3-Phenylfuran-2-one derivatives as cox-2 inhibitor
The present invention relates to 3-phenylfuran-2-ones of formula (I), processes for their preparation, pharmaceutical compositions containing them, and their medical uses.
1 . A compound of formula (I):
wherein the compound of formula (I) is in the form of any of the two different enantiomers;
or a racemic mixture of the enantiomers or a scalemic mixture of the enantiomers.
2 . A compound according to claim 1 , chosen from:
(R) 4-[4(methylsulfinyl)phenyl]-3-phenylfuran-2(5H)-one, and
(S) 4-[4(methylsulfinyl)phenyl]-3-phenylfuran-2(5H)-one.
3 . A process for the preparation of a compound according to claim 1 , comprising:
reacting a compound of formula (IV)
with an oxidizing agent.
4 . A process according to claim 3 wherein the oxidizing agent is chosen from:
(a) sodium metaperiodate; and
(b) a mixture of titanium tetraisopropoxide, t-butyl hydroperoxide and either the (R,R) or the (S,S) form of diethyl tartrate.
5 . A process according to claim 4 , wherein the reaction takes place in at least one chlorinated solvent or in a mixture of at least one chlorinated solvent and at least one C 1 -C 4 alcohol.
6 . A process according to claim 5 , wherein the at least one chlorinated solvent is chosen from 1,2-dichloroethane, methylene chloride, chloroform, and mixtures thereof.
7 . A medicament comprising at least one compound as defined in claim 1 .
8 . (canceled)
9 . A pharmaceutical composition comprising at least one compound according to claim 1 and at least one pharmaceutically acceptable diluent or carrier.
10 . A pharmaceutical composition comprising at least one compound according to claim 2 , and at least one pharmaceutically acceptable diluent or carrier.
11 . (canceled)
12 . A method for treating a subject afflicted with a pathological condition or disease susceptible to amelioration by inhibition of the enzyme cyclooxygenase-2 (COX-2), comprising administering to said subject an effective amount of a compound according to claim 1 .
13 . A method according to claim 12 , wherein the pathological condion or disease is chosen from pain, fever, inflammation, prostanoid-induced smooth muscle contraction, colorectal cancer, and neurodegenerative diseases.
14 . A method for treating a subject afflicted with a pathological condition or disease susceptible of amelioration by inhibition of the enzyme cyclooxygenase-2 (COX-2), comprising administering to the said subject an effective amount of a composition according to claim 10 .
15 . A method according to claim 14 , wherein the pathological condition or disease is chosen from pain, fever, inflammation, prostanoid-induced smooth muscle contraction, colorectal cancer, and neurodegenerative diseases.