(1, 1, 1,3,3,3-hexafluoro-2 hydroxypropan-2-yl) phenyl derivative, pharmaceutical compositions thereof and their use for the treatment of atherosclerosis

1. A (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivative having the general Formula I

wherein

n is 1;

X is NR 4 ;

Y is O and the dotted bond represents a single bond; or

Y has a meta or para substitution pattern on the phenyl ring in relation to the phenyl-NH position;

Z is CH 2 ;

the hexafluoroispopropanol substituent has an ortho, meta or para substitution pattern on the phenyl ring in relation to the phenyl-Z position;

R 1 is a 4-, 5- 6-membered saturated or unsaturated heterocycle ring, comprising 1 or 2 heteroatoms selected from NR 10 , O, S, SO and SO 2 , the ring being optionally substituted by (C 1-3 )alkyl, hydroxy, oxo, NR 11 R 12 or R 9 OCO, and the ring being optionally linked to X via a (C 1-3 )alkylene group which is optionally substituted by hydroxy; or

when X is NR 4 , R 1 may together with R 4 and the N to which they are bonded form a 4-8 membered ring, which can be optionally substituted with hydroxyl or hydroxymethyl;

R 2 is H or 1-3 halogens; or

R 3 is H or (C 1-3 )alkyl;

R 4 , when present, is H or (C 1-3 )alkyl;

R 9 , when present, is H or (C 1-3 )alkyl;

R 10 , when present, is H or (C 1-3 )alkyl;

R 11 and R 12 , when present, are independently H or (C 1-3 )alkyl;

or a pharmaceutically acceptable salt thereof.

2. The (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivative of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is NH.

3. The (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivative of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H and the hexaflouroisopropanol substituent has the para substitution pattern on the phenyl ring in relation to the phenyl-Z position.

4. The (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivative of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 2 represents H or 1 or 2 halogens selected from F and Cl.

5. The (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivative of claim 1 which is selected from the group consisting of:

1-(4-(1-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)-3-(tetrahydro-2H-pyran-4-yl)urea;

1-(4-(1-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)-3-(pyridazin-4-yl)urea;

1(3-fluoropyridin-4-yl)-3-(4-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)urea; and

1-(4-(1-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)-3-(pyridin-4-yl)urea;

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl derivative of claim 1 and pharmaceutically acceptable auxiliaries.

7. A method of treating a disorder associated with cholesterol and bile acids transport and metabolism selected from hypercholesterolemia, cholesterol gallstones, a lipid storage disease, diabetes or obesity in a patient comprising administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.