(METHYLSULFONYL)PHENYL-2-(5H)-FURANONES AS COX-2 INHIBITORS

Abstract: The invention encompasses the novel compound of formula (I) useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of formula (I).

Description: TITLE OF THE INVENTION (METHYLSULFONYL)PHENYL-2-(5H)-FURANONES AS COX-2 INHIBITORS RELATED APPLICATION DATA This PCT application claims as priority US applications 60/005,371, filed on October 13, 1995 and 60/011637, filed on February 14, 1996. This PCT application also claims as priority British application 9602939.2, filed February 13, 1996 and 9605645.2, filed March 18, 1996. BACKGROUND OF THE INVENTION This invention relates to methods of treating cyclooxygenase mediated diseases and certain pharmaceutical compositions therefor. Non-steroidal, antiinflammatory drugs exert most of their antiinflammatory, analgesic and antipyretic activity and inhibit hormone- induced uterine contractions and certain types of cancer growth through inhibition of prostaglandin G/H synthase, also known as cyclooxygenase. Initially, only one form of cyclooxygenase was known, this corresponding to cyclooxygenase- 1 (COX-1) or the constitutive enzyme, as originally identified in bovine seminal vesicles. More recently the gene for a second inducible form of cyclooxygenase, cyclooxygenase-2 (COX-2) has been cloned, sequenced and characterized initially from chicken, murine and human sources. This enzyme is distinct from the COX- 1 which has been cloned, sequenced and characterized from various sources including the sheep, the mouse and man. The second form of cyclooxygenase, COX-2, is rapidly and readily inducible by a number of agents including mitogens, endotoxin, hormones, cytokines and growth factors. As prostaglandins have both physiological and pathological roles, we have concluded that the constitutive enzyme, COX-1, is responsible, in large part, for endogenous basal release of prostaglandins and hence is important in their physiological functions such as the maintenance of gastrointestinal integrity and renal blood flow. In contrast, we have concluded that the inducible form, COX-2, is mainly responsible for the pathological effects of prostaglandins where rapid induction of the enzyme would occur in response to such agents as inflammatory agents, hormones, growth factors, and cytokines. Thus, a selective inhibitor of COX-2 will have similar antiinflammatory, antipyretic and analgesic properties to a conventional non-steroidal antiinflammatory drug, and in addition would inhibit hormone-induced uterine contractions and have potential anti-cancer effects, but will have a diminished ability to induce some of the mechanism-based side effects. In particular, such a compound should have a reduced potential for gastrointestinal toxicity, a reduced potential for renal side effects, a reduced effect on bleeding times and possibly a lessened ability to induce asthma attacks in aspirin- sensitive asthmatic subjects. Furthermore, such a compound will also inhibit prostanoid- induced smooth muscle contraction by preventing the synthesis of contractile prostanoids and hence may be of use in the treatment of dysmenorrhea, premature labour, asthma and eosinophil related disorders. It will also be of use in the treatment of Alzheimer's disease, for decreasing bone loss particularly in postmenopausal women (i.e. treatment of osteoporosis) and for the treatment of glaucoma. A brief description of the potential utility of cyclooxygenase-2 inhibitors is given in an article by John Vane, Nature. Vol. 367, pp. 215-216, 1994, and in an article in Drug News and Perspectives. Vol. 7, pp. 501-512, 1994. SUMMARY OF THE INVENTION The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non¬ toxic therapeutically effective amount of a compound of Formula I. I The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I. DETAILED DESCRIPTION OF THE INVENTION The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non¬ toxic therapeutically effective amount of a compound of Formula I. I or a pharmaceutically acceptable salt thereof wherein: X is selected from the group consisting of (a) CH2, (b) CHOH, (c) CO, ( ) O, (e) S, and ( ) N(Rl5), with the proviso that when R3 and R4 are other than (1) both hydrogen, (2) both C 1-10 alkyl, or (3) joined together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms, then X is selected from CO, O, S or N(Rl5); Y is selected from the group consisting of (a) C(Rl l)(Rl2), (b) CO, (c) O, and (d) S; elected from the group consisting of (c) Sθ2NHC(0)CF3, (d) S(0)(NH)NH2, (e) S(0)(NH)NHC(0)CF3, (f) P(0)(CH3)NH 2 , and ( g) P(0)(CH 3 )2, elected from the group consisting of (a) Cl-lθalkyl, (b) mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkoxy, (4) Cl-lθalkylthio, (5) CN, (6) Cl-6 fluoroalkyl (7) Cl-10 alkyl, (8) N3, (9) -CO2H, (10) -Cθ2-Cl-lθalkyl, (11) -C(R5)(R6)-0H, (12) -C(R5)(R6)-0-Cl-4alkyl, and (13) -Cl-6alkyl-Cθ2-R 5 , (14) benzyloxy, (15) -0-(Cl-6alkyl)-Cθ2R 5 , and (16) -0-(Cl-6alkyl)-NR5R6, (c) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1, 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Ci-ioalkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-0H, (10) -C(R5)(R6)-θ-Cl-lθalkyl, and (11) Cl-6fluoroalkyl; (d) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (I) hydrogen, (2) halo, (3) Cl-10alkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-θH, (10) -C(R5)(R6)-θ-Cl-lθalkyl, and (I I) Cl-6fluoroalkyl; (e) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from 0, S, or N and optionally contains a carbonyl group or a sulfonyl group. (f) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cμioalkoxy, (5) Ci-ioalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-0H, (10) -C(R5)(R6)-O-Cl-l0alkyl, and (11) Cl-6fluoroalkyl; (g) a mono- or di-substituted bicyclic heteroaryl of 8, 9, or 10 members, containing 2 to 5 heteroatoms chosen independently from O, S or N, and in which each ring contains at least one heteroatom, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-ioalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-OH, (10) -C(R*5)(R6)-0-Ci-ioalkyl, and (11) Ci-6fluoroalkyl; or R3 andR^ together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-lθalkyl, or R-5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-6alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-6alkyl, Cl-6alkoxy, C l -6alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-6alkyl, Ci-6alkoxy, Ci-6alkylthio, CN, or CF3, or two R7 groups taken together with the nitrogen to which they are attached form a saturated monocyclic ring of 5, 6 or 7 atoms, optionally containing an additional O, S or NR^; each R 8 is independently selected from the group consisting of (a) Cl-6alkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-6alkyl, Ci-6alkoxy, Ci-6alkylthio, CN, or CF3; R9 and RlO are independently selected from the group consisting of: (a) hydrogen, and (b) Cl-7alkyl, or R9 and RlO together with the carbon atom to which they are attached form a carbonyl or thiocarbonyl group; Ri 1 and R 12 are independently (a) hydrogen, (b) mono- or di-substituted phenyl or mono- or di-substituted benzyl or mono- or di-substituted heteroaryl or mono- or di- substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) fluoro, chloro, bromo and iodo, (3) Ci-6alkyl, (4) Cl-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(Rl3)(Rl4)_OH, (10) -C(Rl3)(Rl4)_0-Cl-4alkyl, and (11) C 1 -6fluoroalkyl, or (c) C 1 -7alkyl, CH20R7, CN, CH2CN, C l -6fluoroalkyl, Ri 1 and Rl2 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; Rl3 and Rl4 are independently selected from the group consisting of: (a) hydrogen, (b) Cl-7alkyl, or Rl3 and Rl4 together with the carbon to which they are attached form a carbonyl, -Ci=S)-, or a saturated monocyclic carbon ring of 3, 4, 5, 6, or 7 atoms. Rl5 is selected from the group consisting of: (a) hydrogen, (b) Cl-ioalkyl, (c) mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Ci-ioalkoxy, (4) Ci-ioalkylthio, (5) CN, (6) Cl-6 fluoroalkyl (7) Ci-io alkyl, (8) N3. (9) -C02H, (10) -Cθ2-Cl-lθalkyl, (11) -C(R5)(R6)-0H, (12) -C(R5)(R6)-0-Cl-4alkyl, and (13) -Ci-6alkyl-C02-R 5 ; (14) benzyloxy, (15) -0-(Ci-6alkyl)-C02R 5 , and (16) -0-(Cl-6alkyl)-NR5R6 (d) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1 , 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-iθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF 3 , (8) N 3 , (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-θ-Cl-lθalkyl, and (11) Cl-6fluoroalkyl; (e) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-iθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF , (8) N3, (9) -C(R-5)(R6)-OH, (10) -C(R5)(R6)-O-Cl-l0alkyl, and (11) Cl-6fluoroalkyl; (f) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group. (g) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Ci-ioalkoxy, (5) Cl-ioalkylthio, (6) CN, (7) CF 3 , (8) N3, (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-θ-Cl-4alkyl, and (11) Cl-6fluoroalkyl; d Rl7 are independently selected from the group consisting of (a) hydrogen (b) Cl-ioalkyl, (c) C l - 1 Oalkanoic acid, (d) C l - 1 oalky 1 amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-lθalkyl, Cl-lθalkoxy, Cl-lθalkylthio, Cl- 1 oalkanoic acid, Cl-lOalkylamine, CN, Cθ2H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-lθalkyl, Cl-lOalkoxy, Cl-lθalkylthio, Cl- 1 Oalkanoic acid, Cl-lOalkylamine, CN, COoH or CF3, or R16 and R17 together with the nitrogen to which they are attached form a saturated monocyclic ring of 5, 6 or 7 atoms, optionally containing an additional O, S or NR5. Within this embodiment there is a genus of compounds wherein R R 9 9 aanndd RF 10 together with carbon atom to which they are attached form a carbonyl. Within this genus there is a class of compounds wherein X is O; Y is O; R is selected from the group consisting of (c) S(0)(NH)NH2; R2 is selected from the group consisting of mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-4alkoxy, (4) Cl-4alkylthio, (5) CN, (6) Cl-3 fluoroalkyl (7) C alkyl, or R andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R-5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Ci-6alkyl, or R5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) CMalkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, C l -4alkyl, C 1 -4alkoxy , C l -4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3 each R is independently selected from the group consisting of (a) CMalkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3; R9 and RlO together with the carbon to which they are connected form a carbonyl; Rl6 and R 17 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl -oalkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, Cθ2H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, C l-6alkylamine, CN, CO2H or CF3. Within this class there is a sub-class of compounds wherein X is O; Y is O; R! is selected from the group consisting of R2 is selected from the group consisting of mono- or di- substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (5) CN, (6) CF3, and (7) Cl-4 alkyl, R3 is hydrogen or C 1-3 alkyl; R is hydrogen or C 1-3 alkyl; R9 and RlO together with the carbon to which they are connected form a carbonyl. R 16 and R 17 equal to hydrogen is preferred. Within this sub-class there is a goup of compounds wherein X is O; Y is O; R is selected from the group consisting of R2 is selected from the group consisting of mono- or di- substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (5) CN, (6) CF3, and (7) Cl-4 alkyl, R is methyl or ethyl; R4 is methyl or ethyl; and R9 and R O together with the carbon to which they are connected form a carbonyl. Within the above embodiment there is another genus of compounds wherein X is selected from the group consisting of (a) CH2, and (b) O, Y is selected from the group consisting of (a) CH2, and (b) O, Ri is selected from the group consisting of (c) S(0)(NH)NH2; R2 is selected from the group consisting of (a) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1, 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Ci-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-0H, and (b) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Ci-6alkyl, (4) Cl-6alkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF , (8) -C(R5)(R6)-OH, and (c) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group. (d) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Cl-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and (e) a mono- or di-substituted bicyclic heteroaryl of 8, 9, or 10 members, containing 2, 3, 4 or 5 heteroatoms chosen independently from O, S or N, and in which each ring contains at least one heteroatom, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Cl-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF , (8) -C(R5)(R6)-0H, and R3 is hydrogen, C 1-6 alkyl, CH20R 7 , CN, CH2CN, C l-3fluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) CMalkyl, (4) CMalkoxy, (5) Cl-4alkylthio, (6) CN, (7) CF 3 , (8) -C(R5)(R6)-0H, and (a) hydrogen (b) CMalkyl, (c) Cl-4alkoxy, (d) Cl-4alkylthio, (e) -OH, (f) -OCOR7, or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) CMalkyl, or R-5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) CMalkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, C 1 -4alky 1, C 1 -4alkoxy , C l -4alkylthio, CN, or CF3 each R is independently selected from the group consisting of (a) CMalkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, C 1 -4alkyl, C 1 -4alkoxy , C l -4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3; R9 and RlO together with the carbon to which they are connected form a carbonyl; Rl6 and Rl7 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl -6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, Cθ2H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, CO2H or CF3. Within this genus there is a class of compounds wherein R2 is a mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of Within this class there is a sub-class of compounds wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, and (b) SO2NH2; R2 is a mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of (1) furanyl, (2) diazinyl, (3) imidazolyl, (4) oxadiazolyl, (5) pyrazolyl, (6) pyridyl, (7) pyrrolyl, (8) thiazolyl, (9) thienyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) methyl, (4) methoxy, and (5) CF3; R3 is hydrogen, Cl-6 alkyl, CH20R 7 , CN, CH2CN, Cl-4fluoroalkyl, F, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-3alkyl, (4) Cl-3alkoxy, (5) Cl-3alkylthio, (6) CN, and (7) CF3; R4 is (a) hydrogen (b) Cl-3alkyl, (c) Cl-3alkoxy, (d) Cl-3alkylthio, and (e) -OH; and R9 and RlO together with the carbon to which they are connected form a carbonyl. Within this sub-class there is a group of compounds wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, and (b) SO2NH2; R2 is a mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of (1) furanyl, (2) diazinyl, (3) imidazolyl, (4) oxadiazolyl, (5) pyrazolyl, (6) pyridyl, (7) thiazolyl, (8) thienyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) Cl or F, (3) methyl, (4) methoxy, and (5) CF3; R3 is hydrogen or C 1-3 alkyl; R4 is hydrogen or C 1-3 alkyl; R9 and RlO together with the carbon to which they are connected form a carbonyl. Within the above embodiment there is another genus wherein X is selected from the group consisting of or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Ci-6alkyl, or R and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) CMalkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, C 1 -4alkyl, C l -4alkoxy , C l -4alkylthio, CN, or CF3 each R8 is independently selected from the group consisting of (a) CMalkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, C 1 -4alkyl, C 1 -4alkoxy , C l -4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3; R9 and RlO together with the carbon to which they are connected form a carbonyl; Rl6 nd R 17 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl-6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, C02H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Ci-6alkyl, Cl-6alkoxy, Ci-6alkylthio, Ci- 6alkanoic acid, Cl-6alkylamine, CN, CO2H or CF3. Within this genus there is a sub-genus of compounds wherein X is O; Y is O; Ri is selected from the group consisting of (c) S(0)(NH)NH2; R 2 is CMalkyl, R3 is hydrogen, Cl-6 alkyl, CH20R 7 , CN, CH2CN, CMfluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) CMalkyl, (4) CMalkoxy, (5) Cl-4alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and R4 is (a) hydrogen (b) Cl-6alkyl, (c) Cl-6alkoxy, (d) Ci-6alkylthio, (e) -OH, (f) -OCOR 7 , (g) -SCOR7, (h) -OC02R 8 , and (i) -SCO2R 8 , or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Ci-6alkyl, or R and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) CMalkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, C l -4alkyl, C 1 -4alkoxy , C 1 -4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3 each R 8 is independently selected from the group consisting of (a) CMalkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3; R9 and RlO together with the carbon to which they are connected form a carbonyl; Rl6 and Rl7 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) C 1 -6alkanoic acid, (d) Ci-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, COOH or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl-6alkanoic acid, Cl- 6alkylamine, CN, COOH or CF3. Within this sub-genus there is a class of compounds wherein X is O; Y is O; Ri is selected from the group consisting of R2 is propyl or butyl, R is hydrogen, C l -6 alkyl, CH20R 7 , CN, CH2CN, C l -4fluoroalkyl, F, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, Within this class there is a sub-class of compounds wherein X is O; Y is O; Ri is selected from the group consisting of R is propyl or butyl, R3 is hydrogen or C 1-3 alkyl; R 4 is hydrogen or C l -3 alkyl; R9 and R O together with the carbon to which they are connected form a carbonyl. Within this sub-class there is a group of compounds wherein X is O; Y is O; Ri is selected from the group consisting of R2 is isopropyl, R3 is methyl or ethyl; R4 is methyl or ethyl; and R9 and RlO together with the carbon to which they are connected form a carbonyl. For purposes of this specification heteroaryl as in R2» R3, or Rl is intended to include, but is not limited to optionally mono- or di- substituted (1) furanyl, (2) diazinyl, (3) imidazolyl, (4) isooxazolyl, (5) isothiazolyl, (6) oxadiazolyl, (7) oxazolyl, (8) pyrazolyl, (9) pyridyl, (10) pyrrolyl, (11) tetrazinyl (12) tetrazolyl. (13) thiadiazolyl, (14) thiazolyl, (15) thienyl, (16) triazinyl, or (17) triazolyl. Similarly, for purposes of this specification cyclic groups such as a heterocycloalkyl or benzocarbocycle or benzoheterocycle such as in R or R 15 is intended to include, but is not limited to optionally mono- or di-substituted (1) tetrahydrothiopyranyl, (2) thiomorpholinyl, (3) pyrrolidinyl, (4) hexahydroazepinyl, (5) indanyl, (6) tetralinyl, (7) indolyl, (8) benzofuranyl, (9) benzothienyl, (10) benzimidazolyl, (11) benzothiazolyl, Similarly, for purposes of this specification bicyclic heteroaryl as in R2 is intended to include, but is not limited to optionally mono- or di-substituted (9) (10) (I D (12) One preferred genus is directed to compounds of Formula I wherein R9 and R 10 together with the carbon atom to which they are attached form a carbonyl (ie R9 and RlO together form a double bonded O). Another preferred genus is directed to compounds of Formula I wherein Y is O. Another preferred genus is directed to compounds of Formula I wherein X is O. Another preferred genus is directed to compounds of Formula I wherein R9 and RlO together with the carbon to which they are attached form a carbonyl; Y is O; and X is O. Another preferred genus is directed to compounds of Formula I wherein 2 R is a mono-, di- or tri-substituted phenyl wherein the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (c) CN, (d) CF 3 , ^d (e) C ι_4 alkyl. Another preferred genus is directed to compounds of Formula I wherein 2 R is mono-, di-, or tri-substituted pyridyl wherein the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (c) Ci_ 4 alkyl, (d) Cι_4 alkoxy (e) Cj_4 alkythio, (f) CN, and (g) CF 3 . Another preferred genus is directed to compounds of Formula I wherein R 9 and R 10 together with the carbon to which they are attached from a carbonyl; Y is O; X is O, and R is a mono-, di- or tri-substituted phenyl wherein the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (c) CN, (d) CF3, and (e) Cl-4 alkyl. Another preferred genus is directed to compounds of Formula I wherein R 9 and R 10 together with the carbon to which they are attached from a carbonyl, Y is O, X is O, and 2 R is a mono-, di-, or tri-substituted pyridyl wherein the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (c) Cl-4 alkyl, (d) Cl-4 alkoxy, (e) Cι_4 alkythio, (f) CN, and (g) CF 3 . Another preferred genus is directed to compounds of Formula I wherein R2 is a mono- or di-substituted phenyl, naphthyl, heteroaryl, benzoheterocycle, benzocarbocycle or bicyclic heteroaryl, wherein the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (d) Cl-4 alkyl, (e) Cι_4 alkoxy, (f) Cl-4 alkythio, (g) CN, and (h) CF 3 . Another preferred genus is directed to compounds of Formula I wherein R 9 and R 10 together with the carbon to which they are attached from a carbonyl,and Y is CH2* Another preferred genus is directed to compounds of Formula I wherein 3 R is hydrogen or Cl-10alkyl, particularly a propyl or butyl. Another preferred genus is directed to compounds of Formula I wherein 3 R is substituted pyridine, particularly a 3-pyridine. Another preferred genus is directed to compounds of Formula I wherein Rl is methyl sulfonyl. Another preferred genus is directed to compounds of formula I wherein R16 and R17 are each hydrogen. In another aspect the invention also encompasses a pharmaceutical composition for treating an inflammatory disease susceptable to treatment with an non-steroidal anti-inflammatory agent comprising: a non-toxic therapeutically effective amount of a compound of formula I and a pharmaceutically acceptable carrier. In another aspect the invention also encompasses a pharmaceutical composition for treating cyclooxygenase mediated diseases advantageously treated by an active agent that selectively inhibits COX-2 in preference to COX-1 comprising: a non-toxic therapeutically effective amount of a compound of formula I and a pharmaceutically acceptable carrier. In another aspect the invention also encompasses a method of treating an inflammatory disease susceptable to treatment with an non- steroidal anti-inflammatory agent comprising: administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of formula I and a pharmaceutically acceptable carrier. In another aspect the invention also encompasses a method of treating cyclooxygenase mediated diseases advantageously treated by an active agent that selectively inhibits COX-2 in preference to COX-1 comprising: administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of formula I. In another aspect the invention also encompasses the use of a compound of formula I or a pharmaceutical composition in the manufacture of a medicament for the treatment of an inflammatory disease susceptable to treatment with an a non-steroidal anti- inflammatory agent. The invention is illustrated by the compounds of the Examples disclosed herein as well as the compounds of Table I. 1) Definitions The following abbreviations have the indicated meanings: 10 15 20 25 30 a r viations Dose Abbreviations bid = bis in die = twice daily qid = quater in die = four times a day id = ter in die = three times a day For purposes of this specification "Alkyl" means linear branched and cyclic structures, and combinations thereof, containing the indicated number of carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, s- and t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, eicosyl, 3,7-diethyl-2,2-dimethyl- 4-propylnonyl, cyclopropyl, cyclopentyl, cycloheptyl, adamantyl, cyclododecylmethyl, 2-ethyl-l- bicyclo[4.4.0]decyl and the like. For purposes of this specification "Fluoro alkyl" means alkyl groups in which one or more hydrogen is replaced by fluorine. Examples are -CF3, -CH2CH2F, -CH2CF3, c-Pr-F5, c-Hex-Fl l and the like. For purposes of this specification "Alkoxy" means alkoxy groups of the indicated number of carbon atoms of a straight, branched, or cyclic configuration. Examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy, and the like. For purposes of this specification "Alkylthio" means alkylthio groups of the indicated number of carbon atoms of a straight, branched or cyclic configuration. Examples of alkylthio groups include methylthio, propylthio, isopropylthio, cycloheptylthio, etc. By way of illustration, the propylthio group signifies -SCH 2 CH 2 CH 3 . For purposes of this specification "Halo" means F, Cl, Br, or I. Exemplifying the invention are Examples hereinunder which include: (1) 3-(3,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (2) 3-(3-Fluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one, (3) 3-(3,5-Difluorophenoxy)-5,5-dimethyl-4-(methylsulfonyl) phenyl)- 5H-furan-2-one, (4) 3-Phenoxy-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2- one, (5) 3-(2,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (6) 3-(4-Chlorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one, (7) 3-(3,4-Dichlorophenoxy)-5,5-dimethyl-4-(methylsulfonyl) phenyl)- 5H-furan-2-one, (8) 3-(4-Fluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H- furan-2-one, (9) 3-(4-Fluorophenylthio)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (10) 3-(3,5-Difluorophenylthio)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (11) 3-Phenylthio-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan- 2-one, (12) 3-(N-Phenylamino)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H- furan-2-one, (13) 3-(N-Methyl-N-phenylamino)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (14) 3-Cyclohexyloxy-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (15 3-Phenylthio-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one, (16 3-Benzyl-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2- one, (17 3-(3,4-Difluorophenylhydroxymethyl)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (18 3-(3,4-Difluorobenzoyl)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (19 3-Benzoyl-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2- one, (20 4-(4-(Methylsulfonyl)phenyl)-3-phenoxy-l-oxaspiro[4.4]non-3-en- 2-one, (21 4-(4-(Methylsulfonyl)phenyl)-3-phenylthio-l-oxaspiro[4.4]non-3- en-2-one, (22 4-(2-Oxo-3-phenylthio- 1 -oxa-spiro[4,4]non-3-en-4-yl) benzenesulfonamide, (23 3-(4-Fluorobenzyl)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H- furan-2-one, (24 3-(3,4-Difluorophenoxy)-5-methoxy-5-methyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (25 3-(5-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (26 3-(2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (27 3-(6-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (28 3-(3-Isoquinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (29 3-(4-(Methylsulfonyl)phenyl)-2-phenoxycyclopent-2-enone, and (30 3-(4-(Methylsulfonyl)phenyl)-2-(3,4-difluoroρhenoxy) cyclopent-2-enone. Further exemplifying the invention are (a) 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(5- bromopyridin-2-yloxy)-5H-furan-2-one, and (b) 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(2- propoxy)-5H-furan-2-one, or a pharmaceutically acceptable salt thereof. Also see Examples 1-205. Some of the compounds described herein contain one or more asymmetric centers and may thus give rise to diastereomers and optical isomers. The present invention is meant to comprehend such possible diastereomers as well as their racemic and resolved, enantiomerically pure forms and pharmaceutically acceptable salts thereof. Some of the compounds described herein contain olefinic double bonds, and unless specified otherwise, are meant to include both E and Z geometric isomers. In a second embodiment, the invention encompasses pharmaceutical compositions for inhibiting cyclooxygenase and for treating cyclooxygenase mediated diseases as disclosed herein comprising a pharmaceutically acceptable carrier and a non-toxic therapeutically effective amount of compound of formula I as described above. Within this embodiment the invention encompasses pharmaceutical compositions for inhibiting cyclooxygenase-2 and for treating cyclooxygenase-2 mediated diseases as disclosed herein comprising a pharmaceutically acceptable carrier and a non-toxic therapeutically effective amount of compound of formula I as described above. In a third embodiment, the invention encompasses a method of inhibiting cyclooxygenase and treating cyclooxygenase mediated diseases, advantageously treated by an active agent that selectively inhibits COX-2 in preference to COX-1 as disclosed herein comprising: administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I as disclosed herein. The pharmaceutical compositions of the present invention comprise a compound of Formula I as an active ingredient or a pharmaceutically acceptable salt, thereof, and may also contain a pharmaceutically acceptable carrier and optionally other therapeutic ingredients. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic salts, manganous, potassium, sodium, zinc, and the like. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, such as arginine, betaine, caffeine, choline, N,N _ dibenzylethylenediamine, diethylamine, 2- diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine, and the like, and basic ion exchange resins. It will be understood that in the discussion of methods of treatment which follows, references to the compounds of Formula I are meant to also include the pharmaceutically acceptable salts. The compound of Formula I is useful for the relief of pain, fever and inflammation of a variety of conditions including rheumatic fever, symptoms associated with influenza or other viral infections, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis, including rheumatoid arthritis, degenerative joint diseases (osteoarthritis), gout and ankylosing spondylitis, bursitis, burns, injuries, following surgical and dental procedures. In addition, such a compound may inhibit cellular neoplastic transformations and metastic tumor growth and hence can be used in the treatment of cancer. Compound I may also be of use in the treatment and/or prevention of cyclooxygenase-mediated proliferative disorders such as may occur in diabetic retinopathy and tumour angiogenesis. Compound I will also inhibit prostanoid-induced smooth muscle contraction by preventing the synthesis of contractile prostanoids and hence may be of use in the treatment of dysmenorrhea, premature labor, asthma and eosinophil related disorders. It will also be of use in the treatment of Alzheimer's disease, and for the prevention of bone loss (treatment of osteoporosis) and for the treatment of glaucoma. By virtue of its high cyclooxygenase-2 (COX-2) activity and/or its specificity for cyclooxygenase-2 over cyclooxygenase- 1 (COX- 1), Compound I will prove useful as an alternative to conventional non- steroidal antiinflammatory drugs (NSAID'S) particularly where such non- steroidal antiinflammatory drugs may be contra-indicated such as in patients with peptic ulcers, gastritis, regional enteritis, ulcerative colitis, diverticulitis or with a recurrent history of gastrointestinal lesions; GI bleeding, coagulation disorders including anemia such as hypoprothrombinemia, haemophilia or other bleeding problems; kidney disease; those prior to surgery or taking anticoagulants. Similarly, Compound I, will be useful as a partial or complete substitute for conventional NSAID'S in preparations wherein they are presently co-administered with other agents or ingredients. Thus in further aspects, the invention encompasses pharmaceutical compositions for treating cyclooxygenase-2 mediated diseases as defined above comprising a non-toxic therapeutically effective amount of the compound of Formula I as defined above and one or more ingredients such as another pain reliever including acetominophen or phenacetin; a potentiator including caffeine; an H2-antagonist, aluminum or magnesium hydroxide, simethicone, a decongestant including phenylephrine, phenylpropanolamine, pseudophedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, or levo- desoxyephedrine; an antiitussive including codeine, hydrocodone, caramiphen, carbetapentane, or dextramethorphan; a prostaglandin including misoprostol, enprostil, rioprostil, ornoprostol or rosaprostol; a diuretic; a sedating or non-sedating antihistamine. In addition the invention encompasses a method of treating cyclooxygenase mediated diseases comprising: administration to a patient in need of such treatment a non-toxic therapeutically effective amount of the compound of Formula I, optionally co-administered with one or more of such ingredients as listed immediately above. For the treatment of any of these cyclooxygenase mediated diseases Compound I may be administered orally, topically, parenterally, by inhalation spray or rectally in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques. In addition to the treatment of warm-blooded animals such as mice, rats, horses, cattle sheep, dogs, cats, etc., the compound of the invention is effective in the treatment of humans. As indicated above, pharmaceutical compositions for treating cyclooxygenase-2 mediated diseases as defined may optionally include one or more ingredients as listed above. The pharmaceutical compositions containing the active ingredient may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example, magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by the technique described in the U.S. Patent 4,256,108; 4,166,452; and 4,265,874 to form osmotic therapeutic tablets for control release. Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredients is mixed with water or miscible solvents such as propylene glycol, PEGs and ethanol, or an oil medium, for example peanut oil, liquid paraffin, or olive oil. Aqueous suspensions contain the active material in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example, sodium carboxymethylcellulose, methylcellulose, hydroxy-propylmethycellulose, sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide, for example lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl, p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose, saccharin or aspartame. Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example, arachis oil, olive oil, sesame oil or coconut oil, or in mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example, beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid. Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example, sweetening, flavoring and coloring agents, may also be present. The pharmaceutical compositions of the invention may also be in the form of an oil-in-water emulsions. The oily phase may be a vegetable oil, for example, olive oil or arachis oil, or a mineral oil, for example, liquid paraffin or mixtures of these. Suitable emulsifying agents may be naturally-occurring phosphatides, for example, soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example, sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example, polyoxy¬ ethylene sorbitan monooleate. The emulsions may also contain sweetening and flavouring agents. Syrups and elixirs may be formulated with sweetening agents, for example, glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleagenous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally- acceptable diluent or solvent, for example, as a solution in 1,3-butane diol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. Cosolvents such as ethanol, propylene glycol or polyethylene glycols may also be used. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. Compound I may also be administered in the form of a suppositories for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials are cocoa butter and polyethylene glycols. For topical use, creams, ointments, gels, solutions or suspensions, etc., containing the compound of Formula I are employed. (For purposes of this application, topical application shall include mouth washes and gargles.) Topical formulations may generally be comprised of a pharmaceutical carrier, cosolvent, emulsifier, penetration enhancer, preservative system, and emollient. Dosage levels of the order of from about 0.01 mg to about 140 mg/kg of body weight per day are useful in the treatment of the above-indicated conditions, or alternatively about 0.5 mg to about 7 g per patient per day. For example, inflammation may be effectively treated by the administration of from about 0.01 to 50 mg of the compound per kilogram of body weight per day, or alternatively about 0.5 mg to about 3.5 g per patient per day. The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. For example, a formulation intended for the oral administration of humans may contain from 0.5 mg to 5 g of active agent compounded with an appropriate and convenient amount of carrier material which may vary from about 5 to about 95 percent of the total composition. Dosage unit forms will generally contain between from about 1 mg to about 500 mg of an active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, or 1000 mg. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease undergoing therapy. The compounds of the present invention can be prepared according to the following methods Method A An appropriately substituted acid halide is reacted with thioanisole in a solvent such as chloroform in the presence of a Lewis acid such as aluminum chloride to afford a ketone which is then hydroxylated with base such as aqueous sodium hydroxide in a solvent such as carbon tetrachloride with a phase transfer agent such as Aliquat 336. Then treatment with an oxidizing agent such as MMPP in solvents such as CH2θ2/MeOH, affords an sulfone which is reacted with an appropriately substituted acetic acid in a solvent such as CH2CI2 in the presence of an esterifying agent such as CMC and DMAP and then treated with DBU to afford lactone la. la R 1 =S0 2 Me Method B An appropriately substituted hydroxyketone is acylated withn appropriately substituted acid halide in a solvent such as dichloromethane in the presence of a base such as pyridine. The ester obtained is then reacted with an appropriately substituted nucleophile R2χH in a solvent such as DMF and with a base such as sodium hydride, then treatment with DBU in a solvent such as acetonitrile affords lactone la. Method C A halo ester of acetic acid is coupled with an appropriately substituted nucleophile in water with sodium hydroxide to give an appropriately substituted acetic acid which is then reacted as in method A to afford lactone la. METHOD A la R 1 =S0 2 Me X=0, S, NR 15 Method D A halo ester is reacted with an appropriately substituted amine R R15NH in a solvent such as toluene to give an intermediate which is then reacted with DBU in a solvent such as acetonitrile to afford lactone la. la X=NR 15 Method E An appropriately substituted bromoketone is reacted with an appropriately substituted acid in a solvent such as ethanol or acetonitrile in the presence of a base such as diisopropylethylamine or triethylamine to afford an ester which is then treated with DBU in a solvent such as acetonitrile to afford lactone la. Amine base Solvent, Δ la Method F An appropriately substituted hydroxyketone is reacted with an appropriately substituted acid halide in a solvent such as dichloromethane and with a base such as pyridine to afford an ester which is then cyclized using sodium hydride in a mixture of THF and DMF to afford a lactone. The lactone is then oxidized with an oxidizing agent such as MMPP, mCPBA or OXONE® in solvents such as dichloromethane and/or methanol to afford lactone la. Method G An appropriately substituted hydroxyketone is acylated with acetyl bromide or chloride in a solvent such as dichloromethane with a base such as DBU and DMAP. Further treatment with a base such as sodium hydride in a solvent such as DMF effects cyclization to afford the 5-membered lactone. Treatment of this lactone with a base such as LDA and an appropriately substituted acid halide in a solvent such as THF, followed by oxidation with a reagent such as MMPP in solvent such as CH2θ2/MeOH and hydrolysis by a base such as NaOH in a solvent such as MeOH/THF gives an alcohol lb which is then oxidized to lactone Ic by a reagent such as Jone's reagent in a solvent such as acetone(the initially formed ketone is reduced in the reaction and acylated, thus requiring hydrolysis and re-oxidation to obtain ketone Ic). Alternatively, alcohol lb can be obtained by using an aldehyde R2CHO as the electrophile instead of an acid halide. S0 2 Me Jone's reagent . Acetone Ic R 1 =SO 2 Me Method H An appropriately substituted methyl sulfide is oxidized to the sulfoxide with a reagent such as MMPP in solvents such as dichloromethane and methanol followed by treatment with trifluoroacetic anhydride, then aqueous sodium hydroxide. Further treatment by Cl2 in aqueous acetic acid followed by treatment by an amine affords an intermediate sulfonamide. This sulfonamide is then esterified with an appropriately substituted acid in the presence of a reagent such as CMC and further treatment with a base such as DBU affords the lactone. In the case where the amine group is protected by an acid labile group treatment with an acid such as trifluoroacetic acid in a solvent such as dichloromethane affords compound la. Method I An appropriately substituted bromoketone is reacted with an appropriately substituted acid in a solvent such as acetonitrile and with a base such as Et3N. Treatment with DBUand then θ2 gives a hydroxy compound Id. Etherification of this hydroxy with an alcohol in a solvent such as THF and with an acid such HC1 gives Ie. By oxidation of the sulfide into a sulfone by a reagent such as m-CPBA and then displacement of this sulfone by an appropriately substituted nucleophile compound If is obtained. R=C 1 . β alkyl If X=0, S, NR 15 Method J An appropriately substituted nucleophile is reacted with an appropriately substituted haloacetate in a solvent such as acetonitrile with a base such as DBU to afford compound la. la X=O, S, NR 15 Method K An appropriately substituted vinyl ketone is coupled with an appropriately substituted benzaldehyde with a catalyst such as 3-benzyl- 5-(2-hydroxyethyl)-4-methylthiazolium chloride in the presence of a base such as triethylamine in a solvent such as 1,4-dioxane to form a diketone. The diketone is cyclized in a solvent such as methanol with a base such as DBU to the final product Ig. When Rl=Sθ2Me, the starting material can also be a p-methylthiobenzaldehyde, with the methylthio group being oxidized to Sθ2Me using MMPP, mCPBA or OXONE® in the last step. Et 3 N, Dioxane ig Method L An appropriately substituted halide is reacted with a base such as DBU in a solvent such as acetonitrile to afford an epoxide which is then reacted with an appropriately substituted nucleophile in solvents such as DMF and a base to afford lactone la. la R 1 =S0 2 Me Method M An appropriately substituted acid halide is reacted with an appropriately substituted hydroxyketone in the presence of a base such as pyridine in a solvent such as acetonitrile, further treatment with a base such as DBU gives an hydroxylactone. The hydroxylactone is reacted with an appropriately substituted halide in a solvent such as benzene with a reagent such as Ag 2 Cθ 3 to afford the lactone Ih. Ih R 1 =SO 2 Me X= O Method N An appropriately substituted hydroxyketone is reacted with an appropriately substituted carboxylic acid with an esterifying agent such as CMC in the presence of DMAP in a solvent such CH2O2, followed by treatment with a base such as DBU to afford a lactone ester. This lactone ester is then reacted with a reagent such as the one formed with piperidine and trimethylaluminium to afford the lactone Ic. Me 2 AIR 2 C»H 2 C»I 2 Method O An appropriately substituted nucleophile such as pentan-3-ol is treated with a base such as sodium hydride in a solvent such as benzene and then reacted with an electrophile such as sodium chloroacetate to afford an acid. This acid is then reacted with an appropriately substituted hydroxyketone with an esterifying reagent such as CMC in a solvent such as dichloromethane to give an ester which is cyclized upon treatment with a base such as sodium hydride in a solvent such as DMF to afford lactone la. Method P An appropriately substituted nucleophile is reacted with an appropriately substituted haloacetate alkaline salt (such as sodium) in a solvent such as benzene and with a reagent such as Ag2Cθ3 to give an ester which is then hydrolyzed with a reagent such as NaOH in solvents such as water and methanol to give an acid. The acid is then esterified with an appropriately substituted hydroxyketone with reagents such as CMC and DMAP in a solvent such as dichloromethane to give an ester which is then cyclized with a base such as DBU in a solvent such as CH3CN to afford a lactone. The sulfide is then oxidized with a reagent such as MMPP in solvents such as CH2O2, MeOH and water to afford lactone la. la R 1 =S0 2 Me Method O An appropriately substituted acetic acid salt is reacted with a nucleophile such as vinyl magnesium bromide in a solvent such as DME to afford a ketone, which is then reacted as in method K to afford cyclopentone Ig. ig Method R 4-Bromothioanisole is reacted with a base such as n-BuLi in a solvent such as THF to form the corresponding lithium reagent which is then reacted with an appropriately substituted lactone (Tetrahedron, 1984, 40, 1313) to give a hemiketal. The acetal is then cleaved with an acidic such as p-TsOH in a solvent such as water to give a hydroxyketone. The sulfide is then oxidized with a reagent such as Oxone®, in the presence of a phase transfer reagent such as Aliquat 336® in solvents such as t-BuOH and water to give a sulfone. The hydroxyketone is then esterified with an appropriately substituted acetic acid with reagents such as CMC and DMAP in a solvent such as CH2CI2 to give an intermediate ester which is cyclized with a base such as DBU to give lactone Im. B Aliquat 336 ® SMe t-BuOH, Oxone ® , H 2 O la R 1 =SO,Me Method S An appropriately substituted aminopyrydine is diazotized with NaNθ2 in an acid such as H2SO4 in water, followed by neutralization with NaOH affords an hydroxypyridine which is reacted following the method J. li R 1 =S0 2 Me Z=alkyl X=0 Method T An appropriately substituted hydroxylactone is treated with a base such as KOH in a solvent such as DMF, followed by treatment with an appropriately substituted halopyridine afford lactone li. R 1 =S0 2 Me R 2 =pyridine X=0 Method U An appropriately substituted nitropyridine is reduced with a reagent such as Fe (powder) and NH4CI in solvents such as ethanol and water to give an aminopyridine which is diazotized with NaNθ2 in aqueous HCl, the diazonium salt is decomposed with copper salts such as CuCl in HCl to give lactone li. li R 1 =S0 2 Me R 2 =pyridine Method W An appropriately substituted halo acetate is reacted with an appropriate secondary amine (R 2 (R15)NH) i n a solvent such as CH3CN; further treatment with a base such as NaH in a solvent such as DMF affords lactone la. la R 1 =S0 2 Me X=N(R 15 ) Method X An appropriately substituted lactone ( etrahedron , 1984, 40, 1313) is treated with a base such as LDA and reacted with 2,2,2- trifluoroiodoethane. Further treatment with the lithium salt of 4- bromothioanisole gives the desired hemiketal, which is then reacted as in method R to give the desired lactone Im. Im R 1 =S0 2 Me Method Y An appropriately substituted alcohol is reacted with an appropriate haloacid such as bromoacetic acid with a base such as NaH in a solvent such as THF to afford an acid ether which is then esterified with an appropriately substituted hydroxyketone with reagents such as CMC and DMAP in a solvent such as CH2CI2 to give a ketoester. The ketoester is then cyclized in the presence of a base such as DBU and a dehydrating reagent such as iso-propyl trifluoroacetate in a solvent such as CH3CN to afford lactone la. Ih R 1 =S0 2 Me Method Z An appropriately substituted hydroxylactone is reacted with an appropriate halide in the presence of a base such as NaH, with a reagent such as B1_4.NI i a solvent such as DMF to afford lactone Ih. Method A- 1 An appropriately substituted carboxylic acid is esterified with an appropriately substituted haloketone in the presence of a base such as (iPr)2NEt in a solvent such as EtOH; further treatment with a base such as DBU and a reagent such as iso-propyl 2,2,2-trifluoroacetate in a solvent such as CH3CN affords lactone la. la R 1 =S0 2 Me Method B-l An appropriately substituted ketone is reacted with a reagent such as TMSCN in the presence of a Lewis acid such as Znl2, further treatment with a metal salt of thioanisole followed by hydrolysis affords an hydroxyketone. Oxidation of the sulfide with an oxidizing reagent such as Oxone® in solvents such as t-BuOH, EtOAc and water gives the sulfone. Esterification of the alcohol and an appropriately substituted acetic acid with a reagent such as CMC and DMAP in a solvent such as CH2CI2 followed by treatment with a base such as DBU gives the lactone In. 11 t-BuOH, EtOAc Oxone ® H 2 0 In R 1 =S0 2 Me Method C-l An appropriately substituted enone is reduced with hydrogen in a solvent such as ethyl acetate with a catalyst such as palladium on activated carbon to give an alcohol. This alcohol was transformed into a leaving group by treatment with reagents such as methanesulfonyl chloride and triethylamine in a solvent such as methylene chloride, followed by treatment in a solvent such as acetone with a reagent such as lithium iodide to afford a compound which was then reacted as in method M to afford lactone Ij. 1 ) MsCI, Et 3 N, CH 2 CI 2 2) Lil , 3) Method M Ij R 1 =SO 2 Me Method D-l 5-Amino-2-alkoxypyridine is converted to the corresponding diazonium salt and heated with acetic anhydride at 100-110°C. The corresponding 5-acetoxy-2-alkoxypyridine is then hydrolysed with sodium hydroxide to give the 5-hydroxy-2-alkoxypyridine which is reacted according to method J. Z=alkyl Ik R 1 = S0 2 Me Z= alkyl Method E-1 2(RS)-2-Methyl-4,4,4-trifluorobutyryl chloride(GB 2238790- A) is reacted with thioanisole in the presence of a Lewis acid such as AICI 3 . The ketone is then hydroxylated by air in the presence of potassium t-butoxide and triethyl phosphite, and the sulfide is then oxidized with m-CPBA to the sulfone. The hydroxyketone is then esterified with an appropriately substituted acid in the presence of CMC and DMAP in a solvent such as CH 2 C1 2 to give an intermediate ester which is cyclized with a base such as DBU to give lactone lo. HO, o 1)CMC, DMAP, CH 2 CI 2 2) DBU lo R 1 =SO Me Method F-1 Hydroquinone is reacted with a halosubstituted acetate, chlorinated with sulfuryl chloride, methylated with iodomethane in the presence of a base and followed by hydrolysis with sodium hydroxide to give the substituted phenoxy acetic acid, which is reacted according to method A to afford lactone la. Method G-1 An appropriately substituted 3-(4-( 1 -hydroxy- 1- methyl)ethylphenoxy)-5H-furan-2-one is reduced with NaBH 3 CN in the presence of Znl 2 to give lactone II. Method H-l An appropriately substituted alkyl (4-thiomethyl)phenyl ketone is alkylated with bromomethylcyclopropane using a base such as KHMDS. The methyl sulfide is oxidized with MMPP to the corresponding sulfone and hydroxylated by NaOH and CC1 4 in toluene in the presence of a phase transfer catalyst such as Aliquat 336 . The hydroxyketone is then esterified with an appropriately substituted acid in the presence of CMC and DMAP in a solvent such as CH 2 C1 2 to give an intermediate ester which is cyclized with a base such as DBU to give lactone Ip. 1 )HOOCCH 2 XR 2 CMC/CH 2 CI 2 2) DBU Ip R =S0 2 Me Method I- 1 An appropriately substituted hydroxylactone is reacted with an appropriately substituted nitropyridine in the presence of a base such as NaOH in DMF at 100-110°C. The nitro group of the coupling product is then reduced with Fe (powder) and NH 4 C1 in solvents such as ethanol and water. The amino group is diazotized and the resulting diazonium salt is decomposed in the presence of appropiate copper salt such as CuCl or CuBr to give lactone lq. Alternatively, the diazonium salt is treated HBF 4 or HPF 6 to give after heating the fluoro-substituted lactone pyridine Iq Iq R 1 =S0 2 Me Method J-l The lithium reagent prepared from 4-bromothioanisole and n-BuLi at -72°C is reacted with methacrolein and the resulting product is oxidized with an oxidizing reagent such as Oxone® to the methyl sulfone. A kinetic resolution by Sharpless epoxidation reaction using (+)- diisopropyl tartrate and t-butyl hydroperoxide provides the (S)-allylic alcohol, which is epoxidized by (-)-diisopropyl tartrate and t-butyl hydroperoxide. The alcohol of the epoxy alcohol is protected as an ethoxyethyl ether and the epoxide is reacted with dimethyl cuprate(from methyllithium and copper(I) iodide. The ethoxyethyl ether is then cleaved and the resulting diol is treated with (Bu 3 Sn) 2 0 and oxidized with Br 2 to give the (S)-alcohol. The hydroxyketone is then esterified with an appropriately substituted acid in the presence of CMC and DMAP in a solvent such as CH 2 C1 2 to give an intermediate ester which is cyclized with a base such as DBU to give lactone Ir. Ir R 1 =S0 2 Me Method K-l 4-Bromothioanisole is reacted with isobutyryl chloride in the presence of aluminum chloride in o-dichlorobenzene(ODCB). The resulting ketone is brominated and oxidized with Na 2 W0 and H 2 0 2 in the presence of Aliquat 336 to the bromoketone methyl sulfone. The bromoketone is then reacted with an appropriate alkoxy or aryloxy acetic acid in the presence DIEA and the ester intermediate is cyclized and dehydrated with DBU in the presence of isopropyl trifluoroacetate to give lactone la. Br Cyclohexane EtOAc la METHOD L-1 Tetronic acid is converted to the α-diazoketone derivative with tosyl azide (see Stachel et al., Liebigs Ann. Chem. 1994, P.129 for a similar preparation). The diazo compound is reacted with an appropriately substituted alcohol in the presence of rhodium acetate (see Stachel et al., Liebigs Ann. Chem. 1994 P. 129) to give an ether. This compound is treated with triflic anhydride followed by a Suzuki type coupling reaction with 4-methylthiophenyl boronic acid (Wong et al., Tetrahedron Lett. 1993, p. 8237.) The sulfide is then oxidized with OXONE® to provide Is. 1) Tf 2 O, iPr 2 NEt,CH 2 CI 2 Is Representative Compounds Tables I illustrates novel compounds of the present invention. Table I Example Method B Table I (continued) Example Method 0 Table I (continued) mple Method Table I (continued) ple Method Table I (continued) od Table I (continued) mple Method K Table I (continued) od Table I (continued) le Method Table I (continued) le Method Table I (continued) le Method Table I (continued) od Table I (continued) od Table I (continued) d Table I (continued) le Method Table I (continued) e Method Table I (continued) ple Method Table I (continued) ple Method Table I (continued) ple Method Table I (continued) le Method Table I (continued) le Method Table I (continued) le Method - 106- Table I (continued) le Method M or K-1 Table I (continued) le Method Table I (continued) e Method Table I (continued) Table I (continued) le Method - Ill - Table I (continued) ple Method Table I (continued) od Table I (continued) le Method -114- Table I ( continued) e Method 157 ¥ ° <XΓ Table I (continued) le Method Table I (continued) d Table I (continued) d Table I (continued) ple Method Table I (continued) Example Method 182 Table I (continued) le Method Table I (continued) d Table I (continued) hod Table I (continued) d 208 L-l O Assays for determining Biological Activity The compound of Formula I can be tested using the following assays to determine their cyclooxygenase-2 inhibiting activity. INHIBITION OF CYCLOOXYGENASE ACTIVITY Compounds are tested as inhibitors of cyclooxygenase activity in whole cell cyclooxygenase assays. Both of these assays measure prostaglandin E2 synthesis in response to arachidonic acid, using a radioimmunoassay. Cells used for these assays are human osteosarcoma 143 cells (which specifically express COX-2) and human U-937 cells (which specifically express COX-1). In these assays, 100% activity is defined as the difference between prostaglandin E2 synthesis in the absence and presence of arachidonate. Whole Cell Assays For cyclooxygenase assays, osteosarcoma cells are cultured in 1 mL of media in 24- well multidishes (Nunclon) until confluent (1-2 x 10*5 cells/well). U-937 cells are grown in spinner flasks and resuspended to a final density of 1.5 x 10^ cells/mL in 24- well multidishes (Nunclon). Following washing and resuspension of osteosarcoma and U-937 cells in 1 mL of HBSS, 1 μL of a DMSO solution of test compound or DMSO vehicle is added, and samples gently mixed. All assays are performed in triplicate. Samples are then incubated for 5 or 15 minutes at 37°C, prior to the addition of arachidonic acid. Arachidonic acid (peroxide-free, Cayman Chemical) is prepared as a 10 mM stock solution in ethanol and further diluted 10-fold in HBSS. An aliquot of 10 μL of this diluted solution is added to the cells to give a final arachidonic acid concentration of 10 μM. Control samples are incubated with ethanol vehicle instead of arachidonic acid. Samples are again gently mixed and incubated for a further 10 min. at 37°C. For osteosarcoma cells, reactions are then stopped by the addition of 100 μL of IN HCl, with mixing and by the rapid removal of the solution from cell monolayers. For U-937 cells, reactions are stopped by the addition of 100 μL of IN HCl, with mixing. Samples are then neutralized by the addition of 100 μL of IN NaOH and PGE2 levels measured by radioimmunoassay. Whole cell assays for COX-2 and COX-1 using CHO transfected cell lines Chinese hamster ovary (CHO) cell lines which have been stably transfected with an eukaryotic expression vector pCDNAIII containing either the human COX-1 or COX-2 cDNA's are used for the assay. These cell lines are referred to as CHO [hCOX-1] and CHO [hCOX-2], respectively. For cyclooxygenase assays, CHO[hCOX-l] cells from suspension cultures and CHO[hCOX-2] cells prepared by trypsinization of adherent cultures are harvested by centrifugation (300 x g, 10 min) and washed once in HBSS containing 15 mM HEPES, pH 7.4, and resuspended in HBSS, 15 mM HEPES, pH 7.4, at a cell concentration of 1.5 x lθ6 cells/ml. Drugs to be tested are dissolved in DMSO to 66.7- fold the highest test drug concentration. Compounds are typically tested at 8 concentrations in duplicate using serial 3-fold serial dilutions in DMSO of the highest drug concentration. Cells (0.3 x IO 6 cells in 200 μl) are preincubated with 3 μl of the test drug or DMSO vehicle for 15 min at 37°C. Working solutions of peroxide-free AA (5.5 μM and 110 μM A A for the CHO [hCOX-1] and CHO [COX-2] assays, respectively) are prepared by a 10-fold dilution of a concentrated AA solution in ethanol into HBSS containing 15 mM HEPES, pH 7.4. Cells are then challenged in the presence or absence of drug with the AA/HBSS solution to yield a final concentration of 0.5 μM AA in the CHOfhCOX- 1] assay and a final concentration of 10 μM AA in the CHO[hCOX-2] assay. The reaction is terminated by the addition of 10 μl 1 N HCl followed by neutralization with 20 μl of 0.5 N NaOH. The samples are centrifuged at 300 x g at 4°C for 10 min, and an aliquot of the clarified supernatant is appropriately diluted for the determination of PGE2 levels using an enzyme-linked immunoassay for PGE2 (Correlate PGE2 enzyme immunoassay kit, Assay Designs, Inc.). Cyclooxygenase activity in the absence of test compounds is determined as the difference in PGE2 levels of cells challenged with arachidonic acid versus the PGE2 levels in cells mock-challenged with ethanol vehicle. Inhibition of PGE2 synthesis by test compounds is calculated as a percentage of the activity in the presence of drug versus the activity in the positive control samples. Assay of COX-1 Activity from U937 cell microsomes U 937 cells are pelleted by centrifugation at 500 x g for 5 min and washed once with phosphate-buffered saline and repelleted. Cells are resuspended in homogenization buffer consisting of 0.1 M Tris- HC1, pH 7.4, 10 mM EDTA, 2 μg/ml leupeptin, 2 μg/ml soybean trypsin inhibitor, 2 μg/ml aprotinin and 1 mM phenyl methyl sulfonyl fluoride. The cell suspension is sonicated 4 times for 10 sec and is centrifuged at 10,000 x g for 10 min at 4° C. The supernatant is centrifuged at 100,000 x g for 1 hr at 4 ° C. The 100,000 x g microsomal pellet is resuspended in 0.1 M Tris-HCl, pH 7.4, 10 mM EDTA to approximately 7 mg protein/ml and stored at -80° C. Microsomal preparations are thawed immediately prior to use, subjected to a brief sonication, and then diluted to a protein concentration of 125 μg/ml in 0.1 M Tris-HCl buffer, pH 7.4 containing 10 mM EDTA, 0.5 mM phenol, 1 mM reduced glutathione and 1 μM hematin. Assays are performed in duplicate in a final volume of 250 μl. Initially, 5 μl of DMSO vehicle or drug in DMSO are added to 20 μl of 0.1 M Tris-HCl buffer, pH 7.4 containing 10 mM EDTA in wells of a 96- deepwell polypropylene titre plate. 200 μl of the microsomal preparation are then added and pre-incubated for 15 min at room temperature before addition of 25 μl of 1 M arachidonic acid in 0.1 M Tris-HCl and 10 mM EDTA, pH 7.4. Samples are incubated for 40 min at room temperature and the reaction is stopped by the addition of 25 μl of 1 N HCl. Samples are neutralized with 25 μl of 1 N NaOH prior to quantitation of PGE-* content by radioimmunoassay (Dupont-NEN or Amersham assay kits). Cyclooxygenase activity is defined as the difference between PGF^ levels in samples incubated in the presence of arachidonic acid and ethanol vehicle. Assay of the activity of purified human COX-2 The enzyme activity is measured using a chromogenic assay based on the oxidation of N,N,N' ,N' -tetramethyl-p-phenylenediamine (TMPD) during the reduction of PGG 2 to PGH 2 by COX-2 (Copeland et al. (1994) Proc. Natl. Acad. Sci. 91, 11202-11206). Recombinant human COX-2 is purified from Sf9 cells as previously described (Percival et al (1994) Arch. Biochem. Biophys. 15, 111-118). The assay mixture ( 180 μL) contains 100 mM sodium phosphate, pH 6.5, 2 mM genapol X-100, 1 μM hematin, 1 mg/ml gelatin , 80-100 units of purified enzyme (One unit of enzyme is defined as the amount of enzyme required to produce an O.D. change of 0.001/min at 610 nm) and 4 μL of the test compound in DMSO. The mixture is pre- incubated at room temperature (22°C) for 15 minutes prior to initiation of the enzymatic reaction by the addition of 20 μL of a sonicated solution of 1 mM arachidonic acid (AA) and 1 mM TMPD in assay buffer (without enzyme or hematin). The enzymatic activity is measured by estimation of the initial velocity of TMPD oxidation over the first 36 sec of the reaction. A non-specific rate of oxidation is observed in the absence of enzyme (0.007 - 0.010 O.D. /min) and is subtracted before the calculation of the % inhibition. IC50 values are derived from 4-parameter least squares non-linear regression analysis of the log-dose vs % inhibition plot. HUMAN WHOLE BLOOD ASSAY Rationale Human whole blood provides a protein and cell-rich milieu appropriate for the study of biochemical efficacy of anti-inflammatory compounds such as selective COX-2 inhibitors. Studies have shown that normal human blood does not contain the COX-2 enzyme. This is consistent with the observation that COX-2 inhibitors have no effect on PGE2 production in normal blood. These inhibitors are active only after incubation of human whole blood with LPS, which induces COX-2. This assay can be used to evaluate the inhibitory effect of selective COX-2 inhibitors on PGE2 production. As well, platelets in whole blood contain a large amount of the COX-1 enzyme. Immediately following blood clotting, platelets are activated through a thrombin-mediated mechanism. This reaction results in the production of thromboxane B2 (TxB2) via activation of COX-1. Thus, the effect of test compounds on TxB2 levels following blood clotting can be examined and used as an index for COX- 1 activity. Therefore, the degree of selectivity by the test compound can be determined by measuring the levels of PGE2 after LPS induction (COX-2) and TxB2 following blood clotting (COX-1) in the same assay. Method A. COX-2 (LPS-induced PGEj production) Fresh blood is collected in heparinized tubes by venipuncture from both male and female volunteers. The subjects have no apparent inflammatory conditions and have not taken any NSAIDs for at least 7 days prior to blood collection. Plasma is immediately obtained from a 2mL blood aliquot to use as blank (basal levels of PGE2). The remaining blood is incubated with LPS (100 μg/ml final concentration, Sigma Chem, #L-2630 from E. coli; diluted in 0.1% BSA (Phosphate buffered saline) for 5 minutes at room temperature. Five hundred μL aliquots of blood are incubated with either 2μL of vehicle (DMSO) or 2μL of a test compound at final concentrations varying from lOnM to 30μM for 24 hours at 37°C. At the end of the incubation, the blood is centrifuged at 12,000 x g for 5 minutes to obtain plasma. A lOOμL aliquot of plasma is mixed with 400μL of methanol for protein precipitation. The supernatant is obtained and is assayed for PGE2 using a radioimmunoassay kit (Amersham, RPA#530) after conversion of PGE2 to its methyl oximate derivative according to the manufacturer's procedure. B. COX-1 (Clotting-induced TxB 2 production) Fresh blood is collected into vacutainers containing no anticoagulants. Aliquots of 500μL are immediately transfeπed to siliconized microcentrifuge tubes preloaded with 2μL of either DMSO or a test compound at final concentrations varying from lOnM to 30μM. The tubes are vortexed and incubated at 37°C for 1 hour to allow blood to clot. At the end of incubation, serum is obtained by centrifugation (12,000 x g for 5 min.). A lOOμL aliquot of serum is mixed with 400μL of methanol for protein precipitation. The supernatant is obtained and is assayed for TxB 2 using a enzyme immunoassay kit (Cayman, #519031) according to the manufacturer's instruction. RAT PAW EDEMA ASSAY Protocol Male Sprague-Dawley rats (150-200 g) are fasted overnight and are given, po, either vehicle (1% methocel or 5% Tween 80) or a test compound. One hr later, a line is drawn using a permanent marker at the level above the ankle in one hind paw to define the area of the paw to be monitored. The paw volume (Vo) is measured using a plethysmometer (Ugo-Basile, Italy) based on the principle of water displacement. The animals are then injected subplantarly with 50 μl of 1% carrageenan solution in saline (FMC Corp, Maine) into the paw using an insulin syringe with a 25-gauge needle (i.e. 500 μg carrageenan per paw). Three hr later, the paw volume (V3) is measured and the increases in paw volume (V3 - Vo) are calculated. The animals are sacrificed by Cθ2 asphyxiation and the absence or presence of stomach lesions scored. Data is compared with the vehicle-control values and percent inhibition calculated. All treatment groups are coded to eliminate observer bias. NSAID-INDUCED GASTROPATHY IN RATS Rationale The major side effect of conventional NS AIDs is their ability to produce gastric lesions in man. This action is believed to be caused by inhibition of Cox- 1 in the gastrointestinal tract. Rats are particularly sensitive to the actions of NSAIDs. In fact, rat models have been used commonly in the past to evaluate the gastrointestinal side effects of current conventional NSAIDs. In the present assay, NSAID-induced gastrointestinal damage is observed by measuring fecal 5 lCr excretion after systemic injection of 51Cr-labeled red blood cells. Fecal SlCr excretion is a well-established and sensitive technique to detect gastrointestinal integrity in animals and man. Methods Male Sprague Dawley rats (150 - 200 g) are administered orally a test compound either once (acute dosing) or b.i.d. for 5 days (chronic dosing). Immediately after the administration of the last dose, the rats are injected via a tail vein with 0.5 mL of 5 lCr-labeled red blood cells from a donor rat. The animals are placed individually in metabolism cages with food and water ad lib. Feces are collected for a 48 h period and 51Cr fecal excretion is calculated as a percent of total injected dose. SlCr-labeled red blood cells are prepared using the following procedures. Ten mL of blood is collected in heparinized tubes via the vena cava from a donor rat. Plasma is removed by centrifugation and replenished with equal volume of HBSS. The red blood cells are incubated with 400 Ci of sodium bichromate for 30 min. at 37C. At the end of the incubation, the red blood cells are washed twice with 20 mL HBSS to remove free sodium bichromate. The red blood cells are finally reconstituted in 10 mL HBSS and 0.5 mL of the solution (about 20 Ci) is injected per rat. PROTEIN-LOSING GASTROPATHY IN SQUIRREL MONKEYS Rationale Protein-losing gastropathy (manifested as appearance of circulating cells and plasma proteins in the GI tract) is a significant and dose-limiting adverse response to standard non-steroidal anti- inflammatory drugs (NSAIDs). This can be quantitatively assessed by intravenous administration of *5 CrCl3 solution. This isotopic ion can avidly bind to cell and serum globins and cell endoplasmic reticulum. Measurement of radioactivity appearing in feces collected for 24 h after administration of the isotope thus provides a sensitive and quantitative index of protein-losing gastropathy. Methods Groups of male squirrel monkeys (0.8 to 1.4 kg) are treated by gavage with either 1% methocell or 5% Tween 80 in H20 vehicles, (3ml/kg b.i.d.) or test compounds at doses from 1 - 100 mg/kg b.i.d. for 5 days. Intravenous SlCr (5Ci/kg in 1 ml/kg phosphate buffer saline (PBS)) is administered 1 h after the last drug/vehicle dose, and feces collected for 24 h in a metabolism cage and assessed for excreted 51Cr by gamma-counting. Venous blood is sampled 1 h and 8 h after the last drug dose, and plasma concentrations of drug measured by RP-HPLC. Representative Biological Data Compounds of the present invention are inhibitors of cyclooxygenase-2 and are thereby useful in the treatment of cyclooxygenase-2 mediated diseases as enumerated above. The activities of the compounds against cyclooxygenase may be seen in the representative results shown below. In the assay, inhibition is determined by measuring the amount of prostaglandin E2 (PGE2) synthesized in the presence of arachidonic acid, cyclooxygenase- 1 or cyclooxygenase-2 and a putative inhibitor. The IC50 values represent the concentration of putative inhibitor required to return PGE2 synthesis to 50% of that obtained as compared to the uninhibited control. The results for certain of the biological assays may be seen in Tables II, III and IV. Table II Table III Table IV Table IV - cont'd Table IV - cont'd Table IV - cont'd The invention will now be illustrated by the following non- limiting examples in which, unless stated otherwise: (i) all operations were carried out at room or ambient temperature, that is, at a temperature in the range 18-25°C; (ii) evaporation of solvent was carried out using a rotary evaporator under reduced pressure (600-4000 pascals: 4.5- 30 mm Hg) with a bath temperature of up to 60°C; (iii) the course of reactions was followed by thin layer chromatography (TLC) and reaction times are given for illustration only; (iv) melting points are uncorrected and d' indicates decomposition; the melting points given are those obtained for the materials prepared as described; polymoφhism may result in isolation of materials with different melting points in some preparations; (v) the structure and purity of all final products were assured by at least one of the following techniques: TLC, mass spectrometry, nuclear magnetic resonance (NMR) spectrometry or microanalytical data; (vi) yields are given for illustration only; (vii) when given, NMR data is in the form of delta (δ) values for major diagnostic protons, given in parts per million (ppm) relative to tetramethylsilane (TMS) as internal standard, determined at 300 MHz or 400 MHz using the indicated solvent; conventional abbreviations used for signal shape are: s. singlet; d. doublet; t. triplet; m. multiplet; br. broad; etc.: in addition "Ar" signifies an aromatic signal; (viii) chemical symbols have their usual meanings; the following abbreviations have also been used v (volume), w (weight), b.p. (boiling point), M.P. (melting point), L (liter(s)), mL (milliliters), g (gram(s)), mg (milligrams(s)), mol (moles), mmol (millimoles), eq (equivalent(s)). EXAMPLE 1 3-(3,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Step 1 : 2-Methyl- 1 -(4-(methylthio)phenyl)-propan- 1 -one To a suspension of aluminum chloride (136 g, 1.02 mol) in chloroform (1.0 L) cooled to -10 °C, was added dropwise isobutyrylchloride (115 mL, 1.10 mol). Then thioanisole (100 mL, 0.85 mol) was added dropwise. Upon completion of addition the reaction was allowed to proceed at r.t. for 1.5h. The reaction was cooled to 10 °C and quenched by addition of water (750 mL). The organic layer was separated, washed with water (2 x 500 mL), saturated NaHCθ3 solution(2 x 500 mL), brine (1 x 500 mL), and then dried over Na2S04. After concentration in vacuo., the resulting crude product crystallized upon standing under high vacuum for 30 min to give the title compound as a brown solid. Step 2: 2-Hvdroxy-2-methyl- 1 -(4-(methylthio)phenyl)propan- 1 -one To a solution of 2-methy 1-1 -(4- (methylthio)phenyl)propan- 1-one (28.5 g, 147 mmol, Step 1), Aliquat 336 (11.0 mL, 24 mmol) and carbon tetrachloride (21 mL, 218 mmol) in toluene (43 mL) was added sodium hydroxide (12.9 g, pellets, 322 mmol). The reaction was stirred at 15 °C for 2h and then at r.t. for 16h. The reaction was diluted with water (100 mL), brine (100 mL) and EtOAc (300 mL). The aqueous phase was acidified with 1 N HCl and extracted with EtOAc (100 mL). The combined organic layers were dried over Na2S04 and concentrated. The crude product was purified by silica gel chromatography eluted with 15% EtOAc in hexane to give the title compound as a thick syrup. Step 3: 2-Hydroxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)propan- 1 - one To a cold (4 °C) solution of 2-hydroxy-2-methyl-l-(4- (methylthio)phenyl)propan-l-one (45.0 g, 214 mmol, Step 2) in t-butanol (500 mL) and CH2CI2 (500 mL) was added a solution of OXONETM (194 g, 316 mmol) in water (1.4 L). The resulting suspension was stirred at r.t. for 18h. The reaction was diluted with EtOAc (400 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (2 x 250 mL). The combined organic layers were dried over Na2Sθ4 and concentrated in vacuo. The crude product was dissolved in diethyl ether (250 mL), hexane was added (150 mL) and the product was swished for 2h. The product was collected by filtration to give the title compound as a yellow solid. Step 4: 3-(3,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one A solution of 3, 4-difluorophenoxy acetic acid (0.5 lg, 2.73 mmol), 2-hydroxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)propan- 1 -one (0.5g, 2.1mmol, Step 3), CMC (1.13g, 2.73mmol) and DMAP (15 mg, O.lOmmol) in dichloromethane (12ml) was stiπed at r.t. for 18 hrs. Then, DBU (0.63ml, 4.2mmol) was added and the reaction mixture was refluxed for 3 h. After cooling to r.t.the mixture was extracted with ethyl acetate and washed successively with water, IN HCl and brine. The organic layer was dried over MgSθ4, filtered and the solvent evaporated under vacuum.The residue was triturated in a mixture of ethyl acetate and hexane affording the title compound as a solid. M.P.: 93-95 °C. IH NMR (CD3COCD3) δ 1.77 (6H, s), 3.15 (3H, s), 6.93-6.97 (IH, m), 7.12-7.29 (2H, m), 7.92 (2H, d), 8.04 (2H, d). Analysis calculated for C19H16F2O5S: C, 57.86; H, 4.09; Found: C, 57.77; H, 4.28 EXAMPLE 2 3-(3-Fluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for example 1 , the title compound was prepared from 3-fluorophenoxy acetic acid. M.P.: 136- 138°C. IH NMR (CD3COCD3) δ 1.79 (6H, s), 3.15 (3H, s), 6.85-6.94 (3H, M), 7.31-7.86 (IH, m), 7.93 (2H, d), 8.03 (2H,d). EXAMPLE 3 3-(3,5-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for example 1, the title compound was prepared from 3, 5-difluorophenoxy acetic acid. M.P.: 159- 161°C. IH NMR (CD3COCD3) δ 1.80 (6H, s), 3.17 (3H, s), 6.78-6.84 (3H, m), 7.96 (2H, d), 8.06 (2H, d). Analysis calculated for C19H16F2O5S: C, 57.86; H, 4.09; Found: C, 57.66; H, 4.30 EXAMPLE 4 3-Phenoxy-5.5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one Step 1: 3-Phenoxy-5,5-dimethyl-4-(4-(methylthio)phenyl)-5H-furan- 2-one Following the procedure described for example 1 , Step 4, the title compound was prepared from phenoxyacetic acid and 2-hydroxy-2- methyl-l-(4-(methylthio)phenyl)propan-l-one (example 1, Step 4). IH NMR (CD3COCD3) δ 1.79 (6H, s), 2.51 (3H, s), 7.03-7.10 (3H, m), 7.30-7.37 (4H, m), 7.72 (2H, d). Step 2: 3-Phenoxy-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- uran-2-one The compound obtained in Step 1 (150 mg, 0.46mmol) was stiπed in dichloromethane (5mL) with 3-chloroperoxybenzoic acid (250 mg, 1.38mmol) for 18 hrs. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine, dried over MgSθ4, filtered and the solvent evaporated under vacuum. The residue was triturated in Et2θ to afford the title compound. M.P.: 135-136°C. iH NMR (CD3COCD3) δ 1.78 (6H, s), 3.14 (3H, s), 7.05-7.08 (3H, m), 7.28-7.30 (2H, m), 7.92 (2H, d), 8.01 (2H, d). Analysis calculated for C19H18O5S: C, 63.67; H, 5.06; S, 8.95; Found: C, 64.02; H, 5.10: S, 8.84 EXAMPLE 5 3-(2,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Step 1: 2-Bromoacetic acid, 2-methyl-l-(4-(methylsulfonyl) phenyl)propan-l-one ester To a 0°C solution of 2-hydroxy-2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one (4.0g, 16.5mmol, example 1, Step 3) in dichloromethane (lOOmL) was added pyridine (23.5mL, 291 mmol) and bromoacetyl bromide (24.9mL, 285.3mmol) portionwise over 2 hrs. The reaction mixture was allowed to warm to r.t. and stirred for a further hour. The mixture was diluted with dichloromethane, washed with IN HCl, brine, filtered through cotton and the solvent was evaporated under vacuum. Purification by silica gel chromatography (40% EtOAc Hex.) provided 3.50g of the title compound. iH NMR (CD3COCD3) δ 1.75 (6H, s), 3.20 (3H, s), 4.00 (2H, s), 8.05 (2H, m), 8.25 (2H, m). Step 2: 2-(2,4-Difluorophenoxy )acetic acid 2-methy 1- 1 -(4- (methylsulfonvDphenyDpropan- 1 -one-2-yl ester Sodium hydride, 60% dispersion (66mg, 1.66mmol), was rinsed with hexane, suspended in 7mL of DMF and cooled to 0°C. To this suspension was added 2,4-difluorophenol (170μL, 1.79mmol). After 5 minutes at 0°C, 2-bromoacetic acid 2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one ester (Step 1) (233mg, 1.79mmol) was added and the reaction mixture was stirred for 30 minutes. Dichloromethane was added and the mixture was washed with IN HCl and the organic solvent was evaporated under vacuum. The residue was dissolved in 25%EtOAc/Et2θ and washed with IN NaOH, water (2X) brine and dried over MgSθ4* After filtration and evaporation of the solvent under vacuum 470mg of the title compound was obtained. iH NMR (CD3COCD3) δ 1.75 (6H, s), 3.20(3H, s), 4.80 (2H, s), 6.60 (IH, m), 6.75 (IH, m), 7.00 (IH, m), 8.05 (2H, m), 8.20 (2H, m). Step 3: 3-(2,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one To a solution of 2-(2,4-difluorophenoxy)acetic acid 2- methyl-l-(4-(methylsulfonyl)phenyl)propan-l-one-2-yl ester (Step 2) (470 mg, 1.14mmol) in acetonitrile (7mL) was added DBU (187μL, 1.25mmol) and the resulting solution was heated at 50 °C for 20 minutes. After cooling to r.t. dichloromethane was added and the mixture was washed with 1 N HCl, brine, filtered over cotton and the solvent evaporated under vacuum. Purification by silica gel chromatography followed by a swish in EtOAc/Et2θ afforded 122 mg of the title compound. iH NMR (CD3COCD3) δ 1.70 (6H, s), 3.15 (3H, s), 6.90 (IH, m), 7.10 (IH, m), 7.30 (IH, m), 7.85 (2H, m), 8.00 (2H, m). EXAMPLE 6 3-(4-Chlorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for example 1 , the title compound was prepared from 4-chlorophenoxyacetic acid. M.P.: 113-114 °C iH NMR (CD3COCD3) δ 1.77 (6H, s), 3.15 (3H, s), 7.11 (2H, d), 7.31 (2H, d), 7.91 (2H, d), 8.04 (2H, d) EXAMPLE 7 3-(3.4-Dichlorophenoxy)-5.5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for example 1 , the title compound was prepared from 3, 4-dichlorophenoxy acetic acid. M.P.: 144- 145 β C. iH NMR (CD3COCD3) δ 1.78 (6H, s), 3.15 (3H, s), 7.12-7.15 (IH, m), 7.35-7.36 (IH, s), 7.49 (IH, d), 7.92 (2H, d), 8.04 (2H, d). EXAMPLE 8 3-(4-Fluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for example 1 , the title compound was prepared from 4-fluorophenoxyacetic acid. iH NMR (CD3COCD3) δ 1.76 (6H, s), 3.14 (3H, s), 7.02-7.13 (4H, m), 7.91 (2H, d), 8.01 (2H, d). EXAMPLE 9 3-(4-Fluorophenylthio)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for Example 1, the title compound was prepared from 4-fluorophenylthioacetic acid. iH NMR (CDC13) δ 1.55 (6H, s), 3.08 (3H, s), 6.85 (2H, m), 7.26 (2H, m), 7.35 (2H, d), 7.94 (2H, d) EXAMPLE 10 3-(3,5-Difluorophenylthio)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one To a mixture of 3,5-difluorothiophenol (l.Og) and methyl bromoacetate (1.2g) in methanol (20mL) was added 2mL of a solution of NaOH (0.69mL of ION in 3mL of water), the mixture was stirred for lh, then 2mL of ION NaOH was added and the mixture stiπed for another hour. The solvent was evaporated under vacuum, the residue taken in water and washed with Et2θ, then acidified with IN HCl and extracted with ether. The ether extract was washed with water, dried over MgS04, filtered and the solvent evaporated under vacuum giving 850mg of 3,5- difluorophenylthioacetic acid. This acid was reacted as in Step 1 to afford the title compound. iH NMR (CDCI3) δ 1.60 (6H, s), 3.10 (3H, s), 6.60-6.80 (3H, m), 7.45 (2H, d), 8.00 (2H, d). EXAMPLE 11 3-Phenylthio-5.5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one Following the procedure described for example 1 , the title compound was prepared from phenylthioacetic acid. M.P.: 98-114°C. iH NMR (CD3COCD3) δ 1.61 (6H, s), 3.16 (3H, s), 7.21-7.30 (5H, m), 7.61 (2H, d), 7.96 (2H, d). Analysis calculated for C19H18O4S2: C, 60.94; H, 4.84; S, 17.12; Found: C, 61.01; H, 4.90: S, 16.94 EXAMPLE 12 3-(N-Phenylamino)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Step 1: 2-Phenylaminoacetic acid 2-methyl-l-(4-(methylsulfonyl) phenyl)propan-l-one ester Following the procedure described in example 13 Step 1 but using aniline the title compound was obtained. iH NMR (CD3COCD3) δ 1.70 (6H, s), 3.15 (3H, s), 3.95 (2H, br s), 5.15 (IH, br s), 6.40 (2H, m), 6.55 (IH, m), 7.00 (2H, m), 8.00 (2H, m), 8.25 (2H, m). Step 2: 3-N-Phenylamino-5,5-dimethyl-4-(4-(methylsulfonyl)- phenyl)-5H-furan-2-one Following the procedure described in example 13 Step 2 but using 2-phenylaminoacetic acid 2-methyl-l-(4-(methylsulfonyl)phenyl) propan-1-one ester the title compound was obtained. iH NMR (CD3COCD3) δ 1.65 (6H, s), 3.05 (3H, s), 6.70 (3H, m), 6.95 (2H, m), 7.25 (IH, br s), 7.50 (2H, m), 7.75 (2H, m). EXAMPLE 13 3-(N-Methyl-N-phenylamino)-5,5-dimethyl-4-(4-(methylsulfonyl)- phenyl)-5H-furan-2-one Step 1: 2-(N-Phenyl-N-methylamino)acetic acid 2-methyl-l-(4- (methylsulfonyl)phenyPpropan- 1 -one ester To a solution of 2-bromoacetic acid 2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one ester (example 5, Stepl) (l .Og, 2.75mmol) in toluene (2.5mL) was added N-methylaniline (3.0mL, 27.5mmol) and the resulting solution was heated at 115°C for 16 hrs. After cooling to r.t. the reaction mixture was washed with brine and filtered through cotton. Purification by silica gel chromatography provided 850mg of the title compound. Step 2: 3-(N,-Methyl-N-phenylamino)-5,5-dimethyl-4-(4- (methylsulfonyl) phenyl)-5H-furan-2-one To a solution of 2-(N-phenyl-N-methylamino)acetic acid 2- methyl-l-(4-(methylsulfonyl)phenyl)propan-l-one ester (700mg, 1.80mmol) in acetonitrile (3mL) was added DBU (2.7mL, 18.0mmol) and the resulting solution was heated at 60°C for 1 h. After cooling to r.t. dichloromethane was added and the mixture was washed with IN HCl, brine and filtered through cotton and the solvent was evaporated under vacuum. Purification by silica gel chromatography followed by swish in EtO Ac/Hex. afforded 266mg of the title compound. iH NMR (CD3COCD3) δ 1.70 (6H, s), 3.05 (3H,s), 3.15 (3H, s), 6.70 (IH, m), 6.80 (2H, m), 7.10 (2H, m), 7.65 (2H, m), 7.90 (2H, m) EXAMPLE 14 3-Cyclohexyloxy-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan- 2-one Step 1 : 2-Bromo-2-methyl- 1 -(4-(methylsulfonyl)phenyl)propan- 1 - one To a solution of 2-methyl-l-(4-(methylthio)phenyl)propan- 1-one (example, 1, Step 1) (417.94g) in ethyl acetate (1.2L) and cyclohexane (1.7L) was added bromine (1 lOmL) portionwise. After stirring for 10 min the mixture was washed with water, saturated sodium bicarbonate and brine. To this mixture was then added sodium tungstate (6.7g), Aliquat 336 (25g) and water (200 mL). The mixture was then heated to 50°C and hydrogen peroxide (30%, 600mL) was added slowly. Ethyl acetate and water were then added to the mixture and the organic layer separated, washed with water, dried over sodium sulfate, filtered and the title compound crystalized and was collected by filtration. Step 2: 2-Cyclohexyloxyacetic acid 2-methyl-l-(4-(methylsulfonyl) phenyl)propan-l-one ester A solution of 2-cyclohexyloxyacetic acid (1.74g, l lmmol), 2-bromo-2-methyl- l-(4-(methylsulfonyl)phenyl)propan- 1 -one (3.05g, lOmmol) and diisopropylethylamine (2.20g, 17mmol) in 30mL of ethanol was refluxed for 15 h. The solvent was evaporated and the residue dissolved in water and extracted with EtOAc, washed with 5% HCl, saturated sodium bicarbonate, brine and dried over MgSθ4, filtered and the solvent evaporated under vacuum. Purification by silica gel chromatography afforded 3.0g of the title compound. Step 3: 3-Cyclohexyloxy-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one A solution of the ester from the previous step (492 mg, 1.29mmol) and DBU (lmL) in 5mL of acetonitrile was heated at reflux for 15h.. To the cooled solution was added 5% HCl and the mixture was extracted with EtOAc, washed with a saturated solution af ammonium chloride and dried over MgS04, filtered and the solvent evaporated under vacuum. Purification by silica gel chromatography afforded the title compound.M.P.: 143-144°C iH NMR (CD3COCD3) δ 1.20-1.35 (3H, m), 1.40-1.50 (3H, m), 1.66 (6H, s), 1.60-1.70 (2H, m), 1.85-1.95 (2H, m), 3.20 (3H, s), 4.85 (IH, m), 8.00-8.10 (4H, m) Analysis calculated for C19H24O5S: C, 62.62; H, 6.64; Found: C, 62.28; H, 6.57 EXAMPLE 15 3-Phenylthio-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one At 0°C, triethylamine (335 μL) was added to a solution of thiophenoxyacetic acid (161 mg) and 2-bromo-l-(4- (methylsulfonyl)phenyl) ethanone (272 mg, WO 9500501, example 9, Step 1) in 5mL of acetonitrile and the mixture was stirred at 0°C for lh. The reaction mixture was then cooled to -20°C and DBU (265 μL) was added. The mixture was stiπed for 30 min. at -20°C and was quenched by addition of IN HCl. The product was extracted with EtOAc, dried over sodium sulfate and partially purified by silica gel chromatography. The impure product was recrystalized from EtOAc/Hexane to afford the title compound as a solid iH NMR (CDCI3) δ 3.10 (3H, s), 5.25 (2H, s), 7.24-7.38 (5H, m), 7.93 (2H, d), 8.03 (2H, d). Analysis calculated for C17H14O4S2: C, 58.94; H, 4.07; Found: C, 58.88; H, 4.18 EXAMPLE 16 3-Benzyl-5.5-dimethyl-4-(4-(methvIsulfonyl)phenyl)-5H-furan-2-one Step 1: 3-Phenylpropanoic acid 2-methyl-l-(4-(methylthio)phenyl) propan-l-on-2-yl ester To a -30 °C solution of 2-hydroxy-2-methyl-l-(4- (methylthio)phenyl)propan-l-one (1.05g, example 1, Step 2) in dichloromethane (20mL) was added 3-phenylpropionyl chloride (1.68g) in dichloromethane (10 mL) followed by pyridine (791mg) and the mixture was allowed to warm up slowly to 25°C and stirred for 12 h. Ethyl acetate was added to the mixture and it was washed with IN HCl, brine, dried over magnesium sulfate filtered and the solvent was evaporated under vacuum. Purification by silica gel chromatography afforded 1.36g of the title compound. H NMR (CD3COCD3) δ 1.65 (6H, s), 2.50 (3H, s), 2.55-2.65 (2H, t), 2.75-2.85( 2H, t), 7.10-7.40 (7H, m), 7.90-8.00 (2H, d) Step 2: 3-Benzyl-5,5-dimethyl-4-(4-(methylthio)ρhenyl)-5H-furan- 2-one To a 0°C solution of the ester from the previous step ( 1.14g) in DMF (lOmL) and THF (2mL) was added sodium hydride (120mg of 80% dispersion) and the mixture was stirred for 2 h at 25°C. Then it was poured over icy IN HCl and extracted with ethyl acetate , the organic layer was washed with water, brine, dried over MgS04 and the solvent evaporated under vacuum. The residue was purified by silica gel chromatography affording 596 mg of the title compound. iH NMR (CD3COCD3) δ 1.50 (6H, s), 2.55 (3H, s), 3.50 (2H, s), 7.05- 7.30 (7H, m), 7.35-7.40 (2H, d) Step 3: 3-Benzyl-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one To a 0°C solution of the lactone from the previous step (596mg) in dichloromethane (10 mL) and methanol (5mL) was added portionwise MMPP (2x590mg) and the mixture was allowed to slowly warm-up to 25°C. After 2h. at 25°C the mixture was partitioned between dichloromethane and water, the organic layer was washed with brine, dried over MgSθ4, filtered and the solvent evaporated under vacuum. The residue was swished in ether to yield 530mg of the title compound. Analysis calculated for C20H20O4S: C, 67.40; H, 5.65; Found: C, 67.28; H, 5.78 EXAMPLE 17 3-(3,4-Difluorophenylhydroxymethyl)-5,5-dimethyl-4-(4- (methylsulfonyl) phenyl)-5H-furan-2-one Using a procedure similar to the Steps 1, 2 and 3 of example 19 but using 3,4-difluorobenzaldehyde as an electrophile the title compound was obtained. iH NMR (CD3COCD3) δ 1.45 (6H, s), 3.15 (3H, s), 5.00 (IH, bs), 5.50 (IH, bs), 6.45-6.55 (2H, d), 7.00-7.30 (3H, m), 7.95-8.05 (2H, d). EXAMPLE 18 3-(3,4-Difluorobenzoyl)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- uran-2-one Using a procedure similar to Step 4 of example 19 and using the compound obtained in example 17, the title compound was obtained lH NMR (CD3COCD3) δ 1.75 (6H, s), 3.10 (3H, s), 7.35-7.45 (IH, m), 7.65-7.75 (2H, d), 7.75-7.90 (2H, m), 7.95-8.05 (2H, d). EXAMPLE 19 3-Benzoyl-5.5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one Step 1 : Acetic acid 2-methyl- 1 -(4-methylthiophenyl)propan- 1 -on-2- yl ester To a 0 β C solution of 2-hydroxy-2-methyl-l-(4- (methylthio)phenyl)propan-l-one (150g, example 1, Step 2), DBU (217g) and DMAP (7g) in dichloromethane (850mL) was added acetyl chloride (112.2g) dropwise and the mixture was stiπed for 6 h. at 25°C. More DBU (32.5g) was added and the mixture was stirred an additionnal 16 h. The reaction mixture was poured over 2N HCl (800mL) and the organic layer was separated, washed with a saturated solution of NaHCθ3, dried over MgS04, filtered and the solvent was evaporated under vacuum. The residue was swished in Et2θ, then 25% ethyl acetate in hexane, then filtered and dried giving 74g of the title compound. iH NMR (CD3COCD3) δ 1.60 (6H, s), 1.90 (3H, s), 2.55 (3H, s), 7.30 (2H, d), 8.00 (2H, d). Step 2: 5.5-Dimethyl-4-(4-(methylthio)phenyl)-5H-furan-2-one To a 0-5 °C solution of the ester from the previous step (74g) in DMF (1.2L) was added NaH (9g, 80% dispersion) portionwise and the mixture was stirred for 3 h. Saturated aquous NH4CI was added slowly . The mixture was then partitioned between ethyl acetate and water, the organic layer was washed with water, dried with Na2Sθ4, filtered and the solvent was evaporated under vacuum. The residue was swished in 30% ethyl acetate/ hexane to yield the title compound (38g). iH NMR (CD3COCD3) δ 1.70 (6H, s), 2.55 (3H, s), 6.40 (IH, s), 7.40 (2H, d), 7.70 (2H, d). Step 3: 5,5-Dimethyl-4-(4-(methylsulfonyl)phenyl)-3- (phenylhydroxymethyl) -5H-furan-2-one To a -78°C solution of the lactone (702mg) obtained in the previous step in THF was added 0.67M LDA (9.25mL) and the mixture was reacted for 5min. Benzoyl chloride (913mg) was then added at -78 °C and after 15 min the mixture was poured over icy IN HCl. The organic material was extracted with ethyl acetate, washed with brine, dried with MgSθ4, filtered and the solvent was evaporated under vacuum.The residue was dissolved in dichloromethane (lOmL) and methanol (lOmL) and the solution cooled to 0°C. MMPP (4.9g) was added and the mixture warmed and stiπed at 25 °C for 2h. The mixture was poured over icy water and the organic layer was dried over MgSθ4, filtered and the solvent evaporated under vacuum. The residue was purified by silica gel chromatography to yield 190 mg of compound which was dissolved in methanol(2mL) and THF (ImL), cooled to 0°C and a catalytic amount of NaOH was added. The mixture was poured in icy water and extracted with ethyl acetate, the organic layer was washed with brine, dried over MgSθ4, filtered and the solvent evaporated under vacuum. Step 4: 3-Benzoyl-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one The residue was dissolved in acetone (3mL), and Jone's reagent (3M, 150μL) was added. The mixture was stirred for lh. then poured over icy water and extracted with ethyl acetate, the organic layer was washed with brine, dried over MgSθ4, filtered and the solvent was evaporated under vacuum. The residue was swished in ether to yield the title compound (123mg). Analysis calculated for C20HI8O5S: C, 64.85; H, 4.84; Found: C, 64.63; H, 5.23 EXAMPLE 20 4-(4-(Methylsulfonyl)phenyl)-3-phenoxy-l-oxaspiror4.41non-3-en-2-one Using a procedure similar to the one used in example 1 but using ( 1 -hydroxycyclopentyl)-(4-(methylsulfonyl)phenyl)methanone from example 21, Step 3 and phenoxyacetic acid the title compound was obtained. iH NMR (CDC13) δ 1.80-2.30 (8H, m), 3.04 (3H, s), 6.95-7.35 (5H, m), 7.75 (2H, d), 7.95 (2H, d). EXAMPLE 21 4-(4-(Methylsulfonyl)phenyl)-3-phenylthio-l-oxaspiro[4.4]non-3-en-2- one Step 1: Cycloρentyl-(4-(methylthio)phenyl)methanone To a suspension of anhydrous aluminum chloride (9.3 g, 69.6 mmol) in 58 mL CHCI3 at 0 °C was added dropwise cyclopentanecarbonyl chloride (10.0 g, 75.4 mmol), followed by thioanisole (7.21 g, 58.0 mmol). The ice bath was removed and the mixture was stirred at room temperature for 2h. Water (200 ml) was added with cooling, the layers were separated and the aqueous layer was extracted with CHCI3 (3 x 50 mL). The combined aqueous layers were dried over MgS04, filtered and concentrated. The residue was chromatographed on silica gel (4% EtOAc/hexane) to give 11.9 g of the tide ketone (93%). iH NMR (CD3COCD3) δ 7.94 (d, 2H), 7.36 (d, 2H), 3.79 (q, IH), 2.56 (s, 3H), 2.00-1.71 (m, 4H), 1.70-1.50 (m, 4H). Step 2: ( 1 -Hydroxycvclopentyl)-(4-(methylthio)phenyl)methanone To a solution of the ketone from Step 1 (7.2 g, 32.7 mmol) in 4.7 ml CCI4 and 9.6 ml toluene was added Aliquat 336 (2.11 g, 5.20 mmol) and powdered NaOH (2.88 g, 71.9 mmol) and the mixture was stiπed for 16h at r.t. To the brown mixture was added 100 ml of 5% aq. HC1 and extracted with EtOAc (4 x 100 ml). The combined organic layers were washed with brine, dried over MgSθ4, filtered and concentrated. Chromatography on silica gel (20% EtOAc/hexane) gave 5.4 g of the title compound as a white waxy solid (70%). iH NMR (CD3COCD3) δ 8.11 (d, 2H), 7.31 (d, 2H), 4.63 (s, IH, disappears by D2O wash), 2.56 (s, 3H), 2.24 (m, 2H), 1.89 (m, 4H), 1.71 (m, 2H). Step 3: (l-Hydroxycyclopentyl)-(4-(methylsulfonyl)phenyl)- methanone The sulfide obtained in Step 2 (56g) was dissolved in dichloromethane (800 mL) and methanol (200 mL) and treated with MMPP (139 g) and stirred for 3 h. The organic layer was diluted with dichloromethane, washed with water and brine, dried over MgS04, filtered and the solvent evaporated to afford the title compound. Step 4: 4-(4-(Methylsulfonyl)phenyl)-3-phenylthio- 1 -oxaspiro The hydroxyketone from the previous step was reacted with phenylthioacetic acid as in the procedure for example 1, Step 4 to afford the title compound. iH NMR (CDCI3) δ 1.70-2.05 (8H, m), 3.06 (3H, s), 7.10-7.25 (5H, m), 7.35 (2H, d), 7.90 (2H, d). EXAMPLE 22 4-(2-Oxo-3-phenylthio-l-oxa-spiro[4,4]non-3-en-4-yl)benzene- sulfonamide To a solution of l-(hydroxycyclopentyl)-(4- methylthiophenyl) methanone (52g, example 21 , Step 2) in CH2CI2 (400 mL) and methanol (200mL) at 0°C was added portionwise MMPP (61g). After stirring for 3 h the reaction mixture was washed with water, dried over Na2Sθ4, filtered and evaporated to dryness to provide the sulfoxide intermediate which (7.56g) was dissolved in TFAA (100.0 mL) and refluxed for 3 h. The mixture was cooled to 0°C and ION NaOH (24mL), was added dropwise and under nitrogen. After vigorous stirring for 0.5h, acetic acid (lOOmL) and water (20mL)was added. The mixture was cooled to 0 β C and chlorine gas was bubbled for 20min. The excess chlorine was removed under vacuum and the mixture was poured over icy water and extracted with ethyl acetate. The extracts were washed with water, saturated NaHCθ3 and brine . The organic layer was cooled to 0°C and f-butylamine (lOmL) was added and stirred for lh. The reaction mixture was diluted with water and neutralized with 6N HCl, washed with brine, dried over MgSθ4 filtered and the solvent evaporated under vacuum. The residue was swished in ether. This hydroxyketone (325mg) was then reacted as in example 1, Step 4 using phenylthioacetic acid (200mg)to give an intermediate (300mg) which was stirred in dichloromethane (2mL) and trifluoroacetic acid (8mL) for 18h. The solvents were then evaporated under vacuum and the residue was recrystallized from ethanol to afford the title compound. iH NMR (CD3COCD3) δ 1.65-2.20 (8H, m), 6.68 (2H, br s), 7.25 (5H, m), 7.55 (2H, d), 7.95 (2H, d). EXAMPLE 23 3-(4-Fluorobenzyl)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-fiιran- 2-one Using a procedure similar to the one for example 16 but using 3-(4-fluorophenyl)propionyl chloride the title compound was obtained. iH NMR (CD3COCD3) δ 1.50 (6H, s), 3.15 (3H, s), 4.45 (2H, s), 7.05- 7.15 (2H, m), 7.50-7.60 (2H, d), 7.85-7.95 (2H, m), 7.95-8.05 (2H, d). EXAMPLE 24 3-(3,4-Difluorophenoxy)-5-methoxy-5-methyl-4-(4-(methylsulfonyl)- phenyl)-5H-furan-2-one Step 1: 2-Bromo- 1 -(4-(methylsulfonyl)phenyl)propan- 1 -one Following a procedure similar to the one used in example 1 , Step 1 but using propionyl chloride, l-(4-(methylsulfonyl)phenyl)propan- 1-one was obtained. A solution of this compund (163.4g) in chloroform (2.2L) was then cooled to 0°C and treated with bromine (40mL in 200mL CHCI3) and concentrated HBr (lOmL). The reaction mixture was washed with water, saturatd sodium bicarbonate and brine, dried over sodium sulfate, filtered and the solvent evaporated under vacuum. The residue was swished in ethyl acetate: hexane 1 : 1 to give the title compound (191g). Step 2: 5-Hydroxy-5-methyl-4-(4-(methylsulfonyl)phenyl)-3- phenylthio-5H-furan-2-one To a mixture of 2-bromo-l-(4-(methylsulfonyl)phenyl) propan-1-one (6.0g, 20.6mmol) and thiophenoxyacetic acid (3.8g, 22.6mmol) in acetonitrile (60mL) was added triethylamine (4.0mL, 28.8mmol). The mixture was stirred at r.t. for 3h. T.L.C. showed no bromoketone remaining and DBU (4.0mL) was added. The mixture was stirred at r.t. for lh., then air was bubbled through the mixture for another hour. After dilution with water, the mixture was extracted with EtOAc. The EtOAc extract was washed with IN aquous HCl, brine, dried over MgSθ4, filtered and the solvent evaporated under vacuum. The residue was swished in Et2θ to give the title compound (6.0g) as a pale yellow powder. iH NMR (CD3COCD3) δ 1.68 (3H, s), 3.16 (3H, s), 6.86 (IH, s), 7.35 (5H, m), 7.78 (2H, d), 7.98 (2H, d). Step 3: 5-Methoxy-5-methyl-4-(4-(methylsulfonyl)phenyl)-3- phenylthio-5H-furan-2-one The alcohol (2.5g, 6.6mmol) from the previous step was dissolved in methanol (lOOmL), THF (20mL) and concentrated HCl (5mL) and heated at 70 β C for 24 h. After cooling to 0°C the precipitate formed was filtered, washed with methanol and dried under vacuum to give the title compound (2.0g) as a yellow solid. iH NMR (CD3COCD3) δ 1.65 (3H, s), 3.15 (3H, s), 3.40 (3H, s), 7.18- 7.40 (5H, m), 7.88 (2H, d), 7.98 (2H, d). Step 4: 3-(3,4-Difluorophenoxy)-5-methoxy-5-methyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one To a solution of the compound obtained in the previous step (2.0g, 5.1mmol) in dichloromethane (lOOmL) at r.t. was added mCPBA (4.0g, Aldrich 57-86%, ~16mmol). The mixture was stirred at r.t. for 3h and more mCPBA (2.0g) was added. After stirring for another hour the mixture was washed with IN NaOH, brine, dried and concentrated under vacuum to yield a disulfone as a white foam (2.0g). To a solution of 3,4- difluorophenol (2.0g, 14.9mmol) in DMF was added ION NaOH (ImL, lOmmol). After 30min. a solution of the above disulfone (2.0g, 4.7mmol) in DMF was added. The mixture was heated at 80-85 "C for 1.5h. After cooling the mixture was diluted with water, extracted with EtOAc, the organic extracts were washed with IN NaOH, IN HCl, brine, dried over MgSθ4, filtered and the solvent evaporated under vacuum. Purification by silica gel chromatography afforded the title compound as a white solid (600mg). iH NMR (CD3COCD3) δ 1.86 (3H, s), 3.16 (3H, s), 3.40 (3H, s), 6.95- 7.40 (3H, m), 8.08 (2H, d), 8.16 (2H, d). EXAMPLE 25 3-(5-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one To a mixture of 2-chloroacetic acid 2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one ester (l.Og, 3.13 mmol, prepared similarly to the compound of example 5, Step 1) and 5-chloro-2-pyridinol (0.4 lg, 3.16 mmol) in CH3CN (20 mL) was added DBU (1.5 mL, 10.0 mmol) at r.t.. The mixture was stirred for lh, then heated at 65-70°C for 3h. The volatile solvents were removed in vacuo. The residue was chromatographed over silica gel and eluted with hexane: EtOAc (1:1) to yield a colorless oily residue which was swished in Et2θ to provide the title compound as a white powder (230mg). iH NMR (CD3COCD3) δ 1.80 (6H, s), 3.20 (3H, s), 7.18 (IH, d), 7.94 (3H, m), 8.06 (2H, d), 8.19 (IH, d). EXAMPLE 26 3-(2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2- one Following the procedure described for example 25, the title compound was prepared from 2-hydroxypyridine. iH NMR (CD3COCD3) δ 1.78 (6H, s), 3.15 (3H, s), 7.00-7.20 (2H, m), 7.80-8.20 (6H, m). EXAMPLE 27 3-(6-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one Following the procedure described for example 25, the title compound was prepared from 2-hydroxy-6-methylpyridine. iH NMR (CD3COCD3) δ 1.75 (6H, s), 3.14 (3H, s), 6.85 (IH, d), 7.00 (IH, d), 7.70 (IH, t), 7.90 (2H, d), 8.00 (2H, d). EXAMPLE 28 3-(3-Isoquinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for example 25, the title compound was prepared from 3-hydroxyisoquinoline. iH NMR (CD3COCD3) δ 1.80 (6H, s), 3.14 (3H, s), 7.40-8.10 (9H, m), 9.00 (IH, s). EXAMPLE 29 3-(4-(Methylsulfonyl)phenyl)-2-phenoxycvclopent-2-enone Step 1: l-(4-(Methylthio)phenyl)-5-phenoxypenta- 1.4-dione To a mixture containing l-phenoxybut-3-en-2-one (l.Og) (A.G. Schultz, R.D. Lucci, W.Y. Fu, M.H. Berger, J. Erhardt and W.K. Hagmann, J. Amer. Chem. Soc. 100, 2150, (1978)), 4- (methylthio)benzaldehyde (0.62g) and triethylamine (0.343mL) in 1,4- dioxane (20 mL) was added 3-benzyl-5-(2-hydroxyethyl)-4- methylthiazolium chloride (HOmg). After stirring 4h. at 100°C the reaction mixture was extracted with EtOAc, dried over MgS04, filtered and the solvent evaporated under vacuum. The residue was purified by silica gel chromatography (20% EtOAc/Hexane) to afford 140mg of the title compound as an oil. Step 2: 3-(4-(Methylthio)phenyl)-2-phenoxycvclopent-2-enone To the diketone of Step 1 (120mg) in methanol (80mL) was added DBU (O.lmL). The resulting mixture was heated at 60°C for 18 h. The methanol was then evaporated and to the crude mixture was added saturated aqueous ammonium chloride, the mixture was then extracted with EtOAc, the organic layer was dried over MgS04, filtered, and the solvent evaporated under vacuum. The residue was purified by silica gel chromatography (20% EtOAc/hexane) to afford the title compound. Step 3: (4-(Methylsulfonyl)phenyl)-2-phenoxycvclopent-2-enone To the compound obtained in Step 2 (60mg) in dichloromethane (4.5mL) and methanol (2.4mL) was added Oxone® (450mg) in water (ImL) and the reaction mixture was stiπed for 1 h.Water was added to the mixture which was then extracted with dichloromethane, the organic layers were combined and dried over MgSθ4, filtered and the solvent evaporated under vacuum. Purification by silica gel chromatograohy afforded the title compound. lH NMR (CD3COCD3) δ 2.65 (2H, t), 3.15 (3H, s), 3.20 (2H, t), 7.05- 7.35 (5H, m), 8.10 (4H, m). EXAMPLE 30 2-(3.4-difluorophenoxy)-3-(4-methylsulfonylphenyl)-cyclopent-2-enone Step 1: 3.4-Difluorophenoxymethyl vinyl ketone To a suspension of 3,4-difluorophenoxy acetic acid (5.00 g, 25.7 mmol) lithium salt in DME (20 mL) was added to a IM THF solution of vinyl magnesium bromide (38 mmol). After a period of 18h, the resulting clear solution was poured over IN HCl (67 mL). The aqueous phase was then extracted with Et2θ. The ethereal phase was washed with H2O, IM K2CO3 then H2O. After drying over MgS04 and evaporation an orange oil was obtained and used as such for the next step. Step 2: 2-(3,4-difluorophenoxy)-3-(4-methylsulfonylphenyl)- cyclopent-2-enone Following the procedure described in Example 29 but using the compound obtained in the previous step the title compound was obtained. iH NMR (CD3COCD3) δ 2.60 (2H, t), 3.15 (3H, s), 3.20 (2H, t), 6.90 (IH, m), 7.15 ( IH, m), 7.25 (IH, Q), 8.10 (4H, 2d). EXAMPLE 32 3-(5-Benzothiophenyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 5-hydroxybenzothiophene. M.P.: 150-152°C iH NMR (CD3COCD3) δ 1.78 (6H, s), 3.08 (3H, s), 7.17 (IH, dd), 7.32 (IH, d), 7.56 (IH, d), 7.68 (IH, d), 7.92 - 7.99 (5H, m). EXAMPLE 37 5,5-dimethyl-4-(4-methylsulfonyl-phenyl)-3-(pyridin-4-yloxy)-5H-furan- 2-one To a R.T. solution of 2-chloroacetic acid 2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one ester (318 mg, 1 mmol) in DMF (5 mL) was added 4-pyridone (380 mg, 4.0 mmol) followed by DBU ( 623 mg, 4.1 mmol) and the mixture was slowly warmed up to R.T. for 16 hrs and then to 60-70 °C for 1-2 hours. The mixture was cooled to R.T. and poured on icy dilute NH4CI and EtOAc; the organic layer was separated and the aqueous further extracted with EtOAc. The combined organic layers were washed with brine, dried with Na2S04 and the solvents were removed in vacuo. The residue was purified on silica gel chromatography (1/1, Acetone/toluene) to provide the title compound. iH NMR (CD3COCT>3)δ 1.8(6H,s), 3.15(3H,s), 7.05-7.15(2H,m), 7.9- 8.1(4H,AB), 8.4-8.5(2H,m). EXAMPLE 38 5,5-dimethyl-4-(4-methylsulfonyl-phenyl)-3-(pyridin-3-yloxy)-5H-furan- 2-one To a R.T. solution of 2-chloroacetic acid 2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one ester (318 mg, 1 mmol) in DMF (5 mL) was added 3-hydroxypyridine (95 mg, 1 mmol) followed by DBU ( 623 mg, 4.1 mmol) and the mixture was slowly warmed up to R.T. for 16 hrs and then to 60-70 °C for 1-2 hours. The mixture was cooled to R.T. and poured on icy dilute NH4CI and EtOAc; the organic layer was separated and the aqueous further extracted with EtOAc. The combined organic layers were washed with brine, dried with Na2S04 and the solvents were removed in vacuo. The residue was purified on silica gel chromatography (1/1, Acetone/toluene) to provide the title compound. Analysis calculated for C18H17NO5S: C, 60.16; H, 4.77; N, 3.90. Found: C, 60.01 ; H, 4.81; N, 3.90. EXAMPLE 39 3-(2-Methyl-5-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared using 5-hydroxy-2-methyl pyridine M.P.: 168 - 169°C. iH NMR (CD3COCD3) δ 1.77 (6H, s), 2.41 (3H, s), 3.15 (3H, s), 7.14 (IH, d), 7.37 (IH, dd), 7.93 (2H, d), 8.03 (2H, d), 8.25 (IH, d). EXAMPLE 44 3(2-Fluoro-4-trifluoromethyl)phenoxy-4-(4-methylsulfonyl)phenyl)-5,5- dimethyl-5H-furan-2-one Following the procedure for Example 25, the title compound was prepared from 2-fluoro-4-trifluoromethylphenol; m.p.: 192-194. iH NMR (CD3COCD3) d 1.78 (6H, s), 3.16 (3H, s), 7.49 (2H, m), 7.64 (IH, d, J = 11.6 Hz), 7.95 (2H, d, J = 8.3 Hz), 8.05 (2H, d, J = 8.5 Hz). Analysis calculated for C20HI6F4O5S: C, 54.06; H, 3.63; Found: C, 54.09, H, 3.72. EXAMPLE 45 3-(5-Chloro-2-ρyridylthio)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Following the procedure described for Example 25, the title compound was prepared from 5-chloro-2-mercaptopyridine. iH NMR(CD3COCD3) δ 1.70(6H, s), 3.20(3H, s), 7.38(1H, d), 7.72(3H, m), 8.06(2H, d), 8.42(1H, m). EXAMPLE 46 2-(3.5-Difluorophenoxy)-3-(4-methylsulfonylρhenyl)-cvclopent-2-enone Using similar protocol described for Example 29 but using l-(3,5-difluorophenoxy)but-3-en-2-one the title compound was obtained. iH NMR (CD3COCD3) δ 2.60 (2H, t), 3.15 (3H, s), 3.20 (2H, t), 6.60 to 6.85 (3H, m), 8.10 (4H, 2d). EXAMPLE 47 3-(2-Pyrimidinoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H-furan- 2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxypyrimidine hydrochloride. iH NMR(CD3COCD3) δ 1.78(6H, s), 3.18(3H, s), 7.34(1H, t), 7.40(2H, d), 8.06(2H, d), 8.68(2H, d). EXAMPLE 48 3-(3-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Step 1: 2-Hydroxy-3-methylpyridine To 10% aqueous H2Sθ4(90mL) at 0θC was added 2-amino- 3-methylpyridine (6.0g, 56mmol). The mixture was stirred at O^C for 30mins and a solution of 4N aqueous NaN02 (13mL) was added dropwise over a period of 15 min. The mixture was further stirred and warmed to rt over lh. The pH was then adjusted to 6-7 by the addition of ION aqueous NaOH. The whole mixture was then extracted with CHCI3, washed with H2O, dried (anhydrous MgS04) and concentrated in vacuo. The crude material was swished with Et2θ to give the title compound (2.5g, 42%) as a white solid. lH NMR(CD3COCD3) δ 2.02(3H, s), 6.10(1H, m), 7.30(2H, m). Step 2: 3-(3-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-3-methylpyridine. iH NMR(CD3COCD3) δ 1.78(6H, s), 2.30(3H, s), 3.14(3H, s), 7.05QH, m), 7.65(1H, m), 7.95(3H, m), 8.02(2H, d). EXAMPLE 49 3-(3-Chloro-5-pyridiloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared using 2-chloro-5-hydroxypyridine. M.P.: 176 - 177°C. iH NMR (CD3COCD3) δ 1.79 (6H, s), 3.16 (3H, s), 7.70 (IH, m), 7.96 (2H, d), 8.05 (2H, d), 8.33 (IH, d), 8.40 (IH, d). EXAMPLE 51 3-(3-(l,2,5-Thiadiazolyl)oxy)-4-(4-(methylsulfonyl)phenyl)-5,5- dimethyl-5H-furan-2-one Following the procedure for example 25, the title compound was prepared from 3-hydroxy-l,2,5-thiadiazol; m.p.: 127-129. H NMR (CD3COCD3) δ 1.78 (6H, s), 3.16 (3H, s), 7.92 (2H, d, J = 8.6 Hz), 8.06 (2H, d, J = 8.6 Hz), 8.49 (IH, s). Analysis calculated for C15H14N2O5S2: C, 49.17; H, 3.85; N, 7.65; Found: C, 49.01, H, 3.84; N, 7.37. EXAMPLE 52 3-(5-Isoquinolinoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H-furan- 2-one Following the procedure described for Example 25, the title compound was prepared from 5-hydroxyisoquinoline. lH NMR(CD3COCD3) d 1.80(6H, s), 3.10(3H, s), 7.38(1H, d), 7.55(1H, t), 7.85(1H, d), 7.95(4H, m), 8.04(1H, d), 8.58(1H, d), 9.30(1H, s). EXAMPLE 53 3-(6-Amino-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-6-aminopyridine. M.P.: 165-166°C. iH NMR (CD3COCD3) δ 1.74 (6H, s), 3.14 (3H, s), 5.52 (2H, s, br), 6.17 (IH, d), 6.24 (IH, d), 7.41 (IH, t), 7.90 (2H, d), 8.02 (2H, d). EXAMPLE 54 3-(3-Chloro-4-fluoro)phenoxy-4-(methylsulfonyl)phenyl)-5,5-dimethyl- 5H-furan-2-one Following the procedure for Example 25, the title compound was prepared from 3-chloro-4-fluorophenol; m.p. : 130- 132°C. H NMR (CD3COCD3) δ 1.76 (6H, s), 3.14 (3H, s), 7.10 (IH, m), 7.24 (IH, t, J = 9Hz), 7.30 (IH, m), 7.92 (2H, d, J = 8.5 Hz), 8.03 (2H, d, J = 8.5 Hz). EXAMPLE 55 3-(6-Quinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan- 2-one Following the procedure described for Example 25, the title compound was prepared using 6-hydroxyquinoline. M.P.: 171-172°C. iH NMR (CD3COCD3) δ 1.82 (6H, s), 3.08 (3H, s), 7.46 (IH, m), 7.53 - 7.60 (3H, m), 7.95 - 8.01 (5H, m), 8.23 (IH, m), 8.80 (IH, m). EXAMPLE 56 3-(5-Nitro-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- uran-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-5-nitropyridine. H NMR(CD3COCD3) δ 1.80(6H, s), 3.18(3H, s), 7.38(1H, d), 7.92(2H, d), 8.05(2H, d), 8.66(1H, m), 9.05(1H, m). EXAMPLE 57 3-(2-Thiazolylthio)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan- 2-one Following the procedure described for Example 25, the title compound was prepared using 2-mercaptothiazole. M.P.: 174-176°C. iH NMR (CD3COCD3) δ 1.67 (6H, s), 3.19 (3H, s), 7.59 (IH, d), 7.68 (IH, d), 7.74 (2H, d), 8.07 (2H, d). EXAMPLE 58 3-(3-Fluoro-5-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared using 5-fluoro-2-hydroxypyridine M.P.: 157 - 159°C. iH NMR (CD3COCD3) δ 1.76 (6H, s), 3.16 (3H, s), 7.16 (IH, m), 7.74 (IH, m), 7.92 (2H, d), 8.03 (2H, d), 8.07 (IH, m). EXAMPLE 109a 5.5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(2-propoxy)-5H-furan-2-one Step 1 5.5-Dimethyl-3-hvdroxy-4-(4-methylsulfonylphenyl)-5H- furan-2-one To a 0°C solution of the alcohol of Example 1 , Step 3 (29.5 g, 122 mmol) in CH3CN (350 mL) were added pyridine (25 mL) and acetoxyacetyl chloride (25 g, 183 mmol). After a period of 7h at r.t., DBU (31 mL) was added to the reaction mixture. After a period of lh at 80°C, a second portion of DBU (35 mL) was added. The reaction mixture was kept at 80°C for 18h. The reaction mixture was allowed to cool to r.t. The mixture was poured onto ice- water (2.5L) containing 100 mL of concentrated HCl. The brown solid was collected and dissolved in hot acetonitrile and was filtered through a plug of silica. The solvent was evaporated and the resultant solid was swished in EtOAc to give the title compound (21.2g, 62%). Step 2 5.5-Dimethyl-4-(4-methylsulfonyl)ρhenyl)-3-(-2-propoxy)- 5H-furan-2-one To a suspension of the alcohol of Step 1 (18.16 g, 64.4 mmol) in benzene (350 mL) were added an excess of 2-iodopropane (19.3 mL) and Ag2Cθ3 (53.3 g, 1.06 mmol). After stirring for 18h , the reaction mixture was filtered and the filtrate was washed with hot EtOAc. After evaporation, the crude compound was purified by flash chromatography (35% to 40% EtOAc/hexane, followed by addition of 5% CH2CI2) to provide 19 g of the title compound. iH NMR (CD3COCD3) δ 1.25 (6H, d), 1.70 (6H, s), 3.20(3H,s), 5.20(lH,septet), 8.05 (4H, s). EXAMPLE 109b 5.5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(2-propoxy)-5H-furan-2-one Step 1: 5,5-Dimethyl-3-hydroxy-4-(4-methylsulfonylphenyl)-5H- furan-2-one To a 0°C solution of the alcohol of Example 1, Step 3 (14.0 g, 57.8 mmol) in CH3CN (180 mL) were added pyridine (10.0 mL) and acetoxyacetyl chloride (12.7 g, 93.0 mmol) after a period of 7h at r.t., DBU (15.0 mL) was added to the reaction mixture. After a period of lh at 80°C, a second portion of DBU (20.0 mL) was added. The reaction mixture was kept at 80°C for 18h. The reaction mixture allowed to cool to r.t. The mixture was diluted with EtOAc (500 mL) and H2O (500 mL) and acidified with 6NHC1. After the addition of brine (100 mL), the aqueous phase was extracted 2 times with EtOAc. The organic phase was evaporated to provide a brown residue. To the solid was added a 2: 1 mixture of CH2CI2 - toluene (150 mL). The solid was filtered and washed with CH2CI2 - toluene to provide 7.0 g of the title compound. Step 2 5,5-Dimethyl-4-(4-methylsulfonyl)phenyl)-3-(-2-ρropoxy)- 5H-furan-2-one To a suspension of the alcohol of Step 1 (100 mg, 0.354 mmol) in benzene (5.0 mL) were added an excess of 2-iodopropane (105 mL) and Ag2Cθ3 (294 mg, 1.06 mmol). After a period of 18h at 45°C, the reaction mixture was filtered over celite and washed with CH2CL2. After evaporation, the crude compound was purified by flash chromatography (35% to 40% EtOAc) to provide 70 mg of the title compound. iH NMR (CD3COCD3) δ 1.25 (6H, d), 1.70 (6H, s), 3.20 (3H, s), 5.20 (IH, Septet), 8.05 (4H, s). EXAMPLE 110 3-(3-Trifluoromethyl)phenoxy-4-(4-methylsulfonyl)phenyl)-5.5- dimethyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 3-trifluoromethylphenol. iH NMR (CD3COCD3) δ 1.79 (6H, s), 3.14 (3H, s), 7.41 (3H, m), 7.55 (IH, m), 7.95 (2H, dd, J = 2, 6.6 Hz), 8.03 (2H, dd, J = 2, 6.7 Hz). Analysis calculated for C 20 H 17 F 3 O 5 S: C, 56.34; H, 4.02; Found: C, 56.21, H, 4.01. EXAMPLE 111 5.5-Dimethyl-4-(4-(methylsulfonyl)phenyl)-3-(piperidine-l-carbonyl)-5- H-furan-2-one. Step 1 5.5-Dimethyl-4-(4-(methylsulfonyl)phenyl)-2-oxo-2.5- dihydrofuran-3-carboxylic acid ethyl ester A mixture of 2-hydroxy-2-methyl-l-(4- (methylsulfonyl) pheny l)propan-l -one (2.87 g, 11.8 mmol), ethyl hydrogen malonate (2.02 g, 15.3 mmol), CMC (6.51 g, 15.4 mmol) and DMAP (0.35 g, 2.8 mmol) was dissolved in 100 mL of CH2CI2. The mixture was stirred for 14h at room temperature, then DBU (4 mL, 27 mmol) was added, stirred lh, then partitioned between CH2CI2 and IM HCl. The organic layer was washed with brine, filtered through cotton and evaporated. Purification by flash chromatography (90% ether/Hex) provided 2.50 g of the title compound. H NMR (CD3COCD3) δ 8.09 (2H, m), 7.68 (2H, m), 4.05 (2H, q), 3.16 (3H, s), 1.58 (6H, s), 0.96 (3H, t). Step 2 5.5-Dimethyl-4-(4-(methylsulfonyl)phenyl)-3- (piperidine- 1 -carbonyl)-5H-furan-2-one To a room temperature solution of piperidine (284 mg, 3.33 mmol) in CH2CI2 (5mL) was added trimethylaluminum (2M in hexane, 1.7 mL, 3.4 mmol). After 15 min, the product from Step 1 (310 mg, 0.92 mmol) was added in one portion and the mixture was heated to reflux for 20h. The resulting solution was cooled and poured into IM HCl (gas evolution). The organic layer was washed with brine, filtered through cotton and evaporated. Purification by flash chromatography (80% EtO Ac/Hex) provided 175 mg of the title compound. iH NMR (CD3COCD3) δ 8.08 (2H, m), 7.80 (2H, m), 3.49 (2H, m), 3.35 (2H, m), 3.17 (3H, s), 1.65 (6H, s), 1.55 (2H, m), 1.40 (4H, m). EXAMPLE 112 5.5-Dimethyl-3-(2-butoxy)-4-(4-methylsulfonylphenyl)-5H-furan-2-one Step 1 5.5-Dimethyl-3-(2-butoxy)-4-(4-methylsulfonyl)phenyl)- 5H-furan-2-one To a suspension of the alcohol of Example 109, Step 1 (300 mg, 1.06 mmol) in benzene (20.0 mL) were added 2-iodobutane (300 μL) and Ag2C03 (400 mg, 3.27 mmol). After a period of 4h at 45°C, the reaction mixture was filtered over celite and washed with CH2CI2. After evaporation, the crude product was purified by flash chromatography (35% EtOAc in Hexane) to give 150 mg of the title compound as a white solid. iH NMR (CD3COCD3) δ 0.09 (3H, t), 1.20 (3H, d), 1.65 (6H, s), 3.20 (3H, s), 5.00 (IH, m), 8.00 (4H, s). EXAMPLE 113 5.5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(3-pentoxy)-5H-furan-2-one Step 1 Pentyl-3-oxyacetic acid To a solution of 3-pentanol (17.6 g, 200 mmol) in benzene (200 mL) was added NaH (6.0 g, 400 mmol). After lh at r.t., chloroacetic acid sodium salt (25.6 g, 200 mmol) was added to the previous mixture. After a period of 2hr. at reflux, the reaction mixture was pourred in H2θ and acidified with HCl. The mixture was extracted with CH2CI2, dried over MgSθ4, filtered over silicic acid (30% EOAc in Hexane). After evaporation of the solvents the title compound was purified by distillation (5.0 g). Step 2 Pentyl-3-oxyacetic acid 2-methyl-l-(4-methylsulfonyl phenyl)propan-l-one-yl ester The title compound was obtained using similar protocol as described for Example 1 Step 3. Step 3 5.5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(3- pentylxy)-5H-furan-2-one. To a solution of the ester of Step 2 (500 mg, 1.35 mmol) in DMF (2.5 mL) was added NaH (50 mg, 1.6 mmol). The reaction mixture was heated gently to give an orange mixture. After standard extractive workup procedure (EtOAc), the crude mixture was purified by flash chromatography (35% EtOAc in hexane to afford 115 mg of the title compound by filtration in Et2θ/hexane. iH NMR (CD3COCD3) δ 0.85 (6H, t), 1.60 (4H, m), 1.65 (6H, s), 3.20 (3H, s), 4.90 (IH, quintet), 8.05 (4H, s). EX AMPLE 115 2-(5-Chloro-2-pyridinoxy)-3-(4-methylsulfonylphenyl)-cyclopent-2- enone Using similar protocol described for Example 29 but using l-(5-chloropyridyl-2-oxy)but-3-en-2-one the title compound was obtained. iH NMR (CD3COCD3) δ 2.50 (2H, t), 2.80 (3H, s), 3.10 (2H, t), 7.10 (IH, d), 7.30 (2H, d), 7.80 (2H, d), 7.85 (IH, dd), 8.05 (IH, d). EXAMPLE 116 3-(4-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-4-methylpyridine. iH NMR(CD3COCD3) δ 1.76(6H, s), 2.36(3H, s), 3.15(3H, s), 6.90(1H, s), 6.98(1H, d), 7.89(2H, d), 7.98(1H, d), 8.02(2H, d). EXAMPLE 117 (5R)-3-(3,4-Difluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Step 1: 2-(S)-t-butyl-5-(R)-ethyl-4-hydroxy-5-methyl-4-(4- (methylthio)phenyl)- 1.3-dioxolan-4-one To a solution of 4-bromothioanisole (27.3 g, 134 mmol) in 300 ml of anhydrous THF at -72°C was added 2.5 M n-BuLi in hexanes (54 ml, 135 mmol) at such a rate as to maintain the internal temperature below -55°C and the mixture was stirred at -72 °C for an hour. A solution of 2-(S)-t-butyl-5-(R)-ethyl-5-methyl-l,3-dioxolan-4-one (16.8 g, 90 mmol, Tetrahedron, 1984, 40, 1313) in 50 ml of THF was added dropwise and the mixture was stirred at -72°C for 15 minutes. Acetic acid (13 ml) was then added slowly and the mixture stiπed for another 10 min. at -72 °C. The reaction was quenched with 25% aq. NH4OAC at -72°C and allowed to warm up to r.t. The title product was extracted in i- PrOAc, dried over Na2S04 and purified by flash chromatography on silica with EtOAc/hexane 2.5 and 5% to yield 22.4 g (80%) of a white solid. iH NMR (CDCI3, mixture of 2 diastereoisomers 1.8: 1) d 0.58, 1.52, 1.68 and 2.05 (2H, 4m), 0.70 and 1.36 (3H, 2s), 0.73 and 0.98 (3H, 2T), 1.00 (9H, 2s), 2.47 (3H, 2s), 2.47 and 2.57 (IH, 2s, )H), 4.80 and 5.00 (IH, 2s), 7.20 (2H, 2d), 7.45 (2H, 2d). Step 2: 2-(R)-hydroxy-2-methyl- 1 -(4-(methylthio)phenyl)- 1 - butanone A mixture of the product of step 1 (32.0 g, 103 mmol), p- toluenesulfonic acid (900 mg) and 35 ml of water was heated to reflux for an hour. The title product was extracted in 200 mL of EtOAc and the solution used as such in the next step. Step 3: 2-(R)-hydroxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)- 1 - butanone- 1 -one To the product of Step 2 in 200 ml of EtOAc in an ice bath (to maintain the temperature of the reaction below 25 °C) was added 100 ml of t-BuOH, 2.3 g of Aliquat 336® and a solution of 73.1 g of Oxone® (238 mmol KHSO5) in 450 ml of water and the mixture was stirred at r.t. overnight. It was then neutralized with ION NaOH. The title product was extracted in i-PrOAc, dried over Na2Sθ4, and purified by flash chromatography on silica with EtO Ac/toluene 20 & 40% to yield 23.8 g of a colorless oil. NMR experiments with the chiral shift reagent Eu (hfc)3 indicated an enantiomeric excess superior than 94%. [α]D^ = - 11.2° (c = 0.8, CHCl3) . iH NMR (CDCI3) δ 0.87 (3H, t), 1.57 (3H, s), 1.93 (2H, m), 3.07 (3H, s), 3.53 (IH, s), 8.00 (2H, d), 8.13 (2H, d). Step 4: (5R)-3-(3,4-Difluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described for Example 1, step 4, the title compound was prepared from 3, 4-difluorophenoxy acetic acid and (2R)-2-hydroxy-2-methyl- 1 -(4-methy lsulfony l)pheny 1-butan- 1 -one . [α]D = +9.4°(c 0.9, acetone). iH NMR(CD3COCD3) δ 0.95(3H, t), 1.80(3H, s), 2.12(2H, q), 3.18(3H, s), 6.95(1H, m), 7.14(1H, m), 7.30(1H, m), 7.95(2H, d), 8.06(2H, d). EXAMPLE 118 (5R)-3-(4-Chlorophenoxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl)phenyl- 5H-furan-2-one Following the procedure described for Example 117, the title compound was prepared from 4-chlorophenoxyacetic acid and (2R)-2- hydroxy-2-methyl- 1 -(4-methylsulfonyl)phenyl-butan- 1 -one. iH NMR(CD3COCD3) δ 0.93(3H, t), 1.78(3H, s), 2.12(2H, q), 3.15(3H, s), 7.11(2H, d), 7.35(2H, d), 7.92(2H, d), 8.03(2H, d). EXAMPLE 119 3-(2-Methyl-3-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Following the procedure described for Example 25, the title compound was prepared from 3-hydroxy-2-methylpyridine. iH NMR(CD3COCD3) δ 1.77(6H, s),2.48(3H, s), 3.14(3H, s), 7.08(1H, m), 7.33(1H, d), 7.93(2H, d), 8.02(2H, d), 8.16(1H, m). EXAMPLE 120 3-(4-Methyl-5-nitro-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)- phenyl-5H-furan-2-one A mixture of 3-hydroxy-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one(1.5g, 5.3mmol, Example 109 step 1), 2-chloro-4-methyl-5-nitropyridine(1.0g, 5.8mmol) and powdered KOH(300mg, 5.4mmol) in DMF(20mL) was heated at 100°C for 12h. After cooling to r.t., the mixture was diluted with H2θ, extracted with EtOAc. The EtOAc extract was washed with brine, dried(anhydrous MgSθ4) and concentrated in vacuo. The residue was swished with EtOH to give the title compound as a pale yellow solid(1.7g, 77%). iH NMR (CD3COCD3) δ 1.80(6H, s), 2.68(3H, s), 3.16(3H, s), 7.20(1H, s), 7.90(2H, d), 8.05(2H, d), 8.85(1H, s). EXAMPLE 121 3-(5-Chloro-4-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)- phenyl-5H-furan-2-one Step 1: 3-(5-Amino-4-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one A mixture of 3-(4-methyl-5-nitro-2-pyridyloxy)-5,5- dimethyl-4-(4-methylsulfonyl)phenyl-5H-furan-2-one(l .4g, 3.3mmol), iron powder(1.5g, 27mmol) and NH4Cl(150mg) in 67% aqueous EtOH(45mL) was refluxed for lh. The hot mixture was filtered through celite. Volatile solvent was evaporated in vacuo. The residue was suspended in water, filtered and dried under vacuum to give the title compound as a brown powder(l .2g, 94%). iH NMR (CD3COCD3) δ 1.72(6H, s), 2.20(3H, s), 3.15(3H, s),4.42(2H, brs), 6.75(1H, s), 7.50(1H, s), 7.90(2H, d), 8.00(2H, d). Step 2: 3-(5-Chloro-4-methyl-2-pyridyloxy )-5 ,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one To a suspension of 3-(5-amino-4-methyl-2-pyridyloxy)-5,5- dimethyl-4-(4-methylsulfonyl)phenyl-5H-furan-2-one(600mg, l.όmmol) in 6M aqueous HCl(3mL) at 0°C was added dropwise a solution of 4M aqueous NaNθ2(450mL, 1.8mmol). The solution became clear and then precipitate formed. After stirring for 30min, the diazotization mixture was added to a solution of CuCl(300mg, 3.0mmol) in concentrated HCl(2mL) at 0°C, then heated to 70-80°C for lOmin, cooled to r.t. and diluted with H2θ and dried under vacuum. Recrystallization from EtOH- Acetone yielded the title compound as a light yellow solid(360mg, 57%). iH NMR (CD3COCD3) δ 1.76(6H, s), 2.40(3H, s), 3.16(3H, s), 7.10(1H, s), 7.90(2H, d), 8.05(2H, d), 8.10(1H, s). EXAMPLE 122 3-(5-Fluoro-4-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)- phenyl-5H-furan-2-one To a suspension of 3-(5-amino-4-methyl-2-pyridyloxy)-5,5- dimethyl-4-(4-methylsulfonyl)phenyl-5H-furan-2-one(650mg, 1.68mmol, Example 121 step 1) in 6M aqueous HCl(4mL) at O^C was added dropwise a solution of 4M aqueous NaNθ2(450mL, l.δmmol). After stirring at O^C for 30min, 60% aqueous HPF6(2mL) was added and the mixture was further stirred for 30min. The precipitate was collected, washed with H2O and dried under vacuum to give 850mg of diazonium salt. The diazonium salt was then heated with a propane torch until the compound started to decompose. The dark brown residue was dissolved in acetone and chromatographed over silica gel, eluted with hexanes:EtOAc(2:3) to provide the title compound as a pale yellow solid(100mg, 17%). lH NMR (CD3COCD3) δ 1.72(6H, s), 2.34(3H, s), 3.16(3H, s), 7.02(1H, m), 7.90(2H, d), 7.94(1H, s), 8.02(2H, d). EXAMPLE 123 3-(3-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Step 1: 3-(3-Nitro-2-pyridyloxy)-5,5-dimethyl-4-(4-methyl- sulfonyl)phenyl-5H-furan-2-one A mixture of 3-hydroxy-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one(1.5g, 5.3mmol), 2-chloro-3- nitropyridine(1.0g, 6.3mmol) and powdered KOH(320mg, 5.7mmol) in DMF(20mL) was heated at 100°C for 12h. After cooling to r.t., the mixture was diluted with H2O, extracted with EtOAc. The EtOAc extract was washed with brine, dried(anhydrous MgSθ4) and concentrated in vacuo. Chromatography over silica gel and elution with hexanes:EtOAc(l: l) gave a solid residue. The residue was swished with EtOH to provide 1.6g(73%) of title compound. iH NMR (CD3COCX>3) δ 1.82(6H, s), 3.18(3H, s), 7.50(1H, m), 8.00(4H, m), 8.50(1H, m), 8.60(1H, d). Step 2: 3-(3-Amino-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one A mixture of 3-(4-methyl-4-nitro-2-pyridyloxy)-5,5- dimethyl-4-(4-methylsulfonyl)phenyl-5H-furan-2-one( 1.5g, 3.7mmol), iron powder(1.5g, 27mmol) and NH4Cl(150mg) in 67% aqueous EtOH(45mL) was refluxed for lh. The hot mixture was filtered through celite. Volatile solvent was evaporated in vacuo. The residue was suspended in water, filtered and dried under vacuum to give the title compound as a brown powder(1.4g, quantitative). lH NMR (CD3COCD3) δl .76(6H, s), 3.18(3H, s),4.88(2H, brs), 6.86(1H, m), 7.10(1H, m), 7.35(1H, m), 7.98(4H, m). Step 3: 3-(3-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one To a suspension of 3-(3-amino-2-pyridyloxy)-5,5-dimethyl- 4-(4-methylsulfonyl)phenyl-5H-furan-2-one(700mg, 1.7mmol) in 6M aqueous HCl(3mL) at 0°C was added dropwise a solution of 4M aqueous NaNθ2(500mL, 2.0mmol). After stirring for 30min, the diazotization mixture was added to a solution of CuCl(400mg, 4.0mmol) in concentrated HCl(2mL) at 0°C, then heated to 70-80°C for lOmin, cooled to r.t., diluted with H2O and extracted with EtOAc. Chromatography over silica gel and elution with hexanes:EtOAc(l: l) to give a solid residue(lθθmg). Recrystallization from EtOH provided the pure title compound(90mg, 13%). iH NMR (CD3COCD3) δ 1.80(6H, s), 3.16(3H, s), 7.20(1H, m), 7.94(2H, d), 7.98(1H, m), 8.05(2H, d), 8.10(1H, m). EXAMPLE 124 3-(4-Fluorophenoxy)-5-methyl-4-(4-methylsulfonyl)phenyl-5-propyl-5H- uran-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-2-methyl- 1 -(4- methylsulfonyl)phenyl-l-pentanone and 4-fluorophenol. iH NMR(CD3COCD3) δ 0.94(3H, t), 1.38(2H, m), 1.78(3H, s), 2.05(2H, m) 3.14(3H, s), 7.08(4H, m), 7.92(2H, d), 8.02(2H, d). EXAMPLE 125 3- (Diethyl amino)-5,5- dimethyl-4-(4-(methylsulfonyl) phenyl)-5H- furan-2-one Step 1: 2-(diethyl amino) acetic acid 2-methyl-l-(4-(methylsulfonyl) phenyl) propan -1- one-2- yl ester To a room temperature solution of 2-chloroacetic acid 2- methyl-l-(4-methylsulfonyl)phenyl)propan -1- one-2- yl ester (2.00 g, 6.27 mmol) in acetonitrile (10 mL) was added diethyl amine (1.62 mL, 15.7 mmol). The resulting solution was heated to 60°C for 16 hours. The reaction mixture was cooled to room temperature and partitioned between dichloromethane and water. The organic layer was separated, washed with brine, filtered through cotton and the solvent was evaporated under vacuum. Purification by silica gel chromatography (80% EtOAC/ Hex.) provided 1.70 g of the title compound. iH NMR (CD3COCD3) δ 0.85 (6H,t), 1.70 (6H, s), 2.37 (4H, q), 3.15 (3H,s) 3.27 (2H,s), 8.00 - 8.07 (2H,m), 8.15- 8.22 (2H,m). Step 2: 3- (Diethyl amino)-5,5- dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one Sodium hydride, 60% dispersion (0.478 g, 11.96 mmol) was washed in hexane and suspended in DMF (5mL). This suspension was added to a 0°C solution of 2-(diethyl amino) acetic acid 2-methyl-l-(4- (methylsulfonyl) phenyl) propan -1- one-2- yl ester (1.70 g, 4.78 mmol) in DMF (20 mL). The resulting mixture was warmed to RT for 15 minutes. The mixture was diluted with ethyl acetate and quenched with water. The organic layer was washed with brine, dried over MgS04 and concentrated to dryness. The residue was purified by swishing in ether/ hexanes to give 500 mg of crystalline solid on filtration. iH NMR (CD3COCD3) δ 0.95 (6H, t), 1.45 (6H,s), 3.07 (4H,q), 3.17 (3H,s), 7.65-7.70 (2H,m), 7.97- 8.05 (2H,m). EXAMPLE 127 5,5-dimethyl-4-(4-methylsulfonyl-phenyl)-3-(3,5-dichloro-pyridin-2- yloxy)-5H-furan-2-one To a R.T. solution of 2-chloroacetic acid 2-methyl-l-(4- (methylsulfonyl)phenyl)propan-l-one ester (954 mg, 3 mmol, example 25) in acetonitrile (15 mL) was added 3,5-dichloro-2-pyridone (656 mg, 4.0 mmol) followed by DBU ( 2.28 g, 15 mmol) and the mixture was slowly warmed up to gentle reflux for 2 hours. The mixture was cooled to 25 °C the volatiles were removed in vacuo. The residue was purified on silica gel chromatography (1/1, EtOAc/Hexanes then 100% EtOAc)) to provide the title compound. Analysis calculated for CI8H15CI2NO5S: C, 50.48; H, 3.53; N, 3.27. Found: C, 50.53; H, 3.49; N, 3.21. EXAMPLE 128 (5R)-3-(4-Bromophenoxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl)phenyl- 5H-furan-2-one Following the procedure described for Example 117, the title compound was prepared from 4-bromophenoxyacetic acid and (2R)-2- hydroxy-2-methyl- 1 -(4-methylsulfonyl)phenylbutan- 1 -one. iH NMR(CD3COCD3) δ 0.93(3H, t), 1.78(3H, s), 2.12(2H, q), 3.15(3H, s), 7.05(2H, d), 7.50(2H, d), 7.94(2H, d), 8.05(2H, d). EXAMPLE 129 (5R)-3-(4-Methoxyphenoxy)-5-e l-5-memyl-4-(4-methylsulfonyl)- phenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from (2R)-2-chloroacetoxy-2-methyl-l-(4- methylsulfonyl)phenylbutan-l-one (prepared similarly to the compound of Example 5 step 1) and 4-methoxyphenol. iH NMR(CD3COCD3) δ 0.92(3H, t), 1.75(3H, s), 2.08(2H, q), 3.14(3H, s), 3.74(3H, s), 6.83(2H, d), 6.97(2H, d), 7.89(2H, d), 7.99(2H, d). EXAMPLE 130 (5R)-3-(5-Chloro-2-pyridyloxy)-5-methyl-4-(4-methylsulfonyl)phenyl-5- (2.2.2-trifluoroethyl)-5H-furan-2-one Step 1: 2-(S)-t-butyl-5-(R)-methyl-5-(2,2,2-trifluoroethyl)- 1 ,3- dioxolan-4-one To a solution of lithium diisopropylamide (prepared from 13 ml of diisopropylamine and 54 ml of 1.6 M n-BuLi in hexanes in 200 ml of anhydrous THF at 0°C) at -72°C was added slowly 2-(s)-t-butyl-5-(s)- methyl-l,3-dioxolan-4-one (12.95 g, 81.9 mmol, Tetrahedron , 1984, 40, 1313) at such a rate as to maintain the internal temperature below -60°C and the mixture was aged at -72°C for an hour. l,l,l-Trifluoro-2- iodoethane (25 g, 119 mmol) was added quickly, the reaction temperature increased to -45°C and the mixture was aged at -72°C for 45 min. and then allowed to warm up to -20°C over 20 min. Saturated aq. NH4CI was then added and the product was extracted in i-PrOAc, dried over Na2S04, concentrated and distilled under reduced pressure to afford 7.51 g of a brown oil BP 90°C / 20 mm Hg. iH NMR (CDCI3, mixture of distereoisomers 3.2: 1) d 0.97 (9H, 2s), 1.50 and 1.54 (3H, 2s), 2.59 (2H, m), 5.22 (IH, 2d). Step 2: 2-(R)-hydroxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)- 4.4.4-trifluoro- 1 -butanone Using the procedures of Example 117 step 1, 2 and 3, the product of Step 1 was converted to the title compound. iH NMR (CDCI3) δ 1.68 (3H, s), 2.72 (IH, m), 2.98 (IH, m), 3.08 (3H, s), 3.35 (IH, br s, OH), 8.03 (2H, d), 8.14 (IH, d). Step 3: (2R)-2-Chloroacetoxy-2-methyl- 1 -(4-methylsulfonyl)- phenyl-4.4.4-trifluoro-butan- 1 -one A mixture of (2R)-2-hydroxy-2-methyl-l-(4- methylsulfonyl)phenyl-4,4,4-trifluoro-l-butanone(5.2g, 16.8mmol), chloroacetic acid(2.0g, 21 mmol), CMC(9.5g, 22mmol) and DMAP(lOOmg) in CH2Cl2(50mL) was stirred at r.t. for 2h. TLC showed the esterification completed. The mixture was washed with H2θ(2x), dried(anhydrous MgSθ4) and concentrated in vacuo. Chromatography over silica gel and elution with hexanes:EtOAc(l : 1) gave 6.0g(92%) of the title compound as an oil. iH NMR(CD3COCD3) δ 1.98(3H, s), 3.18(3H, s), 3.28(2H, m), 4.35(2H, m), 8.08(2H, d), 8.28(2H, d). Step 4: (5R)-3-(5-Chloro-2-pyridyloxy)-5-methyl-4-(4- methylsulfonyl)phenyl-5-(2,2,2-trifluoroethyl)-5H-furan-2- one Following the procedure described for Example 25, the title compound was prepared from (2R)-2-chloroacetoxy-2-methyl-l-(4- methylsulfonyl)phenyl-4,4,4-trifluoro-butan- 1 -one and 5-chloro-2- pyridinol. iH NMR(CD3COCD3) δ 1.94(3H, s), 3.16(3H, s), 3.24(2H, q), 7.20(1H, d), 7.95(1H, m), 7.98(2H, d), 8.04(2H, d), 8.16(1H, m). EXAMPLE 133 3-(5-Chloro-2-pyridyloxy)-5-methyl-4-(4-methylsulfonyl)phenyl-5- propyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 2-chloroacetoxy-2-methyl-l-(4- methylsulfonyl)phenyl-l-pentanone (prepared in a fashion similar to that of the compound in example 1 step 1,2 and 3) and 5-chloro-2-pyridinol. iH NMR(CD3COCD3) δ 0.93(3H, t), 1.42(2H, m), 1.76(3H, s), 2.05(2H, m) 3.15(3H, s), 7.16(1H, d), 7.90(3H, m), 8.02(2H, d), 8.16(1H, m). EXAMPLE 134 3-(l-Cyclopropyl-ethoxy)-5,5-dimethyl-4-(4-methyl sulfonyl)phenyl)- 5H-furan-2-one Step 1: ( 1 -cvclopropyl-ethoxy)acetic acid To a suspension of NaH (80% in oil) (15.7 g, 523 mmol) in THF (180 mL) at 0°C were added bromoacetic acid (28.0 g, 203 mmol) and a-methylcyclopropane methanol (10.0 g, 116 mmol). The resulting mixture was then stirred at 70°C. After a period of 18 h, the reaction mixture was poured over cold H2θ and the H2O phase was extracted once with Et2θ. The water phase was acidified with HCl and extracted twice with Et2θ. The ether was dried over MgSθ4, filtered and evaporated under reduced pressure. The crude oil was then purified by flash chromotography (40% EtOAc in hexane to 40% EtOAc in Hexane + AcOH) to provide 5.0 g of the title compound. Step 2: 2-( 1 -Cyclopropylethoxy )acetic acid 2-methyl- 1 -(4- methylsulfonyPphenyDpropan- 1 -one-2-yl ester A mixture of (1-cyclopropyl-ethoxy) acetic acid (1.0 g, 6.90 mmol; Example 134, Step 1) 2-hydroxy-2-methyl-l-(4- (methylsulfonyl)phenyl) propan-1-one (1.37 g, 5.76 mmol; Example 1, Step 3), CMC (8.90 g, 20.8 mmol) and DMAP (100 mg, 0.820 mmol) in CH2CI2 (100 ml) was left at r.t. for a period of 18h. The resulting mixture was partitioned between NH4OAC (20%) and CH2CI2. The organic phase was dried over MgSθ4, filtered and evaporated under reduced pressure. The resulting mixture was purified by flash chromatography (35% EtOAc in hexane) to provide 590 mg of the title compound. Step 3: 3-(l-Cyclopropylethoxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl)-5H-furan-2-one To a solution of 2-(l-cyclopropyl-ethoxy)acetic acid 2- methyl-l-(4-(methyl sulfonyl)phenyl) propan- l-one-2-yl ester (590 mg, 1.60 mmol; Example 134, Step 2) CH3CN (20 mL) were added isopropyl trifluoro acetate (294 mL, 2.07 mmol) and DBU (782 mg, 5.14 mmol). After a period of 18 h at 70°C. The reacting mixture was evaporated under reduced pressure and purified by flash chromatography (30% EtOAc in toluene) to provide 270 mg of the title compound. iH NMR (CD3COCD3) δ 0.20 to 0.50 (5H, m), 0.90 (IH, m), 1.35 (3H, d), 1.65 (6H, s), 3.20 (3H, s), 4.35 (IH, quintet), 8.10 (4H, m). EXAMPLE 136 5-Methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-(propoxy)-5-(2, 2,2- trifluoroethyl)-5H-furan-2-one Following the procedure described for Example 109, using 2-hydroxy-2-methyl- 1 -(4-methylsulfonyl)phenyl)-4-trifluorobutan- 1 -one the title compound was obtained. Step 2: 3-hydroxy-5-memyl-4-(4-(methylsulfonyl)phenyl-5-(2- trifluoroethyl)-5H-furan-2-one H NMR (CD3COCD3) δ 1.30 (6H, 2d), 1.80 (3H, s), 3.15 (3H, s), 3.15 to 3.40 (2H, m), 5.30 (IH, quintet), 8.10 (4H, m). EXAMPLE 140 5(R)-5-ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-propoxy)-5H- furan-2-one The title compound was prepared as described in Example 109, Step 2 using (5R)-5-ethyl-3-hydroxy-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, which was prepared from the compound of Example 117, Step 3 following the procedure of Example 109, Step 1. iH NMR (CD3COCD3) δ 0.80 (6H, 2d), 1.60 (3H, s), 2.00 (2H, m), 3.15 (3H, s), 5.20 (IH, quintet), 8.00 (4H, s). EXAMPLE 141 5,5-Dimethyl-3-(2,2-dimethylpropyloxy)-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one To a mixture of 5,5-dimethyl-3-hydroxy-4-(4- (methylsulfonyl)phenyl-5H-furan-2-one (500 mg, 1.77 mmol, Example 109, Step 1) in DMF (6 mL) were added NaH (65 mg, 1.2 eq.), and neopentyl iodide (585 μL). After a period of 18 h at 70 °C, the reaction mixture was diluted with EtOAc. The mixture was washed with H 2 0 and the organic phase separated, dried over MgSθ4 and evaporated under reduced pressure. The resulting oil was purified by flash chromatography to provide the title compound (124 mg) as a white solid after precipitation with Et 2 0. Η NMR (CD 3 COCD 3 ) δ 0.95 (9H, s), 1.65 (6H, s), 3.15 (3H, s), 4.00 (2H, s), 8.00 (4H, m). EXAMPLE 143 5(R) 3-( 1 -cyclopropyl-ethoxy)-5-ethyl-5-methyl-4-(4-(methyl sulfonyl)phenyl-5H-furan-2-one Step 1: ( 1 -cyclopropylethoxy )acetic acid 2(R)-methyl- 1 -(4- (methylsulfonvDphenvPbutan- 1 -one-2yl ester The title compound was prepared as described in Example 134 Step 2 using (1 -cyclopropylethoxy )acetic acid and 2(R) 2-hydroxy-2- methyl-l-(4-(methylsulfonyl)phenyl)butan-l-one from Example 117, Step 3. Step 2: 5(R) 3-(l -cyclopropylethoxy )-5-ethyl-5-methy 1-4(4- (methylsulfonyl)phenyl-5H-furan-2-one The title compound was prepared as described in Example 134 Step 3. iH NMR (CD3COCD3) δ 0.1-0.4 (4H, m), 0.75 (2H, m), 1.00 (IH, m), 1.40 (3H, dd), 1.70 (3H, s), 2.05 (2H, m), 3.20 (3H, s), 4.50 (IH, m), 8.05 (m, 4H). EXAMPLE 144 5(S) 5-Ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl-3-(2-propoxy)-5H- furan-2-one Step 1: (+) 2-Methyl- 1 -(4-methylsulfonylphenyl)-prop-2-en- 1 -ol To a solution of 4-bromothioanisole (51 g) in THF (600 mL) cooled to -72°C was added dropwise a solution of n-BuLi (120 mL, 2.4 M in hexane) over a period of 30 min. The mixture was stiπed at -78°C for 2 h and then a solution of methacrolein (20.3 g) in THF (50 mL) was added over a period of 5 min. The reaction mixture was warmed to -20°C over a period of 20 min. and then quenched with saturated NH4CI (200 mL) and H2O (200 mL). The product was extracted with 500 mL of 1 : 1 hexane/EtOAc, and dried over MgS04. The extract was filtered and concentrated to give the title compound as a yellow oil (55 g). Step 2: (± 2-Methyl- 1 -(4-methylsulfonylphen yl)-prop-2-en- 1 -ol To a solution of the product from Step 1 (55 g., crude) in MeOH (1L) cooled to 0°C was added a solution of Oxone® (190 g in 700 mL H2O) over a period of 2 h. The mixture was stirred at 5°C for an additional 3 h and then filtered. The filtrate was concentrated to remove MeOH and the remaining aqueous mixture was extracted with 1L of 2: 1 EtOAc/hexane. The extract was dried over MgSθ4 filtered and concentrated. The residue was purified by silica gel chromatography eluted with 3:2 hexane/EtOAc to give the title compound (22 g) as a colorless oil. Step 3: (S)-2-Methyl- 1 -(4-methylsulfonylphenyl)-prop-2-en- 1 -ol To a solution of dry 4 A molecular sieves (20 g), and Ti (02Pr)4 (24.8 mL) in CH2CI2 (1L) cooled to -25°C was added dropwise (+)-diisopropyltartrate (22.4 mL). After stirring at -25°C for 30 min., a solution of (±)-2-methyl- 1 -(4-methylsulfonylphenyl)-ρrop-2-en- 1 -ol (21 g) in 500 mL of CH2CI2 was added dropwise, followed by a solution of t-butyl hydroperoxide (20 mL, 5M in decane). The reaction mixture was stiπed at -25°C for 5 h and then quenched with 500 mL of 10% aqueous solution of tartaric acid. After stirring for 1 h, the CH2CI2 layer was separated, dried over MgSθ4 and concentrated. The residue was purified by silica gel chromatography eluted first with 3:1 hexane/EtOAc followed by 1:2 hexane/EtOAc to give the title compound as a white solid ( g). Step 4: (R)-(2-Methyloxiran-2-yl)-(4-methanesulfonylphenyl)- methanol Following the same procedure described in Step 3 using 15 g of 4A molecular sieves, 500 mL of CH2CI2, 12.4 mL of Ti(OiPr)4, 11.2 mL of (-)-diisopropyl tartrate, 20 mL of 5M tBuOOH in decane and 9.8 g of the product from Step 3, the title compound (7.6 g, white solid) was obtained. Step 5: (R)-[(l-Ethoxy-ethoxy)-(4-methanesulfonylphenyl)-methyl]- 2-methyloxirane To a solution of the product from Step 4 (7.2 g) and ethylvinyl ether (50 mL) in 200 mL of CH2CI2 cooled to 0°C was added 50 mg of camphorsulfonic acid. The reaction mixture was stirred at r.t. for 20 min. and then treated with 1 mL of Et3N, concentrated to give the crude title compound (9g). Step 6: (R,S)-l-(l-Ethoxy-ethoxy)-2-methyl- 1-(4- methylsulfonylphenyl) -butan-2-ol To a suspension of Cul(20 g) in EtO (450 mL) cooled at -40°C was added dropwise a solution of MeLi (150 mL, 1.4 M in Et2θ). After stirring at -40°C for 20 min., a solution of the crude product from Step 7 (9 g) in 50 mL of Et2θ was added. The reaction mixture was stiπed at -40°C for 30 min. and then quenched with 20 mL of MeOH and 300 mL of saturated NH4CI solution. Air was bubbled into the mixture with stirring at r.t. for 1 h. The resulting mixture was then extracted with 400 mL of Et2θ and the Et2θ extract was dried over MgSθ4 and concentrated to give the crude title compound (10 g) which was used for next step without further purification. Step 7: (R.S)-2-Methyl- 1 -(4-methylsulfonylphenyl)-butane- 1.2-diol A solution of the crude product from Step 8 (10 g) in 200 mL of THF, 50 mL of AcOH and 50 mL of H2θ was heated at 50°C for 15 h. The mixture was then concentrated to give the crude title compound ( 7 g) which was used for next step with further purification. Step 8: (S)-2-Hydroxy-2-methyl- l-(4-methylsulfonylphenyl)-butan- 1-one To a solution of the crude product from Step 7 ( 7 g) and (Bu3Sn)2θ (30 mL) in 150 mL of CH2CI2 cooled at 10°C was added a solution of Br2 (9.3 g in 30 mL of CH2CI2). After stirring at r.t. for 30 min. the mixture was diluted with a solution of KF (500 mL, 3N) and 500 mL of Et2θ. The solid generated was removed by filtration and the filtrate was separated. The organic layer was dried over MgSθ4 and concentrated. The residue was purified by silica gel chromatography eluted with 1:1 hexane/EtOAc to give 5 g of the title compound as a yellow oil. H NMR (acetone-d6) δ 8.31 (2H, d), 8.00 (2H, d), 4.67 (IH, s), 3.18 (3H, s), 2.00 (IH, m), 1.30 (IH, m), 1.50 (3H, s), 0.90 (3H, t). Step 9: 5(S) 5-ethyl-S-methyl-4-(4-(methylsulfonyl)phenyl)-3-(2- propoxy)-5H-furan-2-one The title compound was prepared as described in Example 1 Step 4 using 2-propoxyacetic acid and 2(S) 2-hydroxy-2-methyl-l-(4- (methylsulfonyl)phenyl) butan- 1 -one. iH NMR (CD3COCD3) δ 0.80 (3H, t), 1.30 (6H, t), 1.70 (3H, s), 2.10 (2H, m), 3.20 (3H, s), 5.25 (IH, m), 8.05 (4H, m). EXAMPLE 146 AND 147 3-(l-cyclopropylethoxy)-5,5-dimethyl-4-(4-(methyl sulfonyl)phenyl)-5H- furan-2-one (146) and 3-(l-cyclopropylethoxy)-5,5-dimethyl-4-(4- (methylsulfon yl)phenyl)-5H-furan-2-one ( 147) The racemate of Example 134 was separated on a HPLC CHIRALPAK AD (Daicel) column with 10% isopropanol in hexane. EXAMPLE 148 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl-5H- furan-2-one Step 1: 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl-5H-furan-2-one The title compound was prepared as described in Example 141 using 5,5-dimethyl-3-hydroxy-4-(4-(methylsulfonyl) phenyl-5H- furan-2-one and (bromomethyl)cyclopropane. H NMR (CD3COCD3) δ 0.30 (2H, m), 0.55 (2H, m), 1.15 (IH, m), 1.60 (6H, s), 3.20 (3H, s), 4.20 (2H, d), 8.00 (4H, s). EXAMPLE 149 5.5-dimethyl-3-(isobutoxy)-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one The title compound was prepared as described in Example 141 using 5,5-dimethyl-3-hydroxy-4-(4-(methylsulfonyl) phenyl-5H- furan-2-one and 1 -bromo-2-methylpropane. iH NMR (CD3COCD3) δ 0.90 (6H, d), 1.65 (6H, d), 1.95 (IH, m), 3.20 (3H, s), 4.10 (2H, d), 8.00 (4H, m). EXAMPLE 150 3-(4-Bromophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for Example 1 , the title compound was prepared from bromophenoxy acetic acid. M.P.: 150-152°C H NMR (CD3COCD3) δ 1.77 (6H, s), 3.15 (3H, s), 7.07 (2H, d), 7.46 (2H, d), 7.92 (2H, d), 8.02 (2H, d). EXAMPLE 53 3-(6-Amino-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-6-aminopyridine. M.P.: 165-166°C. iH NMR (CD3COCD3) δ 1.74 (6H, s), 3.14 (3H, s), 5.52 (2H, s, br), 6.17 (IH, d), 6.24 (IH, d), 7.41 (IH, t), 7.90 (2H, d), 8.02 (2H, d). EXAMPLE 31 3-(2-Quinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)ρhenyl)-5H-furan- 2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxyquinoline. M.P.: 141-142°C. iH NMR (CD3COCD3) δ 1.83 (6H, s), 3.11 (3H, s), 7.26 (IH, m), 7.52 (IH, m), 7.70 (IH, m), 7.77 (IH, m), 7.93 - 8.02 (5H, m), 8.39 (IH, s). EXAMPLE 50 3-(2-Chloro-5-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared using 2-chloro-5-hydroxypyridine. M.P.: 196-197°C H NMR (CD3COCD3) δ 1.78 (6H, s), 3.16 (3H, s), 7.33 (IH, m), 7.68 (IH, m), 7.94 (2H, d), 8.04 (2H, d), 8.14 (IH, m). EXAMPLE 159 3-(6-benzothiazolyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H- furan-2-one Following the procedure described for Example 25, the title compound was prepared from 6-hydroxybenzothiazole M.P.: 212°C. iH NMR (CD3COCD3) δ 1.79 (6H, s), 3.10 (3H, s), 7.34 (IH, s), 7.86 (IH, d), 7.93 - 8.00 (5H, m), 9.15 (IH, s). EXAMPLE 160 3-(6-Chloro-2-pyridiloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one Following the procedure described fro Example 25, the title compound was prepared from 6-chloro-2-hydroxypyridine M.P.: 119- 121°C. iH NMR (CD3COCD3) d 1.78 (6H, s), 3.15 (3H, s), 7.10 (IH, d), 7.25 (IH, d), 7.89 - 8.06 (5H, m). EXAMPLE 161 3-(4-Quinazolyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one Following the procedure described for Example 25, the title compound was prepared from 4-hydroxyquinazoline. M.P.: 174 - 177°C. iH NMR (CD3COCD3) δ 1.76 (6H, s), 3.12 (3H, s), 7.58 (IH, t), 7.67 (IH, d), 7.76 (2H, d), 7.85 (IH, t), 8.03 (2H, d), 8.16 (IH, d), 8.22 (IH, s). EXAMPLE 162 (5R)-3-(5-Fluoro-2-pyridyloxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl)- phenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from (2R)-2-chloroacetoxy-2-methyl-l-(4- methylsulfonyl)phenylbutan-l-one (prepared similarly to the compound of Example 5, Step 1 but using the 2-(R) compound of Example 117, Step 3) and 5-fluoro-2-hydroxy-pyridine. M.S.: (Cl, CH4) m/z 392 (M+H)+ iH NMR (CD3COCD3) δ 0.95 (3H, t), 1.76 (3H, s), 2.12 (2H, m), 3.15 (3H, s), 7.18 (IH, m), 7.73 (IH, m), 7.91 (2H, d), 8.02 - 8.07 (3H, m). EXAMPLE 163 (5R)-3-(4-Fluorophenoxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl) phenyl-5H-furan-2-one Following the procedure described in Example 1, Step 4, the title compound was prepared using (2R)-2-hydroxy-2-methyl-l-(4- methylsulfonyl)phenylbutan-l-one (Example 117, Step 3) and 4- fluorophenoxy acetic acid. M.P.: 96.8 - 97.4 °C. lH NMR (CD3COCD3) δ 0.92 (3H, t), 1.77 (3H, s), 2.11 (2H, q), 3.14 (3H, s), 7.08 - 7.11 (4H, m), 7.9 (2H, d), 8.02 (2H, d). EXAMPLE 164 (5R)-3-(5-Fluoro-2-pyridyloxy)-5-methyl-4-(4-methylsulfonyl) phenyl-5- (2.2.2-trifluoroethyl)-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from (2R)-2-chloroacetoxy-2-methyl-l-(4- methylsulfonyl)phenyl-4,4,4-trifluorobutan-l-one (Example 130, Step 3) and 5-fluoro-2-hydroxypyridine. iH NMR (CD3COCD3) δ 1.94 (3H, s), 3.15 (3H, s), 3.24 (2H, q), 7.20 (IH, m), 7.75 (IH, m), 7.98 - 8.07 (5H, m). EXAMPLE 165 3-(l-Isoquinolinyloxy)-5,5-dimethyl-4-(methylsulfonyl)phenyl-5H-furan- 2-one Following the procedure described for Example 25, the title compound was prepared using 1-hydroxyisoquinoline. M.P.: 193.5 - 194.5 iH NMR (CD3COCD3) δ 1.75 (6H, s), 3.12 (3H, s), 6.57 (IH, d), 7.27 (IH, d), 7.50 - 7.76 (5H, m), 8.02 (2H, d), 8.24 (IH, d). EXAMPLE 166 (5R)-3-(4-fluorophenoxy)-5-methyl-4-(4-methylsulfonyl)ρhenyl-5-(2,2,2- trifluoroethyl)-5H-furan-2-one Following the procedure described in Example 1, Step 4, the title compound was prepared using 2-(R)-hydroxy-2-methyl-l-(4- (methylsulfonyl)phenyl)-4,4,4-trifluoro-l -butanone (Example 130, Step 2) and 4-fluoroρhenoxy acetic acid. M.P.: 104.7 - 107.0°C H NMR (CD3COCD3) δ 1.94 (3H, s), 3.15 (3H, s), 3.27 (2H, m), 7.07 - 7.13 (4H, m), 7.98 - 8.04 (4H, m), M.S.: (Cl, CH4) m/z 463 (M+H)+ EXAMPLE 167 3-(3-Fluoro-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl) phenyl-5H- furan-2-one Following the procedure described for Example 5, the title compound was prepared using 3-fluoro-2-hydroxypyridine M.P. : 156 - 157°C iH NMR (CD3COCD3) δ 1.78 (6H, s), 3.14 (3H, s), 7.23 (IH, m), 7.72 (IH, m), 7.91 (2H, d), 7.96 (IH, d), 8.03 (2H, d). EXAMPLE 168 (5R)-3-(3,4-difluorophenoxy)-5-methyl-4-(4-methylsulfonyl) phenyl-5- (2.2.2-trifluoroethyl)-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from (2R)-2-chloroacetoxy-2-methyl-l-(4- methylsulfonyl)phenyl-4,4,4-trifluorobutan-l-one (Example 130, Step 3) and 3,4-difluorophenol. EXAMPLE 169 (5R)-3-(5-chloro-2-pyridyloxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl) phenyl-5H-furan-2-one To a solution of 2-(R)-hydroxy-2-methyl-l-(4- (methylsulfonyl)phenyl)-l -butanone (800 mg, 30 mmol), Example 117, Step 3, in 24 mL of acetonitrile was added chloroacetic acid (383 mg), CMC (1.7 g) and DMAP (20 mg). The mixture was then stirred at r.t. for 4 hours. Then 5-chloro-2-hydroxypyridine (602 mg) and DBU (1.85 mL) were added and the mixture was stirred for 18 hours. Water was then added to the mixture which was extracted with CH2CI2, then washed with IN Hcl, brine, dried over MgS04, filtered and the solvent evaporated under vacuum purification by flash chromatography on silica gel 40% EtOAc/Hexane afforded the title compound. M.P.: 191°C iH NMR (CD3COCD3) δ 0.95 (3H, t), 1.76 (3H, s), 2.11 (2H, m), 3.15 (3H, s), 7.18 (IH, d), 7.89 - 7.93 (3H, m), 8.03 (2H, d), 8.16 (IH, d). EXAMPLE 170 3-(3,4-difluorophenoxy)-5-methyl-5-trifluoromethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Step 1: 2-Trifluoromethyl-2-trimethylsilyloxypropionitrile A mixture of 1,1,1 -trifluoroacetone (8.9 mL, 0.1 mmol), trimethylsilylcyanide (13.3 mL, 0.1 mmol) and zinc iodide (5 mg) was stiπed for 18 hours, to afford the title compound. Step 2: 2-Hydroxy- 1 -(4-methylthio)phenyl-2-trifluromethyl propanone To a solution of 4-bromothioanisole (19 g, 94 mmol) in THF (200 mL) at -78°C was added 1.33 M n-Butyl lithium (71 mL, 94 mmol). The mixture was stirred for 1 hr at -78°C then lOg (47 mmol) of the compound from Step 1 was added and the mixture was left to warm to r.t. The reaction mixture was quenched with 25% NH40Ac extracted with EtOAc, washed with brine, dried over MgS04, filtered and the solvent evaporated to afford 9.7 g of the title compound. Step 3: 2-Hydroxy- 1 -(4-methylsulfonyl)phenyl-2-trifluoromethyl propanone Following the procedure described in Example 117, Step 3, and using the compound from the previous step, the title compound was obtained. Step 4: 3-(3,4-difluorophenoxy)-5-methyl-5-trifluoromethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described in Example 1 , Step 4, and using the compound obtained in the previous step, the title compound was obtained. M.P.: 154.1°C iH NMR (CD3COCD3) δ 2.06 (3H, s), 3.15 (3H, s), 6.98 (IH, s)7.7 (IH, m), 7.26 (IH, dd), 7.77 (2H, d), 8.02 (2H, d). EXAMPLE 171 3-(3,4-Difluorophenoxy)-5-methyl-4-(4-(methylsulfonyl)phenyl)-5- propyl-5H-furan-2-one Step 1: 2-Methyl- 1 -(4-methylthiophenyl)-pentan- 1 -one Following the procedure described for Example 1, Step 1, the title compound was prepared from 2-methyvaleryl chloride and thioanisole. Step 2: 2-Hvdroxy-2-methyl- 1 -(4-methylthiophenyl)-pentan- 1 -one Following the procedure described for Example 1 , Step 2, the title compound was prepared from the product obtained in Step 1. Step 3: (3,4-Difluorophenoxy)-acetic acid 1 -methyl- 1 -(4- methythiobenzoylbutyDester A solution of 3,4-difluorophenoxyacetic acid (0.38 g), the product from Step 2 (0.24 g), CMC (1.0 g), and DMAP (100 mg) in 5 mL of CH2CI2 was stirred at r.t. for 15h. The reaction mixture was then treated with saturated solution of NaHCθ3 (20 mL) and extracted with 1 :1 EtOAc/hexane (100 mL). The organic layer was dried over MgSθ4 filtered and concentrated to give the crude product which was used for next step without further purification. Step 4: (3,4-Difluorophenoxy)-acetic acid 1 -methyl- 1 -(4- methvsulfonylbenzoylbutyl ester A solution of the crude product from Step 3 in 50 mL of 10: 1 CH2Cl2/MeOH (v/v) was treated with MMPP (1.0 g). The mixture was stiπed at r.t. for 30 min. and then diluted with saturated NaHC03 solution (50 mL). The mixture was extracted with EtOAc (50 mL) and the organic layer was dried over MgSθ4, filtered and concentrated to give the title compound as a white solid. Step 5: 3-(3,4-Difluorophenoxy)-5-methy-4-(4-(methylsulfonyl) phenyl)-5-propyl-5H-furan-2-one A solution of the product from Step 4, CF3Cθ2iPr (0.5 mL) and DBU (0.2 mL) in CH3CN (30 mL) was heated to reflux for 30 min. The mixture was then cooled to r.t. treated with ACOH (1 mL) and concentrated. The residue was dissolved in 2:1 EtOAc/hexane (20 mL) and filtered through a pad of silica gel. The filtrate was concentrated and the residue was stirred at 5°C 5:1 hexane/EtOAc (10 mL) for 15 h. The title compound was isolated by filtration as a white solid (380 mg). iH NMR (acetone-d6) δ 8.04 (2H, d), 7.93 (2H, d), 7.28 (IH, m), 7.12 (IH, m), 6.92 (IH, m)(, 3.15 (3H, s), 2.06 (2H, m), 1.79 (3H, s), 1.80 - 1.96 (2H, m), 0.92 (3H, t). EXAMPLE 174 3-Cyclobutyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl-5H-furan-2- one Following the procedure described for Example 14, the title compound was obtained using cyclobutyloxyacetic acid. M.P. 111 - 112°C; Ms (Cl, CH4) m z 337 (M+H)+; anal, calcd for C17H20O5S: C, 60.70; H, 5.99; S, 9.53; found: C, 60.39; H, 6.05; S, 9.60. EXAMPLE 175 3-(l-Indanyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H-furan-2- ΩB≤ Following the procedure described for Example 14, the title compound was obtained using 1-indanyloxyacetic acid. M.p. 128 - 129°C; MS (Cl, CH4) m/z 398 (M+H)+; and anal, calcd. for C22H22O5S: C, 66.31 ; H, 5.56; S, 8.05; found: C, 66.27; H, 5.47; 5, 8.34. EXAMPLE 176 3-(2-Indanyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2- one Following the procedure described for Example 14, the title compound was obtained using 2-indanyloxyacetic acid. M.p. 142-143°C; Ms (Cl, CH4) m z 3.99 (M+H)+; anal, calcd. for C22H22O5S: C, 66.31; H, 5.56; found: C, 66.50; H, 5.64. EXAMPLE 177 3-Cyclopentyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)5H-furan-2- one Following the procedure described for Example 109 the title compound was prepared from cyclopentyl bromide. M.P.: 121 - 122°C. iH NMR (CD3COCD3) δ 1.55 - 1.85 (8H, m), 1.65 (6H, s), 3.15 (3H, s), 5.43 (IH, m), 7.98 - 8.07 (4H, m). EXAMPLE 178 3-(3,3-Dimethylcyclopentyloxy)-5,5-dimethyl-4-(4-methylsulfonyl- phenyl)-5H-furan-2-one Step 1: 3.3-Dimethylcy clopentanol To a solution of 4,4-Dimethyl-2-cyclopenten-l-one (1.65 g, 15 mmol) in EtOAc (50 mL) was added palladium on activated carbon (270 mg). The resulting suspension was vigorously stirred under an hydrogen atmosphere for 22 hours. The reaction was diluted with CH2CI2 (150 mL) and filtered on a pad of silica gel washed with EtOAc. The solvents were removed by distillation under atmospheric pressure using a 15 cm Vigreux column. The distillation residue was dissolved in MeOH (50 mL) cooled to 0°C and sodium borohydride (304 mg, 8 mmol) was added and te reaction mixture was stiπed at r.t. for 24 h. The reaction was diluted with NH40Ac eq. 25% w/r and extract with EtOAc. The organic layer was separated, dried over MgS04 and concentrated. Purification by silica gel chromatography (50% Et20/pentane) provided 1.14 g of the title compound as a colorless liquid. H NMR (CD3COCD3) δ 0.94 (3H, s)1.07 (3H, s). 1.25 - 1.4 (2H, m), 1.55 - 1.63 (2H, m), 1.67 (IH, dd), 1.85 - 1.95 (IH, m), 3.42 (IH, d), 4.27 (IH, m). Step 2: 3-Iodo- 1.1 -dimethylcvclopentane To a 0°C solution of 3,3-Dimethylcyclopentanol (Step 1) (1.14 g, 10 mmol) and triethylamine (2.0 mL, 14.3 mmol) in dichloromethane was added dropwise methanesulfonyl chloride (1.0 mL, 12.9 mmol). The reaction was allowed to proceed for 30 min. at 0°C, then it was diluted with water and extracted twice with CH2CI2. The combined organic layers were dried over MgS04 and concentrated in vacuo. The resulting residue was dissolved in acetone (50 mL), cooled to 0°C and lithium iodide (6.68, 50 mmol) was added). The resulting suspension was stiπed at r.t. for 20 hours. Most of the solvent was removed in vacuo, the residue was taken in EtOAc and washed twice with water. The organic layer was dried over MgSθ4 and concentrated. This crude product was purified by flash chromatography eluted with 40 Et2θ/pentane to give the title compound as a colorless oil. lH NMR (CD3COCD3) δ θ.98 (3H, s), 1.14 (3H, s), 1.38 - 1.46 (IH, m), 1.57 - 1.64 (IH, m), 1.93 (IH, dd), 2.06 - 2.16 (2H, m), 2.29 (IH, m), 4.38 (IH, quintet) Step 3: Following the procedure described for Example 109, the title compound was prepared from 3-iodo-l,l-dimethylcyclopentanol (Step 2). M.P.: 99 - 100°C. iH NMR (CD3COCD3) δ 0.93 (3H, s), 0.99 (3H, s), 1.32 - 1.40 (IH, m), 1.48 - 1.62 (2H, m), 1.65 (6H, s), 1.74 (IH, dd), 1.78 - 1.88 (IH, m), 1.93 - 2.02 (IH, m), 3.17 (3H, s), 5.90 (IH, m), 8.02 (4H, dm). EXAMPLE 179 3-Isopropoxy-5-methyl-4-(4-methylsulfonylphenyl)-5-propyl-5H-furan- 2-one Following the procedure described for Example 171, the title compound was prepared from isopropoxyphenyl acetic acid. M.P.: 95 - 96°C. iH NMR (CD3COCD3) δ 0.88 (3H, t), 1.12 - 1.32 (2H, m), 1.28 (6H, 2d), 1.67 (3H, s), 2.00 (2H, m), 3.17 (3H, s), 5.22 (IH, heptet), 8.04 (4H, s). EXAMPLE 180 3-(2-Methoxy-5-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl- 5H-furan-2-one Step 1: 5-Hydroxy-2-methoxypyridine To 6M aqueous HCl(20mL) at 00C was added 5-amino-2- methoxypyridine(3.1g, 25mmol), stiπed for lOmin and a solution of 4M aqueous NaN02(7mL, 28mmol) was added dropwise over a period of lOmin. After further stirring for 30min, 60%HPF6(2mL) was added and precipitate formed immediately. The mixture was stiπed for 15 min, H2O(50mL) was added. The precipitate was collected, washed with H20(3x) and dried under vacuum to give the coπesponding diazonium salt as brown powders(6.5g, 92%). The above diazonium salt in acetic anhydride(25mL) was heated at 100- HOOC for lh. Solvent was evaporated in vacuo. The residue was diluted with H20 and extracted with Et20. Solid residue was filtered and the ethereal layer was separated, washed with saturated aq. NaHC03 brine, dried(anhydrous MgS04) and concentrated to provide the 5-acetoxy-2-methoxypyridine as a brown oil(600mg). iH NMR(CD3COCD3) δ 2.26(3H, s), 3.85(3H, s), 6.78(1H, d), 7.48(1H, dd), 7.92(lH, d). To a solution of the 5-acetoxy-2-methoxypyridine(600mg, 3.59mmol) in MeOH(lOmL) was added IM aq. NaOH(10mL, lOmmol). After stirring at r.t. for 30min, volatile solvent was removed in vacuo, acidified with HOAc and extracted with CHC13(3x). The combined CHC13 extracts were washed with H20, dried(anhydrous MgS04) and evaporated to give the title compoud as a brown oil(240mg, solidified on standing). iH NMR(CD3COCD3) δ 3.78(3H, s), 6.60(1 H, d), 7.20(1 H, dd), 7.70(1H, d), 8.20(1H, br s). Step 2: 3-(2-Methoxy-5-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonvPphenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 5-hydroxy-2-methoxypyridine. iH NMR(CD3COCD3) δ 1.75(6H, s), 3.16(3H, s), 3.85(3H, s), 6.66(1H, d), 7.47(1H, dd), 7.90(2H, d), 7.95(1H, d), 8.04(2H, d). EX AMPLE 181 3-(5-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Step 1: 2-Hvdroxy-5-methylpyridine Following the procedure described for Example 48, step 1, the tide compound was prepared from 2-amino-5-picoline. iH NMR(CD3COCD3) δ 2.05(3H, s), 6.36(1H, d), 7.24(1H, d), 7.35(1H, dd). Step 2: 3-(5-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonvPphenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 2-hydroxy-5-methylpyridine. iH NMR(CD3COCD3) δ 1.75(6H, s), 2.28, 3.16(3H, s), 6.98(1H, d), 7.68(1H, dd), 7.90(2H, d), 7.96(1H, d), 8.04(2H, d). EXAMPLE 184 (5RS)-3-(3,4-Difluorophenoxy)-5-methyl-4-(4-me ylsulfonyl)phenyl-5- (2.2.2-trifluoroethvP-5H-furan-2-one Step 1: 2(RS)-2-Methyl-l-(4-(methylthio)phenyl)-4,4,4-trifluoro-l- butanone Following the procedure described for example 1 , step 1 , the title compound was prepared from 2(RS)-2-methyl-4,4,4-trifluoro-butryl chloride(GB 2238790- A) and thioanisole. iH NMR(CD3COCD3) δ 1.22(3H, d), 2.30(1H, m), 2.52(3H, s), 2.82(1H, m), 3.88(1H, m), 7.35(2H, d), 7.92(2H, d). Step 2: 2-(RS)-2-Hydroxy-2-methyl- 1 -(4-(methylthio)phenyl)-4,4,4- trifluoro- 1 -butanone To 2-(RS)-2-hydroxy-2-methyl- 1 -(4-(methylthio)phenyl)- 4,4,4-trifluoro-l-butanone(12g, 45.8mmol) and triethyl phosphite(16mL) in DMF(250mL) at -10°C was added IM t-BuOK(46mL, 46mmol) in t- BuOH and air was bubbled through the mixture for 3h. After quenching with 2.5M aq. HOAc(20mL), the mixture was diluted with H2θ, extracted with Et2θ. The etheral extract was washed with H2θ(2x), 0.5M aq. NaOH, dried(anhydrous MgS04) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc(4: 1) gave the title compound as a yellow oil(6.0g, -90% pure). H NMR(CD3COCD3) δ 1.62(3H, s), 2.54(3H, s), 2.70-3.20(2H, m), 7.32(2H, d), 8.15(2H, d). Step 3: 2-(RS)-2-Hydroxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)- 4.4.4-trifluoro- 1 -butanone To a solution of 2-(RS)-2-hydroxy-2-methyl-l-(4- (methylthio)phenyl)-4,4,4-trifluoro-l-butanone(6.0g, 21.6mmol) in CH3Cl(200mL) was added mCPBA(12g, Aldrich 27,303-1, 57-86%) at 0°C. The mixture was slowly warmed to r.t. over a period of lh, washed with IM aq. NaOH(2x), brine, dried(anhydrous MgSO^) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc(2:l) provided the title compound(4.0g, 60%). iH NMR(CD3C0CD3) δ 1.66(3H, s), 2.70-3.20(2H, m), 3.18(3H, s),5.35(lH, s), 8.04(2H, d), 8.30(2H, d). Step 4: (5RS)-3-(3,4-Difluorophenoxy)-5-methyl-4-(4- methylsulfonyl)phenyl-5-(2,2,2-trifluoroethyl)-5H-furan-2- one Following the procedure described for example 1, step 4, the title compound was prepared from 3, 4-difluorophenoxy acetic acid and 2- (RS)-2-hydroxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)-4,4,4-trifluoro- 1 butanone. NMR of the title compound is the same as Example 168. EXAMPLE 185 3-(3-Chloro-4-methoxyphenoxy)-5,5-dimethyl-4-(4-methylsulfonyl)- phenyl-5H-furan-2-one Step 1: 3-Chloro-4-methoxyphenoxyacetic acid To a mixture of hydroquinone(24g, 0.22mol) and ethyl bromoacetate(24mL, 0.22mol) in DMF(300mL) was added 10M aq. NaOH(22mL, 0.22mol). The mixture was stiπed at 0°C for lh, diluted with H20, acidified with 6M aq. HCl and extracted with EtOAc. The EtOAc extract was dried(anhydrous MgSθ4) and concentrated in vacuo. The residue was swished with Et20 to give ethyl 4-hydroxyphenoxy- acetate(5.8g) as a white powder. Ethyl 4-hydroxyphenoxyacetate(1.5g, 7.6mmol) was reacted with Sθ2Cl2(l * 5mL) to give ethyl 3-chloro-4-hydroxyphenoxyacetate (700mg, -80% pure) as a white powder. To a solution of ethyl 3-chloro- 4-hydroxyphenoxyacetate(700mg, 3.0mmol) and MeI(0.280mL, 4.5mmol) in DMF(5mL) at 0°C was added 10M aq.NaOH(0.320mL, 3.2mmol). The mixture was stirred at r.t. for 12h, then diluted with H2O and extracted with EtOAc to give ethyl 3-chloro-4-methoxyphenoxy- acetate (700mg). The above ethyl 3-chloro-4-methoxyphenoxyacetate (700mg) was hydrolysed with IM aq. NaOH in THF-MeOH (30 mL, 2:1) to provide the title compound as a white powder. iH NMR(CD3COCD3) δ 3.84(3H, s), 4.70(2H, s), 6.85-7.10(3H, m). Step 2: 3-(3-Chloro-4-methoxyphenoxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described for example 1 , step 4, the title compound was prepared from 3 -chloro-4-methoxyphenoxy acetic acid and 2-hydroxy-2-methyl-l-(4-methylsulfonyl)phenyl)propan-l- one(example 1, step 3). iH NMR(CD3COCD3) δ 1.75(6H, s), 3.14(3H, s), 3.84(3H, s), 6.95- 7.20(3H, m), 7.86(2H, d), 8.00(2H, d). EXAMPLE 186 (5R)-3-(3-Chloro-4-methoxyphenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described for Example 1, step 4, the title compound was prepared from 3-chloro-4-methoxyphenoxyacetic acid and (2R)-2-hydroxy-2-methyl- 1 -(4-methylsulfonyl)phenyl-butan- 1 - one (Example 117, Step 3). iH NMR(CD3COCD3) δ 0.94(3H, t), 1.76(3H, s), 2.10(2H, q), 3.15(3H, s), 3.85(3H, s), 6.95-7.20(3H, m), 7.90(2H, d), 8.00(2H, d). EXAMPLE 188 (5R)-3-(4-Chlorophenoxy)-5-(2, 2, 2-trifluoroethyl)-5-methyl-4-(4- methylsulfonvPphenyl-5H-furan-2-one Following the procedure described for Example 1, Step 4, the title compound was prepared from 4-chlorophenoxyacetic acid and (2R)-2-hydroxy -2-methyl- 1 -(4-methylsulfonyl)phenyl-4,4,4-trifluoro- butan-1-one (Example 130, Step 2). iH NMR(CD3COCD3) δ 1.95 (3H, s), 3.15 (3H, s), 3.25 (2H, m), 7.12 (2H, d), 7.36 (2H, d), 8.02 (4H, m). Analysis calculated for C20HI6CIF3O5S: C, 52.13; H, 3.50. Found: C, 52.27; H, 3.63. EX AMPLE 189 (5R)-3-(4-Bromophenoxy)-5-(2, 2, 2-trifluoroethyl)-5-methyl-4-(4- methylsulfonyPphenyl-5H-furan-2-one Following the procedure described for Example 1 , Step 4, the title compound was prepared from 4-bromophenoxyacetic acid and (2R)-2-hydroxy -2-methyl- 1 -(4-methylsulfonyl)phenyl-4,4,4-trifluoro- butan-1-one (Example 130, Step 2). iH NMR(CD3COCD3) δ 1.94 (3H, s), 3.15 (3H, s), 3.25 (2H, m), 7.07 (2H, d), 7.50 (2H, d), 8.02 (4H, m). EXAMPLE 195 5-Cyclopropylmethyl-3-(3,4-difluorophenoxy)-5-methyl--(4- methylsulfonvPphenyl-5H-furan-2-one Step 1: 2-Cyclopropylmethyl-2-methyl- 1 -(4-thiomethyl)phenyl- propan-1-one To a cold (-78 °C) solution of l-(4-thiomethyl)phenyl- propan-1-one (900 mg, 5 mmol) in dry THF (15 mL) was added a solution of KHMDS (5.5 mmol, 11 mL). The mixture was warmed to r.t. for 5 min and then cooled to 0 °C. Bromomethylcyclopropane (810 mg, 6 mmol) was added. The mixture was warmed to r.t. and stiπed for 20 h. Aqueous NH4CI solution was added. The mixture was extracted with EtOAc and the concentrated crude extract was purified by chromatography on silica gel (eluted with 20% EtOAc/hexane) to give 435 mg (37%) of the title compound. Step 2: 2-Cyclopropylmethyl-2-methyl-l-(4-methylsulfonyl)phenyl- propan-1-one To a solution of the product of step 1 (435 mg, 1.87 mmol) in a mixture of CH2CICH2CI (10 mL) and methanol (10 mL) was added MMPP (2.3 g 3.7 mmol) in 2 portions . The mixture was stiπed at r.t. for 6 h. H2θ was added and the product was extracted with EtOAc. The extracts were washed with H2O and brine, dried and concentrated to an oil. The crude oil was purified by chromatography on silica gel (eluted with 30% EtOAc/hexane) to give 363 mg (83%) of the title compound. Step 3: -Cyclopropylmethyl-2-hydroxy-2-methyl- 1 -(4- methylsulfonyPphenyl-propan- 1 -one To a mixture of the product of step 2 (310 mg, 1.16 mmol), CCI4 (268 mg, 1.74 mmol), Aliquat 336® (75 mg, 0.185 mmol) and toluene (293 mg, 3.19 mmol) was added powered NaOH ( 102 mg, 2055 mmol) in portions. Aqueous NH4CI solution was added. The mixture was neutralized with IN HCl and extracted with EtOAc and the concentrated crude extract was purified by chromatography on silica gel (eluted with 30% EtOAc/hexane) to give 124 mg (38%) of the title compound. Step 4: 5-Cyclopropylmethyl-3-(3,4-difluorophenoxy)-5-methyl-4- (4-methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described for Example 117, the tide compound was prepared from the product of step 3 and 3,4- difluorophenoxyacetic acid. iH NMR(CD3COCD3) δ-.Ol (IH, m), 0.19 (IH, m), 0.42 (IH, m), 0.51 (IH, m), 0.71 (IH, m), 1.82 (3H, s), 1.87 (IH, dd), 2.26 (IH, dd), 3.15 (3H, s), 6.95 (IH, m), 7.14 (IH, m), 7.29 (IH, q), 8.05 (4H, q). EXAMPLE 196 (5R)-3-(3-Fluorophenoxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl)phenyl- 5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 3-fluorophenol and (2R)-2-chloroacetoxy- 2-methyl-l-(4-methylsulfonyl)phenyl -butan-1-one, prepared as in Example 162. H NMR(CD3COCD3) δ 0.93 (3H, t), 1.79 (3H, s), 2.13 (2H, q), 3.15 (3H, s), 6.89 (3H, m), 7.46 (IH, q), 7.93 (2H, d), 8.05 (2H, d). EXAMPLE 197 (5R)-3-(4-Ciιloro-3-fluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 4-chloro-3-fluorophenoxyacetic acid and (2R)-2-chloroacetoxy -2-methyl- 1 -(4-methy lsulfonyl)pheny 1 -butan- 1 - one. iH NMR(CD3COCD3) δ 0.94 (3H, t), 1.80 (3H, s), 2.13 (2H, q), 3.15 (3H, s), 6.95 (IH, m), 7.10 (IH, m), 7.48 (IH, t), 7.94 (2H, d), 8.04 (2H, d). EXAMPLE 198 (5R)-3-(3-Phenoxy)-5-ethyl-5-methyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one Following the procedure described for Example 25, the title compound was prepared from phenol and (2R)-2-chloroacetoxy -2- methyl-l-(4-methylsulfonyl)phenylbutan-l-one, prepared as in Example 162. iH NMR(CD3COCD3) δ 0.94 (3H, t), 1.78 (3H, s), 2.15 (2H, q), 3.14 (3H, s), 7.09 (3H, m), 7.33 (2H, m), 7.93 (2H, d), 8.01 (2H, d). Analysis calculated for C20H20O5S: C, 64.50; H, 5.41. Found: C, 63.94; H, 5.48. EX AMPLE 199 (5R)-3-(4-Chloro-3-methylphenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyPphenyl-5H-furan-2-one Following the procedure described for Example 25, the title compound was prepared from 4-chloro-3-methylphenol and (2R)-2- chloroacetoxy -2-methyl- l-(4-methylsulfonyl)phenyl -butan- 1 -one, prepared as in Example 162. H NMR(CD3COCD3) δ 0.93 (3H, t), 1.78 (3H, s), 2.12 (2H, q), 2.30 (3H, s), 3.15 (3H, s), 6.91 (IH, dd), 7.04 (IH, d), 7.30 (IH, d), 7.92 (2H, d), 8.02 (2H, d). Analysis calculated for C21H21CIO5S: C, 59.93; H, 5.03. Found: C, 59.59; H, 5.02. EXAMPLE 200 3-(4-Chloro-3-methylphenoxy)-5-5-dimethyl-4-(4- methylsulfonvPphenyl-5H-furan-2-one Following the procedure described for Example 108, the title compound was prepared from 4-chloro-3-methylphenoxyacetic acid and 2-chloroacetoxy-2-methyl- 1 -(4-(methylsulfonyl)phenyl)propan- 1 -one. iH NMR(CD3COCD3) δ 1.76 (6H, s), 2.79 (3H, s), 3.15 (3H, s), 6.92 (IH, dd), 7.06 (IH, d), 7.28 (IH, d), 7.92 (2H, d), 8.02 (2H, d). Analysis calculated for C21H19CIO5S: C, 59.04; H, 4.71. Found: C, 59.18; H, 4.78. EXAMPLE 201 (5R)-3-(5-bromo-2-pyridyloxy)-4-(4-methylsulfonylphenyl)-5-methyl-5- (2.2.2-trifluoroethyl)-5H-furan-2-one Step 1: (5R)-4-me yl-4-(2,2,2-trifluoroethyl)-5-(4-methylsulfonyl- phenvP-3.6-dioxabicvclor3.1.01hexan-2-one To a 0 °C solution of the chloroacetate(1.16 g, 3 mmol) from step 3, Example 130, in acetonitrile(15 mL) was added DBU(0.491 mL, 3.3 mmol) and the mixture was warmed up to 25 °C. After 2 hours, the mixture was poured on icy IN HCl and ethyl acetate; the organic layer was separated and the aquous further extracted once with ethyl acetate. The combined organic layers were washed with brine, dried with MgS04 and the solvents were removed in vacuo to yield the essentially pure title compound(0.930 g). iH NMR (CD3COCD3) δ 1.60-1.70(3H, 2s), 2.50-3.05(2H, m), 3.13(3H, S ), 4.40-4.30(lH, 2s), 7.95-8.05(4H, 2d). Step 2: (5R)-3-(5-bromo-2-pyridyloxy)-4-(4-methylsulfonylphenyl)- 5-methyl-5-(2.2.2-trifluoroethyl)-5H-furan-2-one To a 0 °C mixture of the epoxide(0.930 g) from step 1 in dimethylformamide(3 mL) and isopropanol(12 mL) was added the potassium salt of 5-bromo-2-hydroxypyridine, prepared from 5-bromo-2- hydroxypyridine and one equivalent of 8N KOH followed by evaporation to dryness with toluene and high vacuum drying, (0.742 g, 3.5 mmol) and the mixture was warmed up slowly to reflux for 16 hrs. It was then cooled to room temperature and poured on icy dilute ammonium chloride and ethyl acetate; the organic layer was separated and the aquous further extracted ounce with ethyl acetate. The combined organic layers were washed with brine, dried with MgS04 and the solvents were removed in vacuo to yield after purification on silica gel(10% acetone/toluene) the title compound (0.380 g). iH NMR (CD3COCD3) δ 1.90(3H,s), 3.15(3H,s), 3.15-3.30(2H,AB), 7.15(lH,d), 7.95-8.10(5H,m), 8.25(lH,d). EXAMPLE 202 (5R)-3-(5-bromo-2-pyridyloxy)-4-(4-methylsulfonylphenyl)-5-ethyl-5- methyl-5H-furan-2-one Step 1: To a 25°C mixture of (2R)-chloroacetic acid 2-methyl- 1 -(4- (methylsulfonyl)phenyl)butan-l-one ester(0.896 g, 2.7 mmol prepared as in Example 162) and 5-bromo-2-hydroxypyridine(0.560 g, 3.2 mmol) in acetonitrile(20 mL) was added DBU( 1.5 mL) and the mixture was warmed up to 70-80°C for 2 hrs. The volatils were then removed in vacuo and the mixture purified on silica gel(10% acetone/toluene) to yield the title compound(0.587 g) iH NMR (CD3COCD3) δ 0.90-1.0(3H,t), 1.75(3H,s), 2.00-2.15(2H,m), 3.15(3H,s) 7.10-7.15(lH,d), 7.85-8.05(4H,2d), 8.20-8.30(lH,d). EXAMPLE 203 3-(5-CWoro-6-memyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one Step 1: 3-(5-Nitro-6-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one A suspension made of the alcohol(2.82 g, 10 mmol) from step 1 Example 109, 3-nitro-6-chloro-2-picoline[C.A.70:114970s](2.06 g, 12 mmol) and ION NaOH(l.lmL) in DMF(35 mL) was warmed up to to 105°C for 8 hrs. It was then cooled to room temperature and poured on icy H2O and ethyl acetate. The pH was adjusted to ca. 8 then the organic layer was separated and the aqueous further extracted ounce with ethyl acetate. The combined organic layers were washed with brine, dried with MgSθ4 and the solvents were removed in vacuo to yield after purification on silica gel(10% acetone/toluene) the title compound (4.180 g)* lH NMR (CD3COCD3) δ 1.75(6H,s), 2.70(3H,s), 3.15(3H,s), 7.15- 7.20(lH,d), 7.85-8.05(4H,2d), 8.45-8.55(lH,d). Step 2: 3-(5-Amino-6-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one A mixture of the compound from the previous step(3.19g, 7.6 mmol), ammonium chloride(0.250 g) and iron powder(3 g) in ethanol(50 mL) and H2θ(20 mL) was warmed up to reflux for 1.5 hrs after what it was filtered quickly, while hot, over celite. To the filtrate was added water(250 mL) and ethyl acetate. The organic layer was separated and the aquous further extracted ounce with ethyl acetate. The combined organic layers were washed with brine, dried with MgS04 and the solvents were removed in vacuo to yield after purification by swish in diethyl ether the title compound (3.0 g). iH NMR (CD3SOCD3) δ 1.75(6H,s), 2.10(3H,s), 3.25(3H,s), 4.75-4.85 (2H,bs), 6.65-6.70(lH,d), 7.00-7.05(1 H,d), 7.80-8.00(4H,2d). Step 3: 3-(5-chloro-6-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonvDphenyl-5H-furan-2-one Sodium nitrite(0.152 g, 2.2 mmol) in H2θ(l mL) was added dropwise to a 0°C suspension of the compound(0.776 g) from the previous step in 6N HC1(4 mL) and the mixture was stirred at 0°C for 0.5 hr. It was then transfered dropwise into a CuCl(0.396 g, 4 mmol) solution in 12N HC1(3 mL). The reaction mixture was warmed up to 80°C for ca. 10 min. then cooled to 25°C. The mixture was poured on icy H2O and the pH adjusted to ca. 4-5 then ethyl acetate was added. The organic layer was separated and the aquous further extracted ounce with ethyl acetate. The combined organic layers were washed with brine, dried with MgS04 and the solvents were removed in vacuo to yield after purification by swish in diethyl ether the title compound (0.310 g). iH NMR (CD3COCD3) δ 1.75(6H,s), 2.40(3H,s), 3.15(3H,s),6.90- 7.00(lH,d), 7.75-7.85(lH,d), 7.85-8.05(4H,2d). EXAMPLE 207 3-(l-Cvclopropylethoxy)-4-(4-methylsulfonyl)phenvP-5H-furan-2-one Step 1: 3-Diazo-2.4-(3H. 5H)-furandione To tetronic acid (5.00 g, 49.9 mmol) in CH2C12 (250 mL) at 0°C were added Et3N (8.3 mL, 59.6 mmol) and tosyl azide (7.37 g, 37.4 mmol). After a period of 2 h at r.t., the reaction mixture was partitioned between NH40Ac (25%) and CH2C12. The organic phase was dried over Na2S04, filtered and evaporated under reduced pressure. The resulting mixture was purified by flash chromatography (20% to 35% EtOAc in Hexane) to provide 1.4 g of the title compound as a white solid. Step 2: 3-( 1 -c vclopropylethox v)-4-hvdroxy-2(5H)-furanone To the mixture of 3-diazo-2,4-(3H, 5H)-furandione (300 mg, 2.38 mmol; Example 207, Step 1) and α-methylcyclopropanemethanol (2.0 mL) was added rhodium acetate (30 mg). The mixture was heated at 130°C for a period of 18 h. The excess of alcohol was evaporated under reduced pressure and the resulting crude mixture was purified by flash chromatography (10% to 20% MeOH in CH2C12) to provide 50 mg of the title compound. Step 3: 3-( 1 -cyclopropylethoxy )-4-(4-methylthio)phenyl)-5H-furan- 2-one To a mixture of 3-(l-cyclopropylethoxy)-4-hydroxy-2- (5H)furanone (50 mg, 0.27 mmol; Example 207, Step 2) and diisopropylethylamine (0.066 mL, 0.38 mmol) in CH2C12 (2.0 mL) at -20°C was added trifluoromethanesulfonic anhydride (0.060 mL, 0.36 mmol). After a period of 5 min. at -20°C, the reaction mixture was brought to 0°C then to r.t. The reaction mixture was partitioned between NH40Ac (25%) and CH2C12. The organic phase was dried over Na2S04, filtered and evaporated under reduced pressure. The title compound was purified by flash chromatography to provide 30 mg of material. Step 4: 3-( 1 -cyclopropylethoxy)-4-(4-methylsulfonyl)pheny 1)-5H- furan-2-one To a mixture of 3-(l -cyclopropylethoxy )-4-(4- methylthio)phenyl)-5H-furan-2-one (30 mg, 0.10 mmol; Example 207, Step 3) in CH2C12 ((1.0 mL) MeOH (3.0 mL) were added an excess of OXONE® (150 mg). After the TLC showed completion, the reaction mixture was extracted with EtOAc The organic phase was dried over Na2S04 filtered and evaporated under reduced pressure. The title compound was purified by flash chromatography to provide 6 mg of material. iH NMR (CD3COCD3) δ 0.20 - 0.60 (4H,m), 1.10 (lH,m), 1.45 (3H,d), 3.20 (3H,s), 4.50 (lH,m), 5.30 (2H, s), 8.10 (4H, m). EXAMPLE 208 3-(l-Cyclopropylmethoxy)-4-(4-methylsulfonyl)phenvP-5H-furan-2-one The title compound was prepared as described in Example 207. iH NMR (CD3COCD3) δ 0.40 - 0.65 (4H,m), 1.30 (lH,m), 3.20 (3H,s), 4.30 (2H, d), 5.30 (2H, s), 8.05 (4H, m).

Claims: WHAT IS CLAIMED IS: A compound of Formula I or a pharmaceutically acceptable salt thereof wherein: X is selected from the group consisting of (a) CH2, (b) CHOH, (c) CO, (d) O, (e) S, and (f) N(Rl5), with the proviso that when R3 and R^ are other than (1) both hydrogen, (2) both C 1-10 alkyl, or (3) joined together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms, then X is selected from CO, O, S or N(Rl5); Y is selected from the group consisting of (a) C(Rl l)(Rl2), (b) CO, (c) O, and (d) S; Ri is selected from the group consisting of (c) S02NHC(0)CF3, (d) S(0)(NH)NH2, (e) S(0)(NH)NHC(0)CF3, (f) P(0)(CH3)NH2, and ( g) P(0)(CH3)2, elected from the group consisting of (a) Cl-ioalkyl, (b) mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-10alkoxy, (4) Cl-10alkylthio, (5) CN, (6) Ci-6 fluoroalkyl (7) Cl-10 alkyl, (8) N3, (9) -CO2H, (10) -Cθ2-Cl-lθalkyl, (11) -C(R5)(R6)-OH, (12) -C(R5)(R6)-0-Cl-4alkyl, and (13) -Cl-6alkyl-Cθ2-R 5 , (14) benzyloxy, (15) -0-(Cl-6alkyl)-C02R 5 , and (16) -0-(Cl-6alkyl)-NR5R6, (c) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1, 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-10alkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-0H, (10) -C(R5)(R6)-θ-Cl-lθalkyl, and (11) Cl-6fluoroalkyl; (d) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-lθalkoxy, (5) Cl-10alkylthio, (6) CN, (7) CF3, (8) N 3 , (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-0-Cl-iθalkyl, and (11) Cl-6fluoroalkyl; (e) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group. (f) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF 3 , (8) N 3 , (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-θ-Cl-lθalkyl, and (11) Cl-6fluoroalkyl; (g) a mono- or di-substituted bicyclic heteroaryl of 8, 9, or 10 members, containing 2 to 5 heteroatoms chosen independently from O, S or N, and in which each ring contains at least one heteroatom, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-lθalkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF 3 , (8) N 3 , (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-θ-Cl-iθalkyl, and (11) Cl-6fluoroalkyl; R3 is hydrogen, Cl-lO alkyl, CH20R7, CN, CH2CN, Cl-6fluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted or R3 andR^ together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R-5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-ioalkyl, or R5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-6alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, C 1 -6alkyl, C 1 -6alkoxy , C 1 -6alkylthio, CN, or CF3, or two R7 groups taken together with the nitrogen to which they are attached form a saturated monocyclic ring of 5, 6 or 7 atoms, optionally containing an additional O, S or NR-5; each R° * is independently selected from the group consisting of (a) Cl-6alkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-6alkyl, Cl-6alkoxy, Ci-6alkylthio, CN, or CF 3 ; R9 and R 10 are independently selected from the group consisting of: (a) hydrogen, and (b) Cl-7alkyl, or R9 and RlO together with the carbon atom to which they are attached form a carbonyl or thiocarbonyl group; R and R 12 are independently (a) hydrogen, (b) mono- or di-substituted phenyl or mono- or di-substituted benzyl or mono- or di-substituted heteroaryl or mono- or di- substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) fluoro, chloro, bromo and iodo, (3) Cl-6alkyl, (4) Cl-6alkoxy, (5) Ci-6alkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(Rl3)(Rl4)-OH, (10) -C(Rl3)(Rl4)-0-Cl-4alkyl, and (11) Ci-6fluoroalkyl, or (c) Cl-7alkyl, CH20R7, CN, CH2CN, Cl-6fluoroalkyl, Ri 1 and Rl2 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; Rl and R 14 are independently selected from the group consisting of: (a) hydrogen, (b) Cl-7alkyl, or Rl3 and Rl4 together with the carbon to which they are attached form a carbonyl, -C(=S)-, or a saturated monocyclic carbon ring of 3, 4, 5, 6, or 7 atoms. Rl5 is selected from the group consisting of: (a) hydrogen, (b) Cl-ioalkyl, (c) mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-lOalkoxy, (4) Cl-lOalkylthio, (5) CN, (6) Cl-6 fluoroalkyl (7) Ci-io alkyl, (8) N 3 , (9) -Cθ2H, (10) -Cθ2-Cl-lθalkyl, (11) -C(R5)(R6)-0H, (12) -C(R5)(R6)-0-Cl-4alkyl, and (13) -Ci-6alkyl-C02-R 5 ; (14) benzyloxy, (15) -0-(Ci-6alkyl)-C02R 5 , and (16) -0-(Cl-6alkyl)-NR5R6, (d) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1 , 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-lθalkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-θ-Cl-lθalkyl, and (11) Cl-6fluoroalkyl; (e) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-10alkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-OH, (10) -C(R5)(R6)-0-Cl-lθalkyl, and (11) Cl-6fluoroalkyl; (f) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group. (g) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) N3, (9) -C(R5)(R6)-0H, (10) -C(R5)(R6)-0-Cl-4alkyl, and (11) Cl-6fluoroalkyl; nd R 17 are independently selected from the group consisting of (a) hydrogen (b) Cl-ioalkyl, (c) Cl-lθalkanoic acid, (d) C 1 - 1 Qalkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-lθalkyl, Cl-lθalkoxy, Cl-lθalkylthio, C\- lOalkanoic acid, Cl-lOalkylamine, CN, CO2H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-10alkyl, Cl-lθalkoxy, Cl-lθalkylthio, Cl- 1 Oalkanoic acid, Cl-lOalkylamine, CN, CO2H or CF3, or R16 and R17 together with the nitrogen to which they are attached form a saturated monocyclic ring of 5, 6 or 7 atoms, optionally containing an additional O, S or NR5. 2. A compound according to Claim 1 wherein R 9 and R 10 together with carbon atom to which they are attached form a carbonyl. 3. A compound according to Claim 2 wherein X is selected from the group consisting of (a) CH2, and (b) O, Y is selected from the group consisting of (a) CH2, and (b) O, R is selected from the group consisting of (c) S(0)(NH)NH2; R2 is selected from the group consisting of (a) Cl-6alkyl, (b) mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkoxy, (4) Cl-6alkylthio, (5) CN, (6) Cl-4 fluoroalkyl (7) Cl-6 alkyl, (8) -C02H, (9) -Cθ2-Cl-lθalkyl, (10) -C(R5)(R6)-0H, (11) -C(R5)(R6)-0-Cl-4alkyl, and (12) -Ci-6alkyl-Cθ2-R 5 , (13) -0-(Cl-6alkyl)-Cθ2R 5 , and (c) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1 , 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Ci-6alkyl, (4) Cl-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF 3 , (8) -C(R5)(R6)-OH, and (d) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-ioalkyl, (4) Cl-lθalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and (e) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group, (f) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Ci-βalkyl, (4) Cl-6alkoxy, (5) Cl-10alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-θH, and (g) a mono- or di-substituted bicyclic heteroaryl of 8, 9, or 10 members, containing 2 to 5 heteroatoms chosen independently from O, S or N, and in which each ring contains at least one heteroatom, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Ci-ioalkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and R3 is hydrogen, Cl-6 alkyl, CH2θR 7 , CN, CH2CN, Cl-4fluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Ci-6alkyl, or R-5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-4alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, C l -4alkyl, C l -4alkoxy, C 1 -4alkylthio, CN, or CF3 each R is independently selected from the group consisting of (a) Cl-4alkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, C l -4alkyl, C l -4alkoxy , C l -4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3; R9 and R O together with the carbon to which they are connected form a carbonyl; Rl6 and Rl7 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl -oalkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, CO2H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Ci-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, CO2H or CF3. 4. A compound according to Claim 3 wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, (b) S(0)2NR16R17, and (c) S(0)(NH)NH2; R2 is selected from the group consisting of mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-4alkoxy, (4) Cl-4alkylthio, (5) CN, (6) Cl-3 fluoroalkyl (7) Cl-4 alkyl, (8) -Cθ2H, (9) -Cθ2-Cl-lθalkyl, (10) -C(R5)(R6)-OH, R3 is hydrogen, C 1 -6 alkyl, CH20R7, CN, CH2CN, C 1 -4fluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-4alkyl, (4) Cl-4alkoxy, (5) Ci-4alkylthio, (6) CN, (7) CF 3 , (8) -C(R5)(R6)-0H, and R4 IS (f) -OCOR7, (g) -SCOR7, (h) -OCO2R 8 , and (i) -SCO2R 8 , or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R-5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-6alkyl, or R-5 and R^ together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-4alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3 each R8 is independently selected from the group consisting of (a) Cl-4alkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3; R9 and R O together with the carbon to which they are connected form a carbonyl; Rl6 and R 17 re independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl-6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Ci-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, COOH or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl-6alkanoic acid, Cl- 6alkylamine, CN, COOH or CF3. 5. A compound according to Claim 4 wherein X is O; Y is O; Ri is selected from the group consisting of R2 is selected from the group consisting of mono- or di- substituted phenyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-4alkoxy, (4) Cl-4alkylthio, (5) CN, (6) Cl-3 fluoroalkyl (7) Cl-4 alkyl, (8) -CO2H, (9) -Cθ2-Cl-lθalkyl, R3 is hydrogen, Cl-6 alkyl, CH20R 7 , CN, CH2CN, Cl-4fluoroalkyl, F, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-3alkyl, (4) Cl-3alkoxy, R4 IS R9 and RlO together with the carbon to which they are connected form a carbonyl. 6. A compound according to Claim 5 wherein X is O; Y is O; Ri is selected from the group consisting of R2 is selected from the group consisting of mono- or di- substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (5) CN, (6) CF3, and (7) Cl-4 alkyl, R3 is hydrogen or C 1-3 alkyl; R4 is hydrogen or C 1-3 alkyl; R9 and RlO together with the carbon to which they are connected form a carbonyl. 7. A compound according to Claim 6 wherein X is O; Y is O; Ri is selected from the group consisting of R2 is selected from the group consisting of mono- or di- substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (5) CN, (6) CF3, and (7) Cl-4 alkyl, R3 is methyl or ethyl; R4 is methyl or ethyl; and R9 and RlO together with the carbon to which they are connected form a carbonyl. 8. A compound according to Claim 3 wherein X is selected from the group consisting of (a) CH2, and (b) O, Y is selected from the group consisting of (a) CH2, and (b) O, Ri is selected from the group consisting of (c) S(0)(NH)NH2; R2 is selected from the group consisting of (a) mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1 , 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Cl-6alkoxy, (5) Ci-6alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and (b) a mono- or di- substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Ci-6alkoxy, (5) Cl-lθalkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and (c) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group. (d) a mono- or di- substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Cl-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-OH, and (e) a mono- or di-substituted bicyclic heteroaryl of 8, 9, or 10 members, containing 2, 3, 4 or 5 heteroatoms chosen independently from O, S or N, and in which each ring contains at least one heteroatom, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-6alkyl, (4) Cl-6alkoxy, (5) Cl-6alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-0H, and R3 is hydrogen, Cl-6 alkyl, CH20R7, CN, CH2CN, Cl-3fluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-4alkyl, (4) Cl-4alkoxy, (5) Cl-4alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-0H, and R4 IS or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R5 and R^ are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-4alkyl, or R5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-4alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, C 1 -4alkyl, C l -4alkoxy , C l -4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3 each R8 is independently selected from the group consisting of (a) Cl-4alkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Ci-4alkoxy, Cl-4alkylthio, CN, or CF3; R 0 - and RlO together with the carbon to which they are connected form a carbonyl; Rl6 and R 17 are independently selected from the group consisting of (a) hydrogen (b) Ci-6alkyl, (c) Cl -6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, C02H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Ci-6alkylthio, Cl- όalkanoic acid, Cl-6alkylamine, CN, CO2H or CF3. 9. A compound according to Claim 8 wherein X is selected from the group consisting of (a) CH2, and (b) O, Y is selected from the group consisting of (a) CH2, and (b) O, Ri is selected from the group consisting of R2 is selected from the group consisting of mono- , di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1 , 2, or 3 or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-4alkyl, or R5 and R > together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-4alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3 each R8 is independently selected from the group consisting of (a) Cl-4alkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, C 1 -4alkyl, C 1 -4alkoxy, C 1 -4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3; R9 and RlO together with the carbon to which they are connected form a carbonyl; Rl6 and Rl7 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl-6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, C l-6alkylamine, CN, C02H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, CO2H or CF3. 10. A compound according to Claim 9 wherein mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of (1) furanyl, (2) diazinyl, (3) imidazolyl, (4) isooxazolyl, (5) isothiazolyl, (6) oxadiazolyl, (7) oxazolyl, (8) pyrazolyl, (9) pyridyl, (10) pyπolyl, (11) tetrazinyl (12) tetrazolyl. (13) thiadiazolyl, (14) thiazolyl, (15) thienyl, (16) triazinyl, or (17) triazolyl, and the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-4alkyl, (4) Cl-4alkoxy, (5) Cl-4alkylthio, (6) CN, and (7) CF 3 . 11. A compound according to Claim 10 wherein R2 is a mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of (I) furanyl, (2) diazinyl, (3) imidazolyl, (4) isooxazolyl, (5) isothiazolyl, (6) oxadiazolyl, (7) oxazolyl, (8) pyrazolyl, (9) pyridyl, (10) pyπolyl, (I I) thiazolyl, (12) thienyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-3alkyl, (4) Cl-3alkoxy, (7) CF3. 12. A compound according to Claim 11 wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, and (b) SO2NH2; R2 is a mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of (1) furanyl, (2) diazinyl, (3) imidazolyl, (4) oxadiazolyl, (5) pyrazolyl, (6) pyridyl, (7) pyπolyl, (8) thiazolyl, (9) thienyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) methyl, (4) methoxy, and (5) CF 3 ; R3 is hydrogen, Cl-6 alkyl, CH20R 7 , CN, CH2CN, Cl-4fluoroalkyl, F, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, 13. A compound according to Claim 12 wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, and (b) SO2NH2; R2 is a mono- or di-substituted heteroaryl wherein heteroaryl is selected from the group consisting of (1) furanyl, (2) diazinyl, (3) imidazolyl, (4) oxadiazolyl, (5) pyrazolyl, (6) pyridyl, (7) thiazolyl, (8) thienyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) Br, Cl or F, (3) methyl, (4) methoxy, and (5) CF ; R3 is hydrogen or C 1-3 alkyl; R4 is hydrogen or C 1-3 alkyl; R9 and RlO together with the carbon to which they are connected form a carbonyl. 14. A compound according to Claim 13 wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, and (b) SO2NH2; R2 is a mono- or di-substituted pyridyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) Br, Cl or F, (3) methyl, (4) methoxy, and (5) CF3; R3 is hydrogen or C 1-3 alkyl; R4 is hydrogen or C 1-3 alkyl; R9 and R O together with the carbon to which they are connected form a carbonyl. 15. A compound according to Claim 14 wherein X is O; Y is O; Ri is selected from the group consisting of (a) SO2CH3, and (b) SO2NH2; R3 is methyl or ethyl; R 4 is methyl or ethyl; and R9 and RlO together with the carbon to which they are connected form a carbonyl. 16. A compound according to Claim 1 selected from the group consisting of (1) 3-(3,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (2) 3-(3-Fluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one, (3) 3-(3,5-Difluorophenoxy)-5,5-dimethyl-4-(methylsulfonyl) phenyl)-5H-furan-2-one, (4) 3-Phenoxy-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (5) 3-(2,4-Difluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (6) 3-(4-Chlorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (7) 3-(3,4-Dichlorophenoxy)-5,5-dimethyl-4-(methylsulfonyl) phenyl)-5H-furan-2-one, (8) 3-(4-Fluorophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (9) 3-(4-Fluorophenylthio)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (10) 3-(3,5-Difluorophenylthio)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (11) 3-Phenylthio-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (12) 3-(N-Phenylamino)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (13) 3-(N-Methyl-N-phenylamino)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (14) 3-Cyclohexyloxy-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (15) 3-Phenylthio-4-(4-(methylsulfonyl)phenyl)-5H-furan-2-one, (16) 3-Benzyl-5,5-dimethyl-4-(4-(methylsulfonyl)ρhenyl)-5H- furan-2-one, (17) 3-(3,4-Difluorophenylhydroxymethyl)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (18) 3-(3,4-Difluorobenzoyl)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (19) 3-Benzoyl-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (20) 4-(4-(Methylsulfonyl)phenyl)-3-phenoxy- 1 -oxaspiro[4.4] non-3-en-2-one, (21) 4-(4-(Methylsulfonyl)phenyl)-3-phenylthio- 1 -oxaspiro[4.4] non-3-en-2-one, (22) 4-(2-Oxo-3-phenylthio-l-oxa-spiro[4,4]non-3-en-4-yl) benzenesulfonamide. (23) 3-(4-Fluorobenzyl)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (24) 3-(3,4-Difluorophenoxy)-5-methoxy-5-methyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, 5 (25) 3-(5-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (26) 3-(2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (27) 3-(6-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- 10 (methylsulfonyl) phenyl)-5H-furan-2-one, (28) 3-(3-Isoquinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (29) 3-(4-(Methylsulfonyl)phenyl)-2-phenoxycyclopent-2-enone, and (30) 3-(4-(Methylsulfonyl)phenyl)-2-(3,4-difluorophenoxy) 15 cyclopent-2-enone. 17. A pharmaceutical composition for treating an inflammatory disease susceptible to treatment with a non-steroidal anti- inflammatory agent comprising a non-toxic therapeutically effective amount 20 of a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16, and a pharmaceutically acceptable carrier. 18. A pharmaceutical composition for treating cyclooxy- ~ < - genase mediated diseases advantageously treated by an active agent that selectively inhibits COX-2 in preference to COX-1 comprising a non-toxic therapeutically effective amount of a compound of formula (I), or a pharma¬ ceutically acceptable salt thereof, according to Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16, and a pharmaceutically acceptable carrier. 30 19 A method of treating an inflammatory disease susceptible to treatment with a non-steroidal anti-inflammatory agent comprising administration to a patient in need of such treatment of a non¬ toxic therapeutically effective amount of a compound according to Claim 1 and a pharmaceutically acceptable carrier. 20. A method of treating cyclooxygenase mediated diseases advantageously treated by an active agent that selectively inhibits COX-2 in preference to COX-1 comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound according to Claim 1. 21. A compound according to Claim 3 wherein X is selected from the group consisting of (a) CH2, and (b) O, Y is selected from the group consisting of (a) CH2, and (b) O, Ri is selected from the group consisting of (c) S(0)(NH)NH2; R 2 is Cl-6alkyl, R3 is hydrogen, Cj-6 alkyl, CH20R 7 , CN, CH2CN, Cl-4fluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) CMalkyl, (4) Cl-4alkoxy, (5) Ci-4alkylthio, (6) CN, (7) CF3, (8) -C(R5)(R6)-0H, and (a) hydrogen (b) Cl-6alkyl, (c) Cl-6alkoxy, (d) Cl-6alkylthio, (e) -OH, (f) -OCOR7, (g) -SCOR7, (h) -OC02R 8 , and (i) -SC02R 8 , or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-6alkyl, or R5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) Cl-4alkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, Cl-4alkyl, Cl-4alkoxy, Cl-4alkylthio, CN, or CF3 each R 8 is independently selected from the group consisting of (a) CMalkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Ci-4alkylthio, CN, or CF3; R9 and R O together with the carbon to which they are connected form a carbonyl; Rl6 and R 7 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) C 1 -6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, C\. 6alkanoic acid, Cl-6alkylamine, CN, C02H or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, C 1 -6alky 1, C 1 -6alkoxy , C 1 -6alky lthio, C 1 - 6alkanoic acid, C l-6alkylamine, CN, CO2H or CF3. 22. A compound according to Claim 21 wherein X is O; Y is O; Ri is selected from the group consisting of (c) S(0)(NH)NH2; R2 is CMalkyl, R3 is hydrogen, Cl-6 alkyl, CH2θR 7 , CN, CH2CN, CMfluoroalkyl, F, CON(R7)2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) CMalkyl, (4) CMalkoxy, R4 is or R3 andR4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms; R-5 and R6 are each independently selected from the group consisting of (a) hydrogen, and (b) Cl-6alkyl, or R-5 and R6 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; each R7 is independently selected from the group consisting of (a) hydrogen, (b) CMalkyl, (c) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, CMalkylthio, CN, or CF3, and (d) benzyl or monosubstituted benzyl wherein the substituents may be halo, C l -4alkyl, C l -4alkoxy , C l -4alkylthio, CN, or CF3 each R8 is independently selected from the group consisting of (a) CMalkyl, (b) phenyl or monosubstituted phenyl wherein the substituents may be halo, CMalkyl, CMalkoxy, Cl-4alkylthio, CN, or CF3, and (c) benzyl or monosubstituted benzyl wherein the substituents may be halo, C l -4alkyl, C l -4alkoxy , C 1 -4alkylthio, CN, or CF3; R9 and RlO together with the carbon to which they are connected form a carbonyl; Rl6 and R 17 are independently selected from the group consisting of (a) hydrogen (b) Cl-6alkyl, (c) Cl-6alkanoic acid, (d) Cl-6alkyl amine, (e) phenyl or monosubstituted phenyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl- 6alkanoic acid, Cl-6alkylamine, CN, COOH or CF3, and (f) benzyl or monosubstituted benzyl wherein the substituents are halo, Cl-6alkyl, Cl-6alkoxy, Cl-6alkylthio, Cl -oalkanoic acid, Cl- 6alkylamine, CN, COOH or CF3. 23. A compound according to Claim 22 wherein X is O; Y is O; R is selected from the group consisting of R2 is propyl or butyl, R3 is hydrogen, Cl-6 alkyl, CH2θR 7 , CN, CH2CN, CMfluoroalkyl, F, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of (1) hydrogen, (2) halo, (3) Cl-3alkyl, 24. A compound according to Claim 23 wherein XisO; YisO; Ri is selected from the group consisting of R2 is propyl or butyl, R3 is hydrogen or C 1-3 alkyl; R4 is hydrogen or C 1-3 alkyl; R9 and R O together with the carbon to which they are connected form a carbonyl. 25. A compound according to Claim 24 wherein XisO; YisO; Ri is selected from the group consisting of R2 is isopropyl, R3 is methyl or ethyl; R4 is methyl or ethyl; and R and RlO together with the carbon to which they are connected form a carbonyl. 26. A compound according to Claim 25 wherein Rl6 and R 17 are each hydrogen. 27. A compound according to Claim 26 wherein Rl is Sθ2CH3. 28. A compound according to Claim 1 selected from the group consisting of (a) 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(5- bromopyridin-2-yloxy)-5H-furan-2-one, and (b) 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(2- propoxy)-5H-fiιran-2-one, or a pharmaceutically acceptable salt thereof. 29. A compound according to Claim 1 which is 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(2- propoxy)-5H-furan-2-one, or a pharmaceutically acceptable salt thereof. 30. A pharmaceutical composition for treating an inflammatory disease susceptable to treatment with an non-steroidal anti- inflammatory agent comprising: a non-toxic therapeutically effective amount of a compound according to Claim 29 and a pharmaceutically acceptable carrier. 31. A method of treating an inflammatory disease susceptable to treatment with an non-steroidal anti-inflammatory agent comprising: administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound according to Claim 29 and a pharmaceutically acceptable carrier. 32. A compound according to Claim 1 selected from the group consisting of: (1) 2-(3,4-difluorophenoxy)-3-(4-methylsulfonylphenyl)-cyclopent-2- enone, (2) 3-(5-Benzothiophenyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (3) 5,5-dimethyl-4-(4-methylsulfonyl-phenyl)-3-(pyridyl-4-oxy)-5H- furan-2-one, (4) 5,5-dimethyl-4-(4-methylsulfonyl-phenyl)-3-(pyridyl-3-oxy)-5H- furan-2-one, (5) 3-(2-Methyl-5-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-fiιran-2-one, (6) 3 (2-Fluoro-4-trifluoromethyl)phenoxy-4-(4-methylsulf ony l)phenyl)- 5,5-dimethyl-5H-furan-2-one, (7) 3-(5-Chloro-2-pyridylthio)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl- 5H-furan-2-one, (8) 2-(3,5-Difluorophenoxy)-3-(4-methylsulfonylphenyl)-cyclopent-2- enone, (9) 3-(2-Pyrimidinoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one, ( 10) 3-(3-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (11) 3-(3-Chloro-5-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, ( 12) 3-(3-( 1 ,2,5-Thiadiazolyl)oxy)-4-(4-(methylsulfonyl)phenyl)-5,5- dimethyl-5H-furan-2-one, (13) 3-(5-Isoquinolinoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one, (14) 3-(6-Amino-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (15) 3-(3-Chloro-4-fluoro)phenoxy-4-(methylsulfonyl)phenyl)-5,5- dimethyl-5H-furan-2-one, ( 16) 3-(6-Quinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (17) 3-(5-Nitro-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl- 5H-furan-2-one, (18) 3-(2-Thiazolylthio)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (19) 3-(3-Chloro-5-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (20) 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(2-propoxy)-5H-furan- 2-one, (21 ) 3-(3-Trifluoromethyl)phenoxy-4-(4-methylsulfonyl)phenyl)-5,5- dimethyl-5H-furan-2-one, (22) 5,5-Dimethyl-(4-(4-methylsulfonyl)phenyl)-3-(piperidine- 1 - carbonyl)-5-H-furan-2-one, (23) 5,5-Dimethyl-3-(2-Butoxy)-4-(4-methylsulfonylphenyl)-5H-furan-2- one, (24) 5,5-Dimethyl-4-(4-methylsulfonylphenyl)-3-(3-pentoxy)-5H-furan- 2-one, (25) 2-(5-Chloro-2-pyridyloxy)-3-(4-methylsulfonyl)phenylcyclopent-2- enone, (26) 3-(4-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (27) (5R)-3-(3,4-Difluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (28) (5R)-3-(4-Chlorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (29) 3-(2-Methyl-3-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (30) 3-(4-Methyl-5-nitro-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (31 ) 3-(5-Chloro-4-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (32) 3-(5-Fluoro-4-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (33) 3-(3-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (34) 3-(4-Fluorophenoxy)-5-methyl-4-(4-methylsulfonyl)phenyl-5- propyl-5H-furan-2-one, (35) 3- (N,N-Diethylamino)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)- 5H-furan-2-one, (36) 5,5-dimethyl-4-(4-methylsulfonyl-phenyl)-3-(3,5-dichloro-2- pyridyloxy)-5H-furan-2-one, (37) (5R)-3-(4-Bromophenoxy)-5-ethyl-5-methyl-4-(4- methy lsulfonyl)phenyl-5H-furan-2-one, (38) (5R)-3-(4-Methoxyphenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (39) (5R)-3-(5-Chloro-2-pyridyloxy)-5-methyl-4-(4- methylsulfonyl)phenyl-5-(2,2,2-trifluoroethyl)-5H-furan-2-one, (40) 3-(5-Chloro-2-pyridyloxy)-5-methyl-4-(4-methylsulfonyl)phenyl-5- propyl-5 H-furan-2-one, (41) 3-( 1 -Cyclopropyl-ethoxy)-5,5-dimethyl-4-(4-methyl sulfonyl)phenyl)-5H-furan-2-one, (42) 5-Methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-(propoxy)-5-(2- trifluoroethyl)-5H-furan-2-one, (43) 5(R)-5-ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-proρoxy)- 5H-furan-2-one, (44) 5,5-dimethyl-3-(2,2-dimethylpropyloxy)-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (45) 5(R) 3-(l-cyclopropyl-ethoxy)-5-ethyl-5-methyl-4-(4-(methyl sulfonyl)phenyl-5H-fiιran-2-one, (46) 5(S) 5-Ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl-3-(2-propoxy)- 5H-furan-2-one, (47) 3-(l-cyclopropylethoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (48) 3-(l-cyclopropylethoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-f ran-2-one, (49) 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl- 5H-furan-2-one, (50) 5,5-dimethyl-3-(isobutoxy)-4-(4-(methylsulfonyl)phenyl)-5H-furan- 2-one, (51 ) 3-(4-Bromophenoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)- 5H-furan-2-one, (52) 3-(2-Quinolinoxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (53) 3-(2-Chloro-5-pyridyloxy)-5,5-dimethyl-4-(4- (methylsulfonyl)phenyl)-5H-furan-2-one, (54) 3-(6-benzothiazolyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (55) 3-(6-Chloro-2-pyridyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl) phenyl)-5H-furan-2-one, (56) 3-(4-Quinazolyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (57) (5R)-3-(5-Fluoro-2-pyridyloxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (58) (5R)-3-(4-Fluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (59) (5R)-3-(5-Fluoro-2-pyridyloxy)-5-methyl-4-(4- methylsulfonyl)phenyl-5-(2,2,2-trifluoroethyl)-5H-furan-2-one, (60) 3-(l-Isoquinolinyloxy)-5,5-dimethyl-4-(methylsulfonyl)phenyl-5H- furan-2-one, (61) (5R)-3-(4-fluorophenoxy)-5-methyl-4-(4-methylsulfonyl)phenyl-5- (2,2,2-trifluoroethyl)-5H-furan-2-one, (62) 3-(3-Fluoro-2-pyridyloxy)-5,5-dimethyl-4-(4-methylsulfonyl) phenyl-5H-furan-2-one, (63) (5R)-3-(3,4-difluorophenoxy)-5-methyl-4-(4-methylsulfonyl) phenyl-5-(2,2,2-trifluoroethyl)-5H-furan-2-one, (64) (5R)-3-(5-chloro-2-pyridyloxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (65) 3-(3,4-difluorophenoxy)-5-methyl-5-trifluoromethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (66) 3-(3,4-Difluorophenoxy)-5-methyl-4-(4-(methylsulfonyl)phenyl)-5- propyl-5H-furan-2-one, (67) 3-Cyclobutyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl-5H-furan- 2-one, (68) 3-( 1 -Indanyloxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-5H- furan-2-one, (69) 3-(2-Indanyloxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H- fύran-2-one, (70) 3-Cyclopentyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)5H- furan-2-one, (71 ) 3-(3,3-Dimethylcyclopentyloxy)-5,5-dimethyl-4-(4-methylsulfonyl- phenyl)-5H-furan-2-one, (72) 3-Isopropoxy-5-methyl-4-(4-methylsulfonylphenyl)-5-propyl-5H- furan-2-one, (73) 3-(2-Methoxy-5-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (74) 3-(5-Methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-fiιran-2-one, (75) (5RS)-3-(3,4-Difluorophenoxy)-5-methyl-4-(4- methylsulfonyl)phenyl-5-(2,2,2-trifluoroethyl)-5H-furan-2-one, (76) 3-(3-Chloro-4-methoxyphenoxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (77) (5R)-3-(3-Chloro-4-methoxyρhenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (78) (5R)-3-(4-Chlorophenoxy)-5-trifluoroethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (79) (5R)-3-(4-Bromophenoxy)-5-trifluoroethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-fiιran-2-one, (80) 5-Cyclopropylmethyl-3-(3,4-difluorophenoxy)-5-methyl-(4- methylsulfonyl)phenyl-5H-furan-2-one, (81) (5R)-3-(3-Fluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (82) (5R)-3-(4-Chloro-3-fluorophenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-fiiran-2-one, (83) (5R)-3-Phenoxy-5-ethyl-5-methyl-4-(4-methylsulfonyl)phenyl-5H- furan-2-one, (84) (5R)-3-(4-Chloro-3-methylphenoxy)-5-ethyl-5-methyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (85) 3-(4-Chloro-3-methylphenoxy)-5-5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (86) (5R)-3-(5-bromo-2-pyridyloxy)-4-(4-methylsulfonylphenyl)-5- methyl-5-(2,2,2-trifluoroethyl)-5H-furan-2-one, (87) (5R)-3-(5-bromo-2-pyridyloxy)-4-(4-methylsulfonylphenyl)-5-ethyl- 5-methyl-5H-furan-2-one, (88) 3-(5-chloro-6-methyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (89) 3-(5-cyclopropyl-2-pyridyloxy)-5,5-dimethyl-4-(4- methylsulfonyl)phenyl-5H-furan-2-one, (90) 3-( 1 -cyclopropylethoxy )-4-(4-methylsulfonyl)phenyl-5H-furan-2- one, and (91) 3-(cyclopropylmethoxy)-4-(4-methylsulfonyl)phenyl-5H-furan-2- one. 33. A compound according to Claim 1, 5, 6, 7, 21, 23 or 24 wherein Rl6 and R 17 are each simultaneously hydrogen. 34. A compound according to Claim 1, 5, 6, 7, 21, 23 or 24 wherein Rl is SO2CH3. 35. A pharmaceutically acceptable salt of a compound of formula (I), as defined in Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 22 or 34. 36. A compound of formula (I), or a pharmaceutically acceptable salt thereof; as defined in Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 22 or 34, for use in treating an inflammatory disease. 37. A compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined in Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 22 or 34, for use in treating cyclooxygenase mediated diseases. 38. Use of a compound of formula (I), or a pharmaceuti¬ cally acceptable salt thereof, as defined in Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 22 or 34 in the manufacture of a medicament for the treatment of inflammatory disease. 39. An anti-inflammatory pharmaceutical composition comprising an acceptable, anti-inflammatory amount of a compound of formula (I), as defined in Claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 32, 22 or 34, in association with a pharmaceutically acceptable carrier.

Inventors: BELLEY MICHEL, BLACK CAMERON, GAUTHIER JACQUES Y, GRIMM ERICH, LAU CHEUK-KUN, LEBLANC YVES, LI CHUNG-SING, PRASIT PETPIBOON, ROY PATRICK, THERIEN MICHEL, BELLEY, MICHEL, BLACK, CAMERON, GAUTHIER, JACQUES, Y., GRIMM, ERICH, LAU, CHEUK-KUN, LEBLANC, YVES, LI, CHUNG-SING, PRASIT, PETPIBOON, ROY, PATRICK, THERIEN, MICHEL
Applicants: BELLEY MICHEL, BLACK CAMERON, GAUTHIER JACQUES Y, GRIMM ERICH, LAU CHEUK KUN, LEBLANC YVES, LI CHUNG SING, MERCK FROSST CANADA INC, PRASIT PETPIBOON, ROY PATRICK, THERIEN MICHEL, BELLEY, MICHEL, BLACK, CAMERON, GAUTHIER, JACQUES, Y., GRIMM, ERICH, LAU, CHEUK-KUN, LEBLANC, YVES, LI, CHUNG-SING, MERCK FROSST CANADA INC., PRASIT, PETPIBOON, ROY, PATRICK, THERIEN, MICHEL
Application year: 1996
Main classification: C07D307
IPC codes: A61K31, A61P25, A61P29, A61P43, C07C317, C07D213, C07D307, C07D333, C07D405, C07D407, C07D409, C07D417, C07D471, C07D491, C07D495, C07D498, C07D513