyrrolidinyl, piperidinyl, -0-CH₂-piperidinyl, morpholinyl, -0-CH₂-oxabicyclo[2.2.1]heptanyl or -O- oxaspiro[3.3]heptanyl); and

-X-heteroaryl (such as thiophenyl, -O-ChMhiophenyl, pyrazolyl, -O-Chh-isoxazolyl or -0-CH₂-thiazolyl);

wherein said cycloalkyl, heterocyclyl or heteroaryl groups of R¹ may be optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁴ groups.

3. The compound as defined in claim 2, wherein R¹ represents -X-heterocyclyl (such as oxetanyl, -O-Chh-oxetanyl, -O-Chh-CI-h-oxetanyl, dihydrofuranyl, -O-ChMetrahydrofuranyl, - 0-CH₂-CH₂-tetrahydrofuranyl, -O-tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl, -O- ChMetrahydropyranyl, -O-tetrahydropyranyl, pyrrolidinyl, -O-pyrrolidinyl, -O-Chh-pyrrolidinyl, -0-CH₂-CH₂-pyrrolidinyl, piperidinyl, -0-CH₂-piperidinyl, morpholinyl, -O-CH2- oxabicyclo[2.2.1]heptanyl or -0-oxaspiro[3.3]heptanyl) wherein said heterocyclyl groups of R¹ may be optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁴ groups.

4. The compound as defined in claim 2 or claim 3, wherein R¹ represents: -O-CH2- oxetanyl, -O-ChMetrahydrofuranyl or morpholinyl, wherein said oxetanyl and

tetrahydrofuranyl groups may be optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁴ groups, such as Ci-e alkyl (e.g. methyl).

5. The compound as defined in any one of claims 1 to 4, wherein R⁴ represents:

C1 -6 alkyl (such as methyl);

halogen (such as fluorine);

oxo

C1 -6 alkoxy (such as ethoxy or methoxymethyl);

-CO-C1 -6 alkyl (such as -COMe);

C1 -6 alkanol (such as -CH2OH); or

-CO-C2-6 alkenyl (such as -CO-CH=CH2).

6. The compound as defined in claim 5, wherein R⁴ represents Ci-e alkyl (such as methyl).

7. The compound as defined in any one of claims 1 to 6, wherein R² represents:

-(CH2)₃0H ;

piperidinyl; or heteroaryl (such as pyridyl, pyrazolyl, pyrazinyl or pyridazinyl);

wherein said piperidinyl or heteroaryl groups of R² may be optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁵ groups.

8. The compound as defined in claim 7, wherein R² represents piperidinyl optionally substituted by one or more (e.g. 1 , 2, 3 or 4) R⁵ groups.

9. The compound as defined in claim 7 or claim 8, wherein R² represents piperidinyl optionally substituted by one or more (e.g. 1 , 2, 3 or 4) methyl groups.

10. The compound as defined in any one of claims 1 to 9, wherein R⁵ represents: methyl;

halogen (such as fluorine);

haloCi-₆ alkyl (such as fluoroethyl or difluoroethyl);

C1 -6 alkoxy (such as methoxy);

oxo; or

C1 -6 alkylamino (such as -CH2NH2).

11. The compound as defined in claim 10, wherein R⁵ represents methyl.

12. The compound as defined in any one of claims 1 to 11 , wherein n represents an integer selected from 0 to 2.

13. The compound as defined in any one of claims 1 to 12, wherein R³ represents:

C1 -6 alkyl (such as methyl or ethyl);

halogen (such as fluorine or chlorine); or

C1 -6 alkoxy (such as methoxy or ethoxy).

14. The compound as defined in any one of claims 1 to 13, wherein R³ represents:

C1 -6 alkyl (such as methyl);

halogen (such as chlorine); or

C1 -6 alkoxy (such as methoxy).

15. The compound as defined in any one of claims 1 to 12, wherein n represents 0.

16. The compound as defined in any one of claims 1 to 12, wherein n represents 1 and

R³ represents:

129 C1-6 alkyl (such as methyl or ethyl);

halogen (such as fluorine or chlorine); or

C1-6 alkoxy (such as methoxy or ethoxy).

17. The compound as defined in any one of claims 1 to 12, wherein n represents 1 and R³ represents:

C1-6 alkyl (such as methyl);

halogen (such as chlorine); or

C1-6 alkoxy (such as methoxy).

18. The compound as defined in any one of claims 1 to 12, wherein n represents 1 and R³ represents:

C1-6 alkyl (such as 3-methyl or 3-ethyl);

halogen (such as 3-fluorine or 3-chlorine); or

C1-6 alkoxy (such as 3-methoxy or 3-ethoxy).

19. The compound as defined in any one of claims 1 to 12, wherein n represents 1 and R³ represents:

C1-6 alkyl (such as 3-methyl);

halogen (such as 3-chlorine); or

C1-6 alkoxy (such as 3-methoxy).

20. The compound as defined in any one of claims 1 to 12, wherein n represents 2 and R³ represents:

C1-6 alkyl (such as methyl);

halogen (such as chlorine); or

C1-6 alkoxy (such as methoxy).

21. The compound as defined in any one of claims 1 to 12, wherein n represents 2 and both R³ groups represent Ci-₆ alkyl (such as 3,5-dimethyl) or both R³ groups represent halogen (such as 3,5-dichloro) or one R³ group represents halogen and the other represents C1-6 alkoxy (such as 3-chloro, 5-methoxy) or one R³ group represents halogen and the other represents Ci-₆ alkyl (such as 3-chloro, 5-methyl).

22. The compound as defined in claim 1 , wherein the compound is the free base of a compound of Examples 1-127 or a pharmaceutically acceptable salt or solvate thereof.

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23. A pharmaceutical composition comprising a compound of formula (I) as defined in any of claims 1 to 22.

24. A pharmaceutical composition comprising a compound of formula (I) as defined in any of claims 1 to 22, in combination with one or more therapeutic agents.

25. A compound as defined in any of claims 1 to 22 for use in therapy.

26. A compound as defined in any of claims 1 to 22 for use in the prophylaxis or treatment of cancer.

27. A process for preparing a compound of formula (I) as herein defined in claim 1 which comprises:

(a) reacting a compound of formula (II):

wherein R¹ , R³ and n are as defined in claim 1 ; with a compound of formula R²-N=C=0, wherein R² is as defined in claim 1 ;

(b) reacting a compound of formula (II):

wherein R¹ , R³ and n are as defined in claim 1 ; with a compound of formula (III)

wherein U represents a suitable leaving group such as a halogen atom (e.g. chlorine), and a compound of formula R²-NH2, wherein R² is as defined in claim 1 ;

(c) reacting a compound of formula (IV):

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wherein R² is as defined in claim land L² represents a suitable leaving group such as a halogen atom (e.g. bromine), with a compound of formula (V):

wherein R¹, R³ and n are as defined in claim 1 ;

(d) reacting a compound of formula (VI):

wherein R¹, R³ and n are as defined in claim 1 ; with a compound of formula R²-NH2, wherein R² is as defined in claim 1 ;

(e) deprotection of a protected derivative of a compound of formula (I);

(f) interconversion of a compound of formula (I) or protected derivative thereof to a further compound of formula (I) or protected derivative thereof; and

(g) optional formation of a pharmaceutically acceptable salt of a compound of formula (I).

132