Silylated piperidine derivatives

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof; wherein:

p is 0, 1 or 2;

n is 0, 1, 2 or 3;

the moiety —C(R 1 ) 2 —Z is attached to the 3-, 4- or 5-position of the piperidine ring;

Z represents CO 2 H or a tetrazole ring;

each R 1 independently represents H or a non-aromatic hydrocarbon group of up to 6 carbon atoms; or the two R 1 groups complete a C 3-6 alicyclic group;

each R 2 independently represents a non-aromatic hydrocarbon group of up to 6 carbon atoms;

each R 3 independently represents halogen, C 1-6 alkyl bearing 0-3 fluorine substituents, C 1-6 alkoxy bearing 0-3 fluorine substituents, C 2-6 alkenyl, or Si(R 6 ) 3 ;

R 4 is selected from:

(i) H;

(ii) Het-A- where A represents a bond, CH 2 or 1,4-phenylene and Het represents a heterocyclic ring system of up to 10 ring atoms which optionally bears up to 3 substituents selected from halogen, C 1-4 alkyl, CF 3 , Si(R 6 ) 3 , C 1-4 -alkoxy and C 1-4 -alkoxycarbonyl or which optionally bears a phenyl substituent which itself is optionally substituted with halogen, C 1-4 alkyl, Si(R 6 ) 3 , C 1-4 -alkoxy or C 1-4 alkoxycarbonyl; and

(iii) hydrocarbon of up to 12 carbon atoms which optionally bears up to 3 substituents selected from halogen, perfluoroC 1-4 alkyl, CN, Si(R 6 ) 3 , OH, C 1-4 -alkoxy and OCF 3 ;

R 5 is selected from:

(i) H;

(ii) hydrocarbon of up to 12 carbon atoms which optionally bears up to 3 substituents selected from halogen, perfluoroC 1-4 -alkyl, CN, Si(R 6 ) 3 , OH, C 1-4 -alkoxy and OCF 3 ; and

(iii) CO 2 R 7 where R 7 represents hydrocarbon of up to 12 carbon atoms which optionally bears up to 3 substituents selected from halogen, perfluoroC 1-4 -alkyl, CN, Si(R 6 ) 3 , OH, C 1-4 -alkoxy and OCF 3 ; and

each R 6 independently represents a hydrocarbon group of up to 6 carbon atoms;

provided R 4 and R 5 do not both represent H and provided at least one of R 4 and R 5 bears Si(R 6 ) 3 as a substituent.

2. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the moiety —C(R 1 ) 2 —Z is attached to the 4-position of the piperidine ring.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 and R 5 each independently represents a hydrocarbon group of up to 12 carbon atoms which optionally bears up to 3 substituents selected from halogen, perfluoroC 1-4 alkyl, CN, Si(R 6 ) 3 , OH, C 1-4 alkoxy and OCF 3 ; provided at least one of R 4 and R 5 bears a silyl substituent represented by Si(R 6 ) 3 .

4. A compound according to claim 1 defined by formula II:

or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 4 or a pharmaceutically acceptable salt thereof, wherein the relative stereochemistry is as shown in formula IIA:

6. A compound according to claim 5 defined by formula III:

or a pharmaceutically acceptable salt thereof wherein:

R 4a represents hydrocarbon of up to 12 carbon atoms which optionally bears up to 3 substituents selected from halogen, perfluoroC 1-4 alkyl, CN, Si(R 6 ) 3 , OH, C 1-4 alkoxy and OCF 3 ; and

R 8 represents Si(R 6 ) 3 , branched C 1-6 alkyl, C 3-6 cycloalkyl, or phenyl which optionally bears up to 3 substituents selected from halogen, C 1-4 alkyl and CF 3 ;

provided that when R 8 is other than Si(R 6 ) 3 then R 4a bears at least one Si(R 6 ) 3 substituent.

7. A compound according to claim 5 , wherein p is 0, n is 1, R 3 represents CF 3 attached in the 4-position, and R 1 , R 4 and R 5 are as indicated in the following table:

R 1 /R 1

R 4

R 5

H/H

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

H/H

CH 2 CH 2 CF 3

CH 2 CH 2 SiEt 3

H/H

CH 2 CH 2 CF 3

CH 2 CH 2 Si(t-Bu)Me 2

H/H

4-CF 3 —C 6 H 4

CH 2 CH 2 SiMe 3

H/H

CH 2 CH 2 SiMe 3

CH 2 CH 2 SiMe 3

H/H

CH 2 CH 2 SiMe 3

C≡C-t-Bu

H/H

4-SiMe 3 -C 6 H 4

CH 2 CH 2 SiMe 3

H/H

4-CF 3 —C 6 H 4

CH 2 CH 2 SiEt 3

H/H

CH 2 CH 2 SiMe 3

CH 2 CH 2 SiEt 3

H/H

CH 2 CH 2 SiMe 3

CH 2 CH 2 -t-Bu

H/H

CH 2 CH 2 SiMe 3

CH 2 CH 2 Ph

H/H

Cyclohexyl

CH 2 CH 2 SiMe 3

H/H

4-SiMe 3 -C 6 H 4

CH 2 CH 2 SiEt 3

Me/Me

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

Me/Me

4-CF 3 —C 6 H 4

CH 2 CH 2 SiMe 3

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 5 wherein p is 0, n is 1, R 3 is attached in the 4-position, each R 1 is H and R 3 , R 4 and R 5 are as indicated in the following table:

R 3

R 4

R 5

n-propyl

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

Isopropyl

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

t-butyl

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

SiMe 3

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

OCF 3

CH 2 CH 2 CF 3

CH 2 CH 2 SiMe 3

OCF 3

CH 2 CH 2 CH(Me) 2

CH 2 CH 2 SiMe 3

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.