Diarylsulfones as 5-HT2A antagonists
View Patent ↗Compounds of formula I: are potent and selective antagonists of the human 5-HT 2A receptor, and hence useful in treatment of a variety of adverse conditions of the CNS.
1. A compound 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 1 represents hydroxyC 1-6 alkyl;
or a pharmaceutically acceptable salt or hydrate thereof.
2. The compound of claim 1 wherein Z 1 is ortho to the sulfone moiety in formula IV.
3. The compound of claim 1 wherein R 11 represents H.
4. The compound of claim 1 which is selected from the group consisting of:
(1S)-1-[2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]ethanol;
(1S)-1-[2-({4-[(E)-2-(2,4-difluorophenyl)vinyl]phenyl}sulfonyl)phenyl]ethanol;
(1S)-1-[2-({4-[(E)-2-(4-fluorophenyl)vinyl]-3-methylphenyl}sulfonyl)phenyl]ethanol;
[2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]methanol;
[2-({4-[(E)-2-(2,4-difluorophenyl)vinyl]phenyl}sulfonyl)phenyl]methanol;
2-[2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]propan-2-ol
2-[2-({4-[(E)-2-(2,4-difluorophenyl)vinyl]phenyl}sulfonyl)phenyl]propan-2-ol; and
2-[2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]ethanol;
or a pharmaceutically acceptable salt or hydrate thereof.
5. A compound which is:
(1S)-1-[2-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]ethanol;
or a pharmaceutically acceptable salt or hydrate thereof.
6. A compound which is:
(1S)-1-[2-({4-[(E)-2-(4- fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]ethanol.
7. A pharmaceutical composition which comprises an inert carrier and the compound of claim 1 , or a pharmaceutically acceptable salt or hydrate thereof.
8. A pharmaceutical composition which comprises an inert carrier and the compound of claim 5 , or a pharmaceutically acceptable salt or hydrate thereof.