Bis-aromatic alkanols

1. A compound of formula I

wherein

Y is —CH 2 CH 2 —, —CH 2 CH(OH)—, —CH(OH)CH 2 —, —C(O)CH 2 —, —CH 2 C(O)—, —CH═CH—; or 1,2-cyclopropylene;

X is phenylene optionally substituted by one to three substituents selected from halogen, nitro, C 1-10 alkyl and halogen-substituted C 1-6 alkyl;

R 1 is phenyl or phenyl-C 2-4 alkenyl, each being substituted by (i) one to three substituents selected from hydrogen, halogen, amino, phenyl, heteroaryl, heteroaryl-C 1-4 alkyl, C 1-10 alkyl, cycloalkyl-C 1-4 alkyl, cycloalkyl-C 1-4 alkoxy, C 1-10 alkoxy, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkylthio, C 1-10 alkylsulfonyl, C 1-10 alkylsulfinyl, C 1-4 alkyl-S(O) 2 NH—, phenylC 1-6 alkyl, or phenylC 1-6 alkoxy, in each of which any aliphatic part of the group may be straight or branched chain and optionally substituted by up to three substituents selected from halogen, amino, hydroxy, cyano, or cycloalkyl groups and optionally interrupted by a double or triple bond or one or more C(O), NR 12 , S, S(O), S(O) 2 or O groups, wherein R 12 is hydrogen or C 1-6 alkyl; and any aromatic group may be optionally substituted by one to three substituents selected from halogen, cyano, amino, C 1-4 alkyl halogen-substituted-C 1-4 alkyl and C 1-8 alkoxy; and/or (ii) a group of formula (a):

in which

R 6 and R 7 , independently, is hydrogen; phenyl, C 1-10 alkyl, cycloalkyl, heteroaryl, heteroaryl-C 1-4 alkyl, C 1-10 alkoxy, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkylthio, C 1-10 alkylsulfonyl, C 1-10 alkylsulfinyl, phenylC 1-8 alkyl, or phenylC 1-6 alkoxy, in each of which any aliphatic part of the group may be straight chain or branched and may be optionally substituted by up to three halogen, hydroxy, cycloalkyl, or C 1-4 alkoxy groups and optionally interrupted by a double or triple bond or one or more C(O), NR 12 , S, S(O), S(O) 2 or O groups, and any aromatic group may be optionally substituted by one to three substituents selected from halogen, CF 3 , C 1-8 alkyl and C 1-8 alkoxy;

R 2 is hydrogen; halogen; C 1-4 alkyl optionally substituted with one or more halogens; C 2-6 alkenyl; C 2-6 alkynyl; or cycloalkyl optionally substituted by halogen; aryl optionally substituted with hydroxy; or C 1-4 alkyl optionally substituted on the terminal C atom by OH or a residue of formula (h):

in which Z is a direct bond, O, S, (CH 2 ) 1-2 , CF 2 , or NR 11 where R 11 is H, (C 1-4 )alkyl or halogen-substituted (C 1-4 )alkyl; and each of R 9 and R 10 , independently, is H, OH, (C 1-4 )alkyl optionally substituted by one to three halogens, or (C 1-4 )alkoxy optionally substituted by halogen; with the proviso that R 9 and R 10 are not both hydrogen;

each of R 3 and R 4 , independently, is H or C 1-4 alkyl optionally substituted by halogen or acyl; and R 5 is H, —OH, —Oacyl, —NHacyl, or a residue of formula (h) as defined above;

provided that at least either R 2 comprises a terminal OH or a residue of formula (h) or R 5 is OH or a residue of formula (h),

or a salt thereof.

2. A compound according to claim 1 , wherein X is 1,4-phenylene, Y is —CH 2 —CH 2 —, R 1 is phenyl monosubstituted in position para by a group R 15 wherein R 15 is straight chain C 5-8 alkyl; C 2-8 alkenyl; or straight chain or branched C 1-8 alkoxy optionally substituted by one C 3-6 cycloalkyl or by a phenyl group optionally substituted by up to three halogens; or R 1 is para-monosubstituted phenyl substituted by a group of formula (a), as defined in claim 1 , R 2 is C 1-4 alkyl optionally substituted on the terminal C atom by OH or a residue of formula (h) as defined above, R 3 and R 4 are hydrogen, and R 5 is OH, or a salt thereof.

3. A compound according to claim 1 or 2 , wherein R 1 is phenyl monosubstituted in position para by a group of formula (a) as defined above, or a salt thereof.

4. A compound according to claim 1 , wherein Z is O, or a salt thereof.

5. A process for preparing a compound according to claim 1 which process comprises removing the hydrolysable groups present in a compound of formula II

wherein X, Y, R 1 and R 3 are as defined in claim 1 , R 4 ′ is an amino protecting group, R 2 ′ has one of the significances given for R 2 above except that the terminal OH when present in the OH-substituted C 1-4 alkyl is in protected form or the residue of formula (h) is replaced by a residue of formula (h′) and R 5 ′ is R 5 ″ in which R 5 ″ is H, —OH in protected form or a residue of formula (h′), provided that at least one of R 2 ′ and R 5 ′ is OH in protected form or a residue of formula (h′), the residue of formula (h′) being:

wherein Z is as described above, and each of R 9 ′ and R 10 ′ is a hydrolysable group and, where required, converting the compounds of formula I obtained in free form into the desired salt form, or vice versa.

6. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable diluent or carrier therefor.

7. A method for treating acute or chronic transplant rejection in a subject comprising administering to the subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.