TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY

1 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 1) characterised in that it provides an X-ray powder diffraction pattern comprising a peak at 14.5±0.2.

2 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 1) characterised in that it provides an X-ray powder diffraction pattern comprising a peak at 16.7±0.2.

3 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 1) characterised in that it provides an X-ray powder diffraction pattern comprising a peak at 19.1±0.2.

4 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 1) characterised in that it provides an X-ray powder diffraction pattern comprising a peak at 24.0±0.2.

5 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 1) characterised in that it provides an X-ray powder diffraction pattern comprising peaks at 14.5±0.2, 16.7±0.2, 19.1±0.2 and 24.0±0.2.

6 . A polymorphic form of claim 1 having an x-ray powder diffraction pattern substantially in accordance with FIG. 1 .

7 . A polymorphic form of claim 1 having a differential scanning calorimetry trace substantially in accordance with FIG. 2 .

8 . A polymorphic form of claim 1 having a thermogravimetric analysis trace substantially in accordance with FIG. 3 .

9 . A polymorphic form of claim 1 having a raman spectra substantially in accordance with FIG. 4 .

10 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising greater than 60% of a polymorphic form according to claim 1 .

11 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising a polymorphic form of claim 1 as the only polymorphic form.

12 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 2) characterised in that it provides an X-ray powder diffraction pattern comprising peaks at 15.9±0.2, 18.5±0.2 and 23.3±0.2.

13 . A polymorphic form of claim 12 having an x-ray powder diffraction pattern substantially in accordance with FIG. 6 .

14 . A polymorphic form of claim 12 having a differential scanning calorimetry trace substantially in accordance with FIG. 7 .

15 . A polymorphic form of claim 12 having a thermogravimetric analysis trace substantially in accordance with FIG. 8 .

16 . A polymorphic form of claim 12 having a raman spectra substantially in accordance with FIG. 9 .

17 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising greater than 60% of a polymorphic form of claim 12 .

18 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising a polymorphic form of claim 12 as the only polymorphic form.

19 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 3) characterised in that it provides an X-ray powder diffraction pattern comprising peaks at 12.1±0.2, 17.4±0.2, 22.7±0.2, 25.0±0.2 and 26.5±0.2.

20 . A polymorphic form of claim 19 having an x-ray powder diffraction pattern substantially in accordance with FIG. 11 .

21 . A polymorphic form of claim 19 having a differential scanning calorimetry trace substantially in accordance with FIG. 12 .

22 . A polymorphic form of claim 19 having a thermogravimetric analysis trace substantially in accordance with FIG. 13 .

23 . A polymorphic form of claim 19 having a raman spectra substantially in accordance with FIG. 14 .

24 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising greater than 60% of a polymorphic form of claim 19 .

25 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising a polymorphic form of claim 19 as the only polymorphic form.

26 . A polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (polymorphic form 4) characterised in that it provides an X-ray powder diffraction pattern comprising peaks at 14.6±0.2, 16.1±0.2, 17.0±0.2, 19.3±0.2 and 29.2±0.2

27 . A polymorphic form of claim 26 having an x-ray powder diffraction pattern substantially in accordance with FIG. 16 .

28 . A polymorphic form of claim 26 having a differential scanning calorimetry trace substantially in accordance with FIG. 17 .

29 . A polymorphic form of claim 26 having a thermogravimetric analysis trace substantially in accordance with FIG. 18 .

30 . A polymorphic form of claim 26 having a raman spectra substantially in accordance with FIG. 19 .

31 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising greater than 60% of a polymorphic form of claim 26 .

32 . A pharmaceutical composition comprising a compound of the formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole, wherein the compound of formula 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole has a structure comprising a polymorphic form of claim 26 as the only polymorphic form.

33 . A process for synthesising a polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole of claim 1 comprising the steps of:

(i) dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in acetone and then adding IPA until a solid product forms wherein the ratio of acetone:IPA is 20:80; or

dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in EtOAc and then adding IPA until a solid product forms wherein the ratio of EtOAc:IPA is 40:60; or

dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in DMF and then adding IPA until a solid product forms wherein the ratio of DMF:IPA is 40:60; or

dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in acetone and then adding EtOH until a solid product forms wherein the ratio of acetone:EtOH is 40:60; or

dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in acetone at reflux and then cooling to −10° C. to −15° C. until a solid product forms;

and then

(ii) separating the solid product.

34 . A process for synthesising a polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole of claim 12 comprising the steps of:

(i) dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in xylene and then adding IPA until a solid product forms wherein the ration of xylene: IPA is either 20:80 or 80:20;

and then

(ii) separating the solid product.

35 . A process for synthesising a polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole of claim 19 comprising the steps of:

(i) dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in xylene and then adding IPA until a solid product forms wherein the ratio of xylene:IPA is 60:40;

and then

(ii) separating the solid product.

36 . A process for synthesising a polymorphic form of the compound 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole of claim 26 comprising the steps of:

(i) dissolving 5-(ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole in DMF;

and then

(ii) removing the DMF by evaporation to form a solid product.

37 . A method of treating Duchenne muscular dystrophy or Becker muscular dystrophy, comprising administering a polymorphic form of claim 1 .

38 . A method of treating Duchenne muscular dystrophy or Becker muscular dystrophy, comprising administering a polymorphic form of claim 12 .

39 . A method of treating Duchenne muscular dystrophy or Becker muscular dystrophy, comprising administering a polymorphic form of claim 19 .

40 . A method of treating Duchenne muscular dystrophy or Becker muscular dystrophy, comprising administering a polymorphic form of claim 26 .