Compounds which are inhibitors of Notum

1. A compound of formula (I):

where Ar is C 5 heteroaryl, optionally substituted by a group selected from

a) OH, SH, NH 2 , OMe, SMe, NHMe, NMe 2 , OEt, NHCN, Me;

b) CN, CO 2 H;

c) SO 2 Me, SO 3 − Na + ;

d) CH 2 Q 1 , where Q 1 is selected from OH, OMe, Cl, CN, NHCOMe, SO 3 H, NR N1 R N2 , where R N1 and R N2 are either H or Me;

e) C 2-3 alkyl substituted by OH;

where a N-ring heteroatom may additional bear a methyl group; and

X 1 is CR 1 ;

X 2 is CR 2 ;

X 3 is CR 3 ;

X 5 is CR 5 ;

two of R 1 , R 2 , R 3 , R 4 and R 5 are H, two of R 1 , R 2 , R 3 , R 4 and R 5 are Cl and one of R 1 , R 2 , R 3 , R 4 and R 5 is CF 3 .

2. A compound according to claim 1 , wherein Ar is selected from:

where subst represents the substituent.

3. A compound according to claim 2 , wherein Ar is selected from:

where subst represents the substituent.

4. A compound according to claim 1 , wherein there are three heteroatoms in the ring.

5. A compound according to claim 1 , wherein the substituent is selected from OH, OMe, OEt and NHCN.

6. A compound according to claim 5 , wherein the substituent is OH.

7. A compound according to claim 1 , wherein the substituent is CH 2 OH.

8. A compound according to claim 1 , wherein there is no substituent on Ar.

9. A compound according to claim 1 , wherein R 2 is Cl, R 3 is CF 3 and R 4 is Cl.

10. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

11. A compound according to claim 1 , wherein:

(i) Ar is

where subst represents the optional substituent;

(ii) Ar is

and:

a. at least 2 of R 1 to R 5 are not H and one of R 1 to R 5 is not Me; and

R 1 , R 2 , R 3 , R 4 and R 5 (if present) are independently selected from:

i) H;

ii) C 3-6 cycloalkyl, with an optional O ring atom;

ii) CN, NMe 2 , NO 2 ;

iv) OCH 2 Q 2 , where Q 2 is selected from C 3-6 cycloalkyl and phenyl;

v) CH 2 OH;

vi) NR N6 R N7 , where R N6 and R N7 together form a C 4-6 heterocyclyl group optionally substituted with 1 to 2 groups selected from halo, C 1-3 alkyl, cyano and oxetanyl;

or two adjacent groups of R 1 to R 4 together form a group -Q 3 -(CR C 2 )n-Q 4 -, where Q 3 is selected from NR N3 and O, where R N3 is selected from H, C 1-3 alkyl, cyclopropylmethyl and COMe; Q 4 is NR N4 , O or a single bond, where R N4 is selected from H, C 1-3 alkyl, cyclopropylmethyl and COMe; each R C is independently H, F or Me or two R c which are attached to the same atom can be linked together to form a C 3-5 cycloalkyl; and n is 1, 2 or 3;

or two adjacent groups of R 1 to R 5 form a fused benzene or C 5-6 heteroaromatic ring with the phenyl group, which itself is optionally substituted by a C 1-2 alkyl group;

b. at least 1 of R 1 to R 4 (if present) is C 3-6 cycloalkyl;

c. two adjacent groups of R 1 to R 4 together form a group -Q 3 -(CH 2 ) n -Q 4 -, where Q 3 is selected from NR N3 and O, where R N3 is selected from H, Me and COMe; Q 4 is a single bond; and n is 1 or 2;

(iii) Ar is

subst is selected from:

a) H;

b) NH 2 , SH, OMe, SMe;

c) CN, CO 2 H, COmorph;

d) SO 2 Me;

e) C 2-3 alkyl substituted by OH;

and at least 2 of R 1 to R 4 are not H;

(iv) Ar is

or

(v) Ar is

and R 3 is iPr.

12. A compound according to claim 1 , wherein the compound is selected from:

4-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1H-triazole (306);

2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-(methoxy-d3)-1,3,4-oxadiazole (241);

2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-ethoxy-1,3,4-oxadiazole (242);

4,5-dideuterio-1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (308);

5-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-ol (261);

2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-methoxy-1,3,4-oxadiazole (243);

1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295); and

N-(5-(2,4-dichloro-3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)cyanamide, ammonia salt (246).

13. A compound: 1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295).

14. A method of treatment of a disease or disorder ameliorated by the inhibition of Notum, comprising administering to a patient in need of treatment, a compound as defined in claim 1 .

15. A method according to claim 14 , wherein the disease or disorder is a neurodegenerative disorder or a central nervous system disorder.

16. A method according to claim 14 , wherein the disease or disorder is a neurodegenerative disease, and the neurodegenerative disease is Alzheimer's disease.