Diarylsulfones as 5-HT2A antagonists

1. A compound of formula I:

wherein:

m is 0, 1, 2 or 3;

n is 0, 1 or 2;

t is 1 or 2;

A represents a phenyl ring optionally bearing up to 2 additional substituents selected from halogen, CN, CF 3 , OR 8 , CO 2 R a , CONR a R b , NR a R b and C 1-4 alkyl which is optionally substituted with halogen, CN, CF 3 , OR a , CO 2 R a , CONR a R b or NR a R b ;

W represents —CR 3 ═CR 5 , where R 3 and R 5 are selected from H, OH and F but mot more than one of R 3 and R 5 is other than H;

E represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms, optionally incorporating an oxygen atom to form an ether linkage and optionally comprising a hydroxy substituent;

Z is selected from H, halogen, CN, nitro, CF 3 , OCF 3 , —R a , —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —NR a R b , —NR a COR b , —NR a CO 2 R b , —NR a CONR a R b , NR a SOR b , NR a SO 2 R b , CONHCOR a , NHCH 2 CO 2 R a , NHCH 2 CONR a R b , —NR a SO 2 NR a R b , —COR a , —CO 2 R a , —CONR a R b , —CH═NOR a or a five- or six-membered heteroaromatic ring optionally bearing up to 2 substituents selected from halogen, CN, CF 3 , C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, amino, C 1-6 alkylamino and di(C 1-6 )alkylamino;

or the moiety -E-Z may combine with an adjacent R 2 group as defined below;

R a and R b independently represent H or a hydrocarbon group of up to 7 carbon atoms which is optionally substituted with up to 3 halogen atoms or with CN, OH, C 1-4 alkoxy, C 1-4 alkylthio, amino, C 1-4 alkylamino or di(C 1-4 )alkylamino; or R a and R b , when linked through a nitrogen atom, together represent a heterocyclic ring of 4, 5 or 6 members, optionally bearing up to 3 substituents selected from halogen, CN, CF 3 , oxo, OH, C 1-4 alkyl and C 1-4 alkoxy;

each R 1 independently represents halogen, CN, CF 3 , OCF 3 , C 1-6 alkyl, OH, benzylthio, C 1-6 alkoxy or hydroxymethyl; and

each R 2 independently represents halogen, CN, CONH 2 , C 1-4 alkyl or C 1-4 alkoxy; or an R 2 group and the moiety -E-Z when attached to adjacent ring positions may complete a fused 5- or 6-membered carbocyclic or heterocyclic ring optionally bearing up to 3 substituents selected from halogen, CN, CF 3 , oxo, R a and amino; with the proviso that when A represents the residue of a phenyl ring and W represents —CH═CH—, m is not zero and at least one R 1 represents F;

or a pharmaceutically acceptable salt or hydrate thereof.

2. The compound of claim 1 wherein W is selected from: —CH═CH—, —CF═CH—, —CH═CF—, —C(OH)═CH—, and —CH═C(OH)—.

3. The compound of claim 1 wherein (R 1 ) m and the phenyl ring to which it is attached are a 4-fluorophenyl or 2,4-difluorophenyl group.

4. The compound of claim 1 of the formula II:

wherein each A 1 represents CH;

R 7 represents H, halogen, CN, CF 3 , OR a , CO 2 R a , CONR a R b , NR a R b or C 1-4 alkyl which is optionally substituted with halogen, CN, CF 3 , OR a , CO 2 R a , CONR a R b or NR a R b ; or pharmaceutically acceptable salt.

5. The compound of claim 1 wherein Z represents SOR a , SO 2 R a , CONHCOR a , NHCH 2 CO 2 R a or CO 2 R a and R a represents C 1-6 alkyl.

6. The compound of claim 1 of the formula IV:

wherein:

n is 0 or 1;

R 11 represents H or F;

R 22 represents halogen, CN, CONH 2 , C 1-4 alkyl or C 1-4 alkoxy;

R 77 represents H or C 1-4 alkyl; and

Z represents C 1-6 oxycarbonyl, or a 5- or 6-membered heteroaromatic ring which optionally bears a methyl substituent;

or a pharmaceutically acceptable salt.

7. The compound of claim 6 wherein Z 1 is ortho to the sulfone moiety in formula IV.

8. The compound of claim 6 wherein R 11 represents H.

9. The compound of claim 6 wherein Z 1 represents C 1-6 alkoxycarbonyl.

10. The compound of claim 6 wherein Z 1 represents a 5- or 6-membered heteroaromatic ring which optionally bears a methyl substituent.

11. The compound of which is selected from the group consisting of:

methyl 2-({4-[(E)-2-(2,4-difluorophenyl)vinyl]phenyl}sulfonyl)benzoate;

methyl 2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)benzoate;

methyl 3-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)benzoate; and

methyl 2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)-3-methylbenzoate;

or a pharmaceutically acceptable salt.

12. The compound which is methyl 2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)benzoate, or a pharmaceutically acceptable salt.

13. The compound of claim 12 which is methyl 2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)benzoate.

14. A pharmaceutical composition which comprises an inert carrier and compound of claim 1 or a pharmaceutically acceptable salt.

15. A pharmaceutical composition which comprises an inert carrier and the compound of claim 11 or a pharmaceutically acceptable salt.

16. A pharmaceutical composition which comprises an inert carrier and the compound of claim 12 or a pharmaceutically acceptable salt.

17. A pharmaceutical composition which comprises an inert carrier and the compound claim 13 or a pharmaceutically acceptable salt.