US 7,468,393 B2
Diarylsulfones as 5-HT2A antagonists
Jose Luis Castro Pineiro, Bishops Stortford (United Kingdom); Laura Catherine Cooper, Bishops Stortford (United Kingdom); Myra Gilligan, Bishops Stortford (United Kingdom); Alexander Charles Humphries, Stevenage (United Kingdom); Peter Alan Hunt, Saffron Walden (United Kingdom); Tamara Ladduwahetty, London (United Kingdom); Angus Murray MacLeod, Bishops Stortford (United Kingdom); Kevin John Merchant, Ware (United Kingdom); Monique Bodil Van Niel, Welwyn (United Kingdom); and Kevin Wilson, Boston, Mass. (US)
Assigned to Merck Sharp & Dohme Ltd., Hoddesdon, Hertfordshire (United Kingdom)
Filed on Apr. 27, 2007, as Appl. No. 11/796,389.
Application 11/796389 is a division of application No. 11/212789, filed on Aug. 26, 2005, granted, now 7,217,740.
Claims priority of application No. 0419192.0 (GB), filed on Aug. 27, 2004.
Prior Publication US 2007/0203205 A1, Aug. 30, 2007
Int. Cl. A61K 31/10 (2006.01); C07C 317/24 (2006.01); C07C 317/32 (2006.01)
U.S. Cl. 514—710  [568/32; 568/34] 17 Claims
 
1. A compound of formula I:

OG Complex Work Unit Drawing
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, CF3, OR8, CO2Ra, CONRaRb, NRaRb and C1-4alkyl which is optionally substituted with halogen, CN, CF3, ORa, CO2Ra, CONRaRb or NRaRb;
W represents —CR3═CR5, where R3 and R5 are selected from H, OH and F but mot more than one of R3 and R5 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, CF3, OCF3, —Ra, —ORa, —SRa, —SORa, —SO2Ra, —SO2NRaRb, —NRaRb, —NRaCORb, —NRaCO2Rb, —NRaCONRaRb, NRaSORb, NRaSO2Rb, CONHCORa, NHCH2CO2Ra, NHCH2CONRaRb, —NRaSO2NRaRb, —CORa, —CO2Ra, —CONRaRb, —CH═NORa or a five- or six-membered heteroaromatic ring optionally bearing up to 2 substituents selected from halogen, CN, CF3, C1-6alkyl, C1-6alkoxy, C1-6alkylthio, amino, C1-6alkylamino and di(C1-6)alkylamino;
or the moiety -E-Z may combine with an adjacent R2 group as defined below;
Ra and Rb 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, C1-4alkoxy, C1-4alkylthio, amino, C1-4alkylamino or di(C1-4)alkylamino; or Ra and Rb, 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, CF3, oxo, OH, C1-4alkyl and C1-4alkoxy;
each R1 independently represents halogen, CN, CF3, OCF3, C1-6 alkyl, OH, benzylthio, C1-6 alkoxy or hydroxymethyl; and
each R2 independently represents halogen, CN, CONH2, C1-4alkyl or C1-4alkoxy; or an R2 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, CF3, oxo, Ra 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 R1 represents F;
or a pharmaceutically acceptable salt or hydrate thereof.