ARYLPYRIDAZINONES AS PROSTAGLANDIN ENDOPEROXIDE H SYNTHASE BIOSYNTHESIS INHIBITORS

Abstract: The present invention describes pyridazinone compounds which are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX/2), COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important "housekeeping" enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently marketed non-steroidal anti-inflammatory drugs (NSAIDs).

Description: ARYLPYRIDAZINONES AS PROSTAGLANDIN ENDOPEROXIDE H SYNTHASE BIOSYNTHESIS INHIBITORS This application is a continuation-in-part application of U.S. patent application Serial No. 08/917,023 filed August 22, 1997, which was based on provisional application 60/056,733 filed August 22, 1997. Technical Field The present invention encompasses novel pyridazinone compounds useful in the treatment of cyclooxygenase-2 mediated diseases. More particularly, this invention concerns a method of inhibiting prostaglandin biosynthesis, particularly the induced prostaglandin endoperoxide H synthase (PGHS-2, cyclooxygenase-2, COX-2) protein. Background of the Invention The prostaglandins are extremely potent substances which produce a wide variety of biological effects, often in the nanomolar to picomolar concentration range. The discovery of two forms of prostaglandin endoperoxide H synthase, isoenzymes PGHS-1 and PGHS-2, that catalyze the oxidation of arachidonic acid leading to prostaglandin biosynthesis has resulted in renewed research to delineate the role of these two isozymes in physiology and pathophysiology. These isozymes have been shown to have different gene regulation and represent distinctly different prostaglandin biosynthesis pathways. The PGHS-1 pathway is expressed constitutively in most cell types. It responds to produce prostaglandins that regulate acute events in vascular homeostasis and also has a role in maintaining normal stomach and renal function. The PGHS-2 pathway involves an induction mechanism which has been linked to inflammation, mitogenesis and ovulation phenomena. Prostaglandin inhibitors provide therapy for pain, fever, and inflammation, and are useful therapies, for example in the treatment of rheumatoid arthritis and osteoarthritis. The non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen and fenamates inhibit both isozymes. Inhibition of the constitutive enzyme PGHS-1 results in gastrointestinal side effects including ulcers and bleeding and incidence of renal problems with chronic therapy. Inhibitors of the induced isozyme PGHS-2 may provide anti-inflammatory activity without the side effects of PGHS-1 inhibitors. The problem of side-effects associated with NSAID administration has never completely been solved in the past. Enteric coated tablets and co-administration with misoprostol, a prostaglandin derivative, have been tried in an attempt to minimize stomach toxicity. It would be advantageous to provide compounds which are selective inhibitors of the induced isozyme PGHS-2. The present invention discloses novel compounds which are selective inhibitors of PGHS-2. Summary of the Invention The present invention discloses pyridazinone compounds which are selective inhibitors of cyclooxygenase-2 (COX-2). The compounds of the present invention have the formula I: where X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbR 0 , wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, heterocyclic, heterocyclic alkyl, and arylalkyl; and R a , Rb, and R c are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, alkoxy, alkoxyalkyl, carboxy, carboxyalkyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, arylhaloalkyl, arylhydroxyalkyl, aryloxy, aryloxyhydroxyalkyl, aryloxyhaloalkyl, arylcarbonylalkyl, haloalkoxyhydroxyalkyl, heterocyclic, heterocyclic alkyl, heterocyclic alkoxy, heterocyclic oxy, -C(O)R 5 > -(CH2)nC(O)R 5 , -R6-R 7 , -(CH2) n CH(OH)R5, -(CH2) n CH(ORd)R5, -(CH2) n C(NORd)R5, -(CH2)nC(NRd)R5, -(CH2) n CH(NORd)R5, -(CH2)nCH(NRdRβ)R5 , -(CH 2 )nC≡C-R7, -(CH 2 )n[CH(CX'3)]m-(CH2)n-CX'3, -(CH )n(C X'2)m-(CH 2 )n -CX'3, -(CH 2 )n[CH(CX ' 3)]m-(CH 2 )n -R 8 , -(CH 2 )n(C X'2)m-(CH 2 ) n R 8 , -(CH 2 )n(CHX , )m-(CH 2 )n - CX ' 3 , -(CH2)n(CHX ' ) m -(CH 2 )n -R 8 , and - (CH 2 ) n -R 20 , wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic, and heterocyclic alkyl; wherein R 6 is alkylene or alkenylene, or halo-substituted alkyiene halo-substituted alkenylene; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; Rd and R e are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, and m is 0 to about 5; at least one of R , R 2 and R 3 is where X 1 is selected from the group consisting of -SO2-, -SO(NR 10 )-, -SO-, Seθ2-, PO(OR 1 )-, and -PO(NR12R13). I R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, -NHNH2, -N=CH(NR " O R 1 1 ), dialkylamino, alkoxy, thiol, alkylthiol, protecting groups, and protecting groups attached to X 1 by an alkylene; X 2 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, and alkynyl; R 10 , R 1 1 , R 12 , and R 13 are independently selected from the group consisting of hydrogen, alkyl, and cycloalkyl, or R 1 2 and R 1 3 can be taken together, with the nitrogen to which they are attached, to form a heterocyclic ring having from 3 to 6 atoms. The remaining two of the groups of R 1 , R 2 , and R 3 , are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyalkylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, halolkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, cycloalkylidenealkyl, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic(alkyl) amino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxy, hydroxyalkyl, hydroxyalkylamino, hydroxyalkylthio, hydroxyalkoxy, mercaptoalkoxy, oxoalkoxy, cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of -O-, -S-, -C(R 18 ) (R17)., _c(O)NR 1 R 22 -, -C(O)-, -C(O)O-, -NH-, - NC(O)-, -N=C R 21 R 22 , N- R 2 1 R 22 , and -NR19 " . R 1 4 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), R 1 6 , R 7 , and R 1 9 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; heir pharmaceutically acceptable salts, esters, or prodrugs thereof. Detailed Description of the Invention All patents, patent applications, and literature references cited in the specification are hereby incorporated by reference in their entirety. In the case of inconsistencies, the present disclosure, including definitions, will prevail. The present invention discloses pyridazinone compounds which are cyclooxygenase (COX) inhibitors and are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1 ) which is an important "housekeeping" enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. In one embodiment , the compounds of the present invention have the formula I : I where X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NR' D RC I wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, heterocyclic, heterocyclic alkyl, and arylalkyl; and R a , Rb, and R c are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, alkoxy, alkoxyalkyl, carboxy, carboxyalkyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, arylhaloalkyl, arylhydroxyalkyl, aryloxy, aryloxyhydroxyalkyl, aryloxyhaloalkyl, arylcarbonylalkyl, halolkoxyhydroxyalkyl, heterocyclic, heterocyclic alkyl, heterocyclic alkoxy, heterocyclic oxy, -C(0)R 5 > -(CH2)nC(O)R 5 , -R 6 -R 7 , -(CH2)nCH(OH)R5, -(CH2)nCH(OR d )R5, -(CH2) n C(NORd)R5, -(CH2)nC(NRd)R5, -(CH2) n CH(NORd)R5, -(CH2)nCH(NRdRθ)R5 _ -(CH 2 )nC≡C-R 7 > -(CH2)n[CH(CX'3)]rτr(CH2)n-CX'3, -(CH 2 )n(C X'2)m-(CH 2 )n -CX'3, -(CH 2 )n[CH(CX'3)]m-(CH 2 )n -R 8 , -(CH 2 )n(C X'2)m-(CH 2 ) n R 8 , -(CH2)n(CHX')m-(CH 2 )n - CX ' 3 , -(CH2) n (CHX ' )m-(CH 2 )n -R 8 , and - (CH 2 ) n -R 2 °, wherein R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic, and heterocyclic alkyl; wherein R 6 is alkylene or alkenylene, or halo-substituted alkylene halo-substituted alkenylene; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; Rd and R e are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, and m is 0 to about 5; at least one of R 1 , R 2 and R 3 is where X 1 is selected from the group consisting of -SO2-, -SO(NR 1 0 )-, -SO-, Seθ2-, PO(ORl 1 )-, and -P0(NR1 2 R13)., R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, -NHNH2, -N=CH(N R 1 0 R 1 1 ), dialkylamino, alkoxy, thiol, alkylthiol, protecting groups, and protecting groups attached to X 1 by an alkylene; X 2 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, and alkynyl; R 1 0 , R 1 1 , R 1 2 , and R 1 3 are independently selected from the group consisting of hydrogen, alkyl, and cycloalkyl, or R 1 2 and R 1 3 can be taken together, with the nitrogen to which they are attached, to form a heterocyclic ring having from 3 to 6 atoms. The remaining two of the groups of R 1 , R 2 , and R 3 , are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyalkylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, halolkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, cycloalkylidenealkyl, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic alkylamino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxy, hydroxyalkyl, hydroxyalkylamino, hydroxyalkylthio, hydroxyalkoxy, mercaptoalkoxy, oxoalkoxy, cyano, nitro, and -Y-R 14 , wherein Y is selected from the group consisting of -O-, -S-, -C(R16) (R 1 7 )-, -C(O)NR 1 R 22 -, -eta)-, -C(O)O-, -NH-, - NC(O)-, -N=C R 21 R 22 , N- R 2" ! R 22 , and -NR19-. R14 j s selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), R 16 , R 17 , and R 1 9 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another embodiment, compounds of the present invention have the formula II: I I wherein Z is a group having the formula: where X 1 is selected from the group consisting of -SO2-, -SO-, -Seθ2- ,SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, -NHNH2, dialkylamino, alkoxy, thiol, alkylthiol, protecting groups, and protecting groups attached to X 1 by an alkylene; R 1 0 is selected from the group consisting of hydrogen, alkyl, and cycloalkyl; X 2 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, and alkynyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, alkoxy, alkoxyalkyl, carboxy, carboxyalkyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, arylhaloalkyl, arylhydroxyalkyl, aryloxy, aryloxyhydroxyalkyl, aryloxyhaloalkyl, arylcarbonylalkyl, haloalkoxyhydroxyalkyl, heterocyclic, heterocyclic alkyl, heterocyclic alkoxy, heterocyclic oxy, -C(0)R5, -(CH2)nC(O)R5, -R6-R 7 , -(CH2)nCH(OH)R5, -(CH2) n CH(ORd)R5, -(CH2) n C(NORd)R5, -(CH2)nC(NRd)R5, -(CH2) n CH(NORd)R5, -(CH2)nCH(NRdRβ)R5 f -(CH 2 ) n C≡C-R 7> -(CH2)n[CH(CX'3)]m-(CH2)n-CX , 3, -(CH 2 )n(C X'2)m-(CH 2 )n -CX'3, -(CH 2 )n[CH(CX'3)]m-(CH 2 )n -R 8 , -(CH 2 ) n (C X'2)m-(CH 2 )n R 8 , -(CH2)n(CHX') m -(CH 2 )n - CX ' 3 , -(CH 2 )n(CHX') m -(CH2)n -R 8 , and - (CH 2 ) n -R 2 0, wherein R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic, and heterocyclic alkyl; wherein R6 is alkylene or alkenylene, or halo-substituted alkylene halo-substituted alkenylene; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; Rd and R e are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, and m is 0 to about 5; R 1 , and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyaikylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, halolkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloaikenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic(alkyl) amino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxy, hydroxyalkyl, hydroxyalkylamino, hydroxyalkoxy, mercaptoalkoxy, oxoalkoxy, cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of -O-, -S-, -C(R 1 6 ) (R1 7 )-, -C(0)NR 2 1 R 22 -, -OP)-, -C(0)0-, -IMH-, -NC(O)-, -N=C R 1 R 22 , N- R 21 R 22 , and -NR 1 9" . R 4 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), R "1 6 , R 1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 2"1 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In yet another embodiment, compounds of the present invention have the formula III: III wherein X, X , X 2 , R, R 1 , R 3 , and R 9 are as defined in Formula I; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In a preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is selected from the group consisting of -SO2-, -SO-, - Seθ2-, and -SO(NR 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbR C , wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, heterocyclic, heterocyclic alkyl, and arylalkyl; and R a , R b , and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkyicarbonylalkyl, alkylsulfonylalkyl, aikylsulfonylarylalkyl, carboxyalkyl, cyanoalkyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkenyl, arylalkynyl, heterocyclic, heterocyclic alkyl, arylalkyl, -(CH2)nC(O)R 5 > -(CH2)nC=C- R 7 ' -(CH2) n [CH(CX'3)]m(CH 2 )n- R 8 , and -(CH 2 )n-R 2 0; wherein R^ is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl, R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, m is from 0 to about 5; R 1 and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkoxyalkyl, amido, amidoalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, amino, aminocarbonyl, aminocarbonylalkyl, alkylamino, dialkylamino, arylamino, arylalkylamino, diarylamino, aryl, aryloxy, heterocyclic, heterocyclic alkyl, cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of, -O-, -S-, -C(R 1 6) (R 1 )-, -C(O)NR 21 R 22 -, -C(O)-, - C(O)0-, -NH-, -NC(O)-, -N=C R 21 R 22 , N- R 1 R 22 , and -NR 1 9-. R1 4 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), R 1 6 , R 1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is selected from the group consisting of -SO2-, -SO-, -Seθ2-, and -SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NR^R C , wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , R&, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, carboxyalkyl, cyanoalkyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkenyl, arylalkynyl, heterocyclic, heterocyclic alkyl, arylalkyl, -(CH2)nC(O)R 5 > and - wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; n is from 0 to about 10; R 1 and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkylthioalkyl, aryloxyalkyl, arylthioalkyl, amido, amidoalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, amino, aminocarbonyl, aminocarbonylalkyl, alkylamino, alkylaminoalkyl, dialkylamino, arylamino, arylalkylamino, diarylamino, aryl, heterocyclic, heterocyclic(alkyl), cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of, -O-, -S-, -C(R 1 6 ) (R 1 7 )-, -C(0)NR " l R 22 -, -C(O)-, -C(0)0-, -NH-, -NC(O)-, and -NR1 -. R14 is SΘ | e cted from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), and R "1 6 , R "1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is selected from the group consisting of -SO2-, -SO-, -Seθ2-, and -SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NR D RC ; wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , R ) and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, carboxyalkyl, cyanoalkyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkenyl, arylalkynyl, heterocyclic, heterocyclic alkyl, arylalkyl, and -(CH2)nC(O)R 5 >; wherein R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl; and n is from 0 to about 10; R 1 and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkylthioalkyl, aryloxyalkyl, arylthioalkyl, amido, amidoalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, amino, aminocarbonyl, aminocarbonylalkyl, alkylamino, alkylaminoalkyl, dialkylamino, arylamino, arylalkylamino, diarylamino, aryl, heterocyclic, heterocyclic(alkyl), cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of, -O-, -S-, -C(R 16 ) (R 17 )-, -C(O)NR 2" l R 22 -, -C(O)-, -C(O)O-, -NH-, -NC(O)-, and -NR " ! 9 . R14 \ s selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl); R 1 5 , R 1 6 , R 1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl or cyano; R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is selected from the group consisting of -SO2-, -SO-, - Seθ2-, and -SO(NR 10 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-ORa, and N-NRbRC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , R , and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from alkyl, haloalkyl, aryl, heterocyclic, heterocyclic alkyl, and - (CH 2 )n-R 2 0 where is R 20 is substituted and unsubstituted aryl wherein the substituted aryl compounds are substituted with halogen; n is from 0 to about 10; R 1 is selected from the group consisting of alkoxy, alkenyloxy, hydroxyalkoxy, aryloxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, and -Y-R "1 4 , wherein Y is selected from the group consisting of, -0-, -S-, -C(R 1 6 ) (R 1 7 )-, -C(O)-, - C(0)0-, -NH-, -NC(O)-, and -NR 1 9-. R1 4 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl, R 3 is hydrogen; R 1 5 , R 1 6 , R 1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is selected from the group consisting of -SO2-, -SO-, and -SO(NR 1 0 )-, and R9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbRC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from alkyl, haloalkyl, aryl, heterocyclic, heterocyclic alkyl, and - (CH2)n-R 20 where is R 20 is substituted and unsubstituted aryl wherein the substituted aryl compounds are substituted with halogen; n is from 0 to about 10; R 1 is selected from the group consisting of alkoxy, alkenyloxy, hydroxyalkoxy, aryloxy, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is -SO2- and and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-ORa, and N-NRbR C , wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb ; and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from haloalkyl, aryl, heterocyclic, heterocyclic alkyl, and - (CH2)n-R 20 where is R 20 is substituted and unsubstituted aryl wherein the substituted aryl compounds are substituted with halogen; n is from 0 to about 10; R 1 is selected from the group consisting of unsubstituted aryl, and substituted aryl with one, two, or three substituents selected from the group consisting of fluorine and chlorine including, but not limited to, p-chlorophenyl, p- fluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-fluoro-phenyl, and the like; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is -SO2-,and R 9 is selected from the group consisting of alkyl and amino; X 2 is selected from the group consisting of hydrogen and halogen; X is O; R is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, and arylalkyl; R 1 is selected from the group consisting of alkoxy, aryl, alkenyloxy, hydroxyalkoxy, halalkoxy, arylalkyl, alkyl, and aryloxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is -SO2-, and R 9 is selected from the group consisting of alkyl and amino X 2 is selected from hydrogen and fluorine; R is selected from haloalkyl, aryl, and alkyl; n is from 0 to about 10; R 1 is selected from the group consisting of isobutyloxy, isopentyloxy, 1 -(3- methyl-3-butenyl)oxy, 2-hydroxy-2-methyl-propyloxy, 3-hydroxy-3-methyl-butyloxy, neopentyloxy, isopentyl, aryloxy including 4-fluorophenoxy, unsubstituted aryl, and substitued aryl with one, two, or three substituents selected from the group consisting of fluorine and chlorine including, , 4-fluorophenyl, 4-chlorophenyl, 4- chloro-3-fluoro-phenyl, 3-chloro-4-fluoro-phenyl and the like; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is selected from the group consisting of -SO2-, and -S0(NR10)-, and R9 is alkyl, X 2 is selected from the group consisting of hydrogen and fluorine; X is O; R is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, and arylalkyl; R "1 is selected from the group consisting of alkoxy, aryl, alkenyloxy, hydroxyalkoxy, alkyl, and aryloxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is -SO2-, R 9 is amino; X 2 is selected from the group consisting of hydrogen and fluorine; X is O; R is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, and arylalkyl; R 1 is selected from the group consisting of alkoxy, aryl, alkenyloxy, hydroxyalkoxy, alkyl, and aryloxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is -SO2-, and R 9 is methyl; X 2 is selected from the group consisting of hydrogen; X is O; R is selected from the group consisting t-butyl, 3-chlorophenyl, 3,4- difluorophenyl, 4-fluorophenyl, 4-chloro-3-fluoro-phenyl, and CF 3 CH 2 -, ; R 1 is selected from the group consisting of aryloxy including 4- fluorophenoxy, isobutyloxy, isopentyloxy, 1 -(3-methyl-3-butenyl)oxy, 2-hydroxy-2- methyl-propyloxy, 3-hydroxy-3-methyl-butyloxy, neopentyloxy, isopentyl, 4- fluorophenyl, 4-chiorophenyl, 4-chloro-3-fluoro-phenyl, 3-chloro-4-fluoro-phenyl; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. In another preferred embodiment, compounds of the present invention have the formula III, wherein X 1 is -SO2-, and R 9 is amino; X 2 is selected from the group consisting of hydrogen; X is O; R is selected from the group consisting t-butyl, 3-chlorophenyl, 3,4- difluorophenyl, 4-fluorophenyl, 4-chloro-3-fluoro-phenyl, 3-chloro-4-fluoro-phenyl and CF 3 CH 2 -, ; R 1 is selected from the group consisting of aryloxy including 4- fluorophenoxy, isobutyloxy, isopentyloxy, 1 -(3-methyl-3-butenyl)oxy, 2-hydroxy-2- methyl-propyloxy, 3-hydroxy-3-methyl-butyloxy, neopentyloxy, isopentyl, 4- fluorophenyl, 4-chlorophenyl, 4-chloro-3-fluoro-phenyl, 3-chloro-4-fluoro-phenyl; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof Definitions of Terms As used throughout this specification and the appended claims, the following terms have the meanings specified. The term "protecting groups includes "carboxy protecting group" and "N- protecyting groups" . "Carboxy protecting group" as used herein refers to a carboxylic acid protecting ester group employed to block or protect the carboxylic acid functionality while the reactions involving other functional sites of the compound are carried out. Carboxy protecting groups are disclosed in Greene, "Protective Groups in Organic Synthesis" pp. 152-186 (1981 ), which is hereby incorporated herein by reference. In addition, a carboxy protecting group can be used as a prodrug whereby the carboxy protecting group can be readily cleaved in vivo , for example by enzymatic hydrolysis, to release the biologically active parent. T. Higuchi and V. Stella provide a thorough discussion of the prodrug concept in "Pro-drugs as Novel Delivery Systems", Vol 14 of the A.C.S. Symposium Series, American Chemical Society (1975), which is hereby incorporated herein by reference. Such carboxy protecting groups are well known to those skilled in the art, having been extensively used in the protection of carboxyl groups in the penicillin and cephalosporin fields, as described in U.S. Pat. No. 3,840,556 and 3,719,667, the disclosures of which are hereby incorporated herein by reference. Examples of esters useful as prodrugs for compounds containing carboxyl groups can be found on pages 14-21 of "Bioreversible Carriers in Drug Design: Theory and Application", edited by E.B. Roche, Pergamon Press, New York (1987), which is hereby incorporated herein by reference. Representative carboxy protecting groups are Ci to Cs alkyl (e.g., methyl, ethyl or tertiary butyl and the like); haloalkyl; alkenyl; cycloalkyl and substituted derivatives thereof such as cyclohexyl, cylcopentyl and the like; cycloalkylalkyl and substituted derivatives thereof such as cyclohexylmethyl, cylcopentylmethyl and the like; arylalkyl, for example, phenethyl or benzyl and substituted derivatives thereof such as alkoxybenzyl or nitrobenzyl groups and the like; arylalkenyl, for example, phenylethenyl and the like; aryl and substituted derivatives thereof, for example, 5-indanyl and the like; dialkylaminoalkyl (e.g., dimethylaminoethyl and the like); alkanoyloxyalkyl groups such as acetoxy methyl, butyryloxymethyl, valeryloxymethyl, isobutyryloxymethyl, isovaleryloxymethyl, 1 -(propionyloxy)-1 -ethyl, 1 -(pivaloyloxyl)-1 -ethyl, 1 -methyl-1 - (propionyloxy)-l -ethyl, pivaloyloxymethyl, propionyloxymethyl and the like; cycloalkanoyloxyalkyl groups such as cyclopropylcarbonyloxymethyl, cyclobutylcarbonyloxymethyl, cyclopentylcarbonyloxymethyl, cyclohexylcarbonyloxymethyl and the like; aroyloxyalkyl, such as benzoyloxymethyl, benzoyloxyethyl and the like; arylalkylcarbonyloxyalkyl, such as benzylcarbonyloxymethyl, 2-benzylcarbonyloxyethyl and the like; alkoxycarbonylalkyl, such as methoxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1 -methoxycarbonyl-1 -ethyl, and the like; alkoxycarbonyloxyalkyl, such as methoxycarbonyloxymethyl, t- butyloxycarbonyloxymethyl, 1 -ethoxycarbonyloxy-1 -ethyl, 1 -cyclohexyloxycarbonyloxy-1 -ethyl and the like; alkoxycarbonylaminoalkyl, such as t-butyloxycarbonylaminomethyl and the like; alkylaminocarbonylaminoalkyl, such as methylaminocarbonylaminomethyl and the like; alkanoylaminoalkyl, such as acetylaminomethyl and the like; heterocycliccarbonyloxyalkyl, such as 4- methylpiperazinylcarbonyloxymethyl and the like; dialkylaminocarbonylalkyl, such as dimethylaminocarbonylmethyl, diethylaminocarbonylmethyl and the like; (5- (loweralkyl)-2-oxo-1 ,3-dioxolen-4-yl)alkyl, such as (5-t-butyl-2-oxo-1 ,3-dioxolen-4- yl)methyl and the like; and (5-phenyl-2-oxo-1 ,3-dioxolen-4-yl)alkyl, such as (5- phenyl-2-oxo-1 ,3-dioxolen-4-yl)methyl and the like. The term "N-protecting group" or "N-protected" as used herein refers to those groups intended to protect the N-terminus of an amino acid or peptide or to protect an amino group against undersirable reactions during synthetic procedures. Commonly used N-protecting groups are disclosed in Greene, "Protective Groups In Organic Synthesis," (John Wiley & Sons, New York (1981 )), which is hereby incorporated by reference. N-protecting groups comprise acyl groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and the like; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl and the like; carbamate forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p- methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p- bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5- dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1 -(p-biphenylyl)- 1 -methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,- trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9- methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl and the like; alkyl groups such as benzyl, thphenylmethyl, benzyloxymethyl and the like; and silyl groups such as trimethylsilyi and the like. Preferred N-protecting groups are formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (t-Boc) and benzyloxycarbonyl (Cbz). The term "aikanoyl" as used herein refers to an alkyl group as previously defined appended to the parent molecular moiety through a carbonyl (-C(O)-) group. Examples of aikanoyl include acetyl, propionyl and the like. The term "alkanoylamino" as used herein refers to an aikanoyl group as previously defined appended to an amino group. Examples alkanoylamino include acetamido, propionylamido and the like. The term "alkenyl" as used herein refers to a straight or branched chain hydrocarbon radical containing from 2 to 15 carbon atoms and also containing at least one carbon-carbon double bond. Alkenyl groups include, for example, vinyl (ethenyl), allyl (propenyl), butenyl, 1 -methyl-2-buten-1 -yl and the like. The term "alkenylene" denotes a divalent group derived from a straight or branched chain hydrocarbon containing from 2 to 15 carbon atoms and also containing at least one carbon-carbon double bond. Examples of alkenylene include -CH=CH-, -CH 2 CH=CH-, -C(CH 3 )=CH-, -CH 2 CH=CHCH 2 -, and the like. The term "alkenyloxy" as used herein refers to an alkenyl group, as previously defined, connected to the parent molecular moiety through an oxygen (-0-) linkage. Examples of alkenyloxy include isopropenoxy, butenyloxy and the like. The term "alkoxy" as used herein refers to R41 O- wherein R41 is a loweralkyl group, as defined herein. Examples of alkoxy include, but are not limited to, ethoxy, isobutyloxy, isopentyloxy, tert-butoxy, and the like. The term "alkoxyalkylamino" as used herein refers to an alkoxy as defined herein appended to the parent molecular moiety through an alkylamino as defined herein. Examples of alkoxyalkylamino include, but are not limited to, ethoxymethylamino, isobutyloxyethylamino and the like The term "alkoxyalkoxy" as used herein refers to RδoO-Rδl O- wherein Rβo is loweralkyl as defined above and Rδl is alkylene. Representative examples of alkoxyalkoxy groups include methoxymethoxy, ethoxymethoxy, t-butoxymethoxy and the like. The term "alkoxycarbonyl" as used herein refers to an alkoxyl group as previously defined appended to the parent molecular moiety through a carbonyl group. Examples of alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyi and the like. The term "alkoxycarbonylalkenyl" as used herein refers to an alkoxycarbonyl group as previously defined appended to the parent molecular moiety through an alkenylene. Examples of alkoxycarbonylalkenyl include methoxycarbonylethenylene, ethoxycarbonylpropenylene, and the like. The term "alkoxyalkoxyalkyl" as used herein refers to an alkoxyalkoxy group as previously defined appended to an alkyl radical. Representative examples of alkoxyalkoxyalkyl groups include methoxyethoxyethyl, methoxymethoxymethyl, and the like. The term "alkoxyalkoxyalkenyl" as used herein refers to an alkoxyalkoxy group as previously defined appended to an alkenyl radical. Representative examples of alkoxyalkoxyalkenyl groups include methoxyethoxyethenyl, methoxymethoxymethenyl, and the like. The term "alkoxyalkyl" as used herein refers to an alkoxy group as previously defined appended to an alkyl radical as previously defined. Examples of alkoxyalkyl include, but are not limited to, methoxymethyl, methoxyethyl, isopropoxymethyl and the like. The term "(alkoxycarbonyl)thioalkoxy" as used herein refers to an alkoxycarbonyl group as previously defined appended to a thioalkoxy radical. Examples of (alkoxycarbonyl)thioalkoxy include methoxycarbonylthiomethoxy, ethoxycarbonylthiomethoxy and the like. The terms "alkyl" and "loweralkyl" as used herein refer to straight or branched chain alkyl radicals containing from 1 to 15 carbon atoms including, but not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, 1 -methylbutyl, 2,2-dimethylbutyl, 2-methylpentyl, 2,2-dimethylpropyl, n- hexyl and the like. The term "alkylamino" as used herein refers to R51 NH- wherein R51 is a loweralkyl group, for example, ethylamino, butylamino, and the like. The term "alkylaminoalkyl" as used herein refers to a loweralkyl radical to which is appended an alkylamino group. The term "alkylaminocarbonyl" as used herein refers to an alkylamino group, as previously defined, appended to the parent molecular moiety through a carbonyl (-C(O)-) linkage. Examples of alkylaminocarbonyl include methylaminocarbonyl, ethylaminocarbonyl, isopropylaminocarbonyl and the like. The term "alkylaminocarbonylalkenyl" as used herein refers to an alkenyl radical to which is appended an alkylaminocarbonyl group. The term "alkylcarbonylalkyl" as used herein refers to R4rj-C(O)- R41 - wherein R40 is an alkyl group and R41 is an alkylene group. The term "alkylene" denotes a divalent group derived from a straight or branched chain saturated hydrocarbon having from 1 to 15 carbon atoms by the removal of two hydrogen atoms, for example -CH 2 -, -CH 2 CH 2 -, -CH(CH 3 )-, - CH 2 CH 2 CH 2 -, -CH 2 C(CH 3 ) 2 CH 2 - and the like. The term "alkylsulfonyl" as used herein refers to an alkyl group as previously defined appended to the parent molecular moiety through a sulfonyl (-S(O)2-) group. Examples of alkylsulfonyl include methylsulfonyl, ethylsulfonyl, isopropylsulfonyl and the like. The term "alkylsulfonylalkyl" as used herein refers to an alkyl group as previously defined appended to the parent molecular moiety through a sulfonylalkyl (-S(O)2-R-) group. Examples of alkylsulfonylalkyl include methylsulfonylmethyl, ethylsulfonylmethyl, isopropylsulfonylethyl and the like. The term "alkylsulfonylamino" as used herein refers to an alkyl group as previously defined appended to the parent molecular moiety through a sulfonylamino (-S(O)2-NH-) group. Examples of alkylsulfonylamino include methylsulfonylamino, ethylsulfonylamino, isopropylsulfonylamino and the like. The term "alkylsulfonylarylalkyl" as used herein refers to an alkyl group as previously defined appended to the parent molecular moiety through a sulfonylalkyl (-S(O)2-R45R33-) group wherein R45 is aryl and R33 is alkylene. Examples of alkylsulfonylarylalkyl include methylsulfonylphenylmethyl ethylsulfonylphenylmethyl, isopropylsulfonylphenylethyl and the like. The term "alkylthio" as used herein refers to R53S- wherein R53 is alkyl. The term "alkylthioalkyl" as used herein refers to alkylthio as defined herein appended to the parent molecular moiety through an alkylene group. The term "alkylthioalkoxy" as used herein refers to alkylthio as defined herein appended to the parent molecular moiety through an alkoxyl group as defined herein. The term "alkynyl" as used herein refers to a straight or branched chain hydrocarbon radical containing from 2 to 15 carbon atoms and also containing at least one carbon-carbon triple bond. Examples of alkynyl include -C≡C-H, H-C≡C- CH 2 -, H-C≡C-CH(CH 3 )- and the like. The term "amido" as used herein refers to R54-C(O)-NH- wherein R54 is an alkyl group. The term "amidoalkyl" as used herein refers to R34-C(O)-NHR35- wherein R34 is alkyl and R35 is alkylene. The term "amino" as used herein refers -NH2. The term "aminoalkoxy" as used herein refers to an amino group appended to the parent molecular moiety through an alkoxyl group as defined herein. The term "aminocarbonyl" as used herein refers to H2N-C(O)-. The term "aminocarbonylalkyl " as used herein refers to an aminocarbonyl as described above appended to the parent molecular moiety through an alkylene. The term "aminocarbonylalkenyl" as used herein refers to an alkenyl radical to which is appended an aminocarbonyl (NH 2 C(O)-) group. The term "aminocarbonylalkoxy" as used herein refers to H2N-C(O)- appended to an alkoxy group as previously defined. Examples of aminocarbonylalkoxy include aminocarbonylmethoxy, aminocarbonylethoxy and the like. The term "aroyloxyalkyl" as used herein refers to R32-C(0)-0-R33- wherein R32 is an aryl group and R33 is an alkylene group. Examples of aroyloxyalkyl include benzoyloxymethyl, benzoyloxyethyl and the like. The term "aryl" as used herein refers to a mono- or bicyclic carbocyclic ring system having one or two aromatic rings including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl and the like. Aryl groups can be unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, halo, haloalkyl, haloalkoxy, hydroxy, oxo (=O), hydroxyalkyl, alkenyloxy, alkoxy, alkoxyalkoxy, alkoxycarbonyl, alkoxycarbonylalkenyl, (alkoxycarbonyl)thioalkoxy, thioalkoxy, alkylimino (R * N= wherein R * is a loweralkyl group), amino, alkylamino, alkylsulfonyl, dialkylamino, aminocarbonyl, aminocarbonylalkoxy, alkanoylamino, aryl, arylalkyl, arylalkoxy, aryloxy, mercapto, cyano, nitro, carboxy, carboxaldehyde, carboxamide, cycloalkyl, carboxyalkenyl, carboxyalkoxy, alkylsulfonylamino, cyanoalkoxy, heterocyclic alkoxy, -SO3H, hydroxyalkoxy, phenyl and tetrazolylalkoxy. In the case of halo, aryl may have up to five halo substituents. Examples of substituted aryl include 3- chlorophenyl, 3-fluorophenyl, 4-chlorophenyl, 4-fluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-fluoro-phenyl, 4-methylsulfonylphenyl, pentaflurophenyl, and the like. The term "arylalkenyl" as used herein refers to an alkenyl radical to which is appended an aryl group, for example, phenylethenyl and the like. The term "arylalkynyl" as used herein refers to an alkynyl radical to which is appended an aryl group, for example, phenylethynyl and the like The term "arylalkoxy" as used herein refers to R42O- wherein R42 is an arylalkyl group, for example, benzyloxy, and the like. The term "arylalkoxyalkyl" as used herein refers to a loweralkyl radical to which is appended an arylalkoxy group, for example, benzyloxymethyl and the like. The term "arylalkyl" as used herein refers to an aryl group as previously defined, appended to a loweralkyl radical, for example, benzyl and the like. The term "arylalkylamino" as used herein refers to an arylalkyl group as previously defined, appended to the parent molecular moiety through an amino group. The term "arylalkylthio" as used herein refers to an arylalkyl group as previously defined, appended to the parent molecular moiety through an thiol group. The term "arylamino" as used herein refers to R45NH2- wherein R45 is an aryl. The term "arylcarbonylalkyl" as used herein refers to R45C(O)R33- wherein R45 is an aryl group and R33 is an alkylene group. The term "arylhaloalkyl" as used herein refers to an aryl group as previously defined, appended to the parent molecular moiety through a haloalkyl as defined herein. Examples of arylhaloalkyl include, phenyl-2-fluoropropyl, and the like. The term "arylhydroxyalkyl" as used herein refers to an aryl group as previously defined, appended to the parent molecular moiety through a hydroxyalkyl as defined herein. Examples of arylhydroxyalkyl include, phenyl-2- hydroxypropyl, and the like. The term "aryloxy" as used herein refers to R45O- wherein R45 is an aryl group, for example, phenoxy, and the like. The term "aryloxyalkyl" refers to an aryloxy group as previously defined appended to an alkyl radical. Examples of aryloxyalkyl include phenoxymethyl, 2- phenoxyethyl and the like. The term "aryloxyhaloalkyl" as used herein refers to an aryloxy group as previously defined, appended to the parent molecular moiety through a haloalkyl as defined herein. Examples of aryloxyhaloalkyl include, phenyloxy-2-fluoropropyl, and the like. The term "aryloxyhydroxyalkyl" as used herein refers to an aryloxy group as previously defined, appended to the parent molecular moiety through a hydroxyalkyl as defined herein. Examples of aryloxyhydroxyalkyl include, phenyoxy-2-hydroxypropyi, and the like. The term "carboxaldehyde" as used herein refers to a formaldehyde radical, -C(O)H. The term "carboxamide" as used herein refers to -C(O)NH2- The term "carboxy" as used herein refers to a carboxylic acid radical, -C(O)OH. The term "carboxyalkyl" as used herein refers to a carboxy group as previously defined appended to an alkyl radical as previously defined. Examples of carboxyalkyl include 2-carboxyethyl, 3-carboxy-1 -propyl and the like. The term "carboxyalkenyl" as used herein refers to a carboxy group as previously defined appended to an alkenyl radical as previously defined. Examples of carboxyalkenyl include 2-carboxyethenyl, 3-carboxy-1 -ethenyl and the like. The term "carboxyalkoxy" as used herein refers to a carboxy group as previously defined appended to an alkoxy radical as previously defined. Examples of carboxyalkoxy include carboxymethoxy, carboxyethoxy and the like. The term "cyano" as used herein refers a cyano (-CN) group. The term "cyanoalky" as used herein refers to an alkyl radical as previously defined to which is appended a cyano (-CN) group. Examples of cyanoalkyl include 3-cyanopropyl, 4-cyanobutyl, and the like. The term "cyanoalkoxy" as used herein refers to a cyano (-CN) group appended to the parent molecular moiety through an alkoxy radical. Examples of cyanoalkoxy include 3-cyanopropoxy, 4-cyanobutoxy and the like. The term "cycloalkanoyloxyalkyl" as used herein refers to a loweralkyl radical to which is appended a cycloalkanoyloxy group (i.e., Rgg-C(O)-O- wherein Rgø is a cycloalkyl group). The term "cycloalkyl" as used herein refers to an aliphatic ring system having 3 to 10 carbon atoms and 1 to 3 rings including, but not limited to, cyclopropyl, cyciopentyl, cyclohexyl, and the like. Cycloalkyl groups can be unsubstituted or substituted with one, two or three substituents independently selected from hydroxy, halo, oxo (=O), alkylimino (R * N= wherein R * is a loweralkyl group), amino, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, alkoxycarbonyl, thioalkoxy, haloalkyl, mercapto, carboxy, carboxaldehyde, carboxamide, cycloalkyl, aryl, arylalkyl, -SO3H, nitro, cyano and loweralkyl. The term "cycloalkenyl" as used herein refers to an aliphatic ring system having 3 to 10 carbon atoms and 1 to 3 rings containing at least one double bond in the ring structure. Cycloalkenyl groups can be unsubstituted or substituted with one, two or three substituents independently selected hydroxy, halo, oxo (=O), alkylimino (R * N= wherein R * is a loweralkyl group), amino, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, alkoxycarbonyl, thioalkoxy, haloalkyl, mercapto, carboxy, carboxaldehyde, carboxamide, cycloalkyl, aryl, arylalkyl , -SO3H, nitro, cyano and loweralkyl. The term "cycloalkylalkyl" as used herein refers to a cycloalkyl group appended to a loweralkyl radical, including but not limited to cyclohexylmethyl. The term "cycloalkylalkoxy" as used herein refers to a cycloalkyl group appended to an alkoxyl group as defined herein, including but not limited to cyclohexylmethyoxy. The term "cycloalkylamino" as used herein refers to a cycloalkyl group appended to the parent molecular moiety through an amino group as defined herein, including but not limited to cyclohexylamino and the like. The term "cycloalkylalkylamino" as used herein refers to a cycloalkyl group appended to the parent molecular moiety through an alkylamino group as defined herein, including but not limited to cyclohexylmethylamino and the like. The term "cycloalkylidenealkyl" as used herein refers to a cycloalkyl group appended to the parent molecular moiety through a double bond which connects to an alkylene (=(CH 2 ) n -). Examples include cyclopropylideneethyl, cyclobutylidenepropyl and the like. The term "cycloalkyloxy" as used herein refers to a cycloalkyl group appended to the parent molecular moiety through an oxygen atom, including but not limited to cyclohexyloxy and the like. The term "cycloalkenylalkyl" as used herein refers to a cycloalkenyl group appended to a loweralkyl radical, including but not limited to cyclohexenylmethyl. The term "cycloalkenylalkoxy" as used herein refers to a cycloalkenyl group appended to a alkoxyl group as defined herein, including but not limited to cyclohexenylmethyoxy and the like. The term "dialkylamino" as used herein refers to R56R57N- wherein R56 and R57 are independently selected from loweralkyl, for example diethylamino, methyl propylamino, and the like. The term "dialkylaminoaryloxy" as used herein refers a dialkylamino as defined herein appended to the parent molecular moiety through an aryloxy as defined herein. The term "diarylamino" as used herein refers to (R45)(R46)N- wherein R45 and R46 are independently aryl, for example diphenylamino and the like. The term "dialkylaminoalkyl" as used herein refers to a loweralkyl radical to which is appended a dialkylamino group. The term "dialkylaminocarbonyl" as used herein refers to a dialkylamino group, as previously defined, appended to the parent molecular moiety through a carbonyl (-C(O)-) linkage. Examples of dialkylaminocarbonyl include dimethylaminocarbonyl, diethylaminocarbonyl and the like. The term "dialkyiaminocarbonylalkenyl" as used herein refers to an alkenyl radical to which is appended a dialkylaminocarbonyl group. The term "dialkylaminocarbonylalkyl" as used herein refers to R50-C(O)-R51 - wherein R50 is a dialkylamino group and R51 is an alkylene group. The term "halo" or "halogen" as used herein refers to I, Br, Cl or F. The term "haloalkyl" as used herein refers to an alkyl radical, as defined above, which has at least one halogen substituent, for example, chloromethyl, fluoroethyl, trifluoromethyl or pentafluoroethyl, 2,3-difluoropentyl, and the like. The term "haloalkenyl" as used herein refers to an alkenyl radical which has at least one halogen substituent, for example, chloromethenyl, fluoroethenyl, trifiuoromethenyl or pentafluoroethenyl, 2,3-difluoropentenyl, and the like. The term "haloalkenyloxy" as used herein refers to an haloalkenyl group as defined herein appended to the parent molecular moiety through an oxygen atom. The term "haloalkynyl" as used herein refers to an alkynyl radical which has at least one halogen substituent, for example, chloromethynyl, fluoroethynyl, thfluoromethyny! or pentafiuoroethynyl, 2,3-difluoropentynyl, and the like. The term "haloalkoxy" as used herein refers to an alkoxy radical as defined above, bearing at least one halogen substituent, for example, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, trifluoromethoxy, 2,2,3,3,3-pentafluoropropoxy and the like. The term "haloalkoxyalkyl" as used herein refers to a loweralkyl radical to which is appended a haloalkoxy group. The term "haloalkoxyhydroxyalkyl" as used herein refers to a haloalkoxy group as defined herein appended to the parent molecular moiety through a hydroxyalkyl, as defined herein. The term "heterocyclic ring" or "heterocyclic" or "heterocycle" as used herein refers to any 3- or 4-membered ring containing a heteroatom selected from oxygen, nitrogen and sulfur; or a 5-, 6- or 7-membered ring containing one, two or three nitrogen atoms; one oxygen atom; one sulfur atom; one nitrogen and one sulfur atom; one nitrogen and one oxygen atom; two oxygen atoms in non-adjacent positions; one oxygen and one sulfur atom in non-adjacent positions; or two sulfur atoms in non-adjacent positions. Examples of heterocycles include, but are not limited to, thiophene, pyrrole, and furan. The 5-membered ring has 0-2 double bonds and the 6- and 7-membered rings have 0-3 double bonds. The nitrogen heteroatoms can be optionally quaternized. The term "heterocyclic" also includes bicyclic groups in which any of the above heterocyclic rings is fused to a benzene ring or a cycloalkane ring or another heterocyclic ring (for example, indolyl, dihydroindolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, decahydroisoquinolyl, benzofuryl, dihydrobenzofuryl or benzothienyl and the like). Heterocyclics include: aziridinyl, azetidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, oxetanyl, furyl, tetrahydrofuranyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrimidyl and benzothienyl. Heterocyclics also include compounds of the formula where X * is -CH2- or -O- and Y * is -C(O)- or [-C(R")2-]v where R" is hydrogen or Cι -C-4-alkyl and v is 1 , 2 or 3 such as 1 ,3-benzodioxolyl, 1 ,4-benzodioxanyl and the like. Heterocyclics also include bicyclic rings such as quinuclidinyl and the like. Heterocyclics can be unsubstituted or be substituted with one, two , or three substituents independently selected from hydroxy, halo, oxo (=O), alkylimino (R * N= wherein R * is a loweralkyl group), amino, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, alkoxycarbonyl, thioalkoxy, haloalkyl, mercapto, carboxy, carboxaldehyde, carboxamide, cycloalkyl, aryl, arylalkyl, -SO3H, nitro, cyano and loweralkyl. In addition, nitrogen containing heterocycles can be N-protected. The term "heterocyclic alkoxy" as used herein refers to a heterocyclic group as defined above appended to an alkoxy radical as defined above. Examples of heterocyclic(alkoxy) include 4-pyhdylmethoxy, 2-pyridylmethoxy and the like. The term "heterocyclic amino" as used herein refers to a heterocyclic group as defined above appended to an amino as defined above. Examples of heterocyclic amino include 4-pyridylamino, 2-pyridylamino and the like The term "heterocyclic oxy" as used herein refers to a heterocyclic group as defined above appended to the parent molecular moiety through an oxygen. Examples of heterocyclic oxy include 4-pyridyloxy, 2-pyridyloxy and the like. The term "heterocyclic alkyl" as used herein refers to a heterocyclic group as defined above appended to a loweralkyl radical as defined above. The term "heterocyclic alkylamino" as used herein refers to a heterocyclic group as defined above appended to a alkylamino as defined above The term "heterocyclic carbonyloxyalkyl" as used herein refers to R46-C(O)-O-R47- wherein R46 is a heterocyclic group and R47 is an alkylene group. The term "heterocyclic thio" as used herein refers to a heterocyclic group as defined above appended to the parent molecular moiety through an thiol. Examples of heterocyclic thio include 4-pyridylthio, 2-py dylthio and the like The term "hydroxy" as used herein refers to -OH. The term "hydroxyalkenyl" as used herein refers to an alkenyl radical to which is appended a hydroxy group. Examples of hydroxyalkenyl include 3- hydroxypropenyl, 3, 4-dihydroxybutenyl and the like The term "hydroxyalkoxy" as used herein refers to an alkoxy radical as previously defined to which is appended a hydroxy (-OH) group. Examples of hydroxyalkoxy include 3-hydroxypropoxy, 4-hydroxybutoxy and the like. The term "hydroxyalkyl" as used herein refers to a loweralkyl radical to which is appended a hydroxy group. Examples of hydroxyalkyl include 1 -hydroxypropyl, 4-hydroxybutyl, 1 ,3-dihydroxyisopentyl, and the like. The term "hydroxyalkylamino" as used herein refers to a hydroxyalkyl group appenmded to the parent molecular moiety through an amino. Examples of hydroxyalkylamino include 1 -hydroxypropylamino, 4-hydroxybutylamino, 1 ,3- dihydroxyisopentylamino, and the like. The term "hydroxyalkylthio" as used herein refers to a hydroxyalkyl group appenmded to the parent molecular moiety through an thiol. Examples of hydroxyalkylamino include 1 -hydroxypropylthio, 4-hydroxybutylthio, 1 ,3- dihydroxyisopentylthio, and the like The term "mercapto" or "thiol" as used herein refers to -SH. The term "nitro" as used herein refers to -NO2- The term oxoalkoxy refers to a carbonyl group attached to the parent molecular moiety through an alkoxy group. The term "mercaptoalkoxy" or 'thioalkoxy" as used herein refers to R70S- wherein R70 is alkoxy. Examples of thioalkoxy include, but are not limited to, methylthio, ethylthio and the like. The term "tetrazolyl" as used herein refers to a radical of the formula N- N or a tautomer thereof. The term 'tetrazolylalkoxy" as used herein refers to a tetrazolyl radical as defined above appended to an alkoxy group as defined above. Examples of tetrazolylalkoxy include tetrazolylmethoxy, tetrazolylethoxy and the like. The term "thioalkoxyalkoxy" as used herein refers to RδθS-RδlO- wherein RδO is loweralkyl as defined above and Rδl is alkylene. Representative examples of alkoxyalkoxy groups include CH 3 SCH 2 O-, EtSCH 2 O-, t-BuSCH 2 O- and the like. The term "thioalkoxyalkoxyalkyl" as used herein refers to a thioalkoxyalkoxy group appended to an alkyl radical. Representative examples of alkoxyalkoxyalkyl groups include CH 3 SCH 2 CH 2 OCH 2 CH 2 -, CH 3 SCH 2 OCH 2 -, and the like. The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. These salts include but are not limited to the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesuifonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, p-toluenesulfonate and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as loweralkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromides, and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others. Water or oil- soluble or dispersible products are thereby obtained. Examples of acids which may be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. Basic addition salts can be prepared in situ during the final isolation and purification of the compounds of formula (I), or separately by reacting a carboxylic acid function with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia, or an organic primary, secondary or tertiary amine. Such pharmaceutically acceptable salts include, but are not limited to, cations based on the alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium, aluminum salts and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. Other representative organic amines useful for the formation of base addition salts include diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. The term "pharmaceutically acceptable ester" as used herein refers to esters which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyl moiety advantageously has not more than 6 carbon atoms. Examples of particular esters includes formates, acetates, propionates, butyates, acrylates and ethylsuccinates. The term "pharmaceutically acceptable prodrug" as used herein refers to those prodrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term "prodrug" refers to compounds that are rapidly transformed in vivo to provide the parent compound having the above formula, for example by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems. Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design. American Pharmaceutical Association and Pergamon Press, 1967, both of which are incorporated herein by reference. As used throughout this specification and the appended claims, the term metabolically cleavable group denotes a moiety which is readily cleaved in vivo from the compound bearing it, wherein said compound, after cleavage remains or becomes pharmacologically active. Metabolically cleavable groups form a class of groups reactive with the carboxyl group of the compounds of this invention are well known to practitioners of the art. They include, but are not limited to groups such as, for example, aikanoyl, such as acetyl, propionyl, butyryl, and the like; unsubstituted and substituted aroyl, such as benzoyl and substituted benzoyl; alkoxycarbonyl, such as ethoxycarbonyl; trialkylsilyl, such as trimethyl- and triethysilyl; monoesters formed with dicarboxylic acids, such as succinyl, and the like. Because of the ease with which the metabolically cleavable groups of the compounds of this invention are cleaved in vivo, the compounds bearing such groups act as pro-drugs of other prostaglandin biosynthesis inhibitors. The compounds bearing the metabolically cleavable groups have the advantage that they may exhibit improved bioavailability as a result of enhanced solubility and/or rate of absorption conferred upon the parent compound by virtue of the presence of the metabolically cleavable group. Asymmetric centers may exist in the compounds of the present invention. The present invention contemplates the various stereoisomers and mixtures thereof. Individual stereoisomers of compounds of the present invention are made by synthesis from starting materials containing the chiral centers or by preparation of mixtures of enantiomeric products followed by separation as, for example, by conversion to a mixture of diastereomers followed by separation by recrystallization or chromatographic techniques, or by direct separation of the optical enantiomers on chiral chromatographic columns. Starting compounds of particular stereochemistry are either commercially available or are made by the methods detailed below and resolved by techniques well known in the organic chemical arts. Preferred Embodiments Compounds useful in practicing the present invention include, but are not limited to: 2-(2,2,2-Trifluoroethyl)-4-(4-chlorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(3-methyl-3-butenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(4-chloro-3-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone; 2-(4-fluorophenyl)-4-(4-flurophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-hydroxy-2-methyl-1 -propoxy)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone; 2-(4-Fluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone; 2-(f-Butyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)-pyridazinone; 2-(^-Butyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(2,2-dimethylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(2,2,2-Trifiuoroethyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-methylbutoxy)-5-[4-(aminosuifonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(4-fluorophenoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyi)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(4-fluorophenoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(2,2-dimethylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Chloro-3-fluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(4-fluorophenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)- -4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]- 3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2,4-Bis(4-fluorophenyl)-5-(4-methylsulfonyiphenyl)-3(2H)-pyridazinone; 2-(4-fluorophenyl)-4-(4-flurophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; and 2-(3,4-Difluorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-oxopropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methoxy-imino-propoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone; (R)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone; (S)- 2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone; (R)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)- phenyl]-3(2H)-pyridazinone; (S)- 2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)- phenyl]-3(2H)-pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-oxo-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-oxo-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; and 2,4-Bis(4-Flurophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone; or a pharmaceutically acceptable salt, ester, or prodrug thereof. More preffered compounds of the present invention include, but are not limited to: 2-Phenyl-4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)-pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(4-chlorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difiuorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; and 2,4-Bis(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)-pyridazinone; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Preparation of Compounds of the Invention The compounds of the invention may be prepared by a variety of synthetic routes. Representative procedures are outlined in Schemes1 -3, below. A general route to the compounds of the invention having Formula III, where the aryl group at the 5-position on the pyridazinone ring is substituted with a sulfonyl group is described in Scheme 1 , below. The dichloro-3(2H)-pyridazinone is reacted with benzyl chloride and potassium carbonate in methanol. The 2- benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone is then treated with a boronic acid such as 4-fluorobenzeneboronic acid (shown) and a palladium catalyst. The methoxy group was hydrolyzed with 48% hydrobromic acid to furnish the 5- hydroxypyridazinone compound. The 5-hydroxypyridazinone product was treated with triflic anhydride followed by substitution on the pyridazinone ring using 4- methylthiobenzeneboronic acid. This furnished the methyl thioether compound which was reacted with peracetic acid in acetic acid and methylene chloride to provide the methyl sulfone. The benzyl group is removed using aluminum bromide or another suitable Lewis acid. The R group can be added via substitution using an appropriate alkylating agent and base. SCHEME 1 Another route to the compounds of the invention having Formula III is described in Scheme 2, below. The 4-bromothioanisole or other suitable thioether is reacted with a trialkoxyborate, such as trimethoxyborate or triisopropylborate to convert it to 4-(Methylthio)benzeneboronic acid . The boronic acid is reacted with 2-benzyl-4,5-dibromo-3(2H)-pyridazinone using tetrakis(triphenylphosphine)- palladium (0) in dimethoxyethane. The product is then coupled with a second boronic acid such as 4-fluorobenzeneboronic acid (shown) and a palladium catalyst to provide the thioether. This furnished the methyl thioether compound which was reacted with meta-chloroperoxybenzoic acid (MCPBA) in methylene chloride to provide the methyl sulfone. The benzyl group is removed using aluminum bromide or another suitable Lewis acid. The R group can be added via substitution using an appropriate alkylating agent and base. SCHEME 2 A third route to the compounds of the invention having Formula III is described in Scheme 3, below. (4-Thiomethylphenyl)dimethylthioketene acetal, mono-S-oxide was prepared by reaction of 4-thiomethylbenzaldehyde (Y is CH3S) with methyl(methylsulfinylmethyl)sulfide and sodium hydroxide. The thioketene acetal and methyl 4-fluorophenylacetate or suitable ester (X is fluorine) were treated with a strong base such as sodium hexamethyldisilazide in THF to provide the butyrate ester. The dithioacetal ketene was directly cyclized to the unsubstituted pyridazinone using hydrazine and a salt. The pyridazinone was oxidized with peroxyacetic acid to provide the sulfonyl pyridazone. In an alternate route, Scheme 3-A, the thioacetal ketene was treated with perchloric acid to provide an ester-aldehyde as a mixture of diastereomers. The oxidation products were treated with hydrazine and then oxidized with peroxyacetic acid to obtain the sulfonyl dihydropyridazinone. The dihydropyridazinone can be dehydrogenated to form the pyridazinone by treatment with reagents such as bromine in acetic acid. The R group may be added via substitution using an appropriate alkylating agent and base. SCHEME 3 SCHEME 3A The preparation of the 5-hydroxy-2(5H)-furanones can be accomplished by the application of methodologies published in a variety of sources, including: J. Med. Chem., 1987, 30, 239-249 and WO 96/36623, hereby completely incorporated by reference, and are shown in Scheme 4. SCHEME 4 Method IV: A general route to the compounds of the invention having Formula III, where the aryl group at the 5-position on the pyridazinone ring is substituted with a sulfonyl group ring is described in Scheme 5, below. A mucohalo acid, such as, for example, mucobromic or mucochloric acid, is reacted with an hydrazine having the desired R group to provide the dihalopyridazinone compound, 5A. Treatment of the dihalo-compound with an alcohol in the presence of a base, such as, for example, sodium or potassium hydride, will provide an alkoxide, 5B. (If the alkoxy group is to be removed at a . later time then methanol is the preferred alcohol.) Reaction of the alkoxy-halide with a methylthiophenyl boronic will provide the alkoxy-pyridazinone 5C. The alkoxy group can be converted to a hydrocarbyl group by treatment with a Ghgnard reagent to provide the thioether 5D. The thioether can be oxidized with an oxidizing agent, such as, for example, peracetic acid, meta-chloroperoxybenzoic acid and the like, to form the sulfinyl compound 5G, or the methylsulfone compound 5E. Rearrangement and hydrolysis of the sulfinyl compound, 5G, provides the thiophenol. The thiophenol is then oxidized, activated and aminated to convert it to the amino-sulfonyl compound 5H. Alternatively, the methylsulfonyl compound, 5E, can be converted to the amino- sulfonyl compound by 5H by treatment of the methylsulfonyl compound with a diazodicarboxylate, such as, for example, DBAD, DIAD, DEAD and the like, and a disilazane anion, such as, for example, lithium HMDS and the like, followed by treatment with sodium acetate and hydroxylamine-O-sulphonic acid in water provides the aminosulfonyl compound, 5H. SCHEME 5 5A 5B R97 °W R + B(0H)2 5B 5C 5C 5D 5E 5E 5G 5H Alternatively, the alkoxy-pyridazinone 5C can be oxidized, as shown in Scheme 5A. The first step is employing an oxidizing agent, such as, for example, peracetic acid, meta-chloroperoxybenzoic acid and the like, to form the sulfinyl compound 5G\ or the methylsulfone compound 5E'. Rearrangement and hydrolysis of the sulfinyl compound provides the thiophenol. The thiophenol is then oxidized, activated and aminated to convert it to the amino-sulfonyl compound 5H'. Finally, the methylsulfonyl compound can be converted to the aminosulfonyl compound by 5H' by treatment of the methylsulfonyl compound 5E' with a diazodicarboxylate, such as, for example, DBAD, DIAD, DEAD and the like, and a disilazane anion, such as, for example, lithium HMDS and the like, followed by treatment with sodium acetate and hydroxylamine-O-sulphonic acid in water provides the aminosulfonyl compound, 5H'. SCHEME 5A 5C 5G" 5H' Preparation of compounds of the invention having Formula III, where the group at the 4-position on the pyridazinone ring is a substituted alkyl or alkenyl group is described in Scheme 6A, below. The thioether 5E, where R Q 6 is alkyl, e.g., methyl shown, is halogenated with a halogenating reagent, such as, for example, NBS and peroxide, to provide the bromo compound 6A. The bromo compound can be reacted with an alcohol and a weak base, such as, for example, sodium or potassium carbonate to provide the 4-alkyl-ether, 6B. The bromo compound can be reacted with a thio compound in the presence of a base, such as, for example, silver carbonate, to provide the 4-alkyl-thioether, 6C. The bromo compound can be reacted with an amine and a weak base, such as, for example, sodium or potassium carbonate to provide the 4-alkyl amino-alkyl compound 6D. SCHEME 6 4E 5A 5A 5C 5A 5D A general route to the compounds of the invention having Formula III, where the group at the 4-position on the pyridazinone ring can be readily substituted is illustrated in Scheme 6, above. The synthesis starts with the alkoxide, 5E', where R 97 is methyl. The methoxy compound is treated with a base, such as, for example, sodium or potassium hydroxide, to provide the 4-hydroxy-pyradizinone, 6A. The alcohol is treated with p-toluenesulfonyl chloride to provide the tosyloxy compound, 6B. The tosyloxy compound can be readily substituted with a compound R 2z' that ' can undergo an SN2 reaction. Examples of these compounds are compounds such as alcohols, thiols, amines or hydrocarbyl anions. SCHEME 6A As used throughout this specification and the appended claims, the following abbreviations have been used: ACD for acid citrate dextrose, CAP for carrageenan induced air pouch prostaglandin, CIP for rat carrageenan pleural inflammation model, COX-2 for cyclooxygenase-2, CPE for carrageenan induced paw edema in rats, DBAD for di-t- butylazodicarboxylate, DEAD for diethyl azodicarboxylate, DIAD for disopropyl azodicarboxylate, DMAP for 4-(dimethylamino)pyridine, DME for 1 ,2-dimethoxyethane, DMF for N,N-dimethylformamide, DMSO for dimethyl sulfoxide, DMSO for dimethyl sulfoxide, EDTA for ethylenediaminetetraacetic acid, EIA for enzyme immunoassay, FAB for fast atom bombardment, GI for gastrointestinal, HMDS, lithium or Li HMDS for lithium 1 ,1 ,1 ,3,3,3- hexamethyldisilazide, HWPX for Human Whole Platelet Cyclooxygenase-1 , MCPBA for meta-chloroperoxybenzoic acid, NSAIDs for non-steroidal anti- inflammatory drugs, PEG 400 for polyethyleneglycol, PGE2 for prostaglandin E , PGHS for prostaglandin endoperoxide H synthase, RHUCX1 for recombinant human cyclooxygenase-1 , RHUCX2 for recombinant human cyclooxygenase-2, r- hu Cox1 for recombinant human Cox-1 , TEA for Triethylamine, TFA for Trifluoroacetic acid, and THF for Tetrahydrofuran and WISH for human amnionic whole cell cyclooxygenase-2. The following examples illustrate the process of the invention, without limitation. Compounds of the present invention include, but are not intended to be limited to, the following Examples: Example 1 4-( r Methylthio enzeneboronic acid A stirred solution of 4-bromothioanisole (5.0 g, 0.0246 mol) in anhydrous tetrahydrofuran (THF) was chilled to -78 °C under a nitrogen atmosphere. A 2.5 M solution of n-butyl lithium (12 mL, 0.030 mol) in hexanes was added dropwise to the chilled solution. When the addition was complete, the reaction mixture was stirred at -78 °C for about 45 minutes. Trimethylborate (8.5 mL, 0.0748) was introduced via syringe. The reaction mixture was then allowed to warm to room temperature overnight. The room temperature solution was treated successively with 10% aqueous sodium hydroxide solution (50 mL) and water (33.5 mL) and stirred at room temperature for 1 hour. The reaction mixture was lowered to about pH = 4-5 using 10% aqueous citric acid and the THF was removed under reduced pressure. The aqueous residue was saturated with sodium chloride and extracted with ethyl acetate. The organic extract was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to provide a white solid which was washed with hexanes to provide the product as a white solid (yield: 1.5 g; 36%). M.p. 170 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 2.47 (s, 3H), 7.20 (d, J = 8 Hz, 2H), 7.71 (d, J = 8 Hz, 2H), 7.96 (br s, 2H). Example 2 2-Benzyl-4.5-dibromo-3(2H pyridazinone Benzyl bromide (0.59 mL, 0.005 mol) was added to a stirred solution of 4,5- dibromo-3(2H)-pyridazinone (1.27 g, 0.005 mol) and potassium carbonate (0.76 g, 0.0055 mol) in 20 mL of anhydrous dimethylformamide (DMF). The solution was stirred overnight at room temperature, and partitioned between aqueous citric acid and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to provide a beige solid, which was purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate). The product was obtained as a white solid (yield: 1.32 g, 76.7%). M.p. 95-96 °C. 1 H NMR (300 MHz, CDCI3) δ 5.31 (s, 2H), 7.29-7.37 (m, 3H), 7.41 -7.47 (m, 2H), 7.79 (s, 1 H). MS (DCI-NH3) m/z 345 (M+H)+. IR (KBr) 1645 crτf1. Example 3 2-Benzvl-4-bromo-5-[4-(methvlthio^phenvl]-3(2H)-pvridazinone A solution of the boronic acid (0.318 g, 0.0018δ9 mol), prepared according to the method of Example 1 , the dibromopyridazinone (0.975 g, 0.002634 mol), prepared according to the method of Example 2, and tetrakis(triphenylphosphine)- palladium (0) (0.16 g, 0.0142 mol), in dimethoxyethane (30 mL) was prepared. A 2 M aqueous solution of sodium carbonate (2.63 mL, 0.005668 mol) was added to the dimethoxyethane solution and the mixture was heated at reflux. After 16 hours, a chromatographic (TLC) check (9:1 hexanes/ethyl acetate) indicated that both starting materials were still present and a fresh aliquot of palladium catalyst was added. The reaction mixture was stirred at reflux for an additional 5 hours, allowed to cool to room temperature and stand over the weekend. The volatile materials were removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide an oil which was purified by column chromatography (silica gel, 95:5 hexanes/ethyl acetate). Fractions containing the desired product were combined and concentrated under reduced pressure. This material was rechromatographed (95:5 hexanes/ethyl acetate) to furnish 0.200 g of a beige solid. The solid was crystallized from ether/hexanes to provide white crystals (yield: 110 mg, 15%) M.p. 115-118 °C. 1 H NMR (300 MHz, CDCI3) δ 2.53 (s, 3H), 5.40 (s, 2H), 7.30-7.42 (m, 7 H), 7.49-7.54 (m, 2H), 7.65 (s, 1 H). MS (DCI-NH3) m/z 337 (M+H)+. Example 4 2-Benzyl-4-(4-fluorophenvπ-5-[4-(methylthio^phenyl]-3f2HVpyridazinone A solution of the product prepared in Example 3, (0.100 g, 0.000258 mol), 4- fluorobenzeneboronic acid (0.072 g, 0.000516 mol), tetrakis(triphenylphosphine)- palladium (0) (0.015 g, 0.000013 mol), and a 2 M aqueous solution of sodium carbonate (0.64 mL, 0.001291 mol) in 30 mL of dimethoxyethane (DME) was stirred at reflux for 16 hours. A fresh aliquot of palladium catalyst was added with an additional equivalent of the boronic acid. The reaction was maintained at reflux for 24 hours. The volatile materials were removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, and filtered. The filtrate was adsorbed onto silica gel. The silica gel/product was placed at the top of a column of silica gel and the product eluted with 93:7 hexanes/ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure. The residue was purified further by a second column chromatography (silica gel, 95:5 hexanes/ethyl acetate). Fractions containing product were concentrated under reduced pressure to provide a viscous oil (yield: 0.028 g, 27%). 1 H NMR (300 MHz, CDCI3) δ 2.46 (s, 3H), 5.39 (s, 2H), 6.95 (t, J = 9 Hz, 2H), 6.99 (d, J = 9 Hz, 2H), 7.11 (d, J = 9 Hz, 2H), 7.16-7.23 (m, 2H), 7.30-7.40 (m, 3H), 7.52-7.57 (m, 2H), 7.66 (s, 1 H). MS (DCI- NH3) m/z 403 (M+H)+. Example 5 2-Benzyl-4-(4-fluorophenyπ-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone A solution of mefa-chloroperoxybenzoic acid (MPCBA) (0.039 g, 0.00013 mol) in dichloromethane (5 mL) was added dropwise to a stirred solution of the sulfide (0.027 g, 0.000067 mol), prepared according to the method of Example 4, in chilled (0 °C) dichloromethane (10 mL). After 5 minutes, TLC (1 :1 hexanes/ethyl acetate) indicated that the starting sulfide had been consumed. The reaction was quenched with aqueous sodium sulfite. The organic layer was washed twice with aqueous sodium hydroxide and once with brine. The dichloromethane solution was dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 7:3 hexanes/ethyl acetate) to provide the desired sulfone product. Further elution with 100% ethyl acetate removed the sulfoxide from the column. The sulfoxide product was re-subjected to the MCPBA oxidant (0.04 g, 1 hour, 0 °C) and worked-up as described above. The residue obtained was combined with the sulfone from the first column and the mixture was purified by column chromatography (silica gel, 7:3 hexanes/ethyl acetate). Fractions containing product were combined and concentrated under reduced pressure. The residue was crystallized from ether/hexanes to provide the product as white crystals (yield: 13 mg, 44.6%). M.p. 101 -103 °C. 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 5.40 (s, 2H), 6.95 (t, J = 9 Hz, 2H), 7.12-7.20 (m, 2H), 7.28-7.41 (m, 3H), 7.31 (d, J = 9 Hz, 2H), 7.58-7.53 (m, 2H), 7.84 (s, 1 H), 7.87 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 435 (M+H)+. MS (FAB, high res.) calculated: m/z 435.1179 (M+H)+, found: m/z 435.1184 (M+H)+. Example 6 P-Ren?yl-4-t4-fluorophenvn-5-methoxy-3(2HVpyridazinone To a mixture of 2-benzyl-5-methoxy-4-bromo-3(2H)-pyridazinone, prepared according to the method of S. Cho et al. described in J. Het. Chem., 1996,33, 1579-1582, , (2.94 g; 10 mmol), 4-fluorobenzeneboronic acid (1.54 g; 11 mmol), and CsF (3.04 g; 22 mmol) in 25 mL of anhydrous DME, under N2, was added Pd(Ph3P)4 (347 mg 0.3 mmol). After addition, the mixture was heated at reflux for at 100 °C, for 18 hours. The mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The acetate layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The solid residue was suspended in ethyl ether-hexanes and filtered to provide a solid product (yield: 3.1 g; about 100%; > 95% purity). 1 H NMR (300 MHz, CDCI3) δ 3.90 (s, 3H), 5.36 (s, 2H), 7.09 (t, J = 9 Hz, 2H), 7.31 (m, 3H), 7.50 (m, 4H), 7.91 (s, 1 H). MS (DCI-NH3) m/z 311 (M+H)+, 328 (M+NH4)+. Example 7 2-Benzyl-4-f4-fluorophenyl)-5-hvdroxy-3(2H)-pyridazinone A mixture of the product prepared according to the method of Example 6 (1.24 g; 4 mmol) in 20 mL of acetic acid was treated with aqueous 48% HBr (25 mL). The mixture was heated at reflux for about 5 to about 8 hours (TLC analysis). The mixture was concentrated in vacuo. The product was dissolved in ethyl acetate, washed with 10% bicarbonate, brine and concentrated in vacuo. The residue was treated with diethyl ether-hexanes (2:1 ) and the solid was filtered to provide an almost pure product (yield: 1.16 g; 98%) . 1 H NMR (300 MHz, DMSO- dβ) δ 5.24 (2H), 7.21 (m, 2H), 7.30 (m, 5H), 7.55 (m, 2H), 7.85 (s, 1 H), 11.31 (broad s, 1 H). MS (DCI-NH3) m/z 296 (M+H)+, 314 (M+NH4)-*-. Example 8 2-Benzyl-4-(4-fluorophenvπ-5-ftrifluoromethylsulfonyloxyV3^2H pyridazinone A solution of the product prepared according to the method of Example 7, (89 mg, 0.3 mmol) in 2.5 mL of anhydrous pyridine was prepared under a N atmosphere and maintained at 0 °C. Triflic anhydride (Tf2θ; 0.06 mL; 0.32 mmol) was added to the solution, dropwise. The resulting mixture was stirred at 0 °C for 5 minutes and at room temperature for 16 hours. (The pyridine and Tf 2 O should be pure for good results. Occasionally an additional amount of Tf2θ is necessary to force the reaction to completion.) The mixture was then poured to a cold solution of citric acid and extracted with ethyl acetate to obtain an almost pure product (yield: 127 mg, about 99%). 1 H NMR (300 MHz, DMSO-dδ) δ 5.34 (s, 2H), 7.35 (m, 7H), 7.60 (m, 2H), 8.48 (s, 1 H). MS (DCI-NH3) m/z 429 (M+H)+, 446 (M+NH4) + . Example 9 2-Benzyl-4-C4-fluorophenvπ-5-[4-(methylthio^phenyl]-3(2HVpyridazinone A mixture of the product prepared according to the method of Example 8 (154 mg, 0.36 mmol), 4-(methylthio)benzeneboronic acid (67 mg, 0.4 mmol), E.3N (0.11 mmol; 0.8 mmol) and Pd(Ph3P)4 (30 mg, 0.025 mmol) in 15 mL of toluene was heated at reflux, about 100 °C for about 45 minutes. The mixture was concentrated in vacuo and the residue purified by column chromatography (hexanes-ethyl acetate 3:1 ) to provide the title compound (yield: 96 mg, 68%). 1 H NMR (300 MHz, CDCI3) δ 2.47 (s, 3H), 5.38 (s, 2H), 6.98 (m, 4H), 7.12 (m, 2H), 7.20 (m, 2H), 7.35 (m, 3H), 7.54 (m, 2H), 7.86 (s, 1 H). MS (DCI-NH3) m/z 403 (M+H)+, 420 (M+NH4)+. Example 10 2-Benzvl-4-f4-fluorophenvl)-5-[4-(methvlsulfonvhphenvl1-3.2H)-pyridazinons To a solution of the product prepared according to the method of Example 9 (140 mg, 0.348 mmol), in 10 mL of CH2CI2, at 0 °C was added peracetic acid (CH3COOOH; 0.5 mL; 30%). The mixture was stirred at 0 °C for 90 minutes. The dichloromethane was then removed in vacuo. The residue was dissolved in ethyl acetate, washed with 10% NaHCO3, and brine. The ethyl acetate was removed under reduced pressure. The residue was chromatographed (silica gel, CH2CI2- diethyl ether 19:1 ) to provide the title compound (yield: 130 mg, 86%). 1 H NMR (300 MHz, CDCI3) δ 3.04 (s, 3H), 5.40 (s, 2H), 6.95 (m, 2H), 7.16 (m, 2H), 7.33 (m, 5H), 7.55 (m, 2H), 7.86 (m, 3H). MS (DCI-NH3) m/z 434 (M+H)+, 452 (M+NH4)+. Example 11 4-.4-Fluoroph9nyl)-5-[4-(methylsulfonyl.phenyl]-3(2H)-pyridazinone A mixture of the product prepared according to the method of Example 10 (37 mg, 0.0δ5 mmol) and AIBr3 (70 mg, 0.26 mmol) in 10 mL of toluene was heated at reflux, about 80 °C for about 15 minutes and cooled to 0 °C. The cooled mixture was treated with 1 N HCl and extracted with ethyl acetate. The acetate layer was washed with water, brine and concentrated in vacuo. Purification of the residue on silica gel column (ethyl acetate as an eluent) provided the title compound (yield: 22 mg, 76%). 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 7.00 (t, J = 9 Hz, 2H), 7.20 (m, 2H), 7.56 (d, J = 9 Hz, 2H), 7.86 (s, 1 H), 7.91 (d, J = 9 Hz, 2H), 10.94 (broad s, 1 H). MS (DCI-NH3) m/z 345 (M+H)+, 362 (M+NH4)+. Example 12 2-Phenyl-4-(4-fluorophenvπ-5-[4-(methylsulfonvπphenyl]-3(2HVpyridazinone 12A. 2-Phenyl-4-chloro-5-methoxy-3( , 2H1-pyridazinone The 2-phenyl-4-chloro-5-methoxy-3(2H)-pyridazinone compound was prepared according to the method of S. Cho et al. described in J. Het. Chem., 1996, 33, 1579-1582, , starting with the N-phenyl-dichloropyridazinone. A mixture of 2-phenyl-4,5-dichloro-3(2H)-pyridazinone (1 g, 4.1 mmol) and finely powdered, anhydrous K2CO3 (580 mg, 4.2 mmol) in 50 mL of methanol was heated at reflux for 5 hours and concentrated in vacuo. The residue was partitioned between water and ethyl acetate. The acetate layer was washed with water, and brine to provide 2-phenyl-4-chloro-5-methoxy-3(2H)-pyridazinone (yield: 920 mg, 95%). 1 H NMR (300 MHz, DMSO-d6) δ 4.15 (s, 3H), 7.50 (m, 5H), 8.43 (s, 1 H). MS (DCI-NH3) m/z 237 (M+H)+, 254 (M+NH4) + - 12B. 2-Phenyl-4-( , 4-fluorophenvπ-5-methoxy-3(2H pyridazinone The 2-phenyl-4-chloro-5-methoxy-3(2H)-pyridazinone product was coupled with 4-fluorophenylboronic acid according to the method of Example 6 to provide 2- phenyl-4-(4-fluorophenyl)-5-methoxy-3(2H)-pyridazinone (yield: 1.1 g; 96%). 1 H NMR (300 MHz, CDCI3) δ 4.00 (s, 3H), 7.10 (t, J = 9 Hz, 2H), 7.45 (m, 3H), 7.60 (m, 4H), 8.06 (s, 1 H). MS (DCI-NH3) m/z 297 (M+H)+. 12C. 2-Phenyl-4-(4-fluorophenylV5-hvdroxy-3(2HVpyridazinone The 2-phenyl-4-(4-fluorophenyl)-5-methoxy-3(2H)-pyridazinone product was treated with 48% HBr according to the method of Example 7 to furnish 2-phenyl-4- (4-fluorophenyl)-5-hydroxy-3(2H)-pyridazinone (yield: 957 mg, 92%). MS (DCI- NH3) m/z 283 (M+H)+, 300 (M+NH4)+. 12D. 2-Phenyl-4-(4-fluorophenvπ-5-trifluoromethanesulfonyloxy-3(2HV pyridazinone The 2-phenyl-4-(4-fluorophenyl)-5-hydroxy-3(2H)-pyridazinone product was sulfonylated according to the method of Example δ to furnish 2-phenyl-4-(4- fluorophenyl)-5-trifluoromethanesulfonyloxy-3(2H)-pyridazinone (yield: 1.35 g; 96%) MS (DCI-NH3) m/z 415 (M+H)+, 432 (M+NH4)+. 12E. 2-Phenyl-4- ( 4-fluorophenvn-5-[4-fmethylsulfonvnphenyl1-3f2HVpyridazinone The 2-phenyl-4-(4-fluorophenyl)-5-trifluoromethanesulfonyloxy-3(2H)- pyridazinone was coupled with 4-(methylthio)phenylboronic acid as in Example 9 to provide 2-phenyl-4-(4-Fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (yield: 915 mg, 92%) which was immediately oxidized with peracetic acid as in Example 9 to provide the title compound after column chromatography (silica gel, 1 :1 hexanes-ethyl acetate) and crystallization from diethyl ether-hexanes (yield: 2δδ mg, 69%). M.p. 219-220 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 3.25 (s, 3H), 7.15 (t, J = 9 Hz, 2H), 7.30 (m, 2H), 7.46 (m, 1 H), 7.56 (m, 4H), 7.64 (m, 2H), 7.90 (d, J = 9 Hz, 2H), 6.24 (s, 1 H). MS (DCI-NH3) m/z 421 (M+H)+, 438 (M+NH4) + . Example 13 4-Fluorophenylacetic acid, methyl ester A catalytic amount (0.5 mL) of concentrated sulfuric acid was added to a solution of 4-fluorophenyiacetic acid (30.8 g, 0.20 mol) in 500 mL of methanol. The solution was stirred at reflux for 4 hours. The volatile materials were removed under reduced pressure to furnish a colorless oil which was dissolved in ether/ethyl acetate and washed with 2 N aqueous Na2CO3, brine, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide an oil which was dried overnight under high vacuum (yield: 33.6 g; 95%). 1 H NMR (300 MHz, CDCI3) δ 3.59 (s, 2H), 3.65 (s, 3H), 7.01 (t, J = 9 Hz, 2H), 7.20-7.28 (m, 2H). MS (DCI-NH3) m/z 166 (M+NH4)+. Example 14 [4-(Methylthio^phenyl]dimethylthioketene acetal. mono-S-oxide A mixture of methyl(methylsuifinylmethyl)sulfide (50 g, 0.40 mol), and finely powdered sodium hydroxide (3.12 g, 0.07δ mol) was stirred at 70 °C for 4 hours. 4- (Methylthio)benzaldehyde (27.4 mL, 0.195 mol) was then added in one lot and the reaction mixture was stirred at 70 °C for an additional 4 hours. The mixture was cooled to room temperature and partitioned between 10% aqueous citric acid and dichloromethane. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to provide a brown oil. The oil was purified by column chromatography (7:3 hexanes/ethyl acetate) to provide a solid. The solid was crystallized from ether/hexanes (yield: 24.7 g; 72%). M.p. 52- 53 °C. 1 H NMR (300 MHz, CDCI3) δ 2.33 (s, 3H), 2.53 (s, 3H), 2.77 (s, 3H), 7.17 (d, J = 9 Hz, 2H), 7.57 (s, 1 H), 7.36 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 259 (M+H)+ and m/z 276 (M+NH4) + . Example 15 2-(4-Fluorophenyl)-3-[4-(methylthio^phenyl]-4-methylthio-4-methylsulfinyl-n-butyric acid, methvl ester A solution of the ester product, prepared according to the method of Example 13, (16.24 g, 0.0966 mol) in 50 mL of THF was added dropwise to a stirred solution of 1.0 M sodium hexamethyldisilazide in THF (96.6 mL, 0.0966 mol), maintained at 0 °C, under an atmosphere of dry nitrogen. After 30 minutes, a solution of the ketene thioacetal, prepared according to the method of Example 14 (20.8 g, 0.0805 mol), in 50 mL of THF, was added dropwise to the reaction mixture maintained at 0 °C. After 4 hours, the reaction mixture was acidified with 10% aqueous citric acid. The aqueous layer was washed twice with ethyl acetate. The organic extracts were combined, washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to provide a brown oil which was purified by column chromatography (85:15 to 1 :1 dichloromethane/ethyl acetate gradient). Several products having different Rf values and NMR spectra were isolated. These compounds had identical mass spectra. The mixture of compounds was carried on in the following reactions (yield: 22.4 g; 65%). MS (DCI-NH3) m/z 444 (M+NH4)+. Example 16 2-f4-Fluorophenvπ-3-[4-fmethylthio^phenyl]-3-formyl-n-propanoic acid, methyl ester The mixture of compounds, prepared according to Example 17, (9.0 g, 0.021 mol) was dissolved in acetonitrile (80 mL) and cooled to 0 °C. Perchloric acid (60%; 1.06 g, 0.006 mol) was added to the stirred solution. The reaction mixture was stirred at 0 °C for 8 hours, and quenched with 2 N aqueous Na2CO3. The acetonitrile was removed under reduced pressure and the resulting aqueous mixture was extracted with ethyl acetate. The organic solution was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to give a yellow oil which was purified by column chromatography (silica gel, 7:3 hexanes/ethyl acetate). Fractions containing the highest Rf diastereomers from the product mixture were concentrated in vacuo and the residue was crystallized from methanol to furnish the title aldehyde-ester compound as white crystals (yield: 0.27 g, 4.0%). M.p. = 112-113 °C. 1 H NMR (300 MHz, CDCI3) δ 2.49 (s, 3H), 2.46 (s, 3H), 4.39 (s, 2H), 7.03 (t, J = 9 Hz, 1 H), 7.21 (d, J = 9 Hz, 1 H), 7.25 (d, J = 9 Hz, 2H), 7.40-7.47 (m, 2H). MS (DCI-NH3) m/z 333 (M+H)+ and m/z 350 (M+NH4)+. Fractions containing lower Rf compounds from the product mixture were concentrated in vacuo and the residue was identified as the hydrate of the aldehyde-ester (yield: 2.6 g, 35.2%). 1 H NMR (300 MHz, CDCI3) δ 2.44 & 2.46 (2 s, 3H), 3.56 & 3.4δ (2 s, 3H), 3.55 & 3.76 (2 dd, J = 6 Hz, J = 6 Hz, 1 H), 3.93 & 4.26 (2 d, J = 12 Hz, 1 H), 5.41 & 5.47 (2 d, J = 6 Hz, 1 H), 6.96 & 7.00 (t, J = 9 Hz, 2H), 7.11 - 7.26 (m, 6H). MS (DCI-NH3) m/z 333 (M+H)+ and m/z 350 (M+NH4)+. The lowest Rf compound was identified as the hydroxy lactone formed when a hydroxy group from the hydrate displaces the methoxy group from the ester (yield: 1.1 g, 16.4%). 1 H NMR (300 MHz, CDCI3) δ 2.45 (s, 3H), 3.54-3.71 (m, 1 H), 3.98- 4.21 (m, 1 H), 4.61 (broad s, 1 H), 5.85-6.01 (m, 1 H), 6.98 (t, J = 9 Hz, 2H), 7.12-7.27 (m, 6H). MS (DCI-NH3) m/z 336 (M+NH4)+. Example 17 4-(4-Fluorophenyl)-5-[4-(methylthio)phenyl]-4.5-dihydro-3(2H)-pyridazinone The aldehyde-ester, hydrate, and hydroxy lactone prepared in Example 16 (0.10 g, 3 mmol), were dissolved in 100 mL of ethanol. This solution was treated with hydrazine monohydrate (0.15 mL, 30 mmol) and the resulting solution was stirred at reflux in a Soxhelet apparatus containing molcular sieves. After 1 δ hours, the reaction mixture was cooled and the volatile materials removed under reduced pressure. The residue was partitioned between ethyl acetate and aqueous HCl. The aqueous layer was washed twice with ethyl acetate. The combined organic extracts were washed twice with brine, dried over MgS04, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (4:1 hexanes/ethyl acetate) to obtain the title compound (yield: 50 mg, 53%). 1 H NMR (300 MHz, CDCI3) δ 2.46 (s, 3H), 3.75 (d, J = 12 Hz, 1 H), 3.67 (d, J = 12 Hz, 1 H), 6.93-7.08 (m, 6H), 7.16 (d, J = 9 Hz, 2H), 8.71 (s(broad), 1 H). MS (DCI-NH3) m/z 315 (M+H)+ and m/z 332 (M+NH4)+. Example 18 4-(4-Fluorophenyl)-5-[4-(m9thylsulfonvhphenyl]-4.5-dihvdro-3(2H)-pyridazinone A solution of peracetic acid, 32% in acetic acid, (0.4 mL, 1.6 mmol) was added to a stirred solution of the sulfide, prepared according to the method of Example 17, (0.050 g, 0.16 mmol) in dichloromethane, and maintained at 0 °C. The reaction mixture was stirred for 5 hours at 0 °C then diluted with water. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to provide an oil which solidified on trituration with ether (yield: 47 mg, 85%). 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 3.77 (d, J = 12 Hz, 1 H), 4.05 (d, J = 12 Hz, 1 H), 6.95-7.08 (m, 4H), 7.28 (d, J = 9 Hz, 2H), 7.90 (d, J = 9 Hz, 2H), 8.75 (s, broad, 1 H). MS (DCI-NH3) m/z 364 (M+NH4)+. Example 19 4- 4-Fluorophenvn-5-[4-(methylsulfonvπphenyl]-3(2HVpyridazinone The dihydropyridazinone product prepared according to the method of Example 18 (47 mg, 0.136 mmol) was dissolved in acetic acid (25 mL). Bromine (0.025 mL, 0.16 mmol) was added to the solution and the reaction mixture was stirred at 95 °C for 20 minutes. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over MgS04 and filtered. The filtrate was concentrated under reduced pressure to provide a solid which was eluted through a short pad of silica gel with ethyl acetate. The title compound was crystallized from ethyl acetate/hexanes (yield: 35 mg, 75%). M.p. 255-256 °C 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 6.96 (t, J = 9 Hz, 2H), 7.16-7.23 (m, 2H), 7.35 (d, J = 9 Hz, 2H), 7.66 (s, 1 H), 7.91 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 345 (M+H)+ and m/z 362 (M+NH4)+. Example 20 2- 4-Fluorobenzvh-4- 4-fluorophenvn-5-[4-(methylsulfonyl)phenyl1-3(2H pvridazinone A solution of the nitrogen-unsubstituted pyridazinone product, prepared in Example 19 (160 mg, 0.465 mmol), K2CO3 (193 mg, 1.4 mmol), 4-fluorobenzyl- bromide (0.09 mL, 0.7 mmol) and Nal (catalytic) in 10 mL of anhydrous N,N-dimethylformamide (DMF) was stirred at room temperature for 18 hours. The reaction mixture was quenched with 2N HCl, extracted with ethyl acetate (2 x 20 mL), washed with brine and water, dried over MgSθ4, filtered and concentrated in vacuo. The residue was purified by column chromatography (2:2:6 ethyl acetate/dichloromethane/pentanes). Crystallization from ether/pentanes provided white crystals (yield: 110 mg, 52%). M.p. 153-154 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 5.36 (s, 2H), 6.96 (t, J = 8.4 Hz, 2H), 7.04 (t, J = 8.7 Hz, 2H), 7.16 (dd, J = 9.1 Hz, J = 5.4 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 7.54 (dd, J = 8.8 Hz, 5.5 Hz, 2H), 7.84 (s, 1 H), 7.87 (d, J = 8.8 Hz, 2H). MS (DCI-NH3) m/z 453 (M+H)+. Example 21 2-(Phenylproparαvh-4-f4-fluorophenvh-5-f4-fmethylsulfnnyl)phenvη-3ι2H pvridazinone The title compound was prepared according to the method of Example 20, substituting phenylpropargyl bromide for 4-fluorobenzyl bromide. M.p. 100-103 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 5.26 (s, 2H), 6.97 (t, J = 9 Hz, 2H), 7.20 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.31 (m, 3H), 7.34 (d, J = 9 Hz, 2H), 7.48 (m, 2H), 7.89 (d, J = 9 Hz, 2H), 7.9 (s, 1 H). MS (DCI-NH3) m/z 459 (M+H)+. Example 22 2-(2.4-Difluorobsnzvn-4-(4-fluorophenyl.-5-[4-(methylsulfonyhphenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 20, substituting 2,4-difluorobenzyl bromide for 4-fluorobenzyl bromide. M.p. 179-182 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 5.45 (s, 2H), 6.87 (m, 2H), 6.96 (t, J = 9 Hz, 2H), 7.17 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.32 (d, J = 9 Hz, 2H), 7.54 (m, 1 H), 7.86 (s, 1 H), 7.88 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 471 (M+H)+. Example 23 2-(Methyl-2-propenyl.-4-f4-fluorophenvn-5-f4-(methylsulfonyl.phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 20, substituting 3-chloro-2-methylpropene for 4-fluorobenzyl bromide. M.p. 140-142 °C. 1 H NMR (CDCI3, 300 MHz) δ 1.86 (s, 3H), 3.08 (s, 3H), 4.83 (s, 2H), 4.94 (t, J = 1 Hz, 1 H), 5.05 (t, J = 1 Hz, 1 H), 6.9δ (t, J = 9 Hz, 2H), 7.21 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.37 (d, J = 9 Hz, 2H), 7.69 (s, 1 H), 7.91 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 399 (M+H)+. Example 24 2-f3-Methyl-2-butenvh-4-r4-fluorophenvn-5-[4-(methylsulfonyl.phenyl]-3(2H)- pvridazinone The desired compound was prepared according to the method of Example 20 substituting 4-bromo-2-methyl-2-butene for 4-fluorobenzyl bromide. M.p. 169- 172 °C. 1 H NMR (CDCI3, 300 MHz) δ 1.76 (s, 3H), 1.65 (s, 3H), 3.06 (s, 3H), 4.66 (d, J = 7.5 Hz, 2H), 5.47 (t, J = 7.5 Hz, 1 H), 6.96 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.33 (d, J = 9 Hz, 2H), 7.84 (s, 1 H), 7.88 (d, J = 9 Hz, 2H). MS (DCI- NH3) m/z 413 (M+H)+. Example 25 2-(2-Trifluoromethylbenzyl)-4-(4-fluorophenyπ-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-(trifluoromethyl)benzyl bromide for 4-fluorobenzyl bromide. M.p. 87- 90 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.07 (s, 3H), 5.66 (s, 2H), 6.97 (t, J = 9 Hz, 2H), 7.21 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.26 (d, J = 7.7 Hz 1 H), 7.37 (d, J = 9 Hz, 2H), 7.42 (t J = 7.7 Hz, 1 H), 7.53 (t, J = 7.7 Hz, 1 H), 7.73 (d J = 7.7 Hz, 1 H), 7.9 (s, 1 H), 7.91 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 503 (M+H)+. Example 26 2-(Cvclopropylmethvπ-4-(4-fluorophenvπ-5-[4-(methylsulfonvπphenyl -3f2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting 2-(bromomethyl)cyclopropane for 4-fluorobenzyl bromide. M.p. 118- 121 °C. 1 H NMR (CDCI3, 300 MHz) δ 0.45-0.52 (m, 2H), 0.54-0.63 (m, 2H), 1.40- 1.52 (m, 1 H), 3.07 (s, 3H), 4.07 (d, J = 7 Hz, 2H), 6.97 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.35 (d, J = 9 Hz, 2H), 7.83 (s, 1 H), 7.88 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 399 (M+H)+ and m/z 416 (M+NH4)+. Example 27 2-(2-Pyridylmethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)ph9nyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 20, substituting 2-(bromomethyl)pyridine for 4-fluorobenzyl bromide. M.p. 182-184 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.07 (s, 3H), 5.56 (s, 2H), 6.95 (m, 2H), 7.17 (m, 2H), 7.26 (m, 1 H), 7.35 (m, 2H), 7.46 (m, 1 H), 7.71 (m, 1 H), 7.90 (m, 3H), 8.63 (m, 1 H). MS (DCI-NH3) m/z 436 (M+H)+. Example 28 2-f4-Pyridylmethyl>-4-f4-fluorophenyl.-5-[4-(methylsulfonyl)phenyl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting 4-(bromomethyl)pyridine for 4-fluorobenzyl bromide. M.p. 153-156 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.07 (s, 3H), 5.40 (s, 2H), 6.97 (m, 2H), 7.17 (m, 2H), 7.34 (m, 2H), 7.42 (m, 2H), 7.90 (m, 3H), 8.63 (m, 2H). MS (DCI-NH3) m/z 436 (M+H)+. Example 29 2-r3-Pvridvlmethvh-4-f4-fluorophsnvl.-5-f4-.methvlsulfonyliphenyl]-3f2H ) - pvridazinone The title compound was prepared according to the method of Example 20, substituting 3-(bromomethyl)pyridine for 4-fluorobenzyl bromide. M.p. 160-161 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.07 (s, 3H), 5.43 (s, 2H), 6.97 (m, 2H), 7.15 (m, 2H), 7.34 (m, 4H), 7.35 (m, 2H), 7.87 (m, 2H), 7.97 (s, 1 H), 8.60 (m, 1 H), 8.81 (m, 1 H). MS (DCI-NH3) m/z 436 (M+H)+. Example 30 2-(6-Fluoroquinolin-2-ylmethvπ-4-(4-fluorophenvh-5-[4-(methylsulfonvπphenyl]- 3(2H)-pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-(chloromethyl)-6-fluoroquinoline for 4-fluorobenzyl bromide. M.p. 116-119 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.07 (s, 3H), 5.73 (s, 2H), 6.96 (m, 2H), 7.18 (m, 2H), 7.34 (m, 4H), 7.35 (m, 2H), 7.46 (m, 2H), 7.58 (m, 3H), 7.90 (m, 3H), 8.12 (m, 2H). MS (DCI-NH3) m/z 504 (M+H)+. Example 31 2-.Quinolin-2-ylmethyl)-4-(4-fluorophenyn-5-[4-fm9thylsulfonyl)phenyl]-3f2H)- pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-(chloromethyl)-quinoiine for 4-fluorobenzyl bromide. M.p. 97-100 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 5.75 (s, 2H), 6.95 (m, 2H), 7.19 (m, 2H), 7.35 (m, 2H), 7.55 (m, 2H), 7.73 (m, 1 H), 7.82 (m, 1 H), 7.90 (m, 3H), 8.15 (m, 2H). MS (DCI-NH3) m/z 386 (M+H)+. Example 32 2-Benzyl-4-(4-fluorophenyπ-5-[4-(methylsulfonyπphenyl]-3(2HVpyridazinethione A mixture of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone, prepared according to the method of Example 5, (109 mg, 0.25 mmol) and Lawesson's reagent (202 mg, 0.5 mmol) in 15 mL of toluene was stirred at reflux for 48 hours. The mixture was concentrated in vacuo and the residue was chromatographed (silica gel, ethyl acetate) to provide the title compound (yield: 100 mg, 88%). M.p. 8δ-90 °C. 1 H NMR (300 MHz, CDCI3) δ 3.04 (s, 3H), 6.05 (s, 2H), 6.96 (m, 2H), 7.08 (m, 2H), 7.26 (m, 2H), 7.37 (m, 3H), 7.61 (m, 2H), 7.84 (d, J = 9 Hz, 2H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 451 (M+H) + Example 33 2-Benzyl-4-(4-fluorophenyl)-5-[4-(aminosulfonyπphenyl]-3(2H)-pyridazinone 33A. Preparation of 2-Benzyl-4-(4-fluorophenylV5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone A solution of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared according to the method of Example 4, (450 mg, 1.12 mmol) in CH2CI2 (10 mL) was added dropwise to a suspension of hydroxy(tosyloxy)iodobenzene (439 mg, 1.12 mmol) in CH2CI2 (15 mL) and the mixture was stirred until a clear solution was obtained (about 1 hour). The reaction mixture was then washed with water and dried with MgSO4. Removal of solvent in vacuo provided the corresponding sulfoxide (yield: 485 mg, about 100%). 1 H NMR (300 MHz, CDCI3) δ 2.72 (s, 3H), 5.40 (s, 2H), 6.90 (m, 2H), 7.15 (m, 3H), 7.33 (m, 3H), 7.57 (m, 3H), 7.71 (m, 1 H), 7.86 (s, 1 H). MS (DCI-NH3) m/z 419 (M+H)+, 436 (M+NH4) + . 33B. Preparation of 2-benzyl-4-(4-fluorophenyl)-5-(acetoxymethylsulfonylphenyl)- 3(2H)-pyhdazinone The sulfoxide was transformed into the sulfonamide according to a procedure described by M. De Vleeschauwer and J. V. Gauthier in Syn. Lett, 1997,375 with the following modifications: A suspension of the sulfoxide, prepared according to the method of Example 33A, (485 mg, 1.12 mmol) and AcONa (1.4 g) in 15 mL of Ac2θ was stirred at reflux for 2 hours and concentrated in vacuo. The residue was distilled twice with toluene, dissolved in 25 mL of CH2CI2, cooled to 0 °C, and treated with CH3CO3H (1 mL). After 1 hour, the mixture was washed, successively, with saturated NaHCO3 and brine. The solvent was removed in vacuo. The residue was chromatographed (silica gel, 1 :1 hexanes-ethyl acetate) to provide the desired product, 2-benzyl-4-(4-fluorophenyl)-5-(acetoxymethylsulfonylphenyl)-3(2H)- pyridazinone (yield: 150 mg, 27%). MS (DCI-NH3) m/z 493 (M+H)+. 33C. Preparation of 2-Benzyl-4-f4-fluorophenylV5-[4-(sodiumsulfinate',phenyl]- 3(2HVpyridazinone To a solution of the acetoxymethylsulfone, prepared according to the method of Example 33B, (150 mg, 0.305 mmol), in 10 mL of THF and 5 mL of methanol at 0 °C, was added 1 N NaOH (0.305 mL, 0.305 mmol). The mixture was stirred at 0 °C for 1 hour. The mixture was concentrated in vacuo, the residual water was removed via an EtOH/toluene azeotrope followed by a toluene azeotrope. The residue was dried under high vacuum for 48 hours to provide the sodium sulfinate (yield: 140 mg, 96%). MS (DCI-NH3) m/z 443 (M+H)+ 33D. Preparation of 2-Benzyl-4-(4-fluorophenyl)-5-[4-(chlorosulfonyl)ph9nyl]- 3(2H)-pyridazinone The sodium sulfinate (about 0.31 mmol) in CH2CI2 (10 mL) was treated at 0 °C with SOCI2 (0.033 mL, 0.4 mmol) for 2 hours. The mixture was washed with brine, dried with MgSO4 and concentrated in vacuo to provide the crude sulfonyl chloride (yield: 145 mg, about 100%). MS (DCI-NH3) m/z 455 (M+H)+. 33E. Preparation of 2-Benzyl-4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone The crude chloride prepared according to the method of Example 33D, in 10 mL of THF, was added to a solution of 50% NH4OH, in 10 mL of THF, maintained at 0 °C. The mixture was allowed to warm to room temperature over 3.5 hours. The THF was removed in vacuo and the product was extracted with ethyl acetate. The ethyl acetate was removed in vacuo and the residue was treated with diethyl ether- hexanes 2:1 to provide the sulfonamide (yield: 113 mg, 84%). M.p. 188-191 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 2.70 (dd, J = 15 Hz, 2H), 5.36 (s, 2H), 7.13 (t, J = 9 Hz, 2H), 7.22 (m, 2H), 7.40 (m, 7H), 7.73 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (DCI- NH3) m/z 436 (M+H)+. Example 34 2- ( 2.2.2-Trifluoroethvn-4-f4-fluorophenvn-5-[4-(methylsulfonvhphenyl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting 2-iodo-1 ,1 ,1 -trifluoroethane for 4-fluorobenzyl bromide. M.p. 177-179 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 4.88 (q, J = 9 Hz, 2H), 6.98 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.35 (d, J = 9 Hz, 2H), 7.89 (s, 1 H), 7.91 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 427 (M+H)+ and m/z 444 (M+NH4)+. Example 35 2-f3.3-Dichloro-2-propenvn-4-(4-fluorophenvn-5-[4- methylsulfonvnphenyl1-3 2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting 1 ,1 ,3-thchloropropene for 4-fluorobenzyl bromide. M.p. 150-152 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 4.98 (d, J = 7 Hz, 2H), 6.25 (t, J = 7 Hz, 1 H), 6.98 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.33 (d, J = 9 Hz, 2H), 7.85 (s, 1 H), 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 453 (M+H)+ and m/z 470 (M+NH4)+. Example 36 2-(3-Phenyl-2-propenvl.-4-f4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 20, substituting cinnamyl bromide for 4-fluorobenzyl bromide. M.p. 165-167 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 5.01 (d, J = 7 Hz, 2H), 6.48 (dt, J = 15 Hz, 7 Hz, 1 H), 6.79 (d, J = 15 Hz, 1 H), 6.97 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.25-7.44 (m, 5H), 7.37 (d, J = 9 Hz, 2H), 7.86 (s, 1 H), 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 461 (M+H)+ and m/z 478 (M+NH4)+- Example 37 2-(4-Carboxyphenacvh-4-( , 4-fluorophenylV5-[4-(methylsulfonvπphenyl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting methyl 4-(bromomethyl)benzoate for 4-fluorobenzyl bromide and hydrolysis of the resulting ester. M.p. 239-241 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.06 (s, 3H), 5.46 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.17 (dd, J = 9 Hz, 6 Hz, 2H), 7.33 (d, J = 9 Hz, 2H), 7.63 (d, J = 9 Hz, 2H), 7.87 (s, 1 H), 7.89 (d, J = 9 Hz, 2H), 8.08 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 479 (M+H)+ and m/z 496 (M+NH4)+. Example 38 2-(5-Methylthiazol-2-ylmethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3 ( 2H)-pvridazinonθ The title compound was prepared according to the method of Example 20, substituting 2-(bromomethyl)-5-methylthiazole for 4-fluorobenzyl bromide. M.p. 114-116 °C. 1 H NMR (d6-DMSO, 300 MHz) δ 2.64 (s, 3H), 3.23 (s, 2H), 5.37 (s, 2H), 7.13 (m, 2H), 7.23 (m, 2H), 7.40 (s, 1 H), 7.47 (d, J = 8 Hz, 2H), 7.87 (d, J = 8 Hz, 2H), 8.10 (s, 1 H). MS (DCI-NH3) m/z 356 (M+H)+. Example 39 2-f5-Chlorothiazol-2-ylmethvh-4- ( 4-fluorophenvπ-5-[4-( ' methylsulfonvhphenyl]- 3f2HVpyridazinone The title compound was prepared according to the method of Example 20, substituting 2-(bromomethyl)-5-chlorothiazole for 4-fluorobenzyl bromide. M.p. 185-186 °C. 1 H NMR (d6-DMSO, 300 MHz) δ 2.32 (s, 3H), 5.50 (s, 2H), 7.15 (m, 2H), 7.24 (m, 2H), 7.47 (m, 2H), 7.87 (m, 3H), 8.14 (s, 1 H). MS (DCI-NH3) m/z 476 (M+H)+ and m/z 493 (M+NH4) + - Example 40 2-(2.3.3.4.4.4-Hexafluoro-n-buten-1 -vh-4-(4-fluorophθnyl)-5-[4-(mθthylsulfonyl)- phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 20, substituting 2,2,3,3,4,4,4-heptafluoro-1 -iodobutane for 4-fluorobenzyl bromide. Under the alkylation conditions, elimination of HF provided the unsaturated product. M.p. 167-169 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.07 (s, 3H), 7.00 (t, J = 9 Hz, 2H), 7.17 (dd, J = 9 Hz, 6 Hz, 2H), 7.33 (d, J = 9 Hz, 2H), 7.68 (d, J = 24 Hz, 1 H), 7.93 (d, J = 9 Hz, 2H), 8.01 (s, 1 H). MS (DCI-NH3) m/z 507 (M+H)+ and m/z 524 (M+NH4)+. Example 41 2-(2.4-Difluorophenacyl)-4-(4-fluorophenvn-5-f4-(methylsulfonvπphenyl]-3f2H)- pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-chloro-2',4'-difluoroacetophenone for 4-fluorobenzyl bromide. M.p. 191 -192 °C. 1 H NMR (CDCI3, 300 MHz) δ 3.08 (s, 3H), 5.57 (d, J = 3 Hz, 2H), 6.94- 7.07 (m, 2H), 6.96 (t, J = 9 Hz, 2H), 7.39 (dd, J = 9 Hz, 6 Hz, 2H), 7.91 (s, 1 H), 7.91 (d, J = 9 Hz, 2H), 8.03-8.12 (m, 1 H). MS (DCI-NH3) m/z 499 (M+H)+ and m/z 516 (M+NH4) + - Example 42 2-f5-Chlorothien-2-ylmethvh-4-f4-fluorophenvn-5-[4-(methylsulfonvnphenyl1-3(2H - pvridazinone The title compound was prepared according to the method of Example 20, substituting 2-(bromomethyl)-5-chlorothiophene for 4-fluorobenzyl bromide. M.p. 139-141 °C. 1 H NMR (d6-DMSO, 300 MHz) δ 3.23 (s, 3H), 5.43 (s, 2H), 7.03 (d, J = 4 Hz, 1 H), 7.09-7.29 (m, 5H), 7.47 (d, J = 8 Hz, 2H), 7.87 (d, J = 8 Hz, 3H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 474 (M+H)+ and m/z 492 (M+NH4)+. Example 43 2-(5-Methylthien-2-ylmethvh-4-(4-fluorophenvn-5-[4-fmethylsulfonvnphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-(bromomethyl)-5-methylthiophene for 4-fluorobenzyl bromide. M.p. 172-175 °C. 1 H NMR (d6-DMSO, 300 MHz) δ 3.22 (s, 3H), 5.49 (s, 2H), 7.03 (m, 1 H), 7.14 (m, 2H), 7.23 (m, 3H), 7.48 (m, 3H), 7.86 (m, 2H), 8.11 (s, 1 H). MS (DCI- NH3) m/z 441 (M+H)+ and m/z 458 (M+NH4)+. Example 44 2-(4-Diethylaminophenacvπ-4-(4-fluorophenvπ-5-[4-(methylsulfonvπphenyl]-3f2H - pvridazinone The title compound was prepared according to the method of Example 20, substituting 2-chloro-4'-diethylaminoacetophenone for 4-fluorobenzyl bromide. M.p. 105-108 °C. 1 H NMR (CDCI3, 300 MHz) δ 1.23 (t, J = 7 Hz, 3H), 3.07 (s, 3H), 3.44 (q, J = 7 Hz, 2H), 5.61 (s, 2H), 6.66 (d, J = 9 Hz, 2H), 6.94 (t, J = 9 Hz, 2H), 7.21 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.87-7.94 (m, 4H), 7.90 (s, 1 H). MS (DCI-NH3) m/z 534 (M+H)+ . Example 45 2- ( 2.3.4.5.6-Pentafluorobenzvπ-4- ( 4-fluorophenvn-5-[4-(methylsulfonvπphenyl]- 3(2HVpyridazinone The title compound was prepared according to the method of Example 20, substituting 2,3,4,5,6-pentafluorobenzyl bromide for 4-fluorobenzyl bromide. M.p. 115-116 °C. 1 H NMR (CDCI3, 300 MHz) 3.06 (s, 3H), 5.50 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.17 (dd, J = 9 Hz, 6 Hz, 2H), 7.33 (d, J = 9 Hz, 2H), 7.82 (s, 1 H), 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 525 (M+H)+ and m/z 542 (M+NH4)+. Example 46 2-<Phenacvn-4-f4-fluorophenvn-5-[4-(methylsulfonvnphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 20, substituting 2-bromoacetophenone for 4-fluorobenzyl bromide. M.p. 228-230 °C. 1 H NMR (CDCI3, 300 MHz) 3.07 (s, 3H), 5.68 (s, 2H), 6.95 (t, J = 9 Hz, 2H), 7.20 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.53 (t, J = 7 Hz, 2H), 7.65 (t, J = 7 Hz, 1 H), 7.90 (d, J = 9 Hz, 2H), 7.91 (s, 1 H), 8.04 (d, J = 7 Hz, 2H). MS (DCI-NH3) m/z 463 (M+H)+ and m/z 480 (M+NH4)+. Example 47 2-(4-Chlorophenacvn-4-(4-fluorophenvπ-5-[4-(methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-bromo-4'-chloroacetophenone for 4-fluorobenzyl bromide. M.p. 186- 188 °C. 1 H NMR (CDCI3, 300 MHz) 3.07 (s, 3H), 5.63 (s, 2H), 6.95 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.51 (d, J = 9 Hz, 2H), 7.65 (t, J = 7 Hz, 1 H), 7.90 (d, J = 9 Hz, 2H), 7.91 (s, 1 H), 7.98 (d, J = 9 Hz, 2H). MS (DCI- NH3) m/z 497 (M+H)+ and m/z 514 (M+NH4)+. Example 48 2-fPropargvπ-4-(4-fluorophenylV5-[4-(methylsulfonvnphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 20, substituting propargyl bromide for 4-fluorobenzyl bromide. M.p. 196-198 °C. 1 H NMR (CDCI3, 300 MHz) 2.42 (t, J = 3 Hz, 1 H), 3.06 (s, 3H), 5.04 (d, J = 3 Hz, 2H), 6.97 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.34 (d, J = 9 Hz, 2H), 7.90 (s, 1 H), 7.91 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 383 (M+H)+ and m/z 400 (M+NH4)+. Example 49 2-(4-Cvanophenacvn-4-f4-fluorophenvn-5-[4-(methvlsulfonvnphenvl]-3f2HV pyridaziηorie The title compound was prepared according to the method of Example 20, substituting 2-bromo-4'-cyanoacetophenone for 4-fluorobenzyl bromide. M.p. 188- 189 °C. 1 H NMR (CDCI3, 300 MHz) 3.08 (s, 3H), 5.64 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.84 (d, J = 9 Hz, 2H), 7.91 (d, J = 9 Hz, 2H), 7.93 (s, 1 H), 8.14 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 488 (M+H)+ . Example 50 2-( -Methyl-4-fluorobenzvh-4-f4-fluorophenvn-5-[4-(methylsulfonvπphenyl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting α-methyl-4-fluorobenzyl bromide for 4-fluorobenzyl bromide. M.p. 162- 164 °C. 1 H NMR (CDCI3, 300 MHz) 3.06 (s, 3H), 6.40 (t, J = 9 Hz, 2H), 6.95 (t, J = 9 Hz, 2H), 7.05 (t, J = 9 Hz, 2H), 7.15 (dd, J = 9 Hz and 6 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.53 (dd, J = 9 Hz and 6 Hz, 2H), 7.87 (d, J = 9 Hz, 2H), 7.88 (s, 1 H). MS (DCI- NH3) m/z 467 (M+H)+ and m/z 484 (M+NH4)+ . Example 51 2-Phen9thyl-4-(4-fluorophenvn-5-f4-fmethvlsulfonvl.ph9nvl]-3f2H)-pyridazinone The title compound was prepared according to the method of Example 20, substituting (2-bromoethyl)benzene for 4-fluorobenzyl bromide. M.p. 170-171 °C. 1 H NMR (CDCI3, 300 MHz) 3.07 (s, 3H), 3.20 (t, J = 9 Hz, 2H), 4.28 (t, J = 9 Hz, 2H), 6.98 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz and 6 Hz, 2H), 7.22-37 (m, 5 H), 7.34 (d, J = 9 Hz, 2H), 7.83 (s, 1 H), 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 449 (M+H)+ and m/z 466 (M+NH4)+ . Example 52 2-Benzyl-4-f3-chloro-4-fluorophenvn-5-[4-(mθthylsulfonvπphθnyl]-3(2HV pvridazinone The title compound was prepared according to the method described in Examples 6-10 substituting 3-chloro-4-fluorobenzeneboronic acid for 4-fluoro- benzeneboronic acid in Example 6. M.p. 134-136 °C. H NMR (CDCI3, 300 MHz) 3.06 (s, 3H), 5.41 (s, 2H), 6.96-7.02 (m, 2H), 7.29-7.41 (m, 3H), 7.33 (d, J = 9 Hz, 2H), 7.51 -7.56 (m, 2H), 7.85 (s, 1 H), 7.91 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 469 (M+H)+ and m/z 486 (M+NH4) + . Example 53 2-Benzyl-4-(4-chlorophenyπ-5-[4-(methylsulfonyπphenyl]-3(2H)-pyridazinone The title compound was prepared according to the method described in Examples 6-10 except substituting 4-chlorobenzeneboronic acid for 4-fluoro- benzeneboronic acid in Example 6. M.p. 157-159 °C. 1 H NMR (CDCI3, 300 MHz) 3.05 (s, 3H), 5.40 (s, 2H), 7.11 (d, J = 9 Hz, 2H), 7.24 (d, J = 9 Hz, 2H), 7.28-7.40 (m, 2H), 7.31 (d, J = 9 Hz, 2H), 7.51-7.57 (m, 2H), 7.84 (s, 1 H), 7.88 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 451 (M+H)+ and m/z 468 (M+NH4) - - Example 54 2- ( 2.2.2-Trifluoroethyh-4-(3-chloro-4-fluorophenyπ-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone The title compound was prepared by N-debenzylation of the product, prepared in Example 52 according to the method of Example 11 , followed by alkylation with 2-iodo-1 ,1 ,1 -trifluoroethane according to the method of Example 20. M.p. 165-166 °C. 1 H NMR (CDCI3, 300 MHz) 3.07 (s, 3H), 4.89 (q, J = 9 Hz, 2H), 7.00-7.06 (m, 2H), 7.31 -7.35 (m, 1 H), 7.37 (d, J = 9 Hz, 2H), 7.90 (s, 1 H), 7.94 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 461 (M+H)+ and m/z 478 (M+NH4) + . Example 55 2-(4-Trifluoromethoxyphenacyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3.2H)-pyridazinone The title compound was prepared according to the method of Example 20, substituting 2-bromo-4'-trifluoromethoxyacetophenone for 4-fluorobenzyl bromide. M.p. 160-161 °C. 1 H NMR (CDCI3, 300 MHz) 3.08 (s, 3H), 5.65 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.20 (dd, J = 9 Hz, 6 Hz, 2H), 7.37 (d, J = 9 Hz, 2H), 7.91 (d, J = 9 Hz, 2H), 7.93 (s, 1 H), 8.11 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 547 (M+H)+ and m/z 564 (M+NH4) + - Example 56 2-(4-Trifluoromethylphenacyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3(2HVpvridazinone The title compound was prepared according to the method of Example 20, substituting 2-bromo-4'-thfluoromethylacetophenone for 4-fluorobenzyl bromide. M.p. 205-206 °C. 1 H NMR (CDCI3, 300 MHz) 3.07 (s, 3H), 5.66 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.20 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.80 (d, J = 9 Hz, 2H), 7.91 (d, J = 9 Hz, 2H), 7.92 (s, 1 H), 8.15 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 531 (M+H)+ and m/z 548 (M+NH4)+. Example 57 2-[2-(Benzo[b]thien-3-vl.-2-oxoethyl]-4- 4-fluoroph9nyl)-5-[4-fm9thylsulfonyl)- phenvl]-3f2HVpvridazinone The title compound was prepared according to the method of Example 20, substituting 3-chloroacetylbenzo[b]thiophene for 4-fluorobenzyl bromide. M.p. 183- 184 °C. 1 H NMR (CDCI3, 300 MHz) 3.08 (s, 3H), 5.68 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.21 (dd, J = 9 Hz, 6 Hz, 2H), 7.39 (d, J = 9 Hz, 2H), 7.42-7.54 (m, 2H), 7.91 (d, J = 9 Hz, 2H), 7.91 (d, J = 7 Hz, 1 H), 7.94 (s, 1 H), 8.53 (s, 1 H), 8.72 (d, J = 7 Hz, 1 H). MS (DCI-NH3) m/z 519 (M+H)+. Example 58 2-(2.2.2-Trifluoroethyl)-4-f4-chlorophenvh-5-f4-fmethylsulfonvhphenyl]-3(2H)- pvridazinone The title compound was prepared by N-debenzylation of the product, prepared in Example 54 according to the method of Example 12, followed by alkylation with 2-iodo-1 ,1 ,1 -trifluoroethane according to the method of Example 20. M.p. 55-57 °C. 1 H NMR (CDCI3, 300 MHz) 3.07 (s, 3H), 4.88 (q, J = 9 Hz, 2H), 7.13 (d, J = 9 Hz, 2H), 7.26 (d, J = 9 Hz, 2H), 7.36 (d, J = 9 Hz, 2H), 7.89 (s, 1 H), 7.92 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 443 (M+H)+ and m/z 460 (M+NH4)+. Example 59 2-.3.3-Dimethyl-2-oxobutyl)-4-(4-fluorophenyl ) -5-[4-.mθthylsulfonyl)ph8nyl1-3(2H ) - pyridazinone The title compound was prepared according to the method of Example 20, substituting 1 -bromopinacolone for 4-fluorobenzyl bromide. M.p. 168-170 °C. 1 H NMR (CDCI3, 300 MHz) 1.31 (s, 9H), 3.06 (s, 3H), 5.21 (s, 2H), 6.95 (t, J = 9 Hz, 2H), 7.17 (dd, J = 9 Hz, 6 Hz, 2H), 7.35 (d, J = 7 Hz, 2H), 7.86 (s, 1 H) 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 443 (M+H)+ and m/z 460 (M+NH4) + . Example 60 2-(3-Thienylmethyl -f4-fluorophθnyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 20, substituting 3-(chloromethyl)thiophene for 4-fluorobenzyl bromide. M.p. 169-172 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.22 (s, 3H), 5.36 (s, 2H), 7.18 (m, 5H), 7.51 (m, 4H), 7.88 (m, 2H); 8.08 (s, 1 H). MS (DCI-NH3) m/z 441 (M+H)+ and m/z 458 (M+NH4)+ . Example 61 2-(2-Benzofb]thienylmethyπ-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 20 substituting 2-(chloromethyl)benzo[b]thiophene for 4-fluorobenzyl bromide. M.p. 93-96 °C. 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 5.64 (s, 2H), 6.97 (m, 2H), 7.18 (m, 2H), 7.33 (m, 5H), 7.78 (m, 2H), 7.86 (m, 3H). MS (DCI-NH3) m/z 491 (M+H)+ and m/z 508 (M+NH4)+. Example 62 2.4-Bisf4-fluorophsnyl.-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone A mixture of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (172 mg, 0.5 mmol), prepared according to the method of Example 10, Cu powder (32 mg), anhydrous K2CO3 (207 mg, 1.5 mmol) and 4- fluoroiodobenzene (0.12 mL, 1 mmol) was prepared in 20 mL of pyridine . The solution was stirred at reflux for 14 hours. The mixture was then cooled to room temperature and partitioned between water and ethyl acetate. The ethyl acetate layer was washed with 10% citric acid, water, brine and concentrated in vacuo. Separation by column chromatography (silica gel, CH2Cl2-diethyl ether 15:1 ) provided 190 mg of crude product. Crystallization from CH2Cl2-diethyl ether- hexanes furnished the title compound (yield: 175 mg, 79.9%). M.p. 168-169 °C. 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 6.98 (t, J = 9 Hz, 2H), 7.20 (m, 4H), 7.40 (d, J = 9 Hz, 2H), 7.69 (m, 2H), 7.92 (d, J = 9 Hz, 2H), 7.98 (s, 1 H). MS (DCI-NH3) m/z 439 (M+H)+, 456 (M+NH4)+. Anal. calc. for C23H-| 6F2N2θ3S-0.25 H2O: C, 62.36; H, 3.75; N, 6.32. Found: C, 62.23; H, 3.55; N, 6.26. Example 63 4-(4-Fluorophenvn-5-f4-fmethvlsulfonvnphenyl]-6-methyl-3f2H.-pvridazinone The 5-hydroxy-5-methyl-2(5H)-furanone prepared via above cited methods (454 mg, 1.25 mmol) was dissolved in n-butanol (10 mL) and treated with hydrazine hydrate (0.3 mL, 6.2 mmol) and stirred at reflux for 18 hours. On cooling, white crystals (224 mg, 50%) were obtained. M.p. 290 °C (dec.) 1 HNMR (300 MHz, d6-DMSO) δ 1.99 (s, 3H), 3.10 (s, 3H), 7.05 (t, J = 9 Hz, 2H), 7.15 (dd, J = 6 Hz, J = 9 Hz, 2H), 7.48 (d, J = 9 Hz, 2H), 7.85 (d, J = 9 Hz, 2H), 13.10 (br s, 1 H). MS (DCI/NH3) 376 (M+NH4)+. Anal. calc. for C18H15N2FSO3 0.25 H2O: C, 59.57; H, 4.30; N, 7.71. Found: C, 59.28; H, 4.39; N, 8.39 Example 64 2-(2.2.2-TrifluoroethylV4-f4-fluorophenvh-5-[4-fmethylsulfonyl)phenyl]-6-methyl- 3(2H)-pyridazinone The product of Example 63 (100 mg, 0.28 mmol) was dissolved in anhydrous DMF (3 mL) and treated with 1 ,1 ,1 -trifluoro-2-iodoethane (27.5 mL, 280 mmol) in presence of anhydrous sodium carbonate (130 mg, 1.2 mmol) at 50-60 °C for 2 hours. The reaction mixture was partitioned between water and ethyl acetate to provide the desired compound as an amorphous solid (60 mg, 48%). 1 HNMR (300 MHz, CDCI3) δ 2.10 (s, 3H), 3.10 (s, 3H), 4.85 (q, J = 9 Hz, 2H), 6.90 (m, 2H), 7.10 (dd, J = 6 Hz, ' J = 9 Hz, 2H), 7.25 (m, 2H), 7.95 (d, J = 9 Hz, 2H),. MS (DCI/NH3) 458 (M+NH4)+ Anal. calc. for C20H16N2F4SO3: C, 54.54; H, 3.66; N, 6.36. Found: C, 54.41 ; H, 3.56; N, 6.35. Example 65 2-Benzvl-4-(3.4-dichlorophenvn-5-f4-(methylsulfonvnphanvη-3.2HVpyridazinone The title compound was prepared by coupling 3,4-dichlorophenylboronic acid with 2-benzyl-4-bromo-5-methoxy-3(2H)-pyridazinone {J. Het. Chem., 1996, 33, 1579-1582) according to the method of Example 6. This product was converted to the 5-hydroxy-derivative according to the method of Example 7. The 5-hydroxy compound was converted to the 5-trifluoromethylsufonyloxy-derivative according to the method of Example 8. Coupling of 4-(methylthio)phenylboronic acid to the triflate according to the method of Example 9 provided the 5-[4-(methylthio)phenyl]- intermediate which was oxidized according to the method of Example 10 to provide the final product (yield: 780 mg, 84%). M.p. 161 -163 °C. 1 H NMR (300 MHz, DMSO-d6) δ 3.22 (s, 3H), 5.35 (s, 2H), 7.08 (dd, J = 9 Hz, 3 Hz, 1 H), 7.32-7.44 (m, 5H), 7.47 (dd, J = 9 Hz, 3 Hz, 3H), 7.48 (d, J = 3 Hz, 1 H), 7.90 (d, J = 9 Hz, 2H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 485 (M+H)+. Anal. calc. for C24H18CI2N2O3S: C, 59.38; H, 3.73; N, 5.77. Found: C, 59.28; H, 3.92; N, 5.42. Example 66 2-(2.2.2-Trifluoroethvn-4-(4-n-propylphenvn-5-r4-(methylsulfonvnphenyl]-3f2HV pyridazinone The title compound was prepared by coupling 4-(n-propyl)phenylboronic acid with 2-benzyl-4-bromo-5-methoxy-3(2H)-pyhdazinone (J. Het. Chem., 1996, 33, 1579-1582) according to the method of Example 6. This product was converted to the 5-hydroxy- derivative according to the method of Example 7. This product was converted to the 5-trifluoromethylsufonyloxy-derivative according to the method of Example 8. Coupling of 4-(methylthio)phenylboronic acid to the triflate according to the method of Example 9 provided the 5-[4-(methylthio)phenyl]- intermediate which was oxidized according to the method of Example 10 to provide the final product (yield: 220 mg, 70%). M.p. 64-66 °C. 1 H NMR (300 MHz, CDCI3) δ 0.91 (t, J = 7.5 Hz, 3H), 1.6 (h, J = 7.5 Hz, 2H), 2.55 (q, J = 7.5 Hz, 2H), 3.05 (s, 3H), 4.88 (q, J = 9 Hz, 2H), 7.08 (s, 4H), 7.35 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 7.87 (s, 1 H). MS (DCI-NH3) m/z 451 (M+H)+. Anal. calc. for C22H21 F3N2O3S: C, 58.65; H, 4.69; N, 6.21. Found: C, 58.71 ; H, 4.72; N, 6.20. Example 67 2- 2.2.2-TrifluoroethylV4-C4-chloro-3-fluorophenylV5-[4-(methylsulfonvhphenyl]- 3f2HVpvridazinone The title compound was prepared by first coupling 3-fluoro-4- chlorophenylboronic acid with 2-benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone according to the method of Example 6. The product was converted to the 5-hydroxy compound according to the method of Example 7. This 5-hydroxy compound was converted to the 5-trifluoromethylsufonyloxy-derivative according to the method of Example 8. Coupling of 4-(methylthio)phenylboronic acid to the triflate according to the method of Example 9 provided the 5-[4-(methylthio)phenyl]-intermediate which was oxidized according to the method of Example 10 to provide the final product (yield: 170 mg, 84%). M.p. 174-175 °C. 1 H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 4.89 (q, J = 9 Hz, 2H), 6.87 (dm, J = 9 Hz, 1 H), 7.09 (dd, J = 9 Hz, 3 Hz, 1 H), 7.30 (t, J = 9 Hz, 1 H), 7.39 (d, J = 9 Hz, 2H), 7.91 (s, 1 H), 7.95 (d, J = 9 Hz, 2H). MS (DCI- NH3) m/z 461 (M+H)+. Anal. calc. for C19H13CIF4N2O3S: C, 49.52; H, 2.84; N, 6.07. Found: C, 49.66; H, 2.70; N, 5.96. Example 68 2-(2.2.2-Trifluorosthvh-4-.4-fluorophenyl)-5-r4-faminosulfonvl.phenvn-3.2H pvridazinone A solution of 2-(2,2,2-trifluoroethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfinyl)- phenyl]-3(2H)-pyridazinone (680 mg, 1.53 mmol) in trifluoroacetic anhydride (30 mL) was stirred at room temperature for 1 hour. The excess solvent was evaporated in vacuo and the residue was treated with a deoxygenated 1 N solution of methanol-NaOH (50 mL, 4:1) at 0 °C. The solution was stirred at room temperature for 2 hours and quenched with dilute HCl solution until acidic. The white suspension formed was concentrated in vacuo to evaporate the methanol. THF was added to the resulting suspension until a clear solution was obtained. Chlorine gas was slowly bubbled into the solution, maintained at 0 °C. After 10 minutes, nitrogen gas was bubbled into the solution for a few minutes to displace residual chlorine. Ammonium hydroxide solution (30%, 5 to 10 mL), at 0 °C, was slowly added to the solution (to consume all starting sulfonyl chloride) and stirred at room temperature for 5 minutes The solution was partitioned between water and ethyl acetate. The organic layer was washed first with water, then brine, and dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (40:60 ethyl acetate/hexanes) to provide the title compound (yield: 500 mg, 75%). M.p. 193-195 °C. 1 H NMR (300 MHz, CDCI3) δ 4.82 (s, 2H), 4.88 (q, J = 9 Hz, 2H), 6.98 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.30 (d, J = 9 Hz, 2H), 7.88 (d, J = 9 Hz, 2H), 7.90 (s, 1 H). MS (DCI- NH3) m/z 428 (M+H)+. Anal. calc. for C18H13F4N3O3S: C, 50.58; H, 3.06; N, 9.83. Found: C, 51.04; H, 3.26; N, 9.63. Example 69 2-(2.2.2-Trifluorosthyl)-4-f4-chlorophsnyl)-5-[4-(aminosulfonyl)phenyl]-3.2HV pvridazinone 69A. 2-Benzvl-4-chloro-5-r4-fmethvlthio)phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 77. The product was coupled with 4-chlorophenylboronic acid following the method of Example 6. The product was N-debenzylated according to the method of Example 11 and N-alkylated with 2-iodo-1 ,1 ,1 -trifluoroethane according to the method of Example 20 to provide the sulfice compound. 69B. 2-Benzyl-4-chloro-5-[4-(methylsulfinvπphenyl]-3f2H pyridazinone The sulfide was oxidized to the corresponding sulfoxide with one equivalent of mefa-chloroperoxybenzoic acid to provide the corresponding methylsulfoxide which was converted to the sulfonamide final product according to the method of Example 68 (yield: 540 mg, 70%). M.p. 154-156 °C. 1 H NMR (300 MHz, CDCI3) δ 4.86 (s, 2H), 4.87 (q, J = 9 Hz, 2H), 7.14 (d, J = 9 Hz, 2H), 7.29 (d, J = 9 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.89 (d, J = 9 Hz, 2H), 8.00 (s, 1 H). MS (DCI-NH3) m/z 444 (M+H)+. Anal. calc. for C18H13CIF3N3O3S: C, 48.71 ; H, 2.95; N, 9.46. Found: C, 49.05; H, 3.01 ; N, 9.15. Example 70 2-(2.2.2-Trifluoroethyl)-4-f2-propoxy)-5-[4-faminosulfonyl)phenyl]-3(2H)- pyridazinone The methyl sulfide intermediate prepared in Example 83 was oxidized with one equivalent of mera-chloroperoxybenzoic acid to provide the methylsulfoxide which was converted to the sulfonamide final product according to the method of Example 68 (yield: 396 mg, 60%). M.p. 158-160 °C. 1 H NMR (300 MHz, CDCI3) δ 1.21 (d, J = 6 Hz, 6H), 4.83 (q, J = 7.5 Hz, 2H), 4.86 (s, 2H), 5.46 (p, J = 6 Hz, 1 H), 7.72 (d, J = 9 Hz, 2H), 7.82 (s, 1 H), 8.03 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 392 (M+H)+. Anal. calc. for C15H16F3N3O4S: C, 46.03; H, 4.12; N, 10.73. Found: C, 46.08; H, 4.22; N, 10.52. Example 71 2-(2.2.2-TrifluoroBthyl)-4-.4-fluorophsnoxy ) -5-f4-(aminosulfonyl)phenyl]-3(2H)- pvridazinone The methyl sulfide intermediate of Example 76 was oxidized with one equivalent of meta-chloroperoxybenzoic acid to provide the methylsulfoxide which was converted to the sulfonamide final product according to the method of Example 68 (yield: 180 mg, 37%). M.p. 150-152 °C. 1 H NMR (300 MHz, CDCI3) δ 4.71 (q, J = 7.5 Hz, 2H), 4.72 (s, 2H), 6.88 (dd, J = 9 Hz, 4.5 Hz, 2H), 7.0 (t, J = 9 Hz, 2H), 7.73 (d, J = 9 Hz, 2H), 7.98 (s, 1 H), 8.05 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 444 (M+H)+. Anal. calc. for C18H13F4N3O4S: C, 48.76; H, 2.95; N, 9.47. Found: C, 48.49; H, 2.8; N, 8.95. Example 72 2.4-Bis-(4-fluorophenvh-5-r3-fluoro-4-(aminosulfonvhphenyl1-3C2H pyridazinone 72 A- 1. 2-Fluorothioanisole A deoxygenated solution of 2-fluorothiophenol (10 g, 78 mmol) in anhydrous DMF (10 mL) was treated with iodomethane (4.9 mL, 78 mmol) and potassium carbonate (10.8 g, 78 mmol). The reaction mixture was stirred at room temperature for 1 hour. A thin layer chromotography (100% hexanes) sample indicated that the reaction had not gone to completion, so an additional equivalent of base and iodomethane were added and the reaction mixture was stirred overnight at room temperature. The reaction was acidified with 10% aqueous citric acid and extracted with hexanes (2 X 125 mL). The combined organic extracts were washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide the desired compound as a pale yellow oil (yield: 6.68 g; 60%). 72A-2. 2-Fluorothioanisole An alternative method for preparing 2-fluorothioanisole begins with a solution of 1 ,2-difluorobenzene (0.79 mL, 8 mmol) in anhydrous DMF (50 mL) was treated with sodium thiomethoxide (0.59 g, 8 mmol). The reaction mixture was stirred at room temperature for 6 hours, and partitioned between hexanes and water. The organic layer was washed with brine, dried over MgS04, and filtered. The filtrate was concentrated under reduced pressure to provide the desired compound (1.1 g, 100%) slightly contaminated with 1 ,2-bis(methylthio)benzene, a lower Rf material, which was removed by chromatography with 100% hexanes (0.9 g, 80%). 1 H NMR (300 MHz, CDCI3) δ 2.46 (s, 3H), 6.98-7.19 (m, 3H) 2.26 (dt, J = 9 Hz, 3 Hz, 1 H). 72B. 4-Bromo-2-fluorothioanisole A solution of 2-fluorothioanisole (1.42 g, 10 mmol) and iron powder (0.03 g, 0.5 mmol) in dichloromethane (20 mL) was chilled to °C and treated dropwise with Bromine (0.5 mL, 10 mmol). Upon completion of the Bromine treatment, the reaction was sampled for TLC (100% hexanes). A new, higher Rf material was present but the reaction had not gone to completion so another equivalent of bromine was added along with a catalytic amount of aluminum chloride. The reaction mixture was stirred overnight at room temperature. Aqueous sodium sulfite was added to the reaction mixture and the organic layer was isolated, dried over MgSO4, and filtered. The filtrate was filtered through a pad of silica gel to remove color then concentrated under reduced pressure to provide the product as a clear, colorless oil (yield: 1.3 g; 60%). 1 H NMR (300 MHz, DMSO-dδ) δ 2.48 (s, 3H), 7.31 (t, J = 9 Hz, 1 H), 7.43 (dd, J = 9 Hz, 3 Hz, 1 H) 7.54 (dd, J = 9 Hz, 3 Hz, 1 H). 72C. 3-Fluoro-4- ( methylthio^benzeneboronic acid A solution of 4-bromo-2-fluorothioanisole (0.5 g, 22.6 mmol) in dry THF (20 mL) was chilled to -78 °C under a nitrogen atmosphere. The reaction mixture was treated with 1.6 M n-butyllithium in hexanes (1.7 mL, 27.1 mmol), and the mixture was warmed to -40°C where it was maintained for 0.5 hours. The reaction mixture was then chilled to -78°C and three equivalents of triisopropyl borate (1.56 mL, 67.8 mmol) were added. The reaction mixture was allowed to warm to room temperature and stirred for 1.5 hours. At this point, 10% aqueous KOH (200 mL, 360 mmol) was added and the mixture was stirred overnight at room temperature. The reaction mixture was then poured into an ice/concentrated HCl mixture with stirring to yield a white precipitate. This solid was dried in a vacuum oven (65 °C, 29 in Hg) overnight to provide the title compound (yield: 0.22 g; 52.4%). H NMR (300 MHz, DMSO-d6) δ 2.48 (s, 3H), 7.31 (t, J = 9 Hz, 1 H), 7.49 (dd, J = 12 Hz, 1.5 Hz, 1 H) 7.54 (dd, J = 9 Hz, 1.5 Hz, 1 H). 72D. 2.4-Bis-(4-fluorophsnyl.-5-[3-fluoro-4-faminosulfonyl)ph9nyl]-3(2H)- pyridazinone 2-Benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone (J. Het. Chem., 1996, 33, 1579-1582) was converted to the 5-hydroxy-analog according to the method of Example 7 and then to the 5-trifluoromethylsulfonyloxy-analog following the method of Example 8. Subsequent coupling to 3-fluoro-4-(methylthio)phenyl- boronic acid, according to the method of Example 9, provided 2-benzyl-4-chloro-5- [3-fluoro-4-(methylthio)phenyl]-3(2H)-pyridazinone. This intermediate was coupled in the 4-position with 4-fluorophenylboronic acid following the method of Example 6. This product was N-debenzylated according to the method of Example 11 and N-arylated with 4-fluoroiodobenzene according to the method of Example 62. The resulting sulfide was oxidized with one equivalent of meta-chloroperoxybenzoic acid to provide the methylsulfoxide which was converted to the sulfonamide final product according to the method of Example 68 (yield: 500 mg, 75%). M.p. 222- 224 °C. 1 H NMR (300 MHz, CDCI3) δ 5.06 (s, 2H), 7.01 (t, J = 9 Hz, 2H), 7.06 (d, J = 9 Hz, 2H), 7.10 (d, J = 9 Hz, 2H), 7.18 (t, J = 9 Hz, 2H), 7.69 (dd, J = 9 Hz, 3 Hz, 2H), 7.88 (t, J = 9 Hz, 1 H), 7.95 (s, 1 H). MS (DCI-NH3) m/z 458 (M+H)+. Anal. calc. for C22H14F3N3O3S: C, 57.76; H, 3.08; N, 9.18. Found: C, 57.5; H, 3.15; N, 8.8. Example 73 2-f2.2.2-TrifluoroethylV4-(3-fluoro-4-chlorophenyl)-5-[4-(aminosulfonyl)phenyl]- 3(2HY-pvridazinone The methyl sulfide intermediate prepared in Example 67 was oxidized with one equivalent of metø-chloroperoxybenzoic acid, according to the method of Example 68 to provide the methyl sulfoxide. The methyl sulfoxide was converted to the sulfonamide product according to the method of Example 68 (yield: 1.5 g, 63%). M.p. 180-183 °C. " I H NMR (300 MHz, DMSO-dδ) δ 5.09 (q, J = 9 Hz, 2H), 7.01 (dd, J = 9 Hz, 3 Hz, 1 H), 7.15 (dd, J = 9 Hz, 3 Hz, 1 H), 7.39 (dd, J = 9 Hz, 3 Hz, 1 H), 7.47 (dd, J = 9 Hz, 3 Hz, 1 H), 7.55 (t, J = 9 Hz, 1 H), 7.71 (t, J = 9 Hz, 1 H), 7.78 (s, 2H), 8.37 (s, 1 H). MS (DCI-NH3) m/z 480 (M+H)+. Anal. calc. for C18H11 CIF5N3O3S: C, 45.05; H, 2.31 ; N, 8.75. Found: C, 46.19; H, 3.02; N, 7.43. Example 74 2-Benzyl-4-(2-propoxy^5-f4-fmethylsulfonyl)phenyl]-3(2H ) -pyridazinone 2-Benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone (J. Het. Chem., 1996, 33, 1579-1582) was converted to the 5-hydroxy-analog according to the method of Example 7 and then to the 5-trifluoromethylsulfonyloxy-analog following the method of Example 8. Subsequent coupling to 4-(methylthio)phenylboronic acid according to the method of Example 9 provided 2-benzyl-4-chloro-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone. This 4-chloro-intermediate thus prepared was treated with 2-propanol (20 mL, 261 mmol) and potassium f-butoxide (110 mg, 0.98 mmol) at reflux for 45 minutes furnished 2-benzyl-4-(2-propoxy)-5-[4- (methylthio)pentyl]-3(2H)-pyridazinone This methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 180 mg, 80%). M.p. 109-1 11 °C. 1 H NMR (300 MHz, CDCI3) δ 1.18 (d, J = 6 Hz, 6H), 3.12 (s, 3H), 5.36 (s, 2H), 5.49 (h, J = 6 Hz, 1 H), 7.35 (m, 3H), 7.47 (dd, J = 9 Hz, 3 Hz, 2H), 7.74 (d, J = 9 Hz, 2H), 7.79 (s, 1 H), 8.03 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 399 (M+H)+. Anal. calc. for C 2 1 H22N2O4S: C, 63.29; H, 5.56; N, 7.03. Found: C, 63.17; H, 5.57; N, 6.95. Example 75 2-Benzyl-4-(4-fluorophenoxyV5-[4-(methylsulfonyl)phenyl]-3f2H)-pyridazinone The title compound was prepared according to the method of Example 74 substituting 4-fluorophenol in place of 2-propanol (yield: 180 mg, 99%). M.p. 188- 190 °C. 1 H NMR (300 MHz, CDCI3) δ 3.12 (s, 3H), 5.26 (s, 2H), 6.86 (dd, J = 9 Hz, 6 Hz, 2H), 6.99 (t, J = 9 Hz, 2H), 7.34 (m, 3H), 7.46 (dd, J = 9 Hz, 3 Hz, 2H), 7.72 (d, J = 9 Hz, 2H), 7.92 (s, 1 H), 8.02 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 451 (M+H)+. Anal. calc. for C24H19FN2O4S: C, 63.98; H, 4.25; N, 6.21. Found: C, 63.74; H, 4.2; N, 6.12. Example 76 2-(2.2.2-Trifluoroethvh-4-(4-fluorophenoxy 5-[4-(mθthylsulfonyl.phenyl1-3f2H ) - pyridazinone The title compound was prepared according to the method of Example 75 substituting 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-benzyl-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (yield: 180 mg, 63%). M.p. 161 -164 °C. 1 H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 4.81 (q, J = 9 Hz, 2H), 6.88 (dd, J = 9 Hz, 4.5 Hz, 2H), 7.0 (t, J = 9 Hz, 2H), 7.78 (d, J = 9 Hz, 2H), 7.79 (s, 1 H), 8.06 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 443 (M+H)+. Anal. calc. for C19H14F4N2O4S: C, 51.58; H, 3.18; N, 6.33. Found: C, 51.8; H, 3.3; N, 6.22. Example 77 2-(2.2.2-Trifluoroethyl)-4-(4-chlorophenyn-5-f4-fmθthylsulfinyl)phθnyl]-3(2H)- pyridazinone 2-Benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone (J. Her. Chem., 1996, 33, 1579-1582) was converted to the 5-hydroxy-analog according to the method of Example 7 and then to the 5-trifluoromethylsulfonyloxy-analog according to the method of Example 8. Subsequent coupling to 4-(methylthio)phenylboronic acid, according to the method of Example 9, provided 2-benzyl-4-chloro-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone. This intermediate was coupled with 4- chlorophenylboronic acid according to the method of Example 6. This product was N-debenzylated according to the method of Example 11 and N-alkylated with 2- iodo-1 ,1 ,1 -trifluoroethane according to the method of Example 20. The resulting sulfide was oxidized to the corresponding sulfoxide with one equivalent of meta- chloroperoxybenzoic acid, according to the method of Example 5 to provide the title compound (yield: 130 mg, 70%). M.p. 154-155 °C. 1 H NMR (300 MHz, CDCI3) δ 2.74 (s, 3H), 4.88 (q, J = 9 Hz, 2H), 7.14 (d, J = 9 Hz, 2H), 7.26 (d, J = 9 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.61 (d, J = 9 Hz, 2H), 7.82 (s, 1 H). MS (DCI-NH3) m/z 427 (M+H)+. Anal. calc. for C19H14CIF3N2O2S: C, 53.46; H, 3.3; N, 6.56. Found: C, 53.58; H, 3.34; N, 6.42. Example 78 2-Benzyl-4-chloro-5-[4-fmethylsulfonvnphenyl1-3(2H pyridazinone The title compound was prepared by oxidizing 2-benzyl-4-chloro-5-[4- (methylthio)phenyl]-3(2H)-pyridazinone, (prepared as an intermediate in Example 77) according to the method of Example 10 (yield: 180 mg, 83%). M.p. 166-167 °C. 1 H NMR (300 MHz, CDCI3) δ 3.12 (s, 3H), 5.41 (s, 2H), 7.37 (m, 3H), 7.53 (dd, J = 9 Hz, 3 Hz, 2H), 7.68 (d, J = 9 Hz, 2H), 7.74 (s, 1 H), 8.08 (d, J = 9 Hz, 2H). MS (DCI- NH3) m/z 375 (M+H)+. Anal. calc. for C18H15CIN2O3S: C, 57.67; H, 4.03; N, 7.47. Found: C, 57.43; H, 4.06; N, 7.35. Example 79 2-(2.2.2-Trifluoroethyl)-4-(4-methylph9nyl)-5-[4-(mθthylsulfonyl)phenyl]-3(2H)- pvridazinone 2-Benzyl-4-bromo-5-methoxy-3(2H)-pyridazinone (J. Het. Chem., 1996, 33, 1579-1582) was converted to the 5-hydroxy-analog according to the method of Example 7 and then to the 5-(trifluoromethyl)sulfonyloxy-analog according to the method of Example 8. Subsequent coupling to 4-(methylthio)phenylboronic acid, according to the method of Example 9, provided 2-benzyl-4-bromo-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone. This intermediate was coupled with 4- methylphenylboronic acid according to the method of Example 6. This product was N-debenzylated according to the method of Example 11 and N-alkylated with 2- iodo-1 ,1 ,1 -trifluoroethane according to the method of Example 20. The resulting sulfide was oxidized to the title compound according to the method of Example 10 (yield: 210 mg, 98%). M.p. 154-156 °C. 1 H NMR (300 MHz, CDCI3) δ 2.33 (s, 3H), 3.07 (s, 3H), 4.89 (q, J = 9 Hz, 2H), 7.08 (s, 4H), 7.37 (d, J = 9 Hz, 2H), 7.88 (s, 1 H), 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 423 (M+H)+. Anal. calc. for C20H17F3N2O3S: C, 56.86; H, 4.05; N, 6.63. Found: C, 56.59; H, 4.11 ; N, 6.53. Example 80 2-(2.2.2-Trifluoroethvπ-4-C4-chloro-3-fluorophenvπ-5-[4- aminosulfonvπphenyl]- 2-Benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone (J. Het. Chem., 1996, 33, 1579-1582) was converted to the 5-hydroxy-analog according to the method of Example 7 and then to the 5-(trifluoromethyl)sulfonyloxy-analog according to the method of Example 8. Subsequent coupling to 4-(methylthio)phenylboronic acid, according to the method of Example 9, provided 2-benzyl-4-chloro-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone. This intermediate was coupled with 4-chloro-3- fluorophenylboronic acid according to the method of Example 6. This product was N-debenzylated according to the method of Example 11 and N-alkylated with 2- iodo-1 ,1 ,1-trifluoroethane according to the method of Example 20. The resulting sulfide was oxidized to the corresponding sulfoxide with one equivalent of meta- chloroperoxybenzoic acid to provide the methylsulfoxide which was converted to the sulfonamide final product according to the method of Example 68 (yield: 500 mg, 75%). M.p. 214-215 °C. 1 H NMR (300 MHz, CDCI3) δ 4.82 (s, 2H), 4.88 (q, J = 9 Hz, 2H), 6.88 (m, 1 H), 7.09 (dd, J = 9 Hz, 3 Hz, 1 H), 7.31 (d, J = 9 Hz, 1 H), 7.32 (d, J = 9 Hz, 2H), 7.90 (s, 1 H), 7.92 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 462 (M+H)+. Anal. calc. for C18H12F4CIN3O3S: C, 46.81 ; H, 2.61 ; N, 9.09. Found: C, 46.79; H, 2.59; N, 8.86. Example 81 2-(2.2.2-Trifluoroethyl.-4-(3.4-dichlorophenyl)-5-[4-(mθthylsulfonyl)phenyl]-3.2H)- pyridazinone The product described in Example 65 was N-debenzylated according to the method of Example 1 1. The intermediate was N-alkylated according to the method of Example 20, substituting 2-iodo-1 ,1 ,1 -trifluoroethane in place of 4-fluorobenzyl bromide to provide the title compound (yield: 165 mg, 55%). M.p. 197-198 °C. 1 H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 4.88 (q, J = 9 Hz, 2H), 6.98 (dd, J = 9 Hz, 3 Hz, 1 H), 7.37 (d, J = 9 Hz, 4H), 7.91 (s, 1 H), 7.95 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 477 (M+H)+. Anal. calc. for C19H13F3CI2N2O3S: C, 47.81 ; H, 2.74; N, 5.86. Found: C, 47.94; H, 2.87; N, 5.83. Example 82 2-Bflnzyl-4-.2-Dropylamino)-5-f4-(methvlsulfonyl)phenyl]-3 2HVpvridazinonθ 2-Benzyl-4,5-dibromo-3(2H)-pyridazinone (2 g, 6 mmol) was reacted with 2-aminopropane (2 mL, 23.5 mmol) and potassium f-butoxide (910 mg, 6.6 mmol) in toluene (40 mL) at reflux for 18 hours to provide the 4-(2-propylamino)-derivative after column chromatography (silica gel, 92:8 hexanes/ethyl acetate). The intermediate was coupled in the 5-position with 4-(methylthio)phenylboronic acid according to the method of Example 6. The methyl sulfide was oxidized, according to the method of Example 10, to provide the title compound (yield: 120 mg, 48%). M.p. 146-147 °C. 1 H NMR (300 MHz, CDCI3) δ 0.92 (d, J = 6 Hz, 6H), 3.11 (m, 1 H), 3.13 (s, 3H), 5.34 (s, 2H), 5.59 (m, 1 H), 7.33 (m, 3H), 7.42 (s, 1 H), 7.48 (dd, J = 9 Hz, 3 Hz, 2H), 7.56 (d, J = 9 Hz, 2H), 8.00 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 399 (M+H)+. Anal. calc. for C21 H23N3O3S: C, 63.45; H, 5.83; N, 10.57. Found: C, 63.31 ; H, 5.87; N, 10.44. Example 83 2-.2.2.2-Trifluoroethvn-4-f2-propoxy)-5-[4-(methylsulfonyl)phθnvl]-3(2H)- pvridazinone 83A. 2-(2.2.2-Trifluoroethvh-4.5-dibromo-3(2H)-pyridazinone A solution of mucobromic acid (10 g, 38.8 mmol) and trifluoroethyl hydrazine (70% in water, 4.88 mL, 38.8 mmol) in 100 mL of methanol was prepared and heated at reflux for 3 hours. The reaction mixture was concentrated in vacuo and partitioned between ethyl acetate and water. The ethyl acetate layer was dried over MgSO4, filtered, passed through a silica gel pad, and concentrated in vacuo . The product was obtained as yellowish solid (yield: 8.8 g, 68%) . H NMR (300 MHz, CDCI3) δ 4.78 (q, J = 9 Hz, 2H), 7.87 (s, 1 H). MS (DCI-NH3) m/z 337 (M+H)+. 83B. 2-(2.2.2-Trifluoroethyl)-4-(2-propoxy)-5-bromo-3(2H)-pyridazinone A solution of 2-(2,2,2-trifluoroethyl)-4,5-dibromo-3(2H)-pyridazinone (2 g, 6 mmol), isopropyl alcohol (3 mL) and sodium hydride (60% dispersed in oil, 290 mg, 7.2 mmol) in toluene (40 mL) was heated at reflux for 5 hours. The reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was filtered, and concentrated in vacuo . The residue was purified by chromatography (95:5 hexanes/ethyl acetate) to provide the product as a greenish oil (yield: 1.22 g, 65%). 1 H NMR (300 MHz, CDCI3) δ 1.46 (d, J = 7.5 Hz, 6H), 5.48 (h, J = 6 Hz, 1 H), 7.87 (s, 1 H). MS (DCI-NH3) m/z 316 (M+H)+. 83C. 2-(2.2.2-Trifluoroethvn-4-(2-propoxy^-5-[4-(methylthio ) phenyl1-3f2H ) - pvridazinone A solution of 2-(2,2,2-trifluoroethyl)-4-(2-propoxy)-5-bromo-3(2H)- pyridazinone (1.2 g, 3.8 mmol), 4-(methylthio)phenylboronic acid (704 mg, 4.19 mmol), tetrakis(thphenylphosphine)palladium(0) (220 mg, 5% mmol) and cesium carbonate (2.72 g, 8.3 mmol) in 20 mL of ethylene glycol dimethyl ether was heated to reflux for 5 hours. The mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water, brine, dried over MgSO4 and concentrated in vacuo . The residue was purified by chromatography on silica gel (94:6 hexanes/ethyl acetate). The product was obtained as a greenish solid (yield: 1.1 g, 81 %). 1 H NMR (300 MHz, CDCI3) δ 1.19 (d, J = 7.5 Hz, 6H), 2.55 (s, 3H), 4.83 (q, J = 9 Hz, 2H), 5.28 (h, J = 6 Hz, 1 H), 7.32 (d, J = 9 Hz, 2H), 7.52 (d, J = 9 Hz, 2H), 7.85 (s, 1 H). MS (DCI) m/z 359 (M+H)+. 83D. 2-(2.2.2-TrifluoroethylV4-(2-propoxyV5-[4-fmethylsulfonvhphenyl]-3(2H pvridazinone The title compound was prepared according to the method of Example 10, substituting 2-(2,2,2-trifluoroethyl)-4-(2-propoxy)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (yield: 220 mg, 100%). M.p. 152-153 °C. 1 H NMR (300 MHz, CDCI3) δ 1.2 (d, J = 6 Hz, 6H), 3.13 (s, 3H), 4.84 (q, J = 9 Hz, 2H), 5.49 (p, J = 6 Hz, 1 H), 7.78 (d, J = 9 Hz, 2H), 7.82 (s, 1 H), 8.05 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 391 (M+H)+. Anal. calc. for C16H17F3N2O4S: C, 49.22; H, 4.38; N, 7.17. Found: C, 49.34; H, 4.25; N, 7.01. Example 84 2-f2.2.2-Trifluoroethvh-4-cvclohexyloxy-5-[4-(mθthylsulfonvhphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 83, substituting cyclohexanol in place of 2-propanol (yield: 250 mg, 52%). M.p. 129- 130 °C. 1 H NMR (300 MHz, CDCI3) δ 1.1 -1.6 (m, 8H), 1.84 (m, 2H), 3.12 (s, 3H), 4.83 (q, J = 9 Hz, 2H), 5.21 (h, J = 4.5 Hz, 1 H), 7.77 (s, 1 H), 7.80 (d, J = 9 Hz, 2H), 8.06 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 431 (M+H)+. Anal. calc. for C19H21 F3N2O4S: C, 53.01 ; H, 4.91 ; N, 6.50. Found: C, 52.96; H, 4.84; N, 6.45. Example 85 2-(2.2.2-Trifluoroethyl)-4-cvclopentyloxy-5-[4-fmethylsulfonyl)phenvn-3f2H pvridazinone The title compound was prepared according to the method of Example 83, substituting cyciopentanol in place of 2-propanol (yield: 250 mg, 52%). M.p. 148- 150 °C. 1 H NMR (300 MHz, CDCI3) δ 1.35-1.55 (m, 4H), 1.68-1.75 (m, 4H), 3.12 (s, 3H), 4.83 (q, J = 9 Hz, 2H), 5.89 (h, J = 4.5 Hz, 1 H), 7.75 (d, J = 9 Hz, 2H), 7.83 (s, 1 H), 8.04 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 417 (M+H)+. Anal. calc. for C18H19F3N2O4S: C, 51.91 ; H, 4.59; N, 6.72. Found: C, 52.04; H, 4.50; N, 6.65. Example 86 2-(2.2.2-Trifluoroethyl)-4-f2-propylamino)-5-[4-.methylsulfonyl)phenyl]-3(2H)- pvridazinone 86A. 2-.2.2.2-Trifluoroethyl)-4-(2-propylamino)-5-bromo-3(2H)-pyridazinone The title compound was prepared according method of the Example 83B, substituting 2-propylamine in place of 2-propanol (yield: 70%). MS (DCI-NH3) m/z 315 (M+H)+. 86B. 2-(2.2.2-Trifluoroethyl)-4-f2-propylaminoV5-f4-fmethylthio)phenyl]-3(2H)- pvridazinone The title compound was prepared according method of the Example 83C, substituting 2-(2,2,2-trifluoroethyl)-4-(2-propylamino)-5-bromo-3(2H)-pyridazinone in place of 2-(2,2,2-trifluoroethyl)-4-isopropoxy-5-bromo-3(2H)-pyridazinone (yield: 80%). MS (DCI-NH3) m/z 358 (M+H)+. 86C. 2-(2.2.2-Trifluoroethyl)-4-f2-propylamino.-5-[4-.methylsulfonvnphenyl]-3r2H)- pvridazinone The title compound was prepared according to the method of Example 10 , substituting 2-(2,2,2-Trifluoroethyl)-4-(2-propylamino)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (yield: 180 mg, 83%). M.p. 173-174 °C. 1 H NMR (300 MHz, CDCI3) δ 0.95 (d, J = 6 Hz, 6H), 3.13 (s, 3H), 4.81 (q, J = 9 Hz, 2H), 5.97 (s, 1 H), 7.45 (s, 1 H), 7.59 (d, J = 9 Hz, 2H), 8.03 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 340 (M+H)+. Anal, calc. for C16H18F3N3O4S: C, 49.35; H, 4.65; N, 10.79. Found: C, 49.29; H, 4.52; N, 10.65. Example 87 2-Benzyl-4-(4-morpholino 5-[4-(methylsulfonvπphenyl1-3(2HVpyridazinone 2-Benzyl-4,5-dichloro-3(2H)-pyridazinone, prepared following the procedure in Example 2, was reacted with morpholine following the procedure of Example 86 to provide the 4-morpholino-derivative. The morpholino intermediate was coupled at the 5-position with 4-(methylthio)phenylboronic acid according to the method of Example 6. The resulting methyl sulfide was oxidized to the title compound according to the method of Example 10 (yield: 150 mg, 69%). M.p. 158-160 °C. 1 H NMR (300 MHz, CDCI3) δ 3.06 (t, J = 4.5 Hz, 3H), 3.12 (s, 3H), 3.69 (t, J = 4.5 Hz, 3H), 5.33 (s, 2H), 7.35 (m, 3H), 7.5 (m, 4H), 7.58 (s, 1 H), 8.05 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 426 (M+H)+. Anal. calc. for C22H23N3O4S: C, 62.10; H, 5.44; N, 9.87. Found: C, 61.74; H, 5.47; N, 9.59. Example 88 2-f2.3.3-Trifluoro-2-propen-1 -yl')1-4-( ' 4-fluorophenvπ-5-[4-(methylsulfonvπphenyl]- 3(2H)-pyridazinone 88A. 1 -Methylsulfonyloxy-2.3.3-trifluoro-2-propene 2,3,3-Thfluoro-2-propen-1 -ol was prepared as reported in J. Org. Chem., 1989, 54, 5640-5642. The mesylate was obtained by reacting 2,3,3- trifluoro-2-propen-1 -ol with mesyl chloride in diethyl ether. Standard workup provided the product, which was used without purification. 88B. 2-(2.3.3-Trifluoro-2-propen-1 -vn-4-ι4-fluorophenyl)-5-[4-.mθthylthio.phenyl]- 3f2HVpyridazinone. 4-(4-Fluorophenvπ-5-[4-(methylthio^phenyl]-3(2HVpvridazinone is prepared starting with the 2-benzyl-pyhdazinone from Example 9 and debenzylating the compound according to the procedure of Example 11. A mixture of 4-(4-fluorophenvπ-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (250 mg, 0.8 mmol), CS2CO3 (650 mg, 2 mmol), and 3-methylsufonyloxy-1 ,1 ,2- trifluoropropene (mesylate, 250 mg, 1.19 mmol) in ethyl acetate (30 mL) was stirred at 55 °C for 1.5 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried with MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel eluted with 15% ethyl acetate/hexanes, to provide the methyl sulfide, 2-(2,3,3-trifluoro-2-propen-1 -yl)-4-(4-fluorophenyl)-5-[4- (methylthio)phenyl]-3(2H)-pyhdazinone as a greenish oil (yield: 175 mg, 53%). 88C. 2- 2.3.3-Trifluoro-2-propen-1 -yl)]-4- 4-fluorophenvn-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone The methyl sulfide, prepared above, was oxidized to the title compound according to the method of Example 10 (yield: 125 mg, 68%). M.p. 154-156 °C. 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 5.1 (ddd, J = 21 Hz, 3 Hz, 1.5 Hz, 2H), 6.98 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.35 (d, J = 9 Hz, 2H), 7.89 (s, 1 H), 7.9 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 439 (M+H)+. Anal. calc. for C20H14F4N2O3S: C, 54.79; H, 3.21 ; N, 6.38. Found: C, 54.52; H, 3.15; N, 6.21. Example 89 2.4-Bis(4-fluorophenvh-5-[4-(aminosulfonvnphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 68 substituting 2,4-bis(4-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone in place of 2-(2,2,2-thfluoroethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]- 3(2H)-pyridazinone (yield: 118 mg, 43%). M.p. 213-216 °C. 1 H NMR (300 MHz, DMSO-d6) δ 7.15 (t, 2H), 7.27 (m, 2H), 7.4 (m, 6H), 7.7 (dd, 2H), 7.76 (d, J = 9 Hz, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 440 (M+H)+ 439.44 (M+NH4)+- Anal. calc. for C-21 H15FN2O3S2: C, 60.13; H, 3.44; N, 9.56. Found: C, 59.94; H, 3.37; N, 9.46. Example 90 2-(2.2.2-Trifluoroethyl)-4-cyclopropylmethoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone 90A. 2-(2.2.2-Trifluoroethyl)-4-methoxy-5-bromo-3(2H)-pyridazinone The title compound was prepared according method of the Example 83B, substituting methanol in place of isopropanol (yield: 78%). 1 H NMR (300 MHz, CDCI3) δ 4.3 (s, 3H), 4.76 (q, J = 9 Hz, 2H), 7.85 (s, 1 H). MS (DCI-NH3) m/z 288 (M+H)+. 90B. 2- ( 2.2.2-Trifluoroethyl)-4-methoxy-5-[4-(methylthio phenyl]-3(2H,- pvridazinone The title compound was prepared according method of the Example 83C, substituting 2-(2,2,2-trifluoroethyl)-4-methoxy-5-bromo-3(2H)-pyridazinone in place of 2-(2,2,2-trifluoroethyl)-4-(2-propoxy)-5-bromo-3(2H)-pyridazinone (yield: 80%). 1 H NMR (300 MHz, CDCI3) δ 2.54 (s, 3H), 4.11 (s, 3H), 4.82 (q, J = 9 Hz, 2H), 7.33 (d, J = 9 Hz, 2H), 7.48 (d, J = 9 Hz, 2H), 7.84 (s, 1 H). MS (DCI-NH3) m/z 331 (M+H)+. 90C. 2-f2.2.2-Trifluoroethylι-4-hydroxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone A solution of 2-(2,2,2-Trifluoroethyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyhdazinone (2 g, 6.1 mmol) and hydrobromic acid (40% in water, 20 mL) in acetic acid (40 mL) was heated at reflux for 3 hours. The reaction mixture was cooled to room temperature and water (50 mL) was added. The crystals formed were filtered, washed with water and 5% ethyl acetate in hexanes, and dried to constant weight. The product was obtained as a white solid (yield: 1.75 g, 91 %). 1 H NMR (300 MHz, CDCI3) δ 2.54 (s, 3H), 4.82 (q, J = 9 Hz, 2H), 7.47 (d, J = 9 Hz, 2H), 7.65 (d, J = 9 Hz, 2H), 7.73 (br s, 1 H), 8.00 (s, 1 H). MS (DCI) m/z 317 (M+H)+. 90D. 2-.2.2.2-Trifluoroethyl)-4-cvclopropylmsthoxy-5-[4-(methylthio)phenyl]-3(2H)- pvridazinone A solution of 2-(2,2,2-trifluoroethyl)-4-hydroxy-5-[4-(methylthio)phenyl]- 3(2H)-pyhdazinone (150 mg, 0.47 mmol), cyclopropyl methanol (43 mL, 0.52 mmol) and triphenylphosphine (124 mg, 0.47 mmol) in freshly distilled THF was prepared and added dropwise to diethyl azodicarboxylate (75 mL, 0.52 mmol) at 0 °C. The mixture was allowed to warm to room temperature, stirred for 5 hours and concentrated in vacuo. The residue was purified by chromatography on silica gel (95:5 hexanes/ethyl acetate) to provide the product as a colorless oil (yield: 140 mg, 81 %). 1 H NMR (300 MHz, CDCI3) δ 0.22 (m, 2H), 0.48 (m, 2H), 1.6 (m, 1 H), 2.53 (s, 3H), 4.26 (d, J = 7.5 Hz, 2H), 4.72 (q, J = 9 Hz, 2H), 7.32 (d, J = 9 Hz, 2H), 7.55 (d, J = 9 Hz, 2H), 7.87 (s, 1 H). MS (DCI-NH3) m/z 371 (M+H)+. 90E. 2-(2.2.2-Trifluoroethyl)-4-cyclopropylmethoxy-5-[4-(methylsulfonvhphenyl]- 3(2HVpyhdazinone The title compound was prepared according to the method of example 10, substituting 2-(2,2,2-trifluoroethyl)-4-cyclopropylmethoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (yield: 130 mg, 85%). M.p. 133-135 °C. 1 H NMR (300 MHz, CDCI3) δ 0.22 (m, 2H), 0.5 (m, 2H), 1.07 (m, 1 H), 3.12 (s, 3H), 4.4 (d, J = 9 Hz, 2H), 4.83 (q, J = 9 Hz, 2H), 7.79 (s, 1 H), 7.83 (d, J = 9 Hz, 2H), 8.07 (d, J = 9 Hz, 2H). MS (DCI- NH3) m/z 403 (M+H)+. Anal. calc. for C17H17F3N2O4S: C, 50.74; H, 4.25; N, 6.96. Found: C, 50.56; H, 4.09; N, 6.88. Example 91 2-(2.2.2-Trifluoroethvh-4-r3-propen-1 -oxyV5-[4-fmethvlsulfonvhphenvl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 90, substituting 2-propen-1 -ol in place of cyclopropylmethanol (yield: 120 mg, 77%). M.p. 121 -123 °C. 1 H NMR (300 MHz, CDCI3) δ 3.12 (s, 3H), 4.84 (q, J = 12 Hz, 2H), 5.07 (d, J = 6 Hz, 2H), 5.21 (dd, J = 13.5 Hz, 1 Hz, 1 H), 5.27 (dd, J = 15 Hz, 1 Hz, 1 H), 5.85 (m, 1 H), 7.25 (d, J = 9 Hz, 2H), 7.83 (s, 1 H), 8.06 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 389 (M+H)+. Anal. calc. for C16H15F3N2O4S: C, 49.48; H, 3.89; N, 7.21. Found: C, 49.24; H, 3.77; N, 7.16. Example 92 2-f2.2.2-Trifluoroethvn-4-(4-fluoro-a/p/7a-methylbenzyloxyV5-[4-(methylsulfonvn- phenvl]-3(2HVpvhdazinone The title compound was prepared according to the method of Example 90, substituting 4-fluoro-a/p ιa-methylbenzyl alcohol in place of cyclopropylmethanol (yield: 155 mg, 76%). M.p. 133-135 °C. 1 H NMR (300 MHz, CDCI3) δ 1.57 (d, J = 6 Hz, 3H), 3.13 (s, 3H), 4.75 (q, J = 7.5 Hz, 1 H), 4.87 (q, J = 7.5 Hz, 1 H), 6.34 (q, J = 6 Hz, 1 H), 6.83 (t, J = 9 Hz, 2H), 6.98 (dd, J = 9 Hz, 6 Hz, 2H), 7.59 (d, J = 9 Hz), 7.70 (s, 1 H), 8.03 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 471 (M+H)+. Anal. calc. for C21 H18F4N2O4S: C, 53.61 ; H, 3.85; N, 5.95. Found: C, 53.54; H, 3.73; N, 5.86. Example 93 2-[4-fMethvlthio^phenvl1-4- 4-fluorophenvlV5-[4-fmethylsulfonvnphenyl1-3 2H pvridazinone A solution of the product from Example 11 , 4-(4-Fluorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (344 mg, 1.0 mmol), 4-bromothioanisole (812 mg, 4.0 mmol), and copper (70 mg, 1.1 mmol) in 20 mL of pyridine was stirred at reflux under a nitrogen atmosphere for 18 hours. After cooling to room temperature, the reaction mixture was diluted with a mixture of water and ethyl acetate. The two layers were filtered through Celite®, and separated. The organic layer was washed with 10% aqueous citric acid, with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo and the residue purified by column chromatography (silica gel, 93:7 dichloromethane/ethyi acetate) to provide the title compound as a foam (yield: 380 mg, 81.5%). 1 H NMR (300 MHz, CDCI3) δ 2.55 (s, 3H), 3.05 (s, 3H), 6.98 (t, J = 9 Hz, 2H), 7.22 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (dd, J = 8 Hz, 2 Hz, 4H), 7.64 (d, J = 9 Hz, 2H), 7.91 (d, J = 9 Hz, 2H), 7.98 (s, 1 H). MS (DCI- NH3) m/z 467 (M+H)+. Anal. calc. for C24HιgFN2θ3S2-0.5 H2O: C, 60.63; H, 4.21 ; N, 5.90. Found: C, 60.72; H, 3.96; N, 5.70. Example 94 2.5-Bisf4-fmethvlsulfonvnphenvl]-4-(4-fluorophenyl)-3f2H pvridazinone The title compound was prepared by oxidizing the product of Example 93, according to the method of Example 10 (yield: 156 mg, 78%). 1 H NMR (300 MHz, CDCI3) δ 3.10 (s, 3H), 3.12 (s, 3H), 7.02 (m, 2H), 7.24 (m, 2H), 7.42 (br d, J = 9 Hz, 2H), 7.94 (dd, J = 9 Hz, 2 Hz, 2H), 8.02 (dd, J = 9 Hz, 2 Hz, 2H), 8.10 (m, 3H). MS (DCI-NH3) m/z 499 (M+H)+, 516 (M+NH4) + . Anal. calc. for C24H-| gFN2θsS2-0.5 H2O: C, 56.80; H, 3.94; N, 5.53. Found: C, 56.50; H, 3.88; N, 5.38. Example 95 2-(3-Methyl-2-thienyl.-4-(4-fluorophenyl)-5-r4-(methylsulfonyl)ph9nyl]-3.2H)- pyridazinone The title compound was prepared according to Example 93, substituting 2- bromo-3-methylthiophene in place of 4-bromothioanisole (yield: 190 mg, 43%). M.p. 215-217 °C. 1 H NMR (300 MHz, CDCI3) δ 2.21 (s, 3H), 3.08 (s, 3H), 6.90 (d, J = Hz, 1 H), 6.g8 (t, J = 9 Hz, 2H), 7.24 (dd, J = 9 Hz, 6 Hz, 3H), 7.41 (d, J = 9 Hz, 2H), 7.94 (d, J = 9 Hz, 2H), 7.98 (s, 1 H). MS (DCI-NH3) m/z 441 (M+H)+, 458 (M+NH4)+. Anal. calc. for C22H17FN2O3S2-0.5 H2O: C, 58.80; H, 4.01 ; N, 6. 24. Found: C, 58.85; H, 3.78; N, 5.99. Example 96 2- ( 2-Trifluoromethyl-5-nitrophenvn-4-^4-fluorophenvn-5-[4-(methylsulfonvπphenyl]- S^HVpyridazinone The title compound was prepared according to Example 93, substituting 2- bromo-5-nitrobenzotrifluohde in place of 4-bromothioanisole (yield: 390 mg, 73%). 1 H NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 6.98 (t, J = 9 Hz, 2H), 7.21 (dd, J = 9 Hz, 6 Hz, 2H), 7.43 (d, J = 9 Hz, 2H), 7.80 (d, J = 9 Hz, 1 H), 7.96 (d, J = 9 Hz, 2H), 8.02 (s, 1 H), 8.61 (dd, J = 9 Hz, 3 Hz, 1 H), 8.75 (d, J = 3 Hz, 1 H). MS (DCI-NH3) m/z 534 (M+H)+, 551 (M+NH4) + . Anal. calc. for C24H15F4N3O5SO.75 H2O: C, 52.70; H, 3.02; N, 7.69. Found: C, 52.42; H, 3.04; N, 6.82. Example 97 2-[3-fMethylthio)phenyll-4-f4-fluorophθnyl.-5-[4-(mθthylsulfonyl-phenyn-3.2H pvridazinone The title compound was prepared according to Example 93, substituting 3- bromothioanisole in place of 4-bromothioanisole (yield: 355 mg, 76%). M.p. 196 °C. 1 H NMR (300 MHz, CDCI3) δ 2.55 (s, 3H), 3.08 (s, 3H), 6.99 (t, J = 9 Hz, 2H), 7.23 (dd, J = 9 Hz, 6 Hz, 2H), 7.28-7.33 (m, 1 H), 7.37-7.49 (m, 2H), 7.40 (d, J = 9 Hz, 2H), 7.58 (m, 1 H), 7.92 (d, J = 9 Hz, 2H), 7.9g (m, 1 H). MS (DCI-NH3) m/z 467 (M+H)+, 484 (M+NH4) + - Anal. calc. for C24H-| gFN2θ3S2: C, 61.80; H, 4.08; N, 6.01. Found: C, 61.56; H, 3.93; N, 5.86. Example 98 2-[3-(Methylsulfonyl)phenvl1-4-f4-fluorophenyn-5-[4-(mθthylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared by oxidizing the product of Example 97, according to the method of Example 10 (yield: 98 mg, 65.6%). M.p. 141 -142 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 3.25 (s, 3H), 3.35 (s, 3H), 7.18 (t, J = 9 Hz, 2H), 7.32 (dd, J = 9 Hz, 6 Hz, 2H), 7.52 (d, J = 9 Hz, 2H), 7.83 (t, J = 9 Hz, 1 H), 7.95 (d, J = 9 Hz, 2H), 8.05 (m, 1 H), 8.25 (t, J = 1.5 Hz, 1 H), 8.33 (s, 1 H). MS (DCI-NH3) m/z 516 (M+NH4)+. Anal. calc. for C24Hi gFN2θδS2-H2θ: C, 55.81 ; H, 4.07; N, 5.43. Found: C, 56.24; H, 4.2g; N, 5.10. Example 99 2-( ' 4-Fluoroph9nvn-4-C4-chlorophenvπ-5-[4- methylsulfonvnphenyl]-3(;2H - pvridazinone 4-(4-Chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone is prepared starting with the 2-benzylpyridazinone from Example 53 and debenzylating the compound according to the method of Example 11. The title compound was prepared according to the method of Example 93, starting with 4-(4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 1 -fluoro-4-iodobenzene in place of 4-bromothioanisole (yield: 245 mg, 54%). M.p. 195-i 7 °C. 1 H NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 7.19 (m, 4H), 7.25 (m, 2H), 7.41 (d, J = 9 Hz, 2H), 7.70 (m, 2H), 7.95 (d, J = 9 Hz, 2H), 8.01 (s, 1 H). MS (DCI-NH3) m/z 455 (M+H)+, 472 (M+NH4)+. Anal. calc. for C23H16CIFN2O3S: C, 60.78; H, 3.52; N, 6.17. Found: C, 60.81 ; H, 3.53; N, 5.93. Example 100 2-(5-Chloro-2-thienyl)-4-.4-chlorophenvn-5-[4-(m9thylsulfonvhphenyl]-3^2H pvridazinone The title compound was prepared according to Example 93, substituting 4- (4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4- fiuorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 2- bromo-5-chlorothiophene in place of 4-bromothioanisole (yield: 150 mg, 45%). M.p. 249-251 °C. 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 6.92 (d, J = 9 Hz, 1 H), 7.18 (d, J = 9 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.39 (d, J = 9 Hz, 2H), 7.58 (d, J = 6 Hz, 1 H), 7.94 (d, J = 9 Hz, 2 Hz, 2H), 8.04 (s, 1 H). MS (DCI-NH3) m/z 477 (M+H)+, 494 (M+NH4) + . Anal. calc. for C-21 H14CI2N2O3S2Η2O: C, 50.9; H, 3.03; N, 5.60. Found: C, 50.5; H, 2.79; N, 5.26. Example 101 2-(3-Trifluoromethylphenvπ-4-(4-chlorophenvπ-5-[4-(methylsulfonvπphenyl]-3(2H pyridazinone The title compound was prepared according to Example 93, starting with 4- (4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4- fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyhdazinone and substituting 3- iodobenzotrifluoride in place of 4-bromothioanisole (yield: 210 mg, 59.5%). M.p. 103-105 °C. 1 H NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 7.18 (d, J = 9 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.41 (d, J = 9 Hz, 2H), 7.65 (m, 2H), 7.95 (m, 3H), 8.04 (m, 2H). MS (DCI-NH3) m/z 505 (M+H)+, 525 (M+NH4)+. Anal. calc. for C24H16CIF3N2O3S: C, 57.14; H, 3.17; N, 5.56. Found: C, 56.61 ; H, 3.28; N, 5.38. Example 102 2- ( 3-Chloro-4-fluorophenvπ-4- ( 4-chlorophenvn-5-[4-(methylsulfonvπphenyl]-3(2HV pvridazinone The title compound was prepared according to Example 93, starting with 4- (4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (described in Example 99) in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone and substituting 1 -bromo-3-chloro-4-fluorobenzene in place of 4- bromothioanisole (yield: 330 mg, 58.8%). M.p. 205 °C. 1 H NMR (300 MHz, CDCI3) δ 3.10 (s, 3H), 7.17 (d, J = 9 Hz, 2H), 7.23-7.31 (m, 1 H), 7.28 (d, J = 9 Hz, 2H), 7.41 (d, J = 9 Hz, 2H), 7.65 (ddd, J = 9 Hz, 3 Hz, 1.5 Hz, 1 H), 7.85 (dd, J = 9 Hz, 3 Hz, 1 H), 7.93 (d, J = 9 Hz, 2H), 8.01 (s, 1 H). MS (DCI-NH3) m/z 489 (M+H)+, 508 (M+NH4)+. Anal. calc. for C23H15CI2N2O3S: C, 56.44; H, 3.17; N, 5.73. Found: C, 56.37; H, 3.19; N, 5.64. Example 103 2-^3-FluorophenylV4-(4-fluorophenvn-5-[4-(methylsulfonvπphenyl]-3f2HV pyridazinone The title compound was prepared according to Example 93, substituting 1 - fluoro-3-iodobenzene in place of 4-bromothioanisole (yield: 310 mg, 70.8%). M.p. 245-247 °C. 1 H NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 6.98 (t, J = 9 Hz, 2H), 7.14 (m, 1 H), 7.24 (dd, J = 9 Hz, 6 Hz, 2H), 7.40 (m, 2H), 7.52 (m, 3H), 7.92 (d, J = 9 Hz, 2H), 8.01 (s, 1 H). MS (DCI-NH3) m/z 439 (M+H)+, 456 (M+NH4)+. Anal. calc. for C23H-I 6F2N2O3S-0.25 H2O: C, 62.34; H, 3.67; N, 6.38. Found: C, 62.33; H, 3.68; N, 6.22. Example 104 2-[2-fMethylthio^phenyl1-4- ( 4-fluorophenvn-5-[4-(methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to Example 93, substituting 2- bromothioanisole in place of 4-bromothioanisole (yield: 280 mg, 60%). M.p. 206- 208 °C. 1 H NMR (300 MHz, CDCI3) δ 2.49 (s, 3H), 3.08 (s, 3H), 6.95 (t, J = 9 Hz, 2H), 7.25 (dd, J = 9 Hz, 6 Hz, 2H), 7.29-7.51 (m, 4H), 7.43 (d, J = 9 Hz, 2H), 7.92 (d, J = 9 Hz, 3H), 8.01 (s, 1 H), 7.98 (s, 1 H). MS (DCI-NH3) m/z 467 (M+H)+, 484 (M+NH4)+. Anal. calc. for C24Hi gFN2θ3S2-H2θ: C, 59.50; H, 4.13; N, 5.79. Found: C, 59.62; H, 4.15; N, 5.52. Example 105 2-(5-Nitro-2-thienyl)-4- 4-fluorophenyl)-5-[4-.methylsulfonvπphθnyl]-3(2H)- pyridazinone The title compound was prepared according to Example 93, substituting 2- bromo-5-nitrothiophene in place of 4-bromothioanisole (yield: 330 mg, 70%). M.p. 252-253 °C. 1 H NMR (300 MHz, CDCI3) δ 3.06 (s, 3H), 7.05 (t, J = 9 Hz, 2H), 7.25 (dd, J = 9 Hz, 6 Hz, 2H), 7.40 (d, J = 9 Hz, 2H), 7.71 (d, J = 6 Hz, 1 H), 7.95 (m, 3H), 8.14 (s, 1 H). MS (DCI-NH3) m/z 472 (M+H)+, 489 (M+NH4)+. Anal. calc. for C-21 Hi 4FN3O5S2-0.5 H2O: C, 52.50; H, 3.02; N, 8.75. Found: C, 52.79; H, 3.18; N, 8.74. Example 106 2- 3.4-DifluorophenylV4-(4-chlorophenvπ-5-r4-(methylsulfonvπphenyl]-3f2H pvridazinone The title compound was prepared according to Example 93, starting with 4- (4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4- fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 1 - bromo-3,4-difluorobenzene in place of 4-bromothioanisole (yield: 310 mg, 65.7%). M.p. 187-188 °C. 1 H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 7.18 (d, J = 9 Hz, 2H), 7.29 (m, 3H), 7.41 (d, J = 9 Hz, 2H), 7.52 (m, 1 H), 7.65 (m, 1 H), 7.92 (d, J = 9 Hz, 2H), 8.01 (s, 1 H). MS (DCI-NH3) m/z 473 (M+H)+, 490 (M+NH4) + - Anal. calc. for C23H15CIF2N2O3S O.5 H2O: C, 57.38; H, 3.33; N, 5.82. Found: C, 57.44; H, 3.38; N, 5.52. Example 107 2-(3-Benzothiθnylι-4-f4-fluorophθnyl)-5-[4-(methylsulfonyl)ph9nyl]-3(2H)- pyridazinone The title compound was prepared according to Example 93, substituting 3-bromobenzothiophene in place of 4-bromothioanisole (yield: 185 mg, 41 %). M.p. 265-267 °C. " I H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 7.0 (t, J = 9 Hz, 2H), 7.27 (dd, J = 9 Hz, 6 Hz, 2H), 7.39-7.47 (m, 2H), 7.44 (d, J = 9 Hz, 2H), 7.75-7.82 (m, 1 H), 7.87-7.94 (m, 2H), 7.94 (d, J = 9 Hz, 2H), 8.05 (s, 1 H). MS (DCI-NH3) m/z 477 (M+H)+, 494 (M+NH4)+. Anal. calc. for C25H17FN2O3S2: C, 63.03; H, 3.57; N, 5.88. Found: C, 62.89; H, 3.55; N, 5.71. Example 108 2-(4-Fluorophenvπ-4-( , 4-fluorophenoxy 5-[4-(methylsulfonvhphenyl]-3(2HV pvridazinone 108A. 4-( , 4-FluorophenoxyV5-[4-(methylsulfonvπphenyl -3f2H)-pyridazinone The title compound was prepared by treating 2-benzyl-4-(4-fluorophenoxy)- 5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (Example 75) with AIBr3 in toluene according to the procedure in Example 11 (yield: 1.8 g, 95%). 108B. 2-(4-Fluorophθnyl)-4-(4-fluoroph8noxy^-5-[4-.mθthylsulfonyl)phenyl1-3.2H pyridazinone The title compound was prepared according to Example 03, starting with 4- (4-fluorophenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 1 -fluoro-4-iodobenzene in place of 4-bromothioanisole (yield: 60 mg, 53%). M.p. 83-85 °C. 1 H NMR (300 MHz, CDCI3) δ 3.10 (s, 3H), 6.89-7.03 (m, 4H), 7.15 (t, J = 9 Hz, 2H), 7.65 (dd, J = 9 Hz, 6 Hz, 2H), 7.83 (d, J = 6 Hz, 2H), 8.07 (d, J = 9 Hz, 2H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 455 (M+H)+, 472 (M+NH4)+. Example 109 -O^-Difluorophenvπ^-^-fluorophenoxy S-^-fmethylsulfonvhphenyll-S^H pyridazinone The title compound was prepared according to Example 93, substituting 1 - bromo-3,4-difluorobenzene in place of 4-bromothioanisole and 4-(4- fluorophenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (Example 108A) in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 185 mg, 39%). M.p. 178-180 °C. 1 H NMR (300 MHz, CDCI3) δ 3.11 (s, 3H), 6.89- 7.04 (m, 4H), 7.45-7.52 (m, 1 H), 7.45-7.52 (m, 1 H), 7.61 (dt, J = 6 Hz, 3 Hz, 1 H), 7.82 (d, J = 9 Hz, 2H), 8.07 (d, J = 9 Hz, 2H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 473 (M+H)+, 490 (M+NH4)+. Anal. calc. for C23H-| 5F3N2θ4S-0.5 H2O: C, 57.38; H, 3.33; N, 5.83. Found: C, 57.17; H, 3.13; N, 5.62. Example 110 2-f3-Bromophenyl)-4-^4-fluorophenoxy)-5-[4-fmethylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to Example 93, substituting 1 ,3- dibromobenzene in place of 4-bromothioanisole and 4-(4-fluorophenoxy)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (Example 108A) in place of 4-(4- fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 260 mg, 50.5%). M.p. 208-210 °C. 1 H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 6.89-7.04 (m, 4H), 7.34 (t, J = 9 Hz, 1 H), 7.53 (br d, J = 9 Hz, 1 H), 7.64 (br d, J = 9 Hz, 1 H), 7.82 (d, J = 9 Hz, 2H), 7.87 (t, J = 1.5 Hz, 1 H), 8.08 (d, J = 9 Hz, 2H), 8.09 (s, 1 H). MS (DCI- NH3) m/z 517 (M+H)+, 534 (M+NH4)+. Anal. calc. for C-23H-| 6BrFN2θ4S: C, 53.7; H, 3.11 ; N, 5.45. Found: C, 53.46; H, 2.88; N, 5.18. Example 111 2-(3.5-Difluorophenyπ-4-(4-fluorophenoxy)-5-[4-(methylsulfonyπphenyl]-3(2H pyridazinone The title compound was prepared according to Example 93, substituting 1 - bromo-3,4-difluorobenzene in place of 4-bromothioanisole and 4-(4- fluorophenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (Example 108A) in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 175 mg, 37%). M.p. 209-211 °C. 1 H NMR (300 MHz, CDCI3) δ 3.10 (s, 3H), 6.85 (tt, J = 9 Hz, 3 Hz, 1 H), 6.90-7.04 (m, 4H), 7.38 (dd, J = 9 Hz, 3 Hz, 2H), 7.81 (d, J = 9 Hz, 2H), 8.07 (d, J = 9 Hz, 2H), 8.10 (s, 1 H). MS (DCI-NH3) m/z 473 (M+H)+, 490 (M+NH4)+. Anal. calc. for C23H15F3N2O4SΗ2O: C, 58.47; H, 3.18; N, 5.94. Found: C, 58.31 ; H, 3.15; N, 5.82. Example 112 2-(3-Chlorophenyn-4-f4-fluorophθnoxy)-5-f4-(mθthylsulfonyl)phenyl]-3f2H pvridazinone The title compound was prepared according to Example 93, substituting 1 - bromo-3-chlorobenzene in place of 4-bromothioanisole and 4-(4-fluorophenoxy)-5- [4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (Example 108A) in place of 4-(4- fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 25 mg, 5.3%). M.p. 211 -213 °C. 1 H NMR (300 MHz, DMSO-d6) δ 3.30 (s, 3H), 7.15 (d, J = 9 Hz, 4H), 7.51-7.64 (m, 3H), 7.71 -7.75 (m, 1 H), 7.91 (d, J = 9 Hz, 2H), 8.06 (d, J = 9 Hz, 2H), 8.41 (s, 1 H). MS (DCI-NH3) m/z 471 (M+H)+, 488 (M+NH4)+. Anal. calc. for C23H-I 6CIFN2O4S-0.5 H2O: C, 57.62; H, 3.44; N, 5.85. Found: C, 57.62; H, 3.52; N, 5.48. Example 113 2-f4-Nitrobenzyl)-4-f4-fluorophenyl)-5-[4-(m9thylsulfonyl)ph9nvπ-3.2H pvridazinone The title compound was prepared according to the method of Example 20, substituting 4-nitrobenzyl bromide in place of 4-fiuorobenzyl bromide (yield: 164 mg, 58.9%). M.p. 183-184 °C. 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 5.47 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.16 (dd, J = 9 Hz, 3 Hz, 2H), 7.32 (d, J = 9 Hz, 2H), 7.70 (d, J = 9 Hz, 2H), 7.87 (s, 1 H), 7.88 (d, J = 9 Hz, 2H), 8.22 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 480 (M+H)+, m/z 497 (M+NH4)+. Anal. calc. for C24H18FN3O5S: C, 60.12; H, 3.78; N, 8.76. Found: C, 59.89; H, 3.83; N, 8.61. Example 114 2-(4-Acetoxybenzyπ-4-(4-fluorophenvπ-5-[4-(methylsulfonvπphenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 20, substituting 4-(chloromethyl)phenyl acetate in place of 4-fluorobenzyl bromide (yield: 220 mg, 76.9%). M.p. 172-174 °C. 1 H NMR (300 MHz, CDCI3) δ 2.30 (s, 3H), 3.05 (s, 3H), 5.38 (s, 2H), 6.95 (t, J = 9 Hz, 2H), 7.06 (d, J = 9 Hz, 2H), 7.16 (dd, J = 9 Hz, 5 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.60 (d, J = 9 Hz, 2H), 7.81 (s, 1 H), 7.87 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 510 (M+NH4)+. Anal. calc. for C26H21 FN2O5S: C, 63.40; H, 4.30; N, 5.69. Found: C, 63.28; H, 4.41 ; N, 5.39. Example 115 2-(4-Hydroxybenzyπ-4-(4-fluorophenyπ-5-[4-(methylsulfonyπphenyl]-3(2H)- pvridazinone A solution of 2-(4-acetoxybenzyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone (0.2 g, 4.06 mmol) (Example 114) in THF (20 mL) was treated with a solution of lithium hydroxide monohydrate (0.05 g, 1.22 mmol) in water (5 mL). Methanol (2 mL) was added to provide a homogeneous solution which was stirred at room temperature overnight. The reaction mixture was then acidified with 10% aqueous citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to provide a white foam which was purified by column chromatography (silica gel, 65:35 hexanes/ethyl acetate). Product fractions were combined and concentrated in vacuo. The residue was crystallized from ethyl acetate/hexanes (yield: 195 mg, 70%). M.p. 225-226 °C. 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 4.86 (s, 1 H), 5.33 (s, 2H), 6.80 (d, J = 8.5 Hz, 2H), 6.95 (t, J = 9 Hz, 2H), 7.15 (dd, J = 9 Hz, 5 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 7.46 (d, J = 8.5 Hz, 2H), 7.83 (s, 1 H), 7.87 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 451 (M+H)+. Anal. calc. for C24Hi gFN2θ4S: C, 63.99; H, 4.25; N, 6.22. Found: C, 63.73; H, 4.16; N, 6.11. Example 116 2-f3-Nitrobenzyl)-4- ( 4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 20, substituting 3-nitrobenzyl bromide in place of 4-fluorobenzyl bromide (yield: 195 mg, 70%). M.p. 156-157 °C. " Η NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 5.48 (s, 2H), 6.96 (t, J = 9 Hz, 2H), 7.16 (dd, J = 9 Hz, 5 Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H), 7.54 (t, J = 7 Hz, 1 H), 7.88 (s, 1 H), 7.90 (d, J = 8.5 Hz, 2H), 8.19 (br d, J = 7 Hz, 1 H), 8.37 (t, J = 1.7 Hz, 1 H). MS (DCI-NH3) m/z 480 (M+H)+, m/z 497 (M+NH4) + - Anal, calc. for C24H18FN3O5S: C, 60.12; H, 3.78; N, 8.76. Found: C, 59.g8; H, 3.73; N, 8.67. Example 117 2-t3.4.4-Trifluoro-3-butenvn-4-(4-fluorophenvh-5-[4-(methvlsulfonvnphenvl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 20, substituting 4-bromo-1 ,1 ,2-trifluoro-1 -butene in place of 4-fluorobenzyl bromide (yield: 38 mg, 14.5%). M.p. 131 -132 °C. 1 H NMR (300 MHz, CDCI3) δ 2.92 (br d, J = 21.7 Hz, 2H), 3.06 (s, 3H), 4.47 (t, J = 6.6 Hz, 2H), 6.98 (t, J = 9 Hz, 2H), 7.17 (dd, J = 9 Hz, 5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 7.85 (s, 1 H), 7.89 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 453 (M+H)+, m/z 470 (M+NH4)+. Anal. calc. for C21 H16F4N2O3S: C, 55.75; H, 3.56; N, 6.19. Found: C, 55.63; H, 3.62; N, 6.10. Example 118 2-f2-Hexynvπ-4-(4-fluorophenyπ-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 20, substituting 1 -chloro-2-hexyne in place of 4-fluorobenzyl bromide (yield: 170 mg, 69%). M.p. 79-80 °C. 1 H NMR (300 MHz, CDCI3) δ 0.99 (t, J = 7.5 Hz, 3H), 1.56 (h, J = 7.5 Hz, 2H), 2.21 (m, 2H), 3.06 (s, 3H), 5.01 (t, J = 3 Hz, 2H), 6.96 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.34 (d, J = 9 Hz, 2H), 7.88 (s, 1 H), 7.89 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 425 (M+H)+. Anal. calc. for C23H21 FN2O3S: C, 65.07; H, 4.98; N, 6.59. Found: C, 64.87; H, 4.90; N, 6.58. Example 119 2-f3.3-Dichloro-2-propenvn-4- ( 4-fluorophenvn-5-[4-faminosulfonvnphenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 20, substituting 1 ,1 ,3-trichloropropene in place of 4-fluorobenzyl bromide (yield: 1.15 g, 68%). M.p. 184-185 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 4.39 (d, J = 7.5 Hz, 2H), 6.43 (t, J = 7.5 Hz, 1 H), 7.14 (t, J = 9 Hz, 2H), 7.23 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.43 (s, 2H), 7.73 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 454 (M+H)+. Anal. calc. for C19H14CI2F4N3O3S: C, 50.23; H, 3.1 ; N, 9.24. Found: C, 50.28; H, 3.29; N, 9.19. Example 120 2-Cyclohexyl-4-(4-fluorophenyπ-5-[4-(methylsulfonyl)phenyl]-3f2H pyhdazinone The title compound was prepared according to the method of Example 20 substituting cyclohexyl bromide in place of 4-fluorobenzyl bromide (yield: 163 mg, 76%). M.p. 169-171 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 1.23 (m, 1 H), 1.41 (m, 2H), 1.71 (m, 3H), 1.87 (m, 4H), 3.23 (s, 3H), 4.85 (m, 1 H), 7.11 (m, 2H), 7.22 (m, 2H), 7.46 (d, J = 9 Hz, 2H), 7.85 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 427 (M+H)+ and m/z 444 (M+NH4)+. Anal. calc. for C23H23FN2O3SO.5 H2O: C, 63.43; H, 5.55; N, 6.43. Found: C, 63.25; H, 5.28; N, 6.28. Example 121 2-Cvclopentyl-4-(4-fluorophenylV5-[4-( , methylsulfonvhphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 20, substituting cyclopentyl bromide in place of 4-fluorobenzyl bromide (yield: 165 g, 80%). M.p. 191 -193 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 1.67 (m, 2H), 1.85 (m, 4H), 2.05 (m, 2H), 3.23 (s, 3H), 5.36 (m, 1 H), 7.12 (t, J = 9 Hz, 2H), 7.22 (m, 2H), 7.45 (d, J = 9 Hz, 2H), 7.85 (d, J = 9 Hz, 2H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 413 (M+H)+ and m/z 430 (M+NH4)+. Anal. calc. for C22H21 FN2O3S-0.5 H2O: C, 62.69; H, 5.26; N, 6.57. Found: C, 62.53; H, 4.93; N, 6.50. Example 122 2-Cvclobutyl-4-(4-fluorophenylV5-[4-(methylsulfonvπphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 20, substituting cyclobutyl bromide in place of 4-fluorobenzyl bromide (yield: 270 g, 68%). M.p. 202-203 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 1.85 (m, 2H), 2.32 (m, 2H), 2.50 (m, 2H), 5.40 (quintet, J = 7 Hz, 1 H), 7.11 (t, J = 9 Hz, 2H), 7.21 (m, 2H), 7.47 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 8.16 (s, 1 H). MS (DCI-NH3) m/z 399 (M+H)+ and m/z 416 (M+NH4)+. Anal. calc. for C21 H-| gFN2θ3S-0.75 H2O: C, 61.22; H, 5.01 ; N, 6.80. Found: C, 61.19; H, 4.62; N, 6.73. Example 123 2-(3-Methyl-2-butenyl)-4-(4-fluoroph9nyl)-5-f3-fluoro-4-(aminosulfonyl.ph9nvn- 3(2H .-pvridazinone 2-Benzyl-4-(4-fluorophenyl)-5-[3-fluoro-4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone prepared according to the method of Example 68 was N- debenzylated according to the method of Example 11. The intermediate was N- alkylated according to the method of Example 20, substituting 1 -bromo-3-methyl-2- butene in place of 4-fluorobenzyl bromide, to provide the title compound (yield: 50 mg, 30%). M.p. 134-136 °C. 1 H NMR (300 MHz, CDCI3) δ 1.79 (s, 3H), 1.86 (s, 3H), 4.78 (s, 2H), 4.85 (d, J = 7.5 Hz, 2H), 5.48 (t, J = 6 Hz, 1 H), 6.96 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.83 (s, 1 H), 7.85 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 414 (M+H)+. Anal. calc. for C-21 H20FN3O3S: C, 61 ; H, 4.87; N, 10.16. Found: C, 60.98; H, 4.66; N, 9.95. Example 124 2-.2.4-Difluorobenzyl)-4-f4-fluorophenyl)-5-[4-.aminosulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 123, substituting 2,4-difluorobenzyl bromide in place of 1 -bromo-3-methyl-2-butene (yield: 65 mg, 24%). M.p. 236-238 °C. 1 H NMR (300 MHz, CDCI3) δ 4.78 (s, 2H), 5.43 (s, 2H), 6.88 (m, 2H), 6.97 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.38 (d, J = 9 Hz, 2H), 7.55 (m, 1 H), 7.85 (s, 1 H), 7.86 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 472 (M+H)+. Anal. calc. for C23H16F3N3O3S: C, 58.59; H, 3.42; N, 8.91. Found: C, 58.44; H, 3.47; N, 8.72. Example 125 2- (, PentafliJorobenzylV4- ( 4-fluorophenylV5-[4-< ' aminosij|fonvnphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 123, substituting 2,3,4,5,6-pentafluorobenzyl bromide in place of 1-bromo-3-methyl-2- butene (yield: 105 mg, 35%). M.p. 201 -203 °C. 1 H NMR (300 MHz, CDCI3) δ 4.8 (s, 2H), 5.5 (s, 2H), 6.98 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.32 (s, 1 H), 7.37 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 526 (M+H)+. Anal, calc. for C23H13F6N3O3S: C, 52.57; H, 2.49; N, 7.99. Found: C, 52.66; H, 2.68; N, 7.8. Example 126 2-(3-Cvclohexenvh-4-(4-fluorophenvπ-5-[4-<aminosulfonynphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 123, substituting 3-bromocyclohexene in place of 1 -bromo-3-methyl-2-butene (yield: 30 mg, 10%). M.p. 206-208 °C. 1 H NMR (300 MHz, CDCI3) δ 1.75-1.85 (m, 3H), 2.1 - 2.3 (m, 3H), 4.8 (s, 2H), 5.75 (m, 2H), 6.1 (m, 1 H), 6.97 (t, J = 9 Hz, 2H), 7.20 (dd, J = 9 Hz, 6 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 7.90 (s, 1 H). MS (DCI- NH3) m/z 426 (M+H)+. Anal. calc. for C22H20FN3O3S: C, 62.10; H, 4.73; N, 9.87. Found: C, 61.27; H, 4.75; N, 9.56. Example 127 2-(3.4-Difluorobenzyl)-4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 123, substituting 3,4-difluorobenzyl bromide in place of 1 -bromo-3-methyl-2-butene and running the reaction in DMSO instead of DMF to prevent formation of byproducts (yield: 210 mg, 62%). M.p. 253-255 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 5.33 (s, 2H), 7.13 (t, J = 9 Hz, 2H), 7.22 (dd, J = 9 Hz, 6 Hz, 2H), 7.28 (m, 1 H), 7.39 (d, J = 9 Hz, 2H), 7.42 (s, 2H), 7.47 (m, 2H), 7.73 (d, J = 9 Hz, 2H), 8.12 (s, 1 H). MS (DCI- NH3) m/z 472 (M+H)+. Anal. calc. for C23H16F3N3O3S: C, 58.59; H, 3.42; N, 8.91. Found: C, 58.05; H, 3.55; N, 8.49. Example 128 2-.2.3-Dihvdro-1 H-inden-2-vh-4- 4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H ,-pvridazinone A solution of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (172 mg, 0.5 mmol), prepared in Example 11 , 2-indanol (67 mg, 0.5 mmol) and Ph3P (262 mg, 1 mmol) in toluene (20 mL) and ethyl acetate (5 mL) was prepared and added dropwise a solution of DIAD (0.2 mL, 1 mmol) in toluene (10 mL). The mixture was stirred at room temperature for 6 hours and concentrated in vacuo. The residue was chromatographed (silica gel, 19:1 CH2Cl2-ethyl acetate) to provide 200 mg of product (contaminated with reduced DIAD). A second column chromatography (hexanes-ethyl acetate 1 :1 ) furnished the title product (yield: 170 mg, 74%). M.p. 97-100 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 3.22 (s, 3H), 3.32 (m, 2H), 3.44 (dd, J = 9 Hz and 15 Hz, 2H), 5.83 (m, 1 H), 7.25 (m, 4H), 7.34 (m, 4H), 7.46 (d, J = 9 Hz, 2H), 7.85 (d, J = 9 Hz, 2H), 8.06 (s, 1 H). MS (DCI-NH3) m/z 461 (M+H)+ and m/z 478 (M+NH4)+. Example 129 2-(2.3-Dihvdro-1 H-inden-1 -ylV4-f4-fluorophenvπ-5-[4-(methylsulfonvπphenvn- 3(2HVpyhdazinone The title compound was prepared according to the method of Example 128 substituting 1 -indanol in place of 2-indanol (yield: 110 mg, 48%). M.p. 128-130 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 2.40 (m, 1 H), 2.60 (m, 1 H), 3.00 (m, 1 H), 3.22 (s+m, 4H), 6.60 (dd, J = 9 Hz, 6 Hz, 1 H), 7.16 (m, 4H), 7.27 (m, 4H), 7.47 (d, J = 9 Hz, 2H), 7.85 (d, J = 9 Hz, 2H), 8.02 (s, 1 H). MS (DCI-NH3) m/z 461 (M+H)+ and m/z 478 (M+NH4) + . Example 130 2-(4-Tetrahvdro-2H-pyran-4-vπ-4-(4-fluorophenvπ-5-[4-(methylsulfonvhphenyl]- 3(2HVpyridazinone The title compound was prepared according to the method of Example 128 substituting 4-tetrahydropyranol in place of 2-indanol (yield: 140 g, 65%). M.p. 230- 231 °C. 1 H NMR (300 MHz, DMSO-d6) δ 1.75 (m, 2H), 1.93 (m, 2H), 3.14 (s, 3H), 3.46 (m, 2H), 3.93 (m, 2H); 5.02 (m, 1 H), 7.05 (t, J = 9 Hz, 2H), 7.15 (m, 2H), 7.40 (d, J = 9 Hz, 2H), 7.80 (d, J = 9 Hz, 2H), 8.08 (s, 1 H). MS (APCI-) m/z 428 (M-H) " and m/z 463 (M+CI)- . Anal. calc. for C-22H21 FN204S-1.25 H2O: C, 58.59; H, 5.25; N, 6.21. Found: C, 58.31 ; H, 4.75; N, 6.05. Example 131 2-(2-Methylcvclopentvπ-4-(4-fluorophenvπ-5-[4-(methylsulfonvπphenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 128 substituting 2-methylcyclopentanol in place of 2-indanol (yield: 230 g, 86%). M.p. 180-181 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 0.75 (d, J = 7 Hz, 3H), 1.60 (m, 2H), 1.89 (m, 2H), 2.10 (m, 1 H), 2.21 (m, 1 H), 2.40 (m, 1 H), 3.23 (s, 3H), 5.37 (q, J = 7 Hz, 1 H), 7.12 (t, J = 9 Hz, 2H), 7.21 (m, 2H), 7.47 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (APCI+) m/z 427 (M+H)+ and (APCI-) m/z 461 (M+CI)". Anal, calc. for C23H23FN2O3S: C, 64.77; H, 5.43; N, 6.56. Found: C, 64.71 ; H, 5.34; N, 6.28. Example 132 2-(2-Adamantvn-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl1-3.2H ) - pvridazinone The title compound was prepared according to the method of Example 128 substituting 2-adamantanol in place of 2-indanol, (yield: 75 g, 25%). M.p. 195-197 °C. 1 H NMR (300 MHz, DMSO-dε) δ 1.60 (m, 2H), 1.77 (m, 2H), 1.94 (m, 6H), 2.35 (m, 4H), 3.23 (s, 3H), 4.83 (m, 1 H), 7.11 (t, J = 9 Hz, 2H), 7.22 (m, 2H), 7.47 (d, J = 9 Hz, 2H), 7.87 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (APCI+) m/z 479 (M+H)+ and (APCI-) m/z 478 (M-H) " , m/z 513 (M+CI) " . Anal. calc. for C27H27FN2O3S-0.25 H2O: C, 67.13; H, 5.73; N, 5.79. Found: C, 67.06; H, 5.76; N, 5.06. Example 133 2-(3-Methylcvclopentyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phBnyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 128 substituting 3-methylcyclopentanol in place of 2-indanol (yield: 155 g, 73%). M.p. 169-171 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 1.05 (dd, 2:1 , 3H), 1.24 (m, 1 H), 1.63 (m, 1 H), 2.00 (m, 3H), 2.22 (m, 2H), 3.23 (s, 3H), 5.43 (m, 1 H), 7.1 (t, J = 9 Hz, 2H), 7.21 (m, 2H), 7.46 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 8.12 (two s, 2:1 , 1 H). MS (APCI+) m/z 27 (M+H)+ and (APCI-) m/z 426 (M-H) ' , m/z 461 (M+CI) " . Anal. calc. for C27H27FN2O3S-0.25 H2O: C, 64.09; H, 5.49; N, 6.49. Found: C, 64.27; H, 5.62; N, 6.46. Example 134 2-(1 -Methylcyclopentyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonvhphenyl]-3(2H)- pvridazinone A solution of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (206 mg, 0.6 mmol), prepared according to the method of Example 11 , 1 -methyl-1 -cyclopentanol (60 mg, 0.6 mmol), DMAP (18 mg, 0.12 mmol) and Ph3P (262 mg, 1 mmol) in toluene (30 mL) in ethyl acetate (5 mL) was prepared and added dropwise to a solution of DIAD (0.2 mL, 1 mmol) in 10 mL of toluene. The mixture was stirred at room temperature for 6 hours and then concentrated in vacuo. The residue was chromatographed (silica gel, 19:1 CH2Cl2-et yl acetate) to provide 80 mg of product (contaminated with reduced DIAD). A second column chromatography (hexanes-ethyl acetate 1 :1 ) furnished the title product, (yield: 50 mg, 19%). M.p. 107-110 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 1.55 (s, 3H), 1.70 (m, 4H), 2.08 (m, 2H), 2.32 (m, 2H), 3.22 (s, 3H), 7.10 (t, J = 9 Hz, 2H), 7.20 (m, 2H), 7.45 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 8.03 (s, 1 H). MS (APCI+) m/z 427 (M+H)+ and (APCI-) m/z 426 (M-H) " , m/z 461 (M+CI) " . Example 135 2-(3.4-Difluorophenvπ-4-( r 4-fluoro-3-vinylphenyl)-5-[4-(methylsulfonyhphenyl]- 3(2H)-pvridazinone. 135A. 5-Bromo-2-fluorostyrene. A mixture of methyltriphenylphosphonium bromide (2.14 g, 6 mmol) and potassium f-butoxide (672 mg, 6 mmol) in 50 mL of THF was refluxed for 30 minutes under N2 and then cooled to room temperature. 5-Bromo-2- fluorobenzaldehyde (1.02 g, 5 mmol) was added and the resulting mixture was refluxed for 2 hours (until the TLC showed the disappearance of starting aldehyde). The reaction was concentrated in vacuo and partitioned between water and ethyl acetate. The acetate layer was washed with water and brine. The solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (silica gel, 15:1 hexanes-diethyl ether) to provide 900 mg (90%) of 5-bromo-2-fluorostyrene. 135B. 2-(3.4-Difluorophenyl>-4-(4-fluoro-3-vinylphenyl)-5-[4-fmethylthio)phenyl]- 3 ( 2H.-pvridazinone. The bromo-styrene compound, prepared above, in 10 mL of THF was added dropwise to a heated mixture of magnesium turnings (120 mg, 5 mmol) and a few drops of 1 ,2-dibromoethane in THF (20 mL) at a rate to maintain a gentle reflux. The mixture was refluxed for the next 30 minutes and cooled to room temperature. The Grignard reagent solution was cooled to -78 °C and added, dropwise, to a solution of 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (540 mg, 1.5 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature for 12 hours. Afterwards, a saturated solution of NH4CI was added and the mixture was extracted with ethyl acetate to provide 320 mg of crude sulfide. 135C. 2-.3.4-Diflιιorophenvh-4-(4-fluoro-3-vinylphenylV5-f4- ( methylsulfonyl)- phenyl]-3 ( 2H)-pyridazinone. The sulfide, prepared above, was dissolved in CH2CI2 (20 mL) and at 0 °C was treated with 30% CH3CO3H in CH3CO2H (0.5 mL). After 1.5 hours, 10% NaHCO3 was added and the mixture extracted with CH2CI2. The extract was concentrated in vacuo and the residue purified by chromatography (silica gel, 1 :1 hexanes-ethyl acetate) to provide the title compound (yield: 270 mg, 37%). 1 H NMR (DMSO-d6, 300 MHz) δ 3.22 (s, 3H), 5.37 (d, J = 12 Hz, 1 H), 5.65 (d, J = 18 Hz, 1 H), 6.77 (dd, J = 12 Hz and 18 Hz, 1 H), 7.15 (m, 2H), 7.57 (m, 5H), 7.90 (m, 3H), 8.28 (s, 1 H). MS (APCI+) m/z 483 (M+H)+ and (APCI-) m/z 517 (M+CI)-. Anal. calc. for C25H17F3N2O3S-0.5 H2O: C, 61.09; H, 3.69; N, 5.69. Found: C, 61.04; H, 3.71 ; N, 5.34. Example 136 2-(3.4-Difluorophenyl)-4-f6-methyl-3-heptenyl)-5-[4-(methylsulfonyl)phenyl]-3.2H)- pyridazinone A Grignard, prepared as described in Example 135, substituting 2-(2-bromo- ethyl)-1 ,3-dioxane (586 mg, 3 mmol) in place of 5-bromo-2-fluorostyrene, was added to a solution of 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone (720 mg, 2 mmol) in THF (30 mL) at -78 °C. The mixture was left at room temperature for 14 hours, quenched with a saturated solution of NH4CI and extracted with ethyl acetate to obtain 900 mg of crude sulfide. The intermediate sulfide product was dissolved in CH2CI2 (10 mL) and treated at 0 °C with 33% solution of CH3CO3H in CH3CO2H (0.7 mL) for 1 hour. The mixture was concentrated in vacuo and the residue was partitioned between saturated NaHCO3 and ethyl acetate. The acetate layer was dried over MgSO4 and concentrated in vacuo to provide 950 mg of crude sulfonyl derivative. The sulfonyl compound, prepared above, was dissolved in acetone (50 mL) and treated with 2 N HCl (10 mL). The resulting mixture was refluxed for 16 hours and concentrated in vacuo. The residue was extracted with ethyl acetate to provide 900 mg of 2-(3,4-difluorophenyl)-4-(2-formylethyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (crude aldehyde, contaminated with some unreacted starting dioxane derivative). A mixture of isoamyltriphenylphosphonium bromide (414 mg, 1 mmol) and potassium f-butoxide (112 mg, 1 mmol) in toluene (25 mL) was refluxed for 30 minutes and then cooled to room temperature. The crude aldehyde was added and the mixture was refluxed for 14 hours. The reaction mixture was then cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate and was washed with water, 10% citric acid, brine, dried over MgSθ4 and concentrated in vacuo. Purification by column chromatography (silica gel, 1 :1 hexanes-ethyl acetate) provided the title compound as an oil (yield: 120 mg, 13%). 1 H NMR (300 MHz, DMSO-d6) δ 0.74 (d, J = 7 Hz, 6H), 1.44 (m, 1 H), 1.70 (t, J = 7 Hz, 2H), 2.22 (m, 2H), 2.54 (m, 2H); 3.30 (s, 3H), 5.29 (m, 2H), 7.51 (m, 1 H), 7.63 (m, 1 H), 7.74 (d, J = 9 Hz, 2H), 7.82 (m, 1 H), 8.02 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (APCI+) m/z 473 (M+H)+ and (APCI-) m/z 471 (M-H) " , m/z 507 (M+CI) " . Anal. calc. for C25H26F2N2O3S: C, 63.54; H, 5.54; N, 5.92. Found: C, 63.74; H, 5.67; N, 5.58. Example 137 2-f3.4-Difluorophenvπ-4- ( 3-cvclopropylidenepropyπ-5-[4-fmethylsulfonvhphenyl]- 3(2H .-pvridazinone The title compound was prepared according to the method of Example 136 substituting cyclopropyltriphenylphosphonium bromide in place of isoamyltriphenylphosphonium bromide (yield: 55 mg, 12%). M.p. 128-129 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.81 (m, 2H), 0.97 (m, 2H), 2.34 (m, 2H), 2.65 (m, 2H), 3.32 (s, 3H), 5.64 (m, 1 H), 7.52 (m, 1 H), 7.63 (m, 1 H), 7.73 (d, J = 9 Hz, 2H), 7.81 (m, 1 H), 8.02 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (APCI+) m/z 443 (M+H)+ and (APCI-) m/z 441 (M-H) " , m/z 477 (M+CI) " . Anal. calc. for C23H20F2N2O3S-0.5 H2O: C, 61.18; H, 4.68; N, 6.20. Found: C, 61.48; H, 4.60; N, 6.02. Example 138 2-(3.4-DifluorophenylV4-(5-methyl-3-hexenvn-5-[4-(methylsulfonvnphenyl]-3(2H pyridazinone The title compound, an oil, was prepared according to the method of Example 136 substituting isobutyltriphenylphosphonium bromide in place of isoamyltriphenylphosphonium bromide (yield: 170 mg, 74%). 1 H NMR (300 MHz, DMSO-d6) δ 0.75 (d, J = 7 Hz, 6H), 2.22 (m, 3H), 2.54 (m, 2H), 3.32 (s, 3H), 5.12 (m, 2H), 7.52 (m, 1 H), 7.60 (m, 1 H), 7.72 (d, J = 9 Hz, 2H), 7.80 (m, 1 H), 8.02 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (APCI+) m/z 459 (M+H)+ and (APCI-) m/z 457 (M-H) ' , m/z 493 (M+CI) ' . Anal. calc. for C24H24F2N2O3S: C, 62.86; H, 5.27; N, 6.10. Found: C, 62.57; H, 5.32; N, 5.81. Example 139 2-(3.4-Difluorophenyl)-4-(5-methylhexyl)-5-[4-fmathyl-.ulfonylιphsnyl]-3(2H)- pvridazinone The title compound, an oil, was prepared according to the method of Example 135B, substituting 5-methylhexylmagnesium bromide for 3-fluoro-4- vinylphenylmagnesium bromide, (yield: 28 mg, 10%). 1 H NMR (300 MHz, DMSO- dβ) δ 0.77 (d, J = 7 Hz, 6H), 0.88 (m, 1 H), 1.03 (m, 2H), 1.20 (m, 1 H), 1.46 (m, 5H), 3.32 (s, 3H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.75 (d, J = 9 Hz, 2H), 7.82 (m, 1 H), 8.02 (s, 1 H), 8.11 (d, J = 9 Hz, 2H). MS (APCI+) m/z 461 (M+H)+ and (APCI-) m/z 459 (M- H)-, m/z 495 (M+CI) " . Example 140 2-f3-Chloro-1 -methyl-2E-propenvπ-4-C4-fluorophenvπ-5-[4-( , aminosulfonyl1phenyl]- 3(2H)-pyridazinone The title compound was prepared according to the method of Example 127, substituting 1 ,3-dichloro-1 -butene in place of 3,4-difluorobenzyl bromide (yield: 55 mg, 30%). M.p. 152-154 °C. 1 H NMR (300 MHz, CDCI3) δ 4.71 (dt, J = 15 Hz, 7.5 Hz, 2H), 2.28 (d, J = 1.5 Hz, 3H), 4.8 (s, 2H), 4.9g (d, J = 1 Hz, 1 H), 5.02 (d, J = 1 Hz, 1 H), 5.85 (td, J = 4 Hz, 1 Hz, 1 H), 6.98 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.86 (s, 1 H), 7.87 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 434 (M+H)+. Anal. calc. for C20H17CIFN3O3S: C, 55.36; H, 3.94; N, 9.68. Found: C, 54.99; H, 3.83; N, 9.34. Example 141 2-(2.3.3-Trifluoro-2-propen-1 -ylV4-(4-fluorophenyh-5-[4-(aminosulfonyhphenyl]- 3(2H)-pyridazinoηe The title compound was prepared according to the method of Example 127, substituting 1 -methylsufonyloxy-2,2,3-trifluoro-1 -propene (mesylate), prepared in Example 88, in place of 3,4-difluorobenzyl bromide (yield: 10 mg, 4%). M.p. 173- 175 °C. 1 H NMR (300 MHz, CDCI3) δ 4.39 (s, 2H), 5.09 (ddd, J = 26 Hz, J = 3 Hz, J = 1 Hz, 2H), 6.98 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, J = 6 Hz, 2H), 7.29 (d, J = 9 Hz, 2H), 7.78 (s, 1 H), 7.78 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 440 (M+H)+, MS (FAB, high res.) m/z calc. for C-| H-| 4F4N3θ3S: 440.0692 (M+H)+. Found: 440.0695 (M+H)+, (0.7 ppm error). Example 142 2-π .1 .2-Trifluoro-2-propenvh-4-(4-fluorophenyl)-5-[4-(aminosulfonyπphenyl]- 3.2H .-pvridazinone The title compound was isolated from the same reaction mixture (Example 141 ) that was used to prepare 2-(2,3,3-trifluoro-2-propen-1 -yl)-4-(4-fluorophenyl)-5- [4-(aminosulfonyl)phenyl]-3(2H)-pyridazinone (The title product is a result of an SN2' attack.) (yield: 50 mg, 20%). M.p. 230-232 °C. 1 H NMR (300 MHz, CDCI3) δ 4.7 (s, 2H), 5.28 (dd, J = 15 Hz, 4.5 Hz, 1 H), 5.39 (dd, J = 45 Hz, 4.5 Hz, 1 H), 6.98 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.9 (d, J = 9 Hz, 2H), 7.92 (s, 1 H), . MS (DCI-NH3) m/z 440 (M+H)+. Anal. calc. for C19H13F4N3O3S: C, 51.93; H, 2.98; N, 9.56. Found: C, 51.88; H, 3.01 ; N, 9.15. Example 143 2-(3.3-Difluoro-2-propenyl>-4-f4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 127, substituting 1 ,3-dibromo-1 ,1 -difluoropropane in place of 3,4-difluorobenzyl bromide and employing 5 equivalents of potassium carbonate (yield: 220 mg, 65%). M.p. 191 -194 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 4.77 (d, J = 7.5 Hz, 2H), 4.95 (dtd, J = 24 Hz, 7.5 Hz, 1 Hz, 1 H), 7.12 (t, J = 9 Hz, 2H), 7.23 (dd, J = 9 Hz, 6 Hz, 2H), 7.49 (d, J = 9 Hz, 2H), 7.50 (s, 2H), 7.74 (d, J = 9 Hz, 2H), 8.1 (s, 1 H). MS (DCI-NH3) m/z 422 (M+H)+. Anal. calc. for C19H14F3N3O3S: C, 54.15; H, 3.34; N, 9.97. Found: C, 53.88; H, 3.42; N, 9.76. Example 144 2-( -Methyl-3-fluorobenzylV4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 127, substituting 3-fluoro-α-methylbenzyl chloride in place of 3,4-difluorobenzyl bromide (yield: 220 mg, 65%). M.p. 192-194 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.76 (d, 6 Hz, 3H), 6.27 (q, J = 7 Hz, 1 H), 7.1 (t, J = 9 Hz, 2H), 7.22 (dd, J = 9 Hz, 6 Hz, 2H), 7.49 (d, J = 9 Hz, 2H), 7.51 (s, 2H), 7.72 (d, J = 9 Hz, 2H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 468 (M+H)+. Anal. calc. for C24H19F2N3O3S: C, 61.66; H, 4.09; N, 8.98. Found: C, 61.36; H, 3.96; N, 8.86. Example 145 2-π -Cvclohexenylmethvh-4- ( 4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 127, substituting 1 -bromomethylcyclohexene in place of 3,4-difluorobenzyl bromide (yield: 70 mg, 28%). M.p. 192-193 °C. 1 H NMR (300 MHz, DMSO-d6) δ 1.55 (m, 4H), 1.98 (m, 4H), 4.64 (s, 2H), 5.53 (s, 1 H), 7.12 (t, J = 9 Hz, 2H), 7.22 (dd, J = 9 Hz, 6 Hz, 2H), 7.39 (d, J = 9 Hz, 2H), 7.39 (s, 2H), 7.72 (d, J = 9 Hz, 2H), 8.07 (s, 1 H). MS (DCI-NH3) m/z 440 (M+H)+. Anal. calc. for C23H22FN3O3S: C, 62.85; H, 5.04; N, 9.56. Found: C, 62.47; H, 5.23; N, 9.14. Example 146 2-( -Methyl-2.3.4-trifluorobenzyl')-4-( , 4-fluorophenvπ-5-[4-(aminosulfonvπphenyl1- 3(2HVpyridazinone The title compound was prepared according to the method of Example 127, substituting 2,3,4-trifluoro-α-methylbenzyl chloride in place of 3,4-difluorobenzyl bromide (yield: 70 mg, 50%). M.p. 192-194 °C. 1 H NMR (300 MHz, CDCI3) δ 1.84 (d, J = 6 Hz, 3H), 4.8 (s, 2H), 6.54 (q, J = 7 Hz, 1 H), 6.96 (t, J = 9 Hz, 2H), 6.9g (m, 1 H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.2 (m, 1 H), 7.38 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 7.88 (s, 1 H). MS (DCI-NH3) m/z 504 (M+H)+. Anal. calc. for C24H17F4N3O3S: C, 57.25; H, 3.4; N, 8.34. Found: C, 56.84; H, 3.52; N, 7.91. Example 147 2-(α-Methyl-3.5-difluorobenzyl)-4-(4-fluorophenyπ-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone The title compound was prepared according to the method of Example 127, substituting 3,5-difluoro-α-methylbenzyl chloride in place of 3,4-difluorobenzyl bromide (yield: 80 mg, 45%). M.p. 139-141 °C. 1 H NMR (300 MHz, CDCI3) δ 1.83 (d, J = 6 Hz, 3H), 4.79 (s, 2H), 6.32 (q, J = 7 Hz, 1 H), 6.84 (m, 1 H), 6.97 (t, J = 9 Hz, 2H), 7.02 (dd, J = 6 Hz, 1.5 Hz, 2H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.28 (d, J = 9 Hz, 2H), 7.85 (s, 1 H), 7.9 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 486 (M+H)+. Anal. calc. for C24H18F3N3O3S: C, 59.37; H, 3.73; N, 8.65. Found: C, 59.00; H, 3.70; N, 8.35. Example 148 2- ( α-Methyl-3.4-difluorobenzvπ-4- ( 4-fluorophenvh-5-[4-(aminosulfonvπphenyl1- 3 ( 2H )-pvridazinone The title compound was prepared according to the method of Example 127, substituting 3,4-difluoro- -methylbenzyl chloride in place of 3,4-difluorobenzyl bromide (yield: 200 mg, 58%). M.p. 214-215 °C. 1 H NMR (300 MHz, CDCI3) δ 1.82 (d, J = 6 Hz, 3H), 4.7 (s, 2H), 6.35 (q, J = 7 Hz, 1 H), 6.96 (t, J = 9 Hz, 2H), 7.16 (m, 4H), 7.28 (d, J = 9 Hz, 2H), 7.37 (m, 1 H), 7.84 (d, J = 9 Hz, 2H), 7.90 (s, 1 H). MS (DCI-NH3) m/z 486 (M+H)+. Anal. calc. for C24H18F3N3O3S: C, 59.37; H, 3.73; N, 8.65. Found: C, 59.13; H, 3.73; N, 8.54. Example 149 2-(3-Fluorobenzvπ-4-(4-fluorophenvh-5-[4-(aminosulfonvhphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 127, substituting 3-fluorobenzyl bromide in place of 3,4-difluorobenzyl bromide (yield: 160 mg, 61 %). M.p. 220-222 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 5.37 (s, 2H), 7.12 (t, J = 9 Hz, 2H), 7.22 (m, 5H), 7.39 (m, 5H), 7.73 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 454 (M+H)+. Anal. calc. for C23H17F2N3O3S: C, 60.92; H, 3.77; N, 9.26. Found: C, 61.06; H, 4.22; N, 8.88. Example 150 2-(4-FluorobenzylV4-(4-fluorophenvh-5-[4-(aminosulfonyπphenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 127, substituting 4-fluorobenzyl bromide in place of 3,4-difluorobenzyl bromide (yield: 85 mg, 34%). M.p. 237-239 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 5.32 (s, 2H), 7.12 (t, J = 9 Hz, 2H), 7.22 (m, 4H), 7.38 (m, 4H), 7.47 (dd, J = 9 Hz, 6 Hz, 2H), 7.72 (d, J = 9 Hz, 2H), 8.10 (s, 1 H). MS (DCI-NH3) m/z 454 (M+H)+. Anal. calc. for C23H17F2N3O3S: C, 60.92; H, 3.77; N, 9.26. Found: C, 60.61 ; H, 3.96; N, 8.74. Example 151 2-(2.4.6-Trifluorobenzyl)-4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phsnyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 127, substituting 2,4,6-trifluorobenzyl bromide in place of 3,4-difluorobenzyl bromide (yield: 255 mg, 73%). M.p. 201 -203 °C. 1 H NMR (300 MHz, DMSO-dε) δ 5.38 (s, 2H), 7.13 (t, J = 9 Hz, 2H), 7.23 (m, 4H), 7.38 (d, J = 9 Hz, 2H), 7.42 (s, 2H), 7.70 (d, J = 9 Hz, 2H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 400 (M+H)+. Anal. calc. for C23H15F4N3O3S: C, 56.44; H, 3.08; N, 8.58. Found: C, 56.31 ; H, 3.09; N, 8.40. Example 152 2-r2.4.5-Trifluorobenzvh-4-f4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 127, substituting 2,4,5-trifluorobenzyl bromide in place of 3,4-difluorobenzyl bromide (yield: 180 mg, 49%). M.p. 236-238 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 5.35 (s, 2H), 7.13 (t, J = 9 Hz, 2H), 7.23 (dd, J = 9 Hz, 6 Hz, 2H), 7.39 (d, J = 9 Hz, 2H), 7.41 (s, 2H), 7.6 (m, 2H), 7.72 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 490 (M+H)+. Anal. calc. for C23H15F4N3O3S: C, 56.44; H, 3.08; N, 8.58. Found: C, 56.38; H, 3.28; N, 8.41. Example 153 2-(2.3.4-Trifluorobenzvh-4-( , 4-fluorophenvπ-5-[4-(aminosulfonv phenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 127, substituting 2,3,4-trifluorobenzyl bromide in place of 3,4-difluorobenzyl bromide (yield: 220 mg, 63%). M.p. 218-220 °C. 1 H NMR (300 MHz, DMSO-dε) δ 5.40 (s, 2H), 7.13 (t, J = 9 Hz, 2H), 7.22 (dd, J = 9 Hz, 6 Hz, 2H), 7.34 (m, 2H), 7.39 (d, J = 9 Hz, 2H), 7.42 (s, 2H), 7.73 (d, J = 9 Hz, 2H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 4gθ (M+H)+. Anal. calc. for C23H15F4N3O3S: C, 56.44; H, 3.08; N, 8.58. Found: C, 56.32; H, 3.24; N, 8.31. Example 154 2-(4.4.4-Trifluoro-3-methyl-2E-butenylV4-f4-fluorophenvn-5-[4-(aminosulfonyl)- phenvl]-3 2H ,-pvridazinone The title compound was prepared according to the method of Example 123, substituting 1 -bromo-3-methyl-4,4,4-trifluoro-2-butene in place of 1 -bromo-3- methyl-2-butene (yield: 160 mg, 48%). M.p. 155-157 °C. 1 H NMR (300 MHz, CDCI3) δ 2.00 (s, 3H), 4.8 (s, 2H), 4.06 (d, J = 7.5 Hz, 2H), 6.33 (m, 1 H), 6.99 (t, J = 9 Hz, 2H), 7.19 (dd, J = 9 Hz, 6 Hz, 2H), 7.29 (d, J = 9 Hz, 2H), 7.95 (s, 1 H), 7.97 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 468 (M+H)+. Anal. calc. for C21 H17F4N3O3S: C, 53.96; H, 3.66; N, 8.98. Found: C, 53.84; H, 3.51 ; N, 8.77. Example 155 2-(4-Biphenyn-4-f4-fluorophenylV5-r4-fmethylsulfonynphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 62 substituting 4-bromobiphenyl in place of 4-iodo-1 -fluorobenzene (yield: 0.275 g, 100%). M.p. 249-251 °C. 1 H NMR (300 MHz, DMSO d6) δ 3.24 (s, 3H), 7.16 (m, 2H), 7.30 (m, 2H), 7.42 (m, 1 H), 7.48-7.58 (m, 4H), 7.75 (m, 4H), 7.84 (m, 2H), 7.91 (m, 2H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 497 (M+H)+, 514 (M+NH4)+. Anal. calc. for C23H21 FN2O3S: C, 70.15; H, 4.26; N, 5.64. Found: C, 69.81 ; H, 4.42; N, 5.41. Example 156 2-^4-Bromophenvπ-4-(4-fluorophenvn-5-[4-rmethylsulfonvnphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 ,4-dibromobenzene in place of 4-iodo-1 -fluorobenzene (yield: 0.337 g, 93%). 1 H NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.14 (m, 2H), 7.28 (m, 2H), 7.64 (m, 2H), 7.75 (m, 2H), 7.90 (m, 2H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 499 (M+H)+, 518 (M+NH4)+. Anal. calc. for C-23Hi 6BrFN2θ3S-0.75 H2O: C, 53.86; H, 3.43; N, 5.46. Found: C, 53.92; H, 3.16; N, 5.34. Example 157 2-(4-Nitrophenvn-4-(4-fluorophenyl)-5-[4-(msthvlsulfonvl.phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 62 substituting 1 -iodo-4-nitrobenzene in place of 4-iodo-1 -fluorobenzene (yield: 0.45 g, 100%). M.p. 110-116 °C. 1 H NMR (300 MHz, DMSO 6&) δ 3.24 (s, 3H), 7.17 (m, 2H), 7.32 (m, 2H), 7.53 (m, 2H), 7.91 (m, 2H), 8.03 (m, 2H), 8.34 (s, 1 H), 8.40 (m, 2H). MS (DCI-NH3) m/z 466 (M+H)+, 483 (M+NH4) + - Anal. calc. for C23H16FN3O5S: C, 59.35; H, 3.46; N, 9.03. Found: C, 59.02; H, 3.62; N, 8.82. Example 158 2-(4-PhenoxyphenylV4- ( 4-fluorophenvh-5-f4- methylsulfonvhphenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 62 substituting 4-bromodiphenylether in place of 4-iodo-1 -fluorobenzene (yield: 0.667 g, 22%). M.p. 118-125 °C. 1 H NMR (300 MHz, DMSO β) δ 3.24 (s, 3H), 7.12 (m, 5H), 7.15-7.33 (m, 4H), 7.46 (m, 2H), 7.52 (m, 2H), 765 (m, 2H), 7.90 (m, 2H), 8.23 (s, 1 H). MS (DCI-NH3) m/z 513 (M+H)+. Anal. calc. for C25H21 FN 2 O4S-0.75 H2O: C, 66.21 ; H, 4.31 ; N, 5.32. Found: C, 65.98; H, 4.25; N, 5.27. Example 159 2- ( 4-' 1 -ButylphenylV4- 4-fluorophenvn-5-[4-fmethylsulfonvnphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-4-f-butyl-benzene in place of 4-iodo-1 -fluorobenzene. No product was observed. The solution was concentrated in vacuo. The resulting solid was dissolved in DMF (5 mL) and Cul (13.3 mg, 0.07 mmol) was added. The solution was allowed to reflux overnight. Upon completion, the mixture was poured into 10% citric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over MgSO4 and concentrated in vacuo. The crude solid was purified using flash chromatography (Siθ2), eluting with 5% diethyl ether/CH2Cl2 to provide the desired product (yield: 0.292 g, 84%). M.p. 132-136 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.34 (s, 9H), 3.24 (s, 3H), 7.14 (m, 2H), 7.29 (m, 2H), 7.54 (m, 6H), 7.90 (m, 2H), 8.23 (s, 1 H). MS (DCI-NH3) m/z 477 (M+H)+, 494 (M+NH4)+. Anal. calc. for C27H25FN2O3S: C, 68.05; H, 5.29; N, 5.88. Found: C, 67.94; H, 5.31 ; N, 5.67. Example 160 2-/4-Chlorophenvn-4-(4-fluoroDhenvn-5-[4-(methvlsulfonvnphenvl]-3r2HV pvridazinone The title compound was prepared according to the method of Example 62 substituting 4-bromo-1 -chlorobenzene in place of 4-iodo-1 -fluorobenzene (yield: 0.254 g, 83.5%). M.p. 214-216 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.16 (m, 2H), 7.29 (m, 2H), 7.52 (m, 2H), 7.61 (m, 2H), 7.71 (m, 2H), 7.91 (m, 2H), 8.26 (s, 1 H). MS (DCI-NH3) m/z 455 (M+H)+, 472 (M+NH4)+. Anal. calc. for C23H-I6CIFN2O3S: C, 60.73; H, 3.55; N, 6.16. Found: C, 60.45, H, 3.41 ; N, 6.05. Example 161 2-(3-Methylphenyl)-4-(4-fluorophenvn-5-f4-.methylsulfonynphsnyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 62 substituting 3-bromotoluene in place of 4-iodo-1 -fluorobenzene (yield: 0.262 g, 83%). M.p. 213-216 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.39 (s, 3H), 3.24 (s, 3H), 7.14 (m, 2H), 7.28 (m, 3H), 7.43 (m, 3H), 7.53 (m, 2H), 7.80 (m, 2H), 8.22 (s, 1 H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+. Anal. calc. for C24H-| gFN2θ3S: C, 66.35; H, 4.41 ; N, 6.45. Found: C, 66.00, H, 4.16; N, 6.23. Example 162 2-f3-Vinvlphenyl)-4-(4-fluorophsnvn-5-[4-(methylsulfonyl)phenvπ-3f2H)- pvridazinone The title compound was prepared according to the method of Example 62 substituting 3-bromostyrene in place of 4-iodo-1-fluorobenzene (yield: 0.202 g, 62%). M.p. 182-183 °C. " Η NMR (300 MHz, DMSO dβ) δ 3.25 (s, 3H), 5.35 (d, J = 12 Hz, 1 H), 5.92 (d, J = 15 Hz, 1 H), 6.82 (m, 1 H), 7.15 (m, 2H), 7.30 (m, 2H), 7.50- 7.60 (m, 4H), 7.74 (m, 1 H), 7.01 (m, 2H), 8.24 (s, 1 H). MS (DCI-NH3) m/z 447 (M+H)+, 464 (M+NH4)+. Anal. calc. for C25H19FN2O3SO.50 H2O: C, 65.92; H, 4.42; N, 6.14. Found: C, 65.86; H, 4.40; N, 6.07. Example 163 2-f2-FormylDhenvπ-4-f4-fluorophenvh-5-[4-(methylsulfonvπphenyl1-3(2HV pvridazinone The title was prepared according to the method of Example 62 substituting 2- bromobenzaldehyde in place of 4-iodo-1 -fluorobenzene (yield: 0.196 g, 60%). M.p. 234-236 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.15 (m, 2H), 7.27 (m, 2H), 7.54 (m, 2H), 7.64-7.75 (m, 2H), 7.86-7.95 (m, 3H), 8.01 (m, 1 H), 8.29 (s, 1 H), 10.02 (s, 1 H). MS (DCI-NH3) m/z 449 (M+H)+. Anal. calc. for C24H17FN2O4S-0.50 H2O: C, 63.01 ; H, 3.96; N, 6.12. Found: 63.04; H, 3.82; N, 5.88. Example 164 2-(2-Nitrophenvn-4-(4-fluorophenvn-5-[4-(methylsulfonvhphenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-2-nitrobenzene in place of 4-iodo-1 -fluorobenzene (yield: 0.307 g, 90.8%). M.p. 236-239 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.12-7.27 (m, 4H), 7.56 (m, 2H), 7.7-8.01 (m, 5H), 8.18 (m, 1 H), 8.35 (s, 1 H). MS (DCI-NH3) m/z 466 (M+H)+, 483 (M+NH4)+. Anal. calc. for C23H-| βFN3θ5S-0.25 H2O: C, 58.78; H, 3.53; N, 8.94. Found: C, 58.63; H, 3.54; N, 8.88. Example 165 2-f3-Chlorophenvn-4-f4-fluorophenvn-5-[4-(methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-3-chlorobenzene in place of 4-iodo-1 -fluorobenzene (yield: 0.255 g, 77%). M.p. 232-235 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.23 (s, 3H), 7.14 (m, 2H), 7.20 (m, 2H), 7.4g-7.58 (m, 4H), 7.66 (m, 1 H), 7.79 (m, 1 H), 7.90 (m, 2H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 455 (M+H)+, 472 (M+NH4)+. Anal. calc. for C23H16CIFN2O3S: C, 60.73; H, 3.55; N, 6.16. Found: C, 60.40; H, 3.43; N, 5.98. Example 166 2-(3-Bromophenvn-4-(4-fluorophenvh-5-[4- methylsulfonyπphenyl1-3(2H pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 ,3 dibromobenzene in place of 4-iodo-1 -fluorobenzene (yield: 0.216 g, 60%). M.p. 210-212 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.23 (s, 3H), 7.15 (m, 2H), 7.29 (m, 2H), 7.48-7.55 (m, 3H), 7.6g (m, 2H), 7.90 (m, 3H), 8.26 (s, 1 H). MS (DCI-NH3) m/z 499 (M+H)+, 519 (M+NH4) + - Anal. calc. for C23KιβBrFN2θ3S: C, 55.32; H, 3.23; N, 5.61. Found: C, 55.12; H, 3.12; N, 5.51. Example 167 2- -Cvanophenvπ-4-(4-fluorophenvn-5-[4-(methylsulfonvπphenyl1-3(2H pyridazinone The title compound was prepared according to the method of Example 62 substituting 4-bromobenzonitrile in place of 4-iodo-1-fluorobenzene (yield: 0.349 g, 100%). M.p. 273-278 °C. " Η NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.1 1-7.21 (m, 2H), 7.25-7.35 (m, 2H), 7.52 (m, 2H), 7.88-7.96 (m, 4H), 8.04 (m, 2H), 8.31 (s, 1 H). MS (DCI-NH3) m/z 445 (M+H)+. Anal. calc. for C24H16FN3O3S: C, 64.71 ; H, 3.62; N, 9.43. Found: C, 64.50; H, 3.53; N, 9.35. Example 168 2-.5-Methyl-2-thienyl))-4-f4-fluoroph9nyl.-5-[4-fmethylsulfonyl)phenyl]-3f2H)- pyridazinone The title compound was prepared according to the method of Example 62 substituting 2-bromo-5-methylthiophene in place of 4-iodo-1 -fluorobenzene (yield: 0.200 g, 62%). M.p. 210-224 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.45 (s, 3H), 3.23 (s, 3H), 6.80 (m, 1 H), 7.17 (m, 2H), 7.20 (m, 2H), 7.52 (m, 3H), 7.89 (m, 2H), 8.33 (s, 1 H). MS (DCI-NH3) m/z 441 (M+H)+, 458 (M+NH4)+. Anal. calc. for C22H17FN2O3S2: C, 59.99; H, 3.89; N, 6.36. Found: C, 59.90; H, 3.91 ; N, 6.26. Example 169 2-.3-Biphθnvl)-4-(4-fluorophθnyl.-5-[4-(m9thylsulfonyl)ph9nyl]-3f2H.-pyridazinonθ The title compound was prepared according to the method of Example 62 substituting 3-bromobiphenyl in place of 4-iodo-1 -fluorobenzene (yield: 0.28 g, 78%). M.p. 126-134 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.15 (m, 2H), 7.31 (m, 2H), 7.37-7.45 (m, 1 H), 7.51 (m, 4H), 7.64 (m, 2H), 7.68-7.79 (m, 3H), 7.92 (m, 3H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 497 (M+H)+, 514 (M+NH4)+. Anal, calc. for C29H21 FN2O3S: C, 70.15; H, 4.26; N, 5.64. Found: C, 60.91 ; H, 4.33; N, 5.74. Example 170 2-f3.5-Dimethylphenvn-4-f4-fluorophenyn-5-[4-fmethylsulfonvnphenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 62 substituting 5-bromo-m-xylene in place of 4-iodo-1 -fluorobenzene (yield: 0.152 g, 46.5%). M.p. 130-134 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.34 (s, 6H), 3.23 (s, 3H), 7.07-7.12 (m, 2H), 7.15 (m, 1 H), 7.21-7.32 (m, 4H), 7.52 (m, 2H), 7.90 (m, 2H), 8.29 (s, 1 H). MS (DCI-NH3) m/z 449 (M+H)+, 466 (M+NH4)+. Anal. calc. for C25H2I FN2O3S: C, 66.95; H, 4.72; N, 6.25. Found: C, 66.81 ; H, 4.57; N, 6.07. Example 171 2-f3.4-Difluorophenvn-4-f4-fluorobenzvh-5-f4-fmethylsulfonynphenyl1-3f2HV pvridazinone 4-(4-Fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone was prepared according to the method of Example 11 , starting with 2-benzyl-4-(4- fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 2- benzyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 0.3319 g, 83%). The title compound was prepared according to the method of Example 62 substituting 4-(4-fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone and substituting 1-bromo-3,4-difluorobenzene in place of 4-iodo-1 - fluorobenzene (yield: 0.085 g, 54%). M.p. 157-159 °C. 1 H NMR (300 MHz, DMSO d6) δ 3.30 (s, 3H), 3.88 (bs, 2H), 7.04 (m, 4H), 7.49-7.66 (m, 2H), 7.70 (m, 2H), 7.81 (m, 1 H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 471 (M+H)+, 488 (M+NH4)+. Anal. calc. for C24H17F3N2O3SO.25 H2O: C, 60.69; H, 3.71 ; N, 5.84. Found: C, 6.39; H, 3.76; N, 5.81. Example 172 2-f3-Chloro-4-fluorophenyl 4-(4-fluorobenzvn-5-[4-(methylsulfonvπphenyl]-3f2H)- pyridazinone The title compound was prepared according to the method of Example 62 substituting 4-(4-fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone and substituting 4-bromo-2-chloro-1 -fluorobenzene in place of 4- iodo-1 -fluorobenzene (yield: 0.110 g, 74%). M.p. 153-156 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.30 (s, 3H), 3.80 (bs, 2H), 7.02-7.07 (m, 4H), 7.59 (m, 1 H), 7.65-7.72 (m, 4H), 8.07 (m, 2H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 487 (M+H)+, 504 (M+NH4)+. Anal. calc. for C24H17CIF2N2O3SO.25 H2O: C, 58.65; H, 3.58; N, 5.64. Found: C, 58.41 ; H, 3.56; N, 5.36. Example 173 2-(2-Thienvπ-4-(4-fluorophenvπ-5-[4-(methylsulfonynphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 62 substituting 2-bromothiophene in place of 1 -bromo-4-fluorobenzene (yield: 08 mg, 40%). M.p. 215-217 °C. " Η NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), 7.18 (m, J = 9 Hz, 3H), 7.29 (m, 2H), 7.42 (d, 2H), 7.75 (d, 1 H), 7.g3 (d, J = 9 Hz), 8.4 (s, 1 H). MS (DCI-NH3) m/z 427 (M+H)+, 444 (M+NH4)+. Anal. calc. for C21 Hi 5FN2O3S2: C, 59.14; H, 3.54; N, 6.57. Example 174 2-f4-Trifluoromethylphenvπ-4-(4-fluorophenvπ-5-[4-(methylsulfonvπphenyl1-3(2HV pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-4-trifluoromethylbenzene in place of 1 -bromo-4- fluorobenzene (yield: 185 mg, 64%). M.p. 171 -173 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 3.25 (s, 3H), 7.18 (t, 2H), 7.29 (m, 2H), 7.52 (d, J = 9 Hz 2H), 7.91 (d, J = 9 Hz, 2H), 7.93 (s, 4H), 8.32 (s, 1 H). MS (DCI-NH3) m/z 489 (M+H)+, 506 (M+NH4)+. Anal. calc. for C24H16F4N2O3S: C, 59.02; H, 3.3; N, 5.74. Found: C, 58.75; H, 3.35; N, 5.69. Example 175 2-[4-(1 -Pyrroyl.Dhenyl]-4-(4-fluorophenyl)-5-r4-.m8thylsulfonyl.Dhθnyl]-3 ( 2H pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -(4-iodophenyl)pyrrole in place of 1-bromo-4-fluorobenzene (yield: 140 mg, 50%). M.p. 229-231 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), 6.3 (t, 2H), 7.18 (t, 2H), 7.29 (m, 2H), 7.46 (t, 2H) 7.53 (d, J = 9 Hz 2H), 7,75 (s, 4H), 7.91 (d, J = 9 Hz, 2H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 486 (M+H)+, 504 (M+NH4)+. Anal. calc. for C27H20FN3O3SO.5 H2O: C, 66.79; H, 4.15; N, 8.65. Found: C, 65.21 ; H, 4.29; N, 8.12. Example 176 2-(5-Chloro-2-thienyl)-4-(4-fluorophBnyn-5-[4-(methylsulfonyl)phsnyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-5-chlorothiophene in place of 1 -bromo-4-fluorobenzene (yield: 225 mg, 93%). M.p. 190-102 °C. " Η NMR (300 MHz, DMSO-dβ) δ 2.38 (s, 3H), δ 3.25 (s, 3H), 7.15 (t, 2H), 7.29 (m, 4H), 7.5 (D, 4H) 7.91 (d, J = 9 Hz, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+. Anal. calc. for C24H19F N2O3S: C, 66.35; H, 4.41 ; N, 6.45. Found: C, 66.15; H, 4.37; N, 6.3. Example 177 2-(4-Msthylphenyl.-4-f4-fluorophenyl)-5-[4-(metriylsulfonyl.phenyl]-3f2H pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-4-methylbenzene in place of 1 -bromo-4-fluorobenzene (yield: 79 mg, 31 %). M.p. 190-192 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.38 (s, 3H), δ 3.25 (s, 3H), 7.15 (t, 2H), 7.29 (m, 4H), 7.5 (D, 4H) 7.91 (d, J = 9 Hz, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+. Anal. calc. for C24H19F N2O3S: C, 66.35; H, 4.41 ; N, 6.45. Found: C, 66.15; H, 4.37; N, 6.3. Example 178 P-(4-FluoroDhsnvn-4-.2-ethvl-1 -hexyloxy)-5-[4-(methylsulfonvnphenyl]-3.2H pyridazinone To a solution of 2-ethyl-1 -hexanol (65 mg, 0.5 mmol) in THF (15 mL) at room temperature was added NaH (60% oil suspension) (20 mg, 0.5 mmol) and after 10 minutes 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- py dazinone (193 mg, 0.5 mmol) was added. The resulting mixture was stirred at room temperature for the next 2 hours. The mixture was quenched with 10% citric acid and extracted with ethyl acetate. The extract was washed with water, brine, dried with MgSO4, and purified by chromatography (silica gel, 2:1 hexanes-ethyl acetate) to provide the desired product (yield: 140 mg, 60%). M.p. 120-122 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (m, 6H), 1.1 (m, 6H), 1.20 (quintet, J = 7 Hz, 2H), 1.44 (m, 1 H), 3.27 (s, 3H), 4.30 (d, J = 6 Hz, 2H), 7.37 (t, J = 9 Hz, 2H), 7.65 (m, 2H), 7.89 (d, J = 9 Hz, 2H), 8.06 (d, J = 9 Hz, 2H), 8.18 (s, 1 H). MS (APCI+) m/z 473 (M+H)+; (APCI-) m/z 507 (M+CI) ' . Anal. calc. for C25H29FN2O4S-0.5 H2O: C, 62.35; H, 6.27; N, 5.87. Found: C, 62.22; H, 6.14; N, 6.22. Example 179 2-(3-Thienvπ-4-(4-fluorophenvπ-5-[4-fmethylsulfonvhphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 62 substituting 3-bromothiophene in place of 1 -bromo-4-fluorobenzene (yield: 225 mg, 93%). M.p. 200-202 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), 7.15 (t, 2H), 7.29 (m, 2H), 7.5 (d, J = 9 Hz, 2H), 7.6 (M, 1 H) 7.66 (dd, 1 H), 7.91 (d, J = 9 Hz, 2H), 8.13 (dd, 1 H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 427 (M+H)+, 444 (M+NH4)+. Anal. calc. for C-21 H-| 5FN2O3S2: C, 55.07; H, 4.07; N, 6.11. Found: C, 54.63; H, 3.47; N, 6.01. Example 180 2-(3.5-Difluorophenyl)-4-(4-fluorophenvn-5-f4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 62 substituting 3,5-difluorobromobenzene in place of 1 -bromo-4-fluorobenzene (yield: 250 mg, 96%). M.p. 166-168 °C. " Η NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), δ 7.15 (t, 2H), 7.27 (m, 2H), 7.4 (m, 1 H), 7.41 (m, 2H), 7.51 (d, J = 9 Hz, 4H), 7.9 (d, J = 9 Hz, 2H), 8.3 (s, 1 H). MS (DCI-NH3) m/z 457 (M+H)+, 474 (M+NH4)+. Anal. calc. for C23H15F3N2O3S: C, 60.13; H, 3.31 ; N, 6.14. Found: C, 60.49; H, 3.31 ; N, 6.03. Example 181 2-f2.4-Difluorophenvπ-4-(4-fluorophenvn-5-[4-(methylsulfonvhphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 62 substituting 2,4-difluorobromobenzene in place of 1 -bromo-4-fluorobenzene (yield: 40 mg, 15%). M.p. 245-247 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.23 (s, 3H), δ 7.15 (t, 2H), 7.3 (t, 2H), 7.54 (m, 2H), 7.57 (m, 2H), 7.75 (m, 1 H), 7.9 (d, J = 9 Hz, 2H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 457 (M+H)+, 474 (M+NH4)+. Anal. calc. for C28H15F3N2O3S: C, 60.52; H, 3.31 ; N, 6.03. Example 182 2-(3.4-Difluorophenvn-4- 4-fluorophenvn-5-[4-(methylsulfonvnphenyl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 62 substituting 3,4-difiuorobromobenzene in place of 1 -bromo-4-fluorobenzene (yield: 170 mg, 70%). M.p. 109-110 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.23 (s, 3H), δ 7.15 (t, 2H), 7.3 (t, 2H), 7.25 (m, 2H), 7.59 (m, 4H), 7.83 (m, 1 H), 7.9 (d, J = 9 Hz, 2H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 457 (M+H)+, 474 (M+NH4)+. Anal. calc. for C23H15F3N3O3S: C, 60.52; H, 3.31 ; N, 6.14. Found 60.60; H, 3.48; N, 5.89 Example 183 2-^3-Furvπ-4-(4-fluorophenvπ-5-[4- ( methylsulfonv phenyl -3(2HVpyridazinone The title compound was prepared according to the method of Example 62 substituting 3-bromofuran in place of 1 -bromo-4-fluorobenzene (yield: 175 mg, 73%). M.p. 239-242 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), 7.09 (d, 1 H), 7.15 (t, 2H), 7.29 (m, 2H), 7.5 (d, J = 9 Hz 2H), 7.8 (t, 1 H) 7.91 (d, J = 9 Hz, 2H), 8.3 (s 1 H), 8.58 (s, 1 H). MS (DCI-NH3) m/z 411 (M+H)+, 428 (M+NH4)-*-. Anal. calc. for C21 H15F N2O4S-0.5 H2O: C, 61.46; H, 3.68; N, 6.83. Found: C, 59.91 ; H, 3.54; N, 6.54. Example 184 2-(3-Fluoro-4-methoxyph9nyl)-4-(4-fluorophenvπ-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone The title compound was prepared according to the method of Example 62 substituting 3-fluoro-4-methoxybromobenzene in place of 1 -bromo-4- fluorobenzene (yield: 230 mg, 85%). M.p. 97-101 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 3.25 (s, 3H), 3.9 (s, 3H), 7.16 (d, 1 H), 7.29 (m, 3H), 7.5 (m, 4H), 7.91 (d, J = 9 Hz, 2H), 8.23 (s 1 H). MS (DCI-NH3) m/z 469 (M+H)+, 491 (M+NH4)+. Anal. calc. for C24H-I 8F2N2O4S-0.5 H2O: C, 61.53; H, 3.87; N, 5.98. Found: C, 61.18; H, 4.01 ; N, 5.58. Example 185 2-(2-Fluorophenvn-4-(4-fluorophenylV5-[4-(methylsulfonvnphenvπ-3f2HV pvridazinone The title compound was prepared according to the method of Example 62 substituting 2-fluorobromobenzene in place of 1 -bromo-4-fluorobenzene (yield: 195 mg, 75%). M.p. 96-103 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.23 (s, 3H), δ 7.15 (t, 2H), 7.3 (m, 3H), 7.55 (m, 5H), 7.9 (d, J = 9 Hz, 2H), 8.27 (s, 1 H). MS (ESI) m/z 437 (M-H)+). Anal. calc. for C23H16F2N2O3S: C, 63.01 ; H, 3.68; N, 6.39. Found, C, 62.91 ; H, 4.06; N, 5.99. Example 186 2-[4-(Aminosulfonyl.phenyl]-4-(4-fluorophθnyl)-5-[4-(mθthylsulfonyl)phβnyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 62 substituting 4-aminosulfonyl-1 -bromobenzene in place of 1 -bromo-4- fluorobenzene. M.p. 213-216 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), 7.15 (t, 2H), 7.29 (m, 2H), 7.53 (s, 2H) 7.55 (s, 1 H), 7.7 (dd, 2H) 7.91 (t, 4H), 7.98 (d, 2H), 8.3 (s, 1 H). MS (DCI-NH3) m/z 499 (M+H)+, 517 (M+NH4)+. Anal. calc. for C23H18FN3O5S2-0.5 H2O: C, 55.30; H, 3.63; N, 8.41. Found: C, 54.4; H, 3.79; N, 7.78. Example 187 2-(3-Chloro-4-fluorophenvπ-4-(4-fluorophenvn-5-[4-(methylsulfonvπphenyl]-3(2H,- pyridazinone The title compound was prepared according to the method of Example 62 substituting 3-chloro-4-fluoro-1 -bromobenzene in place of 1 -bromo-4- fluorobenzene (yield: 320 mg, 78%). M.p. 155-157 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 3.23 (s, 3H), δ 7.15 (t, 2H), 7.3 (t, 2H), 7.25 (m, 2H), 7.53 (d, J = 9 Hz, 2H), 7.59 (t, 1 H), 7.73 (m, 1 H), 7.9 (d, J = 9 Hz, 2H) 7.96 (m, 1 H), 8.27 (s, 1 H). MS (DCI- NH3) m/z 473 (M+H)+, 490 (M+NH4)+. Anal. calc. for C23H15CIF2N2O3S: C, 58.42; H, 3.2; N, 5.92. Found 58.23; H, 2.87; N, 5.70 Example 188 2-(3.5-Dichlorophenvn-4-f4-fluorophenvn-5-[4- methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 62 substituting 3,5-dichlorobenzene in place of 1 -bromo-4-fluorobenzene (yield: 360 mg, 78%). M.p. 289-294 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), δ 7.15 (t, 2H), 7.27 (m, 2H), 7.51 (d, J = 9 Hz, 4H), 7.75 (t, 1 H), 7.83 (d, 2H), 7.9 (d, J = 9 Hz, 2H), 8.3 (s, 1 H). MS (DCI-NH3) m/z 490 (M+H)+, 507 (M+NH4J+. Anal. calc. for C-23H15CI2FN2O3SO.5 H2O: C, 56.45; H, 3.09; N, 5.72. Found: C, 55.36; H, 3.00; N, 5.50. Example 189 2-f4-Fluoro-3-methylphenvπ-4- -fluorophenvπ-5-[4-('methylsulfonvπphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 62 substituting 1 -bromo-4-fluoro-3-methylbenzene in place of 1 -bromo-4- fluorobenzene (yield: 275 mg, 71 %). M.p. 168-170 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 2.3 (s, 3H), δ 3.25 (s, 3H), 7.15 (t, 2H), 7.3 (m, 3H), 7.56 (m, 4H), 7.9 (d, 2H), 8.23 (s, 2H). MS (DCI-NH3) m/z 453 (M+H)+, 471 (M+NH4)+. Anal. calc. for C24H18F2N2O3S: C, 63.71 ; H, 4.01 ; N, 6.01. Found: C, 63.53; H, 4.06; N, 5.92. Example 190 2-(4-Chloro-3-fluorophenvh-4-f4-fluorophenvh-5-[4-(methylsulfonvnphenyl1-3(2H)- pvridazinone: The title compound was prepared according to the method of Example 62 substituting 4-bromo-1 -chloro-2-fluorobenzene in place of 1 -bromo-4- fluorobenzene (yield: 220 mg, 80%). M.p. 102-110 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 3.23 (s, 3H), 7.11 -7.10 (m, 2H), 7.25-7.32 (m, 2H), 7.51 (d, J = 5.6 Hz, 2H), 7.58-7.64 (m, 1 H), 7.75-7.87 (m, 2H), 7.91 (d, J = 5.6 Hz, 2H), 8.28 (s, 1 H). MS (APCI+) m/z 473 (M+H)+. Example 191 2-(4-Chloro-2-fluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)ph9nvn-3(2H)- pvridazinone: The title compound was prepared according to the method of Example 62 substituting 1 -bromo-4-chloro-2-fluorobenzene in place of 1 -bromo-4- fluorobenzene (yield: 65 mg 24%). M.p. 250-260 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 3.21 (s, 3H), 7.12-7.19 (m, 2H), 7.25-7.32 (m, 2H), 7.49-7.58 (m, 3H), 7.68- 7.78 (m, 2H), 7.91 (d, J = 8.7 Hz, 2H), 8.29 (s, 1 H). MS (APCI+) m/z 473 (M+H)+. Anal. calc. for C23H15CIF2N2O3S: C, 58.41 ; H, 3.19; N, 5.92. Found: C, 58.69; H, 3.45; N, 5.78. Example 192 2-(1 -Adamantyloxycarbonyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phθnyl]-3(2H)- pyridazinone A solution of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone, prepared according to the procedure of Example 11 (200 mg, 0.58 mmol) in CH2CI2 (8 ml) was prepared and stirred. 1 -Adamantylfluoroformate (172 mg, 0.87 mmol), dimethylaminopyridine (14 mg, 0.011 mmol) and triethylamine (0.12 ml, 0.87 mmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with CH2CI2 (50 ml) and washed with 10% citric acid (50 ml), brine (50 ml) and dried over MgS04, and concentrated in vacuo. The resulting crude residue was purified using flash chromatography (Siθ2, eluting with 15:1 CH2Cl2 * diethyl ether) to provide the desired product (yield: 55 mg, 18%). 1 H NMR (300 MHz, DMSO-dβ) δ 1.66 (bs, 6H), 2.25 (bd, 10H), 3.21 (s, 3H), 7.15 (t, 2H), 7.24 (m, 2H), 7.6 (dd, 2H), 7.88 (d, J = 9 Hz, 2H), 8.15 (s, 1 H). MS (ESI) m/z 521 (M-H)+. Anal. calc. for C21 H15F N2O3S2: C, 64.35; H, 5.20; N, 5.36. Example 193 2-(2.2.2-Trifluoroethyl)-4-f4-fluorobenzyl)-5-[4-.m9thylsulfonvnphθnyl]-3(2H)- pyridazinone 193A. 2-(2.2.2-Trifluoroθthvh-4.5-dichloro-3.2H.-pyridazinone 2,2,2-Trifluoroethylhydrazine (70% solution in water, 35.0 g, 0.307 mol) was treated with mucochloric acid (51.88 g, 0.307 mol) in ethanol (300 mL) and refluxed for 5 hours. The solvent was concentrated in vacuo. The crystals obtained were washed with water and air dried (yield: 50 g; 67.5%). 1 H NMR (300 MHz, CDCI3) d 4.8 (q, J = 9 Hz, 2H), 7.85 (s, 1 H). MS (DCI-NH3) m/z 264 (M+NH4)+. 193B. 2-(2.2.2-Trifluoroθthyl)-4-chloro-5-hvdroxy-3.2H)-pyridazinone 2-(2,2,2-Trifluoroethyl)-4,5-dichloro-3(2H)-pyhdazinone (15.0 m 60.7 mmol), and potassium carbonate (10 g, 72.4 mmol.) were mixed with water (500 mL) and stirred at reflux for 6 hours. TLC (1 :1 :2 CH2Cl2/hexanes/ethyl acetate) indicated that all starting material was consumed.) The reaction mixture was cooled to room temperature. The pH of the reaction mixture was adjusted to about 4 with hydrochloric acid (15%). The product was extracted with ethyl acetate (700 mL). The organic phase was washed with brine, dried over anhydrous MgS04 and filtered. The filtrate was concentrated under reduced pressure. The hydroxy compound was obtained as a light brown solid (yield: 13.1 g, 94%). 1 H NMR (300 MHz, DMSO-dβ) δ 4.92 (q, J = 9 Hz, 2H), 7.9 (s, 1 H). MS (DCI-NH3) m/z 229 (M+H)+. 193C. 2-(2.2.2-Trifluoroethvn-4-chloro-5-(trifluoromethylsulfonyloxy)-3(2H)- pvridazinone Anhydrous Na2CO3 (9.04 m, 85.32 mmol) was placed in a 500 mL round bottom flask and anhydrous CH2CL2 (200 mL) was added. The reaction mixture was cooled to 0 °C under N2. The halohydroxy pyridazinone prepared in Example 193B was dissolved in CH2CL2 (100 mL) and added slowly to the flask and stirred overnight. The reaction slowly warmed to room temperature. (TLC (2: 1 hexanes/ethyl acetate) indicated completion of the reaction.) The reaction was quenched with H2O. The organic phase containing the product was separated, washed with brine and dried over MgSO4. The resulting filtrate was concentrated under reduced pressure. The crude product was isolated as deep red-brown residue. Purification using a silica gel column (30:70 ethyl acetate/pentanes) provided the title compound as a dark, reddish residue (14.3 m, 70%). H NMR (300 MHz, CDCI3) δ 4.85 (q, J = 9 Hz, 2H), 7.9 (s, 1 H). MS (DCI-NH3) m/z 378 (M+NH4) + - 193D. 2-f2.2.2-Trifluoroethvn-4-chloro-5-[4-(methylthio^phenyl]-3(2HV pvridazinone A solution of the triflate prepared in Example 193C (1.56 g 4.3 mmol), 4- (methylthio)phenylboronic acid (870 mg, 5.16 mmol), tetrakis(triphenylphosphine)- palladium(O) (250 mg, 5% mmol) and triethylamine (1.44 ml, 10.32 mmol) in toluene was heated at reflux for 1 hour. The mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water, then brine, followed by drying over MgS04 and filtration. The filtrate was concentrated in vacuo . The residue was purified by column chromatography (silica gel, 92:8 hexanes/ethyl acetate) to provide the coupled intermediate as a pale, greenish- yellow solid (yield: 500 mg, 35%). M.p. 130-139 °C. 1 H NMR (300 MHz, CDCI3) δ 2.55 (s, 3H), 4.87 (q, J = 9 Hz, 2H), 7.37 (d, J = Hz, 2H), 7.48 (d, J = g Hz, 2H), 7.82 (s, 1 H). MS (DCI-NH3) m/z 335 (M+H) + . 193E. 2-(2.2.2-Thfluoroethvπ-4-chloro-5-[4-(methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 10, substituting the coupled intermediate prepared in Example 193D in place of 2- benzyl-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (yield: 440 mg, 81 %). M.p. 221-222 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.33 (s, 3H), 5.10 (q, J = 9 Hz, 2H), 7.gθ (d, J = 9 Hz, 2H), 8.12 (d, J = 9 Hz, 2H), 8.20 (s, 1 H). MS (DCI- NH3) m/z 367 (M+H)+. 193F. 2-(2.2.2-Trifluoroethvπ-4-(4-fluorobenzvπ-5-[4-fmethylsulfonvhphenyl1- 3(2H)-pyridazinone Magnesium turnings (500 mg) were placed in a dry 250 mL round bottom flask. Anhydrous ether (20 mL) was added under N2 at room temperature then fluorobenzyl bromide (3 mL) was added and stirred. The reaction was heated at 40 °C for 2 hours. All magnesium was consumed resulting in a pale brownish-yellow solution. The 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone prepared in Example 193E was dissolved in dry THF (25 mL) and transferred to the Grignard solution. The mixture was heated for 3 hours. TLC (2:1 hexanes/ethyl acetate) indicated that the pyridazinone starting material was consumed.) The reaction was cooled to room temperature then quenched with a saturated NH4CI solution. The product was extracted with ethyl acetate (250 mL); and the organic layer was washed with saturated NH4CI, and brine. The ethyl acetate solution was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure. The product was isolated as an orange residue. Purification using a silica gel column (20:80 ethyl acetate/pentanes) provided the title compound as a pale yellow powder (yield: 140 mg, 28%). 1 H NMR (300 MHz, CDCI3) δ 3.13 (s, 3H), 4.85 (m, 2H), 6..93 (m, 4H), 7.49 (d, J = 9 Hz, 2H) 7.72 (s, 1 H), 8.08 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 441 (M+H)+. Anal. calc. for C20HI 6F4N2O3SO.5 H2O: C, 53.45; H, 3.81 ; N, 6.23. Found C, 53.45; H, 3.81 ; N, 6.23. Example 194 2-(4-Fluorophenvπ-4-(4-fluorophenoxymethyl ' )-5-[4-( ' methylsulfonvπphenyl1-3(2HV pyridazinone 194A. 2-(4-Fluorophenvπ-4.5-dibromo-3(2H)-pyridazinone Mucobromic acid (5.0 g, 19.4 mmol) dissolved in acetic acid (110 mL) was treated with 4-fluorophenyl hydrazine-HCI, and the heterogeneous mixture brought to reflux at a bath temperature of 1 15 °C for 15 hours. During the course of reaction, the mixture became a homogeneous deep red solution, and upon cooling to 23 °C, a crystalline precipitate formed. The solution was poured into ice water (1000 mL) and stirred for 20 minutes. The yellow/brown crystals were filtered off, washed with additional cold water, and dried in vacuo to provide 5.8 g (86%) of product. (J. Het. Chem.., 1993, 30, 1501 ; Heterocycles ^ 985, 23, 2603) 1 H NMR (300 MHz, DMSO-dβ) δ 7.31-7.41 (m, 2H), 7.57-7.64 (m, 2H), 8.29 (s, 1 H). MS (DCI+) m/z 347 (Br79Br7g M+H)+, m/z 349 (Br7gBr81 M+H)+, m/z 364 (Br7gBr79 M+NH4) + , and m/z 366 (Br79Brβl M+NH4) + . 194B. 2-(4-Fluorophenvπ-4-methoxy-5-bromo-3(2H')-pyridazinone A 23 °C homogeneous solution of 2-(4-fluorophenyl)-4,5-dibromo-3(2H)- pyridazinone (7.18 g, 20.6 mmol) prepared above in tetrahydrofuran (322 mL) was treated with methanol (0.843 mL, 20.8 mmol) and after 5 minutes with NaH (0.833 g, 20.8 mmol, 60% oil dispersion). The reaction exothermed for several minutes and then was continued for 8 hours at 23 °C (Note: several reactions have run to completion at this point). The reaction did not run to completion, and so the temperature was raised to reflux for 4 hours more. The reaction was still not completed. An additional 0.1 equivalent of NaOMe solution was prepared in a separate flask as above with the quantities: 32 mL of tetrahydrofuran, 0.084 mL of methanol, and 83 mg of 60% NaH oil dispersion. This NaOMe solution was added via syringe to the reaction mixture cooled to 23 °C, and then the temperature raised to reflux for 4 hours The reaction was still not complete, and so another 0.1 equivalent NaOMe solution was prepared, added, and the reaction brought to reflux, as above. After this 4 hours, the reaction was completed. The mixture was cooled to 23 °C and diluted to 2000 mL with water. The yellow/white precipitate that formed was filtered off, washed with additional water, and concentrated in vacuo to provide 5.39 g (88%) of product. (J. Het. Chem., 1988, 25, 1757) 1 H NMR (300 MHz, DMSO-dβ) δ 4.13 (s, 3H), 7.30-7.40 (m, 2H), 7.56-7.62 (m, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 299 (Br7g M+H)+ and m/z 301 (Brβi M+H)+. 194C. 2-f4-Fluorophenvh-4-methoxy-5-[4-(methylthio^phenyl1-3f2H)-pyridazinone The title compound was prepared according to the method of Example 6 starting with 2-(4-fluorophenyl)-4-methoxy-5-bromo-3(2H)-pyridazinone in place of 2-benzyl-4-bromo-5-methoxy-3(2H)-pyridazinone and substituting 4-(methylthio)- benzeneboronic acid in place of 4-fluorobenzeneboronic acid (yield: 70 mg, 61 %). 1 H NMR (500 MHz, DMSO-dβ) δ 2.54 (s, 3H), 4.02 (s, 3H), 7.35 (dd, J = 0.0, 9.0 Hz, 2H), 7.39 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.65 (dd, J = 9.0, 5.0 Hz, 2H), 8.14 (s, 1 H). MS (APCI+) m/z 343 (M+H)+. 194D. 2-f4-Fluorophθnyπ-4-m9thyl-5-[4-(m9thylthio)phenyl1-3f2H)-pyridazinone The title compound was prepared according to the method of Example 228 substituting methyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 0.83 g, 87%). " Η NMR (300 MHz, CDCI3) δ 2.25 (s, 3H), 2.55 (s, 3H), 7.17 (dd, J = 8.8, 8.8 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8.7 Hz, 2H), 7.61 -7.68 (m, 2H), 7.82 (s, 1 H). MS (APCI+) m/z 327 (M+H)+. 194E. 2-.4-Fluorophenyn-4-mθthyl-5-[4-(m9thylsulfonvnph9nyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 10 substituting 2-(4-fluorophenyl)-4-methyl-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone (yield: 473 mg, 86%). 1 H NMR (300 MHz, CDCI3) δ 2.24 (s, 3H), 3.14 (s, 3H), 7.19 (dd, J = 8.8, 8.8 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.63-7.69 (m, 2H), 7.80 (s, 1 H), 8.12 (d, J = 8.4 Hz, 2H). MS (APCI+) m/z 359 (M+H)+ and m/z 376 (M+NH4)+. 194F. 2-f4-Fluorophenvh-4-bromomethyl-5-f4-.mθthylsulfonyl)phθnyl1-3f2H ι- pvridazinone To a heterogeneous, refluxing solution of 2-(4-fluorophenyl)-4-methyl-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (5 o mg, 1.65 mmol) and carbon tetrachloride (24 mL) was quickly added Λ/-bromosuccinimide (yield: 308 mg, 1.73 mmol) followed by benzoyl peroxide (12 mg, 0.05 mmol). After 1 hour the reaction had only run to near 50% completion. Additional benzoyl peroxide (12 mg, 0.05 mmol) was added, and the reaction checked after another 1 hour. The reaction was still not complete, and so more benzoyl peroxide (4 mg, 0.017 mmol) was added. After 30 minutes, the reaction was completed. The mixture was cooled to 23 °C and diluted with ethyl acetate. The acetate solution was washed with saturated NaHCO3, water, and brine. The solution was dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes gradient 1 :1 to 4:1 ) to provide the product (yield: 530 mg, 74%). 1 H NMR (300 MHz, CDCI3) δ 3.16 (s, 3H), 4.34 (s, 2H), 7.20 (dd, J = 8.8, 8.8 Hz, 2H), 7.67-7.74 (m, 2H), 7.82 (d, J = 8.7 Hz, 2H), 7.86 (s, 1 H), 8.17 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 437 (M+H)+. 104G. 2-(4-Fluorophenyl)-4-(4-fluorophenoxymethyl)-5-[4-(methylsulfonyl)phenyl]- 3(2HVpvridazinone To a homogeneous solution of 2-(4-fluorophenyl)-4-bromomethyl-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone, prepared above, (107 mg, 0.246 mmol) and 4-fluorophenol (30.3 mg, 0.270 mmol) dissolved in acetone (4 mL) was added powdered K2CO3 (37.3 mg, 0.270 mmol). The mixture was stirred at 23 °C for 2 hours, filtered through a bed of Celite®, and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes 3:2) to provide the product (yield: 83 mg, 72%). M.p. 65-80 °C. 1 H NMR (300 MHz, CDCI3) δ 3.12 (s, 3H), 4.04 (s, 2H), 6.78-6.86 (m, 2H), 6.91 -7.00 (m, 2H), 7.15-7.24 (m, 2H), 7.65-7.72 (m, 2H), 7.74 (d, J = 8.7 Hz, 2H), 7.93 (s, 1 H), 8.08 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 469 (M+H)+. Anal. calc. for C24H18F2N2O4S: C, 61.53; H, 3.87; N, 5.97. Found: C, 61.22; H, 3.63; N, 5.64. Example 195 2-(4-Fluorophenyl)-4-f3-fluorophBnoxymethyl)-5- 4-(methylsulfonyl)phsnyl]-3f2H pvridazinone The title compound was prepared according to the method of Example 194G substituting 3-fluorophenol in place of 4-fluorophenol (yield: 94 mg, 88%). M.p. 142-144 °C. 1 H NMR (300 MHz, CDCl3) δ 3.12 (s, 3H), 4.98 (s, 2H), 6.49-6.56 (m, 1 H), 6.60-6.73 (m, 2H), 7.15-7.25 (m, 3H), 7.65-7.75 (m, 4H), 7.93 (s, 1 H), 8.07 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 469 (M+H)+. Anal. calc. for C24H18F2N2O4S: C, 61.53; H, 3.87; N, 5.97. Found: C, 61.20; H, 3.92; N, 5.86. Example 196 2-f4-Fluorophenvπ-4-phenoxymethyl-5-[4-fmethylsulfonvπphenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 294G substituting phenol in place of 4-fluorophenol (yield: 67 g, 93%). M.p. 42-75 °C. 1 H NMR (300 MHz, DMSO-dε) δ 3.28 (s, 3H), 4.92 (s, 2H), 6.83-6.90 (m, 2H), 6.91 - 6.99 (m, 1 H), 7.22-7.30 (m, 2H), 7.35-7.44 (m, 2H), 7.66-7.73 (m, 2H), 7.81 -7.88 (m, 2H), 8.02-8.08 (m, 2H), 8.21 (s, 1 H). MS (APCI+) m/z 451 (M+H)+. Example 197 2-(4-Fluorophenyl)-4-(f-butylthiomBthyh-5-[4-(methylsulfonyπphsnyl]-3(2H)- pyridazinone A 0 °C solution of the 2-(4-fluorophenyl)-4-bromomethyl-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone prepared in Example 194F (92.5 mg, 0.212 mmol) in acetone (2.5 mL) was treated with Nal (35 mg, 0.233 mmol), and after 5 minutes, the cooling bath was removed and the reaction warmed to 23 °C. After 30 minutes, conversion to the 2-(4-fluorophenyl)-4-iodomethyl-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone was complete (thin layer chromatography, ethyl acetate/hexanes 4:1 ). The NaBr and residual Nal were filtered off through a pad of Celite®. Additional acetone (2 mL) was added along with 2-methyl-2-propanethiol (20.5 mg, 0.227 mmol), and the solution cooled to 0 °C before addition of Ag2CO3 (63 mg, 0.227 mmol). After 5 minutes, the cooling bath was removed and the solution warmed to 23 °C for 5 hours. The reaction mixture was filtered through Celite® and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes gradient 1 :1 to 3:2) to provide the product (yield: 57 mg, 60%). M.p. 50-70 °C. 1 H NMR (300 MHz, CDCI3) δ 1.34 (s, 9H), 3.14 (s, 3H), 3.65 (s, 2H), 7.13-7.21 (m, 2H), 7.63-7.70 (m, 2H), 7.79 (s, 1 H), 7.84 (d, J = 8.7 Hz, 2H), 8.13 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 447 (M+H)+. Anal. calc. for C-22H23FN2O3S2: C, 59.17; H, 5.19; N, 6.27. Found: C, 59.48; H, 5.36; N, 5.90. Example 198 - -Fluorophenvπ^-^-methylpropylthiomethvπ-S-^-fmethylsulfonvπphenyl]- 3^2H pyridazinone The title compound was prepared according to the method of Example 197 substituting 2-methyl-1 -propanethiol in place of 2-methyl-2-propanethiol (yield: 66 mg, 70%). M.p. 45-60 °C. 1 H NMR (300 MHz, CDCI3) δ 0.05 (d, J = 6.6 Hz, 6H), 1.67-1.82 (m, 1 H), 2.62 (d, J = 6.6 Hz, 2H), 3.15 (s, 3H), 3.61 (s, 2H), 7.19 (dd, J = 8.2, 8.2 Hz, 2H), 7.62-7.71 (m, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.79 (s, 1 H), 8.13 (d, J = 8.4 Hz, 2H). MS (APCI+) m/z 447 (M+H)+. Anal. calc. for C22H23FN2O3S2: C, 59.17; H, 5.19; N, 6.27. Found: C, 59.35; H, 5.25; N, 6.05. Example 199 2-(4-Fluorophenvl)-4-(2-propoxy)-5-[4-(msthylthio)phenyl]-3f2H)-pyridazinone The title compound was prepared by the following sequence of reactions. Mucobromic acid and 4-fluorophenylhydrazine hydrochloride were reacted to provide 2-(4-fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone following the procedure in Example 194A. The dibromo-intermediate was reacted according to the procedure described in Example 194B, substituting isopropanol in place of methanol, to selectively react at the 4-position and provide 2-(4-fluorophenyl)-4-(2- propoxy)-5-bromo-3(2H)-pyridazinone. The 5-bromo-compound was coupled to 4-(methylthio)phenylboronic acid according to the method of Example 6 to provide the title compound (yield: 435 mg, 53.9%). M.p. 135-137 °C. 1 H NMR (300 MHz, CDCI3) δ 1.21 (d, J = 6 Hz, 6H), 2.55 (s, 3H), 5.26 (sept, J = 6 Hz, 1 H), 7.17 (t, J = 9 Hz, 2H), 7.34 (d, J = 9 Hz, 2H), 7.57 (d, J = 9 Hz, 2H), 7.58-7.66 (m, 2H), 7.95 (s, 1 H). MS (DCI-NH3) m/z 371 (M+H)+. Example 200 2-(4-Fluoroph9nyl)-4-(2-propoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H^-pyridazinone Thθ methyl sulfide compound prepared in Example 199 was oxidized according to the method of Example 10 to provide the title compound (yield: 240 mg, 02%). M.p. 160-162 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.30 (d, J = 6 Hz, 6H), 3.41 (s, 3H), 5.41 (m, 1 H), 7.48 (t, J = 9 Hz, 2H), 7.77 (dd, J = 9 Hz, 6 Hz, 2H), 8.05 (d, J = 9 Hz, 2H), 8.19 (d, J = 9 Hz, 2H), 8.31 (s, 1 H). MS (DCI-NH3) m/z 403 (M+H)+, 420 (M+NH4) + . Anal. calc. for C20H19FN2O4S: C, 59.70; H, 4.73; N, 6.97. Found: C, 59.40; H, 4.86; N, 6.69. Example 201 2-^3-Chlorophenvn-4-(2-propoxyV5-[4-fmethylsulfonvπphenyl]-3(2HVpyridazinone 2-(3-Chlorophenyl)-4-(2-propoxy)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone was prepared according to the method of Example 199, substituting 3-chlorophenylhydrazine hydrochloride in place of 4-fluorophenylhydrazine hydrochloride, in the first step. The resulting methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 260 mg, 80%). M.p. 134-136 °C. 1 H NMR (300 MHz, CDCI3) δ 1.24 (d, J = 6 Hz, 6H), 3.13 (s, 3H), 5.48 (sept, J = 6 Hz, 1 H), 7.37-7.48 (m, 2H), 7.59 (dt, J = 7 Hz, 1.5 Hz, 1 H), 7.70 (br s, 1 H), 7.84 (d, J = 9 Hz, 2H), 7.93 (s, 1 H), 8.06 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 419 (M+H)+, 436 (M+NH4) + . Anal. calc. for C20H19CIN2O4S: C, 57.42; H, 4.55; N, 6.70. Found: C, 57.08; H, 4.50; N, 6.44. 0 Example 202 2-(3-Fluorophenvπ-4-(2-propoxy -5-[4-(methylsulfonvπphenyl1-3f2H pyridazinone The methyl sulfide intermediate was prepared according to the method of Example 199, substituting 3-fluorophenylhydrazine hydrochloride in place of 4-fluorophenylhydrazine hydrochloride in the first step. The resulting methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 290 mg, 72%). M.p. 110-112 °C. 1 H NMR (300 MHz, CDCI3) δ 1.31 (d, J = 6 Hz, 6H), 3.11 (s, 3H), 5.47 (sept, J = 6 Hz, 1 H), 7.09-7.18 (m, 1 H), 7.41-7.52 (m, 3H), 7.83 (d, J = 9 Hz, 2H), 7.93 (s, 1 H), 8.08 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 403 (M+H)+, 447 (M+NH4) + - Anal. calc. for C20H19FN2O4S: C, 59.70; H, 4.73; N, 6.97. Found: C, 59.54; H, 4.87; N, 6.70. Example 203 2-f3-Bromophenvπ-4-f2-propoxy 5-[4- ( methylsulfonvπphenyl1-3f2H)-pyridazinone The methyl sulfide intermediate was prepared according to the method of Example 199, substituting 3-bromophenylhydrazine hydrochloride in place of 4-fluorophenylhydrazine hydrochloride. The resulting methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 75 mg, 77.6%). M.p. 130-132 °C. 1 H NMR (300 MHz, CDCI3) δ 1.23 (d, J = 6 Hz, 6H), 3.15 (s, 3H), 5.48 (sept, J = 6 Hz, 1 H), 7.38 (t, J = 9 Hz, 1 H), 7.55 (br d, J = 7 Hz, 1 H), 7.65 (br d, J = 7 Hz, 1 H), 7.79-7.87 (m, 1 H), 7.83 (d, J = 9 Hz, 2H), 8.13 (s, 1 H), 8.06 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 465 (M+H)+, 480 (M+NH4)+. Anal. calc. for C20H1 gBrN2θ4S: C, 51.84; H, 4.10; N, 6.05. Found: C, 51.95; H, 4.18; N, 5.74. Example 204 2-(2.5-Difluorophenvl)-4-(2-propoxy)-5-f4-fmθthvlsulfonvlιphθnvl]-3f2H^- pvridazinone 2-(2,5-Difluorophenyl)-4-(2-propoxy)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone was prepared according to the method of Example 199, substituting 2,5-difluorophenylhydrazine hydrochloride in place of 4-fluorophenylhydrazine hydrochloride . The resulting methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 390 mg, 90%). M.p. 161 -164 °C. 1 H NMR (300 MHz, CDCI3) δ 1.23 (d, J = 6 Hz, 6H), 3.12 (s, 3H), 5.55 (sept, J = 6 Hz, 1 H), 7.12-7.29 (m, 3H), 7.82 (d, J = 9 Hz, 2H), 7.92 (s, 1 H), 8.07 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 421 (M+H)+, 438 (M+NH4)+- Anal. calc. for C20H18 F2N2O4SO.5 H2O: C, 55.04; H, 4.31 ; N, 6.53. Found: C, 55.86; H, 4.19; N, 6.38. Example 205 2-(3-Chloro-4-fluorophenvπ-4-(2-methylpropoxyV5-[3-fluoro-4-(methylsulfonvh- phenvl]-3(2H)-pvridazinone The title compound was prepared by the following sequence of reactions. Mucobromic acid and 3-chloro-4-fluorophenylhydrazine hydrochloride were reacted to provide 2-(3-chloro-4-fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone according to the method of Example 194A. The intermediate was selectively reacted at the 4-position with isobutanol and base to provide 2-(4-fluorophenyl)-4- [1 -(2-methylpropoxy)]-5-bromo-3(2H)-pyridazinone according to the method of Example 1 Θ4B. The 5-bromo-compound was coupled to 3-fluoro-4-(methylthio)- phenylboronic acid prepared in Example 194C according to the method of Example 6 to produce the intermediate methyl sulfide. The sulfide compound was oxidized to the title methyl sulfone according to the method of Example 10 (yield: 810 mg, 83.8%). M.p. 142-144 °C. 1 H NMR (300 MHz, CDCI3) δ 0.90 (d, J = 6 Hz, 6H), 1.95 (sept, J = 6 Hz, 1 H), 3.30 (s, 3H), 4.37 (d, J = 6 Hz, 2H), 7.26 (t, J = 9 Hz, 1 H), 7.52-7.61 (m, 3H), 7.75 (dd, J = 9 Hz, 3 Hz, 1 H), 7.89 (s, 1 H), 8.10 (t, J = 9 Hz, 1 H). MS (DCI-NH3) m/z 469 (M+H)+, 486 (M+NH4)+. Example 206 2-^3.4-Difluorophenvπ-4-( , 4-fluorophenvπ-5-[3-methyl-4-(methylsulfonvπphenyl]- 3f2 -pvridazinone 206A. 2-Methylthioanisole A solution of 2-bromothioanisole (10.53 g, 52 mmol) in tetrahydrofuran (173 mL) was prepared and cooled to -78 °C. n-BuLi (21.8 mL, 54.5 mmol, 2.5 M solution in hexanes) was slowly added along the interior wall of the reaction vessel. The resultant light yellow solution was stirred for 30 minutes before methyl iodide (8.10 g, 57.1 mmol) diluted with tetrahydrofuran (6 mL) was slowly added along the interior wall of the reaction vessel. The mixture was stirred for another 30 minutes at -78 °C. The cooling bath was removed, and the mixture stirred for 1 hour. The solution was cooled to 0 °C and a saturated aqueous NH4CI solution added. The resultant solution was extracted several times with ethyl acetate, and the combined acetate layers washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes 1 :19) to provide the product (yield: 6.74 g, 94%). 1 H NMR (300 MHz, CDCI3) δ 2.34 (s, 3H), 2.46 (s, 3H), 7.02-7.00 (m, 1 H), 7.12-7.22 (m, 3H). 206B. 4-Bromo-2-methylthioanisole. To a 0 °C solution of 2-methylthioanisole (0.50 g, 3.57 mmol) in methylene chloride (40 mL) was added powdered Fe (20 mg, 0.36 mmol) followed by dropwise addition of bromine (0.58 g, 3.54 mmol). After 30 minutes, the starting material had been consumed (thin layer chromatography, hexanes). The excess bromine was quenched by adding a solution of NaHSO3 and stirring for several minutes. The methylene chloride layer was separated, and the aqueous phase extracted with additional methylene chloride. The combined methylene chloride solution was dried over MgS04, filtered, and concentrated in vacuo. The resultant oil was chromatographed (flash silica gel, ethyl acetate/hexanes 1 :49) to provide the product (yield: 0.74 g, 96%). 1 H NMR (300 MHz, CDCI3) δ 2.30 (s, 3H), 2.45 (s, 3H), 7.00 (d, J = 8.4 Hz, 1 H), 7.27-7.33 (m, 2H). C 206C. 3-Methyl-4- ( methylthio1benzeneboronic acid. 3-Methyl-4-(methylthio)benzeneboronic acid was prepared according to the method of Example 1 , substituting 4-bromo-2-(methylthio)anisole in place of 4- bromothioanisole (yield: 5.3 g, 67%). M.p. 208-210 . 1 H NMR 2.28 (s, 3H), 2.46 (S, 3H), 7.20 (d, J = 8.4 Hz, 1 H), 7.62 (s, 1 H), 7.70 (d, J = 8.4 Hz, 1 H). 206D. 2-f3.4-Difluorophenvn-4.5-dibromo-3(2H)-pyridazinone. The title compound was prepared according to the method of Example 1 Θ4A, substituting 3,4-difluorophenyl hydrazine-HCI in place of 4-fluorophenyl hydrazine-HCI (yield: 30 g, 78%). 1 H NMR (300 MHz, DMSO-dβ) δ 7.45 (m, 1 H), 7.61 (m, 1 H), 7.75 (m, 1 H), 8.30 (s, 1 H). MS (DCI-NH3) m/z 382 (M+NH4) + . 206E. 2-(3.4-Difluorophenyl)-4-methoxy-5-bromo-3(2HVpyridazinone. The title compound was prepared according to the method of Example 194B, substituting 2-(3,4-difluorophenyl)-4,5-dibromo-3(2H)-pyridazinone in place of 2-(4- fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (yield: 15 mg, 88%). 1 H NMR (300 MHz, DMSO-d6) δ 4.14 (s, 3H), 7.45 (m, 1 H), 7.60 (m, 1 H), 7.74 (m, 1 H), 8.24 (s, 1 H). MS (DCI-NH3) m/z 317 (M+H)+ and m/z 334 (M+NH4) + - 206 F. 2-(3.4-Difluorophenvh-4-methoxy-5-[3-methyl-4-(methylthio^phenyl]-3f2H)- pyridazinone. The title compound was prepared according to the method of Example 6 starting with 2-(3,4-difluorophenyl)-4-methoxy-5-bromo-3(2H)-pyridazinone in place of 2-benzyl-4-bromo-5-methoxy-3(2H)-pyridazinone and substituting 3- methyl-4-(methylthio)benzeneboronic acid in place of 4-fluorobenzeneboronic acid (yield: 2.0 g, 85%). 1 H NMR (300 MHz, CDCI3) δ 2.39 (s, 3H), 2.53 (s, 3H), 4.11 (s, 3H), 7.22-7.32 (m, 2H), 7.34 (s, 1 H), 7.42-7.50 (m, 2H), 7.55-7.64 (m, 1 H), 7.92 (s, 1 H). MS (APCI+) m/z 375 (M+H)+. 206G. 2-f3.4-Difluorophenvh-4-(4-fluorophenyl)-5-[3-methyl-4-(methylthio)phenyl]- 3(2H1-pyridazinone. 2-(3,4-Difluorophenyl)-4-(4-fluorophenyl)-5-[3-methyl-4-(methylthio)phenyl]- 3(2H)-pyridazinone, was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[3-methyl-4-(methylthio)phenyl]- 3(2H)-pyridazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)- phenyl]-3(2H)-pyridazinone and substituting 4-fluorophenyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 330 mg, 56%). 1 H NMR (300 MHz, CDCI3) δ 2.24 (s, 3H), 2.47 (s, 3H), 6.90-7.03 (m, 6H), 7.22-7.31 (m, 2H), 7.49-7.54 (m, 1 H), 7.60-7.68 (m, 1 H), 8.02 (s, 1 H). MS (APCI+) m/z 439 (M+H)+. 206H. 2-(3.4-Difluorophenyl)-4-(4-fluorophenyl)-5-[3-methyl-4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone. The title compound was prepared according to the method of Example 10, substituting 2-(3,4-difluorophenyl)-4-(4-fluorophenyl)-5-[3-methyl-4-(methylthio)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone (yield: 251 mg, 82%) M.p. 80-100 °C. 1 H NMR (300 MHz, DMSO-d6) δ 2.59 (s, 3H), 3.25 (s, 3H), 7.13-7.34 (m, 5H), 7.45 (s, 1 H), 7.52-7.69 (m, 2H), 7.81 (d, J = 8.4 Hz, 1 H), 7.81 -7.90 (m, 1 H), 8.27 (s, 1 H). MS (APCI+) m/z 471 (M+H)+ and m/z 488 (M+NH4)+. Anal. calc. for C24H17F3N2O3S: C, 61.27; H, 3.64; N, 5.95. Found: C, 61.53; H, 3.92; N, 5.67. Example 207 2-(3-Chlorophenvπ-4-f4-fluorophenoxymethvπ-5-[4-Cmethylsulfonvhphenyl]-3(2HV pyridazinone 207A. 2-(3-Chlorophenvn-4.5-dibromo-3(2HVpvridazinone. The title compound was prepared according to the method of Example 1 Θ4A, substituting 3-chlorophenyl hydrazine-HCI in place of 4-fluorophenyl hydrazine-HCI (yield: 24.8 g, 88%). 1 H NMR (300 MHz, DMSO-dβ) δ 7.53-7.57 (m, 3H), 7.67-7.70 (m, 1 H), 8.29 (s, 1 H). MS (DCI-NH3) m/z 365 (M+H)+ and m/z 382 (M+NH4+)+. 207B. 2-(3-Chlorophenvl)-4-methoxy-5-bromo-3(2H)-pvridazinone. The title compound was prepared according to the method of Example 194B, substituting 2-(3-chlorophenyl)-4,5-dibromo-3(2H)-pyridazinone in place of 2- (4- fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (yield: 12.4 g, 95%). 1 H NMR (300 MHz, DMSO-dβ) δ 4.21 (s, 3H), 7.58-7.62 (m, 3H), 7.73-7.76 (m, 1 H), 8.28 (s, 1 H). MS (DCI-NH3) m/z 317 (M+H)+ and m/z 334 (M+NH4+)+. 207C. 2-(3-Chlorophenyl)-4-methoxy-5-f4-(methylthio)phenyl1-3(2H)-pyridazinone. Thθ title compound was prepared according to the method of Example 6 starting with 2-(3-chlorophenyl)-4-methoxy-5-bromo-3(2H)-pyridazinone in place of 2-benzyl-4-bromo-5-methoxy-3(2H)-pyridazinone and substituting 4-(methylthio)- benzeneboronic acid in place of 4-fluorobenzeneboronic acid (yield: 3.3 g, 68%). 1 H NMR (300 MHz, DMSO-dβ) δ 2.54 (s, 3H), 4.03 (s, 3H), 7.40 (d, J = 9.0 Hz, 2H), 7.50-7.64 (m, 5H), 7.73-7.77 (m, 1 H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 359 (M+H)+. 207D. 2-(3-Chlorophenvn-4-methyl-5-[3-methyl-4-(methylthio ) phenyl]-3(2H pyridazinone. 2-(3-Chlorophenyl)-4-(4-fluorophenyl)-5-[3-methyl-4-(methylthio)phenyl]- 3(2H)-pyridazinone, was prepared according to the method of Example 228, starting with 2-(3-chlorophenyl)-4-methoxy-5-[3-methyl-4-(methylthio)phenyl]- 3(2H)-pyridazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)- phenyl]-3(2H)-pyhdazinone and substituting 4-fluorophenyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 180 mg, 04%). 1 H NMR (300 MHz, CDCI3) δ 2.25 (s, 3H), 2.56 (s, 3H), 7.28-7.45 (m, 6H), 7.58-7.63 (m, 1 H), 7.71 -7.74 (m, 1 H), 7.82 (s, 1 H). MS (APCI+) m/z 343 (M+H)+ and m/z 360 (M+NH4)+. 207E. 2-(3-Chlorophenvn-4-methyl-5-f4-fmethylsulfonylphenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 10, substituting 2-(3-chlorophenyl)-4-methyl-5-[4-(methylthio)phenyl]-3(2H)- pyhdazinone for 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (yield: 125 mg, 67%). M.p. 164-168. 1 H NMR (300 MHz, CDCI3) δ 2.23 (s, 3H), 3.13 (s, 3H), 7.37-7.46 (m, 2H), 7.61 (m, 3H), 7.71 -7.74 (m, 1 H), 7.81 (s, 1 H), 8.13 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 343 (M+H)+ and m/z 360 (M+NH4)+. 207F. 2-f3-Chlorophenvn-4-bromomethyl-5-[4-(methylsulfonvnphenyl]-3f2H pvridazinone 2-(3-Chlorophenyl)-4-bromomethyl-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone was prepared according to the method of Example 194F, substituting 2-(3-chlorophenyl)-4-methyl-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyhdazinone in place of 2-(4-fluorophenyl)-4-methyl-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (yield: 90 mg, 99%). 1 H NMR (300 MHz, CDCI3) δ 3.13 (s, 3H), 4.33 (s, 2H), 7.40-7.47 (m, 2H), 7.66 (ddd, J = 2.4, 2.4, 7.2 Hz, 1 H), 7.76-7.78 (m, 1 H), 7.81 (d, J = 8.7 Hz, 2H), 7.86 (s, 1 H), 8.17 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 453 (M+H)+ and m/z 470 (M+NH4)+. 207G. 2-(3-ChlorophenylV4-(4-fluorophenoxymethyl)-5-[4-(mathylsulfonyl.phenyl]- 3.2H pyridazinone The title compound was prepared according to the method of Example 194G, substituting 2-(3-chlorophenyl)-4-bromomethyl-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone in place of 2-(4-fluorophenyl)-4-bromomethyl-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 30 mg, 31 %). M.p. 50-80 °C. 1 H NMR (300 MHz, CDCI3) δ 3.11 (s, 3H), 4.94 (s, 2H), 6.78-6.85 (m, 2H), 6.91 - 6.99 (m, 2H), 7.39-7.48 (m, 2H), 7.64 (ddd, J = 7.5, 1.9, 1.9 Hz, 1 H), 7.71 -7.77 (m, 3H), 7.03 (s, 1 H), 8.08 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 485 (M+H)+. Example 208 2-.3-Chlorophenyn-4-fbenzoyloxymethyl)-5-[4-fmethylsulfonynphenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 207 substituting benzoic acid in place of 4-fluorophenol (yield: 33 mg, 34%). M.p. 50-70 °C. 1 H NMR (300 MHz, CDCI3) δ 3.00 (s, 3H), 5.36 (s, 2H), 7.36-7.48 (m, 4H), 7.52- 7.5g (m, 1 H), 7.61 -7.68 (m, 3H), 7.75-7.78 (m, 1 H), 7.83-7.88 (m, 2H), 7.89 (s, 1 H), 8.02 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 495 (M+H)+. Example 209 2-(2.2.2-Trifluoroethyn-4-f3-methylbutyl.-5-[4-(methylsulfonyl)phenyη-3f2HV pvridazinone The title compound was prepared according to the method of Example 193 , substituting 1 -bromo-4-methylpentane in place of 4-fluorobenzyl bromide (yield: 80 mg, 19%). 1 H NMR (300 MHz, CDCI3) δ 0.81 (d, J = 7.5 Hz, 6H), 1.3-1.6 (m, 3H), 2.52 (m, 2H), 3.14 (3 H, s) 4.85 (q, J = 0 Hz, 2H), 7.55 (d, J = 9 Hz, 2H) 7.67 (s, 1 H), 8.1 (d, J = 9 Hz, 2H). MS (DCI-NH3), m/z 403 (M+H)+. Anal. calc. for C18H21 F3N2O3SO.25 H 2 O: C, 53.12; H, 5.32; N, 6.88. Found C, 52.90; H, 5.14; N, 6.43. Example 210 2-(2.2.2-TrifluoroBthyπ-4-f4-fluoro-3-ι-nsthylphenyl)-5-[4-.methylsulfonvhphenyl]- 3(2H)-pvridazinone 210A. Preparation of boronic acid: 2-Fluorotoluene-5-Bromo (6 g, 31.7 mmol) was dissolved in dry THF (50 mL) and cooled to -78 C under N . n-Buϋ (14 mL, 2.5M solution in THF) was added slowly using a dry syringe. Cloudiness appeared. The reaction was stirred for 40 minutes at -78 °C. Triisopropyl borate (22 mL, 95 mmol) was slowly added while stirring. The reaction was allowed to warm to room temperature. Stirring continued for an additional 2 hours. A pale yellow, cloudy solution formed. (TLC (1 :2 ethyl acetate /hexanes)) indicated disappearance of the starting material. The reaction was quenched by adding 10% aqueous NaOH (200 mL). After stirring for 45 minutes, 10% citric acid solution (300 mL) was added until, pH -5.0. The product was extracted with ethyl acetate (500 mL). The organic phase was washed with brine and dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide an off white solid (yield: 4.1 g, 84%). 210B. Suzuki Coupling: The boronic acid (231 mg, 1.5 mmol), prepared in example 210A, 2-(2,2,2- trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (500 mg, 1.36 mmol), tetrakis-(triphenylphosphine)-palladium(0) (47 mg, 0.041 mmol), and CsF (413 mg, 2.72 mmol) were stirred at reflux in DME (20 mL) under N2 for 5 hours. TLC (1 :1 hexanes/ethyl acetate) indicated that all the starting material was consumed. Volatiles were removed in vacuo. The residue was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. An off white powder was obtained (yield: 275 mg, 46%). M.p. 88-91 °C; 1 H NMR (300 MHz, CDCI3, a mixture of rotamers) δ 2.2, 2.25 (2d, J = 1.5 Hz, 3H) 3.05, 3.09 (2 s, 3H) 4.78-4.92 (m, 2H) 6.61 -6.8 (m, 1 H) 6.82-6.98 (m, 1 H) 7.35 (d, J = 9 Hz, 1 H) 7.78 (d, J = 9 Hz, 1 H) 7.86-8.00 (m, 4H). MS (DCI-NH3), m/z 441 (M+H)+. Anal. calc. for C20HI 6F4N2O3SO.5 H2O: C, 53.45; H, 3.81 ; N, 6.23. Found C, 53.17; H, 3.65; N, 5.88. Example 211 2-(2.2.2-Trifluoroethvn-4-f3.5-dichlorophenyl)-5-[4-(mBthylsulfonyl)phBnyl]-3(2H)- pyridazinone 2-(2,2,2-Thfluoroethyl)-4-chloro-5-[4-(methyisulfonyl)phenyl]-3(2H)- pyridazinone (150 mg, 0.409 mmol) (Example 193E) was dissolved in anhydrous DME (8 mL) and heated to reflux with 3,5-dimethylbenzeneboronic acid in presence of CsF (150 mg, 0.98 mmol) and tetrakis(triphenylphosphine)-palladium (17.38 mg, 0.015 mmol) for 6 hours. After cooling to room temperature the reaction mixture was diluted with water and extracted with ethyl acetate (100 mL). The organic layer was washed with brine, dried over MgSO4, and evaporated in vacuo. The compound was purified on a silica gel column, eluting with 30% ethyl acetate in pentanes, to provide the title compound (yield: 110 mg, 58%). 1 H NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 4.88 (q, J = 9 Hz, 2H), 7.06 (d, J = 1.5 Hz, 9 Hz, 2H), 7.31 (t, J = 1.5 Hz, 1 H), 7.36 (d, J = 9 Hz, 2H), 7.94 (s, 1 H), 7.96 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 496 (M+NH4)+. Anal. calc. for C19H13CI2F3N2O3S: C, 47.81 ; H, 2.75; N, 5.87. Found: C, 47.77; H, 2.75; N, 5.65 Example 212 2-(2.2.2-Trifluoroethyl)-4-f3-Bthoxyphsnyl)-5-[4-(mBthylsulfonyl.phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 21 1 , substituting 3-ethoxyphenylboronic acid for 3,5-dimethylbenzeneboronic acid (yield: 155 mg, 86%). 1 H NMR (300 MHz, CDCI3) δ 1.42 (t, J = 7.5 Hz, 3H), 3.06 (s, 3H), 3.90 (q, J = 7.5 Hz, 2H), 4.88 (q, J = 9 Hz, 2H), 6.65 (d, J = 7.5 Hz, 1 H), 6.75 (t, J = 1.5 Hz, 1 H), 6.85 (dd, J = 1.5 Hz, 9 Hz, 1 H), 7.15 (t, J = 9 Hz, 1 H), 7.38 (d, J = 9 Hz, 2H), 7.88 (d, J = 9 Hz, 2H), 7.90 (s, 1 H). MS (DCI-NH3) m/z 470 (M+NH4)+. Anal. calc. for C-21 Hi Cl2F3N2θ4S: C, 55.75; H, 4.23; N, 6.19. Found: C, 55.62; H, 4.30; N, 5.99 Example 213 2-(2.2.2-Trifluoroethvπ-4-(4-thfluoromethylphenvπ-5-[4-(methylsulfonvπphenyl1- 3(2HVpyridazinone The title compound was prepared according to the method of Example 21 1 , substituting 4-(trifluoromethyl)benzeneboronic acid in place of 3,4-dimethyl- benzeneboronic acid (yield: 85 mg, 44%). 1 H NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 4.90 (q, J = 0 Hz, 2H), 7.35 (t, J = 9 Hz, 4H), 7.58 (d, J = 9 Hz, 2H), 7.90 (d, J = 9 Hz. 3H). MS (DCI-NH3) m/z 494 (M+NH4) + . Anal. calc. for C20H14F6N2O3S: C, 50.42; H, 2.96; N, 5.88. Found: C, 50.20; H, 3.02; N, 5.70 Example 214 2-(2.2.2-Trifluoroethyli-4-f3-nitrophenvn-5-f4-.methylsulfonyl.phBnyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 21 1 , substituting 3-nitrobenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 40 mg, 22%). 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 4.92 (q, J = 9 Hz, 2H), 7.36 (d, J = 9 Hz, 2H), 7.45-7.60 (m, 2H), 7.91 (d, J = 9 Hz, 2H), 7.95 (s, 1 H), 8.05 (m, 1 H), 8.15-8.21 (m, 1 H). MS (DCI-NH3) m/z 471 (M+NH4)+ Anal, calc. for Cι gHi4Cl2F3N3θsS-0.5 EtOAc: C, 50.70; H, 3.64; N, 8.44. Found: C, 50.61 ; H, 3.58; N, 8.53 Example 215 2-(2.2.2-Trifluoroethyh-4-(2-methylphθnyl)-5-[4-(mBthylsulfonyl)phBnyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 21 1 , substituting 2-methylbenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 45 mg, 27%). 1 H NMR (300 MHz, CDCI3) δ 2.05, 2.12 (2s, 3H), 3.01 (s, 3H), 4.75-5.05 (m, 2H), 6.88 (d, J = 9 Hz, 1 H), 7.03-7.25 (m, 3H), 7.31 (d, J = 9 Hz, 2H), 7.85 (d, J = 9 Hz, 2H), 7.95 (s, 1 H). MS (DCI-NH3) m/z 440 (M+NH4)+. Anal, calc. for C20H17F3N2O3S: C, 55.10; H, 4.27; N, 6.42. Found: C, 55.17; H, 4.18; N, 6.10 Example 216 2-(2.2.2-TrifluoroBthvl)-4- 4-vinvlphenvn-5-[4-fmBthylsulfonyhphBnyl]-3f2H pyridazinone The title compound was prepared according to the method of Example 21 1 , substituting 4-vinylbenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 56 mg, 32%). 1 H NMR (300 MHz, CDCI3) δ 3.06, 3.08 (2s, 3H), 4.78- 4.05 (m, 2H), 5.30 (t, J = 6 Hz, 1 H), 5.65, 5.75(2d, J = 18 Hz, 1 H), 6.58-6.92 (m, 1 H), 7.1 -7.4 (m, 6H), 7.75-8.08 (m, 3H). MS (DCI-NH3) m/z 452 (M+NH4)+. Anal. calc. for C-21 H17F3N2O3S: C, 58.06; H, 3.04; N, 6.45. Found: C, 57.82; H, 4.01 ; N, 6.09 Example 217 2-.2.2.2-Trifluoroethyl 4-f3-ftrifluoromsthyl)phBnyl]-5-[4-(msthylsulfonyl)ph8nyl]- 3(2H)-pvridazinons The title compound was prepared according to the method of Example 21 1 , substituting 3-trifluoromethylbenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 120 mg, 63%). 1 H NMR (300 MHz, CDCI3) δ 3.03, 3.08 (2s, 3H), 4.75-4.98 (m, 2H), 7.30-7.60 (m, 6H), 7.75-8.10 (m, 3H). MS (DCI-NH3) m/z 494 (M+NH4)+. Anal. calc. for C20H14F6N2O3S: C, 50.42; H, 2.96; N, 5.88. Found: C, 50.38; H, 2.97; N, 5.74 Example 218 2-(2.2.2-Trifluoroethyh-4- ( 3-fluoro-4-methoxyphenyl)-5-[4-(methylsulfonyπphenyl]- 3(2H)-pyridazinonB The title compound was prepared according to the method of Example 21 1 , substituting 3-fluoro-4-methoxybenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 32 mg, 18%). 1 H NMR (300 MHz, CDCI3) δ 3.05, 3.00 (2s, 3H), 3.85, 3.87 (2s, 3H), 4.78-4.90 (m, 2H), 6.60-7.10 (m, 3H), 7.30-8.15 (m, 5H). MS (DCI-NH3) m/z 474 (M+NH4)+. Anal. calc. for C-2θHi 6F4N 2 θ4S-0.5 H2O: C, 51.61 ; H, 3.68; N, 6.01. Found: C, 51.52; H, 3.65; N, 5.93 Example 219 2-f2.2.2-Trifluoroethvn-4-f3-fluoro-4-methylphenvn-5-[4-fmethylsulfonvnphenyl]- 3(2HVpvridazinone The title compound was prepared according to the method of Example 21 1 substituting 3-fluoro-4-methylbenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 58 mg, 33%). 1 H NMR (300 MHz, CDCI3) δ 2.21 , 2.25 (2d, J = 1.5 Hz, 3H), 3.50, 3.55 (2s, 3H), 4.75-4.05 (m, 2H), 6.56-7.15 (m, 3H), 7.30- 8.10 (m, 5H). MS (DCI-NH3) m/z 458 (M+NH4)+. Anal. calc. for C20H16F4N2O3S-0.5 H2O: C, 53.45; H, 3.81 ; N, 6.23. Found: C, 53.14; H, 3.80; N, 5.07 Example 220 2-f2.2.2-Trifluoroethvlι-4-.3.5-difluoro-4-mBthoxvphBnvn-5-f4-fmBthvlsulfonvh- phθnyl]-3(2H)-pyridazinonθ The title compound was prepared according to the method of Example 21 1 , substituting 3,5-difluoro-4-methoxybenzeneboronic acid in place of 3,4- dimethylbenzeneboronic acid. 1 H NMR (300 MHz, CDCI3) δ 2.9, 3.1 (2s, 3H), 3.92, 4.01 (2s, 3H), 4.78-4.95 (m, 2H), 6.25-6.80 (m, 1 H), 7.30-7.5 (m, 2H), 7.7-8.15 (m, 4H). MS (DCI-NH3) m/z 402 (M+NH4) + - Anal. calc. for C20H15F5N2O4S: C, 50.64; H, 3.19; N, 5.90. Found: C, 50.542; H, 3.41 ; N, 5.67 Example 221 2-(2.2.2-Trifluoroethyl)-4-π .3-dihvdro-1-oxo-5-isobsnzofuranvh-5-[4-.methyl- sulfonyl)phenyl]-3 ( 2H.-pyridazinone 6-Bromophthalide (300 mg, 1.40 mmol, Teppema et al Reel. Trav. Chim. Pays-Bays ,1923, 42, 47) and hexamethylditin (326 μL, 1.55 mmol) were dissolved in toluene (5 mL), degassed with a nitrogen stream for 5 minutes, treated with (Ph3P)4Pd (79 mg) and heated at reflux for 1 hour. The reaction was cooled and directly purified by chromatography on a Biotage 40S column (pretreated with hexanes-TEA 400:1 then rinsed with hexanes) eluted with 4:1 hexanes-ethyl acetate. The product fractions were combined and evaporated to provide the intermediate, 6-(trimethyltin)phthalide (yield: 362 mg, 87%). The tin reagent (180 mg, 0.61 mmol), prepared above, and 2-(2,2,2-trifluoro- ethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone, prepared in Example 193E, (223 mg, 0.61 mmol) were dissolved in dry toluene (10 mL), degassed with an nitrogen stream for 5 minutes, treated with (Ph3P)4Pd (34 mg) and heated at reflux for 1 day. The reaction was cooled and directly purified by chromatography on a Biotage 40S column eluted with 4:1 hexanes-ethyl acetate. The product fractions were combined and evaporated to provide the title compound along with the 4-(1 ,3-dihydro-1 -oxo-6-isobenzofuranyl)-isomer in a 9:1 ratio. Further manipulations to attempt to remove the minor isomer (ie chromatography, recrystallization from ethyl acetate-hexanes) failed (yield: 176 mg, 62%). M.p. 237- 239 °C. 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 4.91 (q, J = 8 Hz, 2H), 5.30 (s, 2 H, major isomer), 5.33 (s, 2 H, minor isomer), 7.20 (dd, J = 1 Hz, 7 Hz, 1 H), 7.36 (d, J = 8 Hz, 2H), 7.52 (s, 1 H), 7.79 (d, J = 7 Hz, 1 H), 7.92 (d, J = 8 Hz, 2H), 7.96 (s, 1 H). MS (DCI-NH3) m/z 482 (M+NH4)+. Anal. calc. for C-21 H15F3N2O5S: C, 54.31 ; H, 3.26; N, 6.03. Found: C, 54.15; H, 3.12; N, 5.76. Example 222 2-(2.2.2-Trifluoroethyl.-4-(2-propsnyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone A suspension of 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (200 mg, 0.546 mmol), prepared according to the method of Example 193E, in THF (27 mL) was cooled to -78 °C. A solution of isopropenyl- magnesium bromide (2.8 mL, 0.5 M in THF, Aldrich) was added. The reaction was warmed to room temperature and stirred for 30 minutes. The reaction was quenched at 0 °C by the addition of saturated ammonium chloride solution and partitioned between ethyl acetate and additional ammonium chloride solution. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide a reddish brown solid. The crude material was dissolved in methylene chloride and adsorbed onto silica gel (2 g). Solvent was removed under reduced pressure, the adsorbed silica gel layered over an Extract-Clean Cartridge® (Alltech, packing: 5 g silica gel) and the cartridge eluted with a hexanes/acetone step gradient consisting of 40 mL of the following mixtures: hexanes, 8:1 hexanes/acetone, 4:1 , 2:1 , and 1 :1. Fractions containing desired product were combined, concentrated, and further purified using HPLC (Technikrom Kromasil 60-5sil column, 20 mm x 25 cm). The column was eluted with a linear gradient consisting of 30% ethyl acetate/hexanes to 100% ethyl acetate at 10 mL/min over 50 minutes. Fractions containing the title product were combined and concentrated under reduced pressure to provide a pale yellow solid (yield: 99.3 mg, 49%). M.p. 192-195 °C. 1 H NMR (300 MHz, CDCI3) δ 8.03 (d, J = 17.4 Hz, 2H), 7.76 (s, 1 H), 7.55 (d, 2H, J = 17.4 Hz), 5.23 (br s, 1 H), 4.84 (m, 3H), 3.11 (s, 3H), 1.98 (s, 3H). MS (DCI-NH3) m/z 373 (M+H)+, m/z 390 (M+NH4)+. Anal. calc. for C16H15F3N2O3S: C, 51.61 ; H, 4.06; N, 7.52. Found: C, 51.72; H, 4.24; N, 7.35. Example 223 2-(2.2.2-Trifluoroethyn-4- 2-buten-2-vn-5-[4-(methylsulfonylιphenyl1-3f2Hι- pyridazinone The product was prepared according to the method of Example 222 substituting 1 -methyl-1 -propenylmagnesium bromide in place of isopropenylmag- nesium bromide to provide a mixture of geometric isomers (-3:1 ratio) as an off- white solid (yield: 44.8 mg, 21 %). M.p. 175-180 °C. 1 H NMR (300 MHz, CDCI3) δ 8.03 (d, J = 18.0 Hz, 1.5H), 8.01 (d, J = 18.0 Hz, 0.5H), 7.28 (s, 0.75H), 7.28 (s, 0.25H), 7.56 (d, J = 17.4 Hz, 1.5H), 7.51 (d, J = 17.4 Hz, 0.5H), 5.55 (m, 0.75H), 5.33 (m, 0.25H), 5.86 (q, J = 17.4 Hz, 2H), 3.12 (s, 2.25H), 3.11 (s, 0.75H), 2.88 (m, 2H), 2.85 (m, 1 H), 1.27 (m, 3H). MS (DCI-NH3) m/z 387 (M+H)+, m/z 404 (M+NH4)+, m/z 421 (M+2NH4-H)+. Anal. calc. for C17H17F3N2O3S: C, 52.85; H, 4.43; N, 7.25. Found: C, 53.16; H, 4.68; N, 6.92. Example 224 2-(2.2.2-Trifluoroethvn-4-f3-fluorobenzyl.-5-[4-fmethylsulfonyl.phenyl]-3(2H)- pvridazinone 224A. 3-Fluorobenzyl magnesium bromide. 3-Fluorobenzyl bromide (613 μL, 5 mmol), followed by dibromoethane (10 μL), was added dropwise to an oven-dried flask containing small pieces of magnesium ribbon (134 mg, 5.5 mmol) and diethyl ether (12 mL). Gas evolution was noted followed by gentle reflux of the ether. The reaction was stirred until gas evolution ceased and most of the magnesium had dissolved. The resulting pale yellow solution of 3-fluorobenzylmagnesium bromide was used directly in the next reaction. 224B. 2-(2.2.2-Trifluoroethyl)-4-(3-fluorobenzyl)-5-f4-fmethylsulfonvnphenyl]- 3(2H)-pvridazinone. A suspension of 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyi]- 3(2H)-pyhdazinone (200 mg, 0.546 mmol), prepared according to the method of Example 193E, in THF (10 mL) was cooled to 0 °C. A solution of 3-fluorobenzyl magnesium bromide (4.0 mL, -0.42 M in diethyl ether), prepared above was added. The reaction was stirred at 0 °C for 3 hours, quenched by the addition of saturated ammonium chloride solution, and partitioned, between ethyl acetate and additional ammonium chloride solution. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide a yellow oil. The crude material was dissolved in methylene chloride and adsorbed onto silica gel (2 g). Solvent was removed under reduced pressure, the silica gel with the product adsorbed was layered over an Extract-Clean Cartridge® (Alltech, packing: 10 g silica gel) and the cartridge eluted with a hexanes/acetone step gradient consisting of 60 mL of each of the following mixtures: hexanes, 8:1 hexanes/acetone, 4:1 , 2:1 , and 1 :1. Fractions containing desired product were combined, concentrated, and further purified using HPLC (Technikrom Kromasil 60-5 sil silica column, 20 mm x 25 cm). The column was eluted with a linear gradient consisting of 30% ethyl acetate/hexanes to 100% ethyl acetate at 10 mL/min. for 50 minutes. Fractions containing the title product were combined and concentrated under reduced pressure to provide a pale yellow solid (yield: 130.0 mg, 54%). M.p. 58-62 °C. 1 H NMR (300 MHz, CDCI3) δ 8.07 (d, J = 18.0 Hz, 2H), 7.73 (s, 1 H), 7.47 (d, J = 17.4 Hz, 2H), 7.18 (m, 1 H), 6.88 (m, 1 H), 6.76 (br d, J = 15.6 Hz, 1 H), 6.68 (br d, J = 18.6 Hz, 1 H), 4.86 (q, J = 17.4 Hz, 2H), 3.93 (s, 2H), 3.12 (s, 3H). MS (DCI-NH3) m/z 441 (M+H)+, m/z 458 (M+NH4)+, m/z 475 (M+2NH4-H)+. Anal. calc. for C20H16F4 2O3S: C, 54.54; H, 3.66; N, 6.36. Found: C, 54.52; H, 3.81 ; N, 6.17. Example 225 2-(2.2.2-Trifluoroethyn-4-(1 -cyclohexenyl.-5-r4-fmethylsulfonvhphenyl]-3f2H.- pyridazinone 225A. 1 -Cvclohexenyltriflate. n-Butyllithium (2.5M in hexanes, 2.20 mL, 5.50 mmol) was added to a solution of diisopropylamine (0.77 mL, 5.50 mmol) in THF (20 mL) at-78 °C. The resulting pale yellow solution was warmed to 0 °C for 30 minutes then was cooled to -78 °C. Cyclohexanone (0.52 mL, 5.0 mmol) was added and the nearly colorless solution was warmed to 0 °C for 1 hour. N-Phenyltrifluoromethanesulfonimide (1.79 g, 5.5 mmol) was added as a solid. The solution was stirred at room temperature for 12 hours. The reaction mixture was then partitioned between diethyl ether and saturated sodium bicarbonate solution. The ether layer was washed with water then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (20:1 hexanes/ethyl acetate) to provide the triflate as a pale yellow oil (yield: 0.73 g, 64%). 225B. 1 -Cvclohexenyltrimethyltin. A solution of 1 -cyclohexenyltriflate (412 mg, 1.79 mmol), prepared according to the method of Example 225A, and LiCI (380 mg, 8.05 mmol) in THF (9 mL) was deoxygenated by bubbling a stream of N2 through the solution. Hexamethylditin (339 μL, 1.61 mmol) and tetrakis(triphenylphosphine)palladium(0) (414 mg, 0.36 mmol) were added and the reaction heated at reflux for 12 hours. The reaction was cooled to room temperature and partitioned between diethyl ether and saturated sodium bicarbonate solution. The ether layer was washed with water then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was dissolved in hexanes (1 mL) and loaded onto an Extract-Clean Cartridge® (Alltech, packing: 10 g silica gel) which had been wetted with 10% triethylamine in hexanes. The cartridge was eluted with hexanes and fractions containing the triflate combined and concentrated under reduced pressure to provide 1 -cyclohexenyltrimethyltin as a clear oil (yield: 150 mg, 34%). 225C. 2-(2.2.2-Trifluoroethyπ-4- -cvclohexenvh-5-[4-(methylsulfonyl)phsnvπ- 3f2HVpyridazinone. A solution of 1 -cyclohexenyltrimethyltin (150 mg, 0.61 mmol), prepared according to the method of Example 225B, and 2-(2,2,2-trifluoroethyl)-4-chloro-5- [4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (172 mg, 0.47 mmol), prepared according to the method of Example 193E, in anhydrous N-methylpyrrolidinone (1 mL) was deoxygenated with nitrogen. Dichlorobis(triphenylphosphine) palladium(ll) (6.6 mg, 0.009 mmol) and [1 ,1 '-bis(diphenylphosphino)ferrocene] dichloropalladium(ll) (7.7 mg, 0.009 mmol) were added and the reaction heated at 80 °C for 16 hours. The reaction mixture was cooled to room temperature and partitioned between diethyl ether and water. The ether was washed with two additional portions water then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was dissolved in acetone and adsorbed onto silica gel (1 g). Solvent was removed under reduced pressure, the adsorbed silica gel layered over an Extract-Clean Cartridge® (Alltech, packing: 10 g silica gel) and the cartridge eluted with a hexanes/acetone step gradient consisting of the following mixtures: hexanes (60 mL), 8:1 hexanes/acetone (80 mL), 4:1 hexanes/acetone (150 mL). Fractions containing desired product were combined, concentrated, and further purified using HPLC (Technikrom Kromasil 60-5 sil silica column, 20 mm x 25 cm). The column was eluted with a linear gradient consisting of 30% ethyl acetate/hexanes to 100% ethyl acetate at 10 mL/min. over 50 minutes. Fractions containing the title product were combined and concentrated under reduced pressure to provide a pale yellow foam (yield: 05.0 mg, 49%). M.p. 75-81 °C. 1 H NMR (300 MHz, CDCI3) δ 8.02 (d, J = 17.4 Hz, 2H), 7.76 (s, 1 H), 7.55 (d, J = 17.4 Hz, 2H), 5.51 (br s, 1 H), 4.83 (br q, J = 16.2 Hz, 3H), 3.11 (s, 3H), 2.18 (br, 2H), 1.06 (br, 2H), 1.70-1.50 (m, 4H). MS (DCI- NH3) m/z 413 (M+H)+, m/z 430 (M+NH4) + , m/z 447 (M+2NH4-H)+. Anal. calc. for Ci gHι gF3N2θ3S: C, 55.33; H, 4.64; N, 6.79. Found: C, 55.53; H, 4.71 ; N, 6.55. Example 226 2-(2.2.2-Trifluoroethyl.-4- ( 3-methylbutyπ-5-f3-fluoro-4-(aminosulfonyl)phenyl]- 3(2H)-pvridazinone 226A. 3-Fluoro-4-(methylthio)benzeneboronic acid. 3-Fluoro-4-(methylthio)benzeneboronic acid was prepared according to the method of Examplel , substituting 4-bromo-3-fluorothioanisole in place of 4-bromothioanisole. 226B. 2-Benzyl-4-methoxy-5-bromo-3(2H' ■-pyridazinone 2-Benzyl-4-methoxy-5-bromo-3(2H)-pyridazinone is prepared according to the method of Example 83B starting with 2-benzyl-4,5-dibromo-3(2H)-pyridazinone, in place of 2-(2,2,2-trifluoroethyl)-4,5-dibromo-3(2H)-pyridazinone and substituting methanol in place of isopropanol. 226C. 2-Benzyl-4-methoxy-5-[3-fluoro-4-(methylthio)phenyl]-3.2H)-pyridazinone 3-Fluoro-4-(methylthio)benzeneboronic acid and 2-benzyl-4-methoxy-5- bromo-3(2H)-pyridazinone were coupled according to the method of Example 83C to provide 2-benzyl-4-methoxy-5-[3-fluoro-4-(methylthio)phenyl]-3(2H)- pyridazinone as a yellow solid (yield: 4.08 g, 91 %). 1 H NMR (300 MHz, CDCI3) d 7.76 (s, 1 H), 7.47 (m, 2H), 7.30-7.21 (m, 7H), 5.34 (s, 2H), 4.13 (s, 3H), 2.51 (s, 3H). MS (DCI-NH3) m/z 357 (M+H)+, m/z 374 (M+NH4)+. 226D. 3-Methylbutylmagnesium bromide An oven-dried flask containing small pieces of magnesium ribbon (134 mg, 5.5 mmol) was charged with diethyl ether (12 mL). 1 -Bromo-3-methylbutane (600 μL, 5 mmol) was added dropwise, followed by dibromoethane (10 μL). The reaction required heating at gentle reflux before gas evolution was observed. The reaction was refluxed for 3 hours and cooled to room temperature. The pale gray solution of 3-methylbutylmagnesium bromide was used in the next reaction. 226E. 2-Benzyl-4-f3-methylbutyl)-5-[3-fluoro-4-(methylthio.phenyl]-3(2H)- pyridazinone A solution of 2-benzyl-4-methoxy-5-[3-fluoro-4-(methylthio)phenyl]-3(2H)- pyridazinone (500 mg, 1.40 mmol), prepared according to the method of Example 226C, in THF (20 mL) was cooled to-78 °C. 3-Methylbutylmagnesium bromide (5 mL, 1.96 mmol), prepared in Example 226D, was added, dropwise. Upon completion of the addition, the reaction mixture was placed in an ice bath. After 2.5 hours, the reaction was quenched by adding saturated ammonium chloride solution. The crude reaction mixture was partitioned between ethyl acetate and additional ammonium chloride solution. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide a yellow oil (yield: 550 mg, 00%). 1 H NMR (300 MHz, CDCI3) 3 7.67 (s, 1 H), 7.49 (m, 2H), 7.39-7.25 (m, 4H), 7.02 (m, 2H), 5.35 (s, 2H), 2.57-2.40 (m, 2H), 2.52 (s, 3H), 1.62-1.36 (m, 3H), 0.83 (d, 6H, J = 12.0 Hz). MS (DCI-NH3) m/z 397 (M+H)+, m/z 414 (M+NH4)+. MS (DCI-NH3) m/z 397 (M+H)+, m/z 414 (M+NH4)+. 226 F. 4- 3-Methylbutvn-5-[3-fluoro-4-fmethylthio)phenyl]-3(2HVpyridazinone. 2-Benzyl-4-(3-methylbutyl)-5-[3-fluoro-4-(methylthio)phenyl]-3(2H)- pyhdazinone (550 mg, 1.39 mmol), prepared in Example 226E, was debenzylated according to the method of Example 11 to provide 4-(3-methylbutyl)-5-[3-fluoro-4- (methylthio)phenyl]-3(2H)-pyridazinone as a pale yellow solid (yield: 375 mg, 88%). 1 H NMR (300 MHz, CDCI3) δ 7.65 (s, 1 H), 7.34 (dd, 1 H, J = 16.2, 16.2 Hz), 7.11 -6.98 (m, 2H), 2.60-2.50 (m, 2H), 2.54 (s, 3H), 1.65-1.37 (m, 3H), 0.83 (d, 6H, J = 12.0 Hz). MS (DCI-NH3) m/z 307 (M+H)+, m/z 324 (M+NH4)+ MS (DCI-NH3) m/z 307 (M+H)+, m/z 324 (M+NH4) + . 226G. 2-f2.2.2-Trifluoroethvn-4-(3-methylbutyn-5-[3-fluoro-4-(methylthio phenyl]- 3f2HVpvridazinone. 4-(3-Methylbutyl)-5-[3-fluoro-4-(methylthio)phenyl]-3(2H)-pyridazinone (375 mg, 1.23 mmol), prepared in Example 226F, was alkylated according to the method of Example 20 to provide 2-(2,2,2-trifluoroethyl)-4-(3-methylbutyl)-5-[3-fluoro-4- (methylthio)phenyl]-3(2H)-pyridazinone as a clear oil (yield: 331 mg, 69%). 1 H NMR (300 MHz, CDCI3) δ 7.67 (s, 1 H), 7.34 (dd, 1 H, J = 16.8, 16.8 Hz), 7.11 -6.98 (m, 2H), 4.82 (dd, 2H, J = 17.4, 17.4 Hz), 2.60-2.51 (m, 2H), 2.53 (s, 3H), 1.61 -1.32 (m, 3H), 0.85 (d, 6H, J = 12.0 Hz). MS (DCI-NH3) m/z 389 (M+H)+, m/z 406 (M+NH4)+. MS (DCI-NH3) m/z 389 (M+H)+, m/z 406 (M+NH4)+. 226H. 2-(2.2.2-Trifluoro8thyn-4-f3-methylbutyn-5-[3-fluoro-4-(methylsulfinyl)- phanyl]-3(2HVpvridazinone. 2-(2,2,2-Trifluoroethyl)-4-(3-methylbutyl)-5-[3-fluoro-4-(methylthio)phenyl]- 3(2H)-pyhdazinone (331 mg, 0.85 mmol), prepared in Example 226G, was oxidized according to the method of Example 5 using only one equivalent of MCPBA to provide 2-(2,2,2-trifluoroethyl)-4-(3-methylbutyl)-5-[3-fluoro-4-(methylsulfinyl)- phenyl]-3(2H)-pyridazinone as an off-white solid (yield: 240 mg, 69%). 1 H NMR (300 MHz, CDCI3) δ 8.02 (dd, 1 H, J = 15.0, 15.0 Hz), 7.67 (s, 1 H), 7.37 (dd, 1 H, J = 17.4, 3.0 Hz), 7.11 (dd, 1 H, J = 18.6, 3.0 Hz), 4.84 (dd, 2H, J = 17.4, 17.4 Hz), 2.91 (s, 3H), 2.53 (m, 2H), 1.60-1.35 (m, 3H), 0.57 (d, 6H, J = 12.0 Hz). MS (DCI-NH3) m/z 405 (M+H)+, m/z 422 (M+NH4)+. MS (DCI-NH3) m/z 405 (M+H)+, m/z 422 (M+NH4) + . 226I. 2-(2.2.2-Trifluoroethvn-4-(3-methylbutvn-5-[3-fluoro-4-(aminosulfonvπ- phenyl]-3(2H)-pyridazinone 2-(2,2,2-Trifluoroethyl)-4-(3-methylbutyl)-5-[3-fluoro-4-(methylsulfinyl)- phenyl]-3(2H)-pyridazinone (240 mg, 0.594 mmol), prepared in Example 226H, was converted to the sulfonamide according to the procedure of Example 68 to provide the title compound as a white solid (yield: 100 mg, 44%). M.p. 153-156 °C. 1 H NMR (300 MHz, CDCI3) δ 8.07 (dd, J = 15.0, 15.0 Hz, 1 H), 7.74 (s, 1 H), 7.27- 7.i g (m, 2H), 5.14 (br s, 2H), 4.83 (q, J = 18.0 Hz, 2H), 2.52 (m, 2H), 1.55 (m, 1 H), 1.41 (m, 2H), 0.85 (d, J = 12.6 Hz, 6H). MS (ESI (-)) m/z 420 (M-H)". Anal. calc. for Ci 7Hi gF4N3θ3S: C, 48.45; H, 4.54; N, 9.97. Found: C, 48.24; H, 4.56; N, 9.80. Example 227 2-(2.2.2-Trifluoroethvπ-4-benzyl-5-[4-(methylsulfonvπphenyl1-3(2H)-pyridazinone The title compound was prepared by adding 1.0 M benzylmagnesium chloride in ether (0.53 mL, 0.53 mmol) to a THF (20 mL) solution of 2-(2,2,2- trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (150 mg, 0.41 mmol), prepared according to the method of Example 193E, at 0 °C, then allowing the mixture to warm to room temperature over 2 hours. After an aqueous work-up, the crude material was purified by column chromatography (silica gel, 65:35 hexanes/ethyl acetate) and crystallized from ethyl acetate/hexanes to provide white, crystalline product (yield: 74 mg, 43%). M.p. 112-114 °C. 1 H NMR (300 MHz, CDCI3) δ 3.12 (s, 3H), 3.94 (s, 2H), 4.85 (q, J = 12 Hz, 2H), 6.99 (dd, J = 7.5 Hz, 3 Hz, 2H), 7.2 (m, 3H), 7.48 (d, J = 9 Hz, 2H), 7.72 (s, 1 H), 8.06 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 423 (M+H)+. Anal. calc. for C20H17F3N2O3S: C, 56.86; H, 4.05; N, 6.63. Found: C, 56.60; H, 4.13; N, 6.57. Example 228 2- (' 4-Fluorophenvπ-4-cvclohexyl-5-[4-(methylsulfonvπphenyl1-3(2HVpyridazinone A solution of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 194C, (200 mg, 0.51 mmol) in THF (8 ml) was cooled to -78 °C and treated with cyclohexylmagnesium chloride, 2 M solution in ether (0.31 ml, 0,7 mmol). The reaction mixture was stirred at -78 °C for 2 hours and then was warmed up to room temperature by removing the cooling bath. Stirred at room temperature for 2 hours water (50 ml) was added to the reaction mixture and extracted with ethyl acetate (50 ml). The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting methyl sulfide compound was purified by flash chromatography (Siθ2, eluting with 0:1 hexanes:ethyl acetate) to provide the desired product (yield: 128 mg, 60%). MS (DCI-NH3) m/z 305 (M+H)+, 412 (M+NH4)+- The methyl sulfide compound, prepared above, (122 mg, 0.3 mmol) in CH2CI2 (10 ml) at 0 °C, was treated with CH3CO3H (0.3 ml, 1 mmol). The reaction was complete in 2 hours. The reaction mixture was diluted with CH2CI2 and washed with saturated NaHCO3 and brine respectively. The resulting crude residue was purified by flash chromatography (Siθ2, eluting with 1 :1 hexanes:ethyl acetate) to provide the desired product (yield: 1 10 mg, 93%). M.p. 231 -233 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.1 (m, 3H), 1.6 (m, 6H), 2.15 (m, 2H), 7.35 (t, 2H), 7.65 (m, 2H), 7.73 (dd, 2H) 7.03 (s, 1 H), 8.1 (d, 2H). MS (DCI-NH3) m/z 427 (M+H)+, 444 (M+NH4)+. Anal. calc. for C23 H23FN2O3S-0.75 H2O: C, 64.77; H, 5.44; N, 6.57. Found: C, 62.86; H, 5.53; N, 5.78. Example 229 2-(4-Fluorophenyl)-4-(4-methylphenvπ-5-[4-(methylsulfonvπphenyl]-3(2H'>- pyridazinone The title compound was prepared according to the method of Example 228, substituting p-tolylmagnesium bromide in place of cyclohexylmagnesium chloride (yield: 90 mg, 39%). M.p. 242-244 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.25 (s, 3H), δ 3.25 (s, 3H), 7.1 (t, 4H), 7.35 (t, 2H), 7.5 (d, J = 0 Hz, 2H), 7.7 (dd, 2H) 7.g (d, J = Hz, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+. Anal. calc. for C24H-| gFN2θ3S-0.5 H2O: C, 66.34; H, 4.41 ; N, 6.45. Found: C, 64.61 ; H, 4.57; N, 6.10. Example 230 2-(4-Fluorophenyl)-4-benzyl-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 228, substituting benzylmagnesium bromide in place of cyclohexylmagnesium chloride (yield: 179 mg, 81 %). M.p. 180-182 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.3 (s, 3H), 7.0 (d, 2H), 7.2 (m, 3H), 7.35 (t, 2H), 7.65 (m, 2H)7.72 (d, 2H) 8.05 (m, 3H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+. Anal. calc. for C24H-| gFN2θ3S-0.5 H2θ: C, 66.34; H, 4.41 ; N, 6.45. Found: C, 66.48; H, 4.17; N, 6.36. Example 231 2-f4-FluorophenylV4- henylethvnvπ-5-[4-(methylsulfonvhphenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 228, substituting phenylacetylene magnesium bromide in place of cyclohexylmagnesium chloride (yield: 150 mg, 55.5%). M.p. 203-204 °C. 1 H NMR (300 MHz, DMSO-d6) δ 3.3 (s, 3H), 7.4 (m, 8H), 7.7 (m, 2H), 8.16 (m, 4H) ; 8.35 (s, 1 H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+. Anal. calc. for C25H17FN2O3S: C, 67.56; H, 3.86; N, 6.30. Found: C, 67.63; H, 3.86; N, 6.30. Example 232 2-(3.4-Difluorophenvn-4-cvclohexyl-5-[4-(mθthylsulfonvπphθnyl]-3 2H)- pvridazinonθ Thθ title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]3(2H)- py dazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (yield: 245 mg, 80%). M.p. 80-83 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.1 (m, 3H), 1.6 (m, 6H), 2.15 (m, 2H), 7.5 (m, 1 H), 7.6 (m, 2H), 7.7 (d, 2H), 7.78 (m, 2H), 7.93 (s, 1 H), 8.1 (d, 2H). MS (DCI-NH3) m/z 445 (M+H)+, 462 (M+NH4)+. Anal. calc. for C23H22F2N2O3S: C, 62.15; H, 4.99; N, 6.30. Found: C, 62.65; H, 5.25; N, 5.97. Example 233 2-(3.4-Difluorophenvπ-4-benzyl-5-[4-(methylsulfonyl)phenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting benzylmagnesium bromide in place of cyclohexylmagnesium chloride (yield 206 mg, 66%). M.p. 166-168 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.3 (s, 3H), 3.0 (s, 2H), 7.0 (d, 2H), 7.2 (m, 3H), 7.6 (m, 2H), 7.72 (d, 2H), 7.8 (d, 1 H), 8.05 (d, 2H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 453 (M+H)+, 470 (M+NH4)+. Anal. calc. for C24H1 gF2N2θ3S: C, 63.71 ; H, 4.01 ; N, 6.10. Found: C, 63.53; H, 4.33; N, 5.76. Example 234 2- 3.4-Difluorophenvn-4-(4-methylphenvn-5-[4-(methylsulfonvhphenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting cyclohexylmagnesium chloride in place of p- tolylmagnesium bromide (yield: 140 mg, 56%) . M.p. 190-102 °C. H NMR (300 MHz, DMSO-d6) δ 2.28 (s, 2H), δ 3.25 (s, 3H), 7.1 (s, 4H), 7.5 (m, 4H), 7.89 (m, 3H), 8.05 (d, 2H), 8.23 (s, 1 H). MS (DCI-NH3) m/z 453 (M+H)+, 470 (M+NH4)+ Anal, calc. for C24F2H18N2O3S: C, 63.71 ; H, 4.01 ; N, 6.10. Found: C, 63.69; H, 4.29; N, 5.96. Example 235 2-(3.4-Difluorophenvπ-4-(4-fluoro-3-methylphenvh-5-[4-(methylsulfonvhphenyl]- 3(2HVpyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting 4-fluoro-3-methylbenzenemagnesium bromide in place of cyclohexylmagnesium chloride (yield: 180 mg, 72.5%) . M.p. 166-168 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.15 (s, 3H), δ 3.25 (s, 3H), 7.01 (m, 2H), 7.25 (d, 1 H), 7.6 (m, 4H), 7.9 (m, 3H), 8.26 (s, 2H). MS (DCI-NH3) m/z 471 (M+H)+, 488 (M+NH4)+. Anal. calc. for C24F3H17N2O3S: C, 61.27; H, 3.64; N, 5,95. Found: C, 61.47; H, 3.84; N, 5.67. Example 236 2-f3.4-Difluorophenvn-5-[4-fmethvlsulfonvnphenyl]-4-vinyl-3(2H pyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting vinyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 85 mg, 31.8%). 1 H NMR (300 MHz, DMSO- dβ) δ 2.15 (s, 3H), δ 3.3 (s, 3H), 5.7 (dd, 1 H), 6.4 (dd, 1 H), 6.7 (dd, 1 H) 7.01 (m, 2H), 7.5 (m, 1 H), 7.65 (m, 1 H), 7.8 (m, 3H), 8.1 (s, 3H). MS (DCI-NH3) m/z 380 (M+H)+, 406 (M+NH4)+. Example 237 2-f3.4-Difluorophenvn-4-(2-thienvn-5-[4-(methylsulfonvhphenyll-3f2H pyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting 2-thienylmagnesium bromide in place of cyclohexylmagnesium chloride (yield: 66 mg, 28%). M.p. 180-191 °C 1 H NMR (300 MHz, DMSO-d6) δ 3.3 (s, 3H), 6.95 (m, 2H), 7.55 (m, 1 H), 7.7 (m, 5H), 7.85 (m, 1 H), 8.03 (d, J = 9 Hz, 2H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 445 (M+H)+, 462 (M+NH4)+. Anal. calc. for C21 H14F2N2O3S2: C, 56.75; H, 3.17; N, 6.30. Found: C, 56.92, H. 3.92, N, 5.79. Example 238 2-(3.4-Difluorophsnyl)-4-(1 -propvnyl)-5-[4-(methylsulfonynphenyl]-3(2H .- pyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting methylacetylenemagnesium bromide in place of cyclohexylmagnesium chloride (yield: 65 mg, 24%) . M.p. 149-150 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.1 (s, 3H), 3.3 (s, 3H), 7.51 (m, 1 H), 7.65 (m, 1 H), 7.8 (m, 1 H), 8.1 (m, 4H) ; 8.3 (s, 1 H). MS (DCI-NH3) m/z 463M+H)+, 480 (M+NH4)+. Anal, calc. for C20H14F2N2O3SO.25 H2O: C, 50.94; H, 3.52; N, 7.00. Found: C, 59.49; H, 3.63; N, 6.34. Example 239 2-.3.4-Difluorophenyl)-4-i*-butvl-5-y4-rmethylsulfonvnphenvη-3f2HVpyridazinon9 The title compound was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- py dazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting t-butylmagnesium bromide in place of cyclohexylmagnesium chloride (yield: 60 mg, 24%). M.p. 158-161 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.21 , (s, OH), 3.3 (s, 3H), 7.51 (m, 1 H), 7.45 (m, 1 H), 7.75 (m, 4H), 8.02 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 419 (M+H)+, 436 (M+NH4)+. Anal. calc. for C-21 H20F2N2O3S: C, 60.27; H, 4.82; N, 6.60. Found: C, 60.15; H, 5.10; N, 6.39 Example 240 2-(2.2.2-Trifluoroethyl)-4-cyclohexvl-5-f4-(mθthylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 228, starting with 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone, prepared in Example 193E, in place of 2-(4-fluorophenyl)-4-methoxy- 5-[4-(methylthio)phenyl]-3(2H)-pyridazinone, (yield: 120 mg, 53%). M.p. 215-218 °C. 1 H NMR (300 MHz, CDCI3) δ 1.1 (tt, J = 9 Hz, J = 4.5 Hz, 2H), 1.25 (tt, J = 9 Hz, 4.5 Hz, 1 H), 1.49 (d, J = 12 Hz, 2H), 1.63 (d, J = 12 Hz, 1 H), 1.75 (dt, J = 12 Hz, 3 Hz, 2H), 2.21 (qd, J = 9 Hz, 4.5 Hz, 2H), 2.51 (tt, J = 12 Hz, 3 Hz, 1 H), 3.17 (s, 3H), 4.83 (q, J = 12 Hz, 2H), 7.49 (d, J = 9 Hz, 2H), 7.6 (s, 1 H), 8.09 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 415 (M+H)+. Anal. calc. for C-|gH2l F3N2θ3S: C, 55.06; H, 5.1 ; N, 6.75. Found: C, 55.08; H, 5.10; N, 6.70. Example 241 2-(3-Chlorophenyl)-4-(3-fluorobθnzvn-5-r4-fmθthvlsulfonvnphenyl]-3(2H)- pvridazinone 2-(3-Chlorophenyl)-4-(3-fluorobenzyl)-5-[4-(methylthio)phenyl]-3(2H)- pyhdazinone was prepared according to the method of Example 228, starting with 2-(3-chlorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone, prepared in Example 331 , and substituting 3-fluorobenzylmagnesium chloride in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 180 mg, 55%). M.p. 142-143 °C. 1 H NMR (300 MHz, CDCI3) δ 3.14 (s, 3H), 3.98 (s, 2H), 6.75 (br d, J = 9 Hz, 1 H), 6.82 (br d, J = 9 Hz, 1 H), 6.88 (br t, J = 9 Hz, 1 H), 7.15-7.23 (m, 1 H), 7.37-7.47 (m, 2H), 7.54 (d, J = 9 Hz, 2H), 7.63 (dt, J = 9 Hz, 2 Hz, 1 H), 7.75 (t, J = 2 Hz, 1 H), 7.82 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 469 (M+H)+, 486 (M+NH4)+. Anal. calc. for C24H18CIF2N2O3SO.5 H2O: C, 60.38; H, 3.88; N, 5.87. Found: C, 60.62; H, 3.80; N, 5.82. Example 242 2-(4-Fluorophenvπ-4-(3-fluorobenzvn-5-[4-(methylsulfonvnphenyl]-3f2H pvridazinone 2-(4-Fluorophenyl)-4-(3-fluorobenzyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone was prepared according to the method of Example 228, starting with 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone, prepared in Example 194C, and substituting 3-fluorobenzylmagnesium chloride in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide compound was oxidized according to the method of Example 10, to provide the title compound (yield: 450 mg, 66.8%). M.p. 176-178 °C. 1 H NMR (300 MHz, CDCI3) δ 3.14 (s, 3H), 3.05 (s, 2H), 6.75 (br d, J = 9 Hz, 1 H), 6.82 (br d, J = 9 Hz, 1 H), 6.88 (br t, J = 9 Hz, 1 H), 7.14-7.23 (m, 3H), 7.54 (d, J = 9 Hz, 2H), 7.67 (dd, J = 9 Hz, 6 Hz, 2H), 7.81 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 516 (M+NH4) + - Anal. calc. for C24H1 gF2N2θ5S-H2θ: C, 61.28; H, 4.04; N, 5.96. Found: C, 61.24; H, 4.09; N, 5.77. Example 243 2-(3.4-Difluorophenyl)-4-(3-fluorobenzyl)-5-[4-(methylsulfonyliphsnyl]-3(2H pyridazinone 2-(3,4-Difluorophenyl)-4-(3-fluorobenzyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone was prepared according to the method of Example 228, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone prepared in Example 206E, and substituting 3-fluorobenzylmagnesium chloride in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 390 mg, 68%). M.p. 161 -163 °C. 1 H NMR (300 MHz, CDCI3) δ 3.14 (s, 3H), 3.05 (s, 2H), 6.74 (br d, J = 9 Hz, 1 H), 6.82 (br d, J = 9 Hz, 1 H), 6.89 (br t, J = 9 Hz, 1 H), 7.15-7.33 (m, 2H), 7.48-7.57 (m, 1 H), 7.53 (d, J = 9 Hz, 2H), 7.59-7.67 (m, 1 H), 7.83 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 471 (M+H)+, 488 (M+NH4)+. Anal. calc. for C24H17F3N2O3SO.5 H2O: C, 60.13; H, 3.65; N, 5.85. Found: C, 60.08; H, 3.81 ; N, 5.54. Example 244 -(3-ChloroDhenyl.-4-f4-fluoro-3-methylphenyl)-5-r4-.methylsulfonvnphenyl]-3.2HV pyridazinone 2-(3-Chiorophenyl)-4-(4-fluoro-3-methylphenyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone was prepared according to the method of Example 228, starting with 2-(3-chlorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 207B, and substituting 4-fluoro-3- methylphenylmagnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 620 mg, 57%). M.p. 228-230 °C. 1 H NMR (300 MHz, CDCI3) δ 2.20 (s, 3H), 3.06 (s, 3H), 6.83-6.93 (m, 2H), 7.19 (br d, J = 9 Hz, 1 H), 7.37-7.47 (m, 2H), 7.40 (d, J = 9 Hz, 2H), 7.65 (dt, J = 7 Hz, 3 Hz, 1 H), 7.68 (t, J = 3 Hz, 1 H), 7.91 (d, J = 9 Hz, 2H), 7.98 (s, 1 H). MS (DCI-NH3) m/z 469 (M+H)+, 486 (M+NH4)+. Anal. calc. for C24H18CIFN2O3S: C, 61.54; H, 3.85; N, 5.99. Found: C, 61.39; H, 3.84; N, 5.82. Example 245 2-(4-Fluorophenvl)-4-(4-fluoro-3-methylphBnyl)-5-f4-fmethvlsulfonyl)phenvπ-3f2H)- pyridazinone 2-(4-Fluorophenyl)-4-(4-fluoro-3-methylphenyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyhdazinone was prepared according to the method of Example 228, starting with 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 194C, and substituting 4-fluoro-3-methyl- phenylmagnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 590 mg, 74.4%). M.p. 245-247 °C. 1 H NMR (300 MHz, CDCI3) δ 2.01 (s, 3H), 3.07 (s, 3H), 6.87 (m, 2H), 7.21 (m, 3H), 7.41 (d, J = 9 Hz, 2H), 7.68 (m, 2H), 7.92 (d, J = 9 Hz, 2H), 7.97 (s, 1 H). MS (DCI-NH3) m/z 453 (M+H)+, 470 (M+NH4)+. Anal. calc. for C24H-| 8F2N2θ3S-0.5 H2O: C, 62.47; H, 3.90; N, 6.08. Found: C, 62.11 ; H, 4.11 ; N, 5.81. Example 246 2-(3-Chloro-4-fluorophenvπ-4-cvclohexyl-5-[4-(methylsijlfonvnphenyl]-3(2HV pvridazinone. 246A. 2-f3-Chloro-4-fluorophenylV4.5-dibromo-3f2HVpyridazinone. The title compound is prepared according to the method of Example 194A, substituting 3-chloro-4-fluorophenyl hydrazine-HCI in place of 4-fluorophenyl hydrazine-HCI (yield: 9.1 g, 9%). 1 H NMR (300 MHz, CDCI3) 7.22 (d, J = 9 Hz, 1 H), 7.53-7.58 (m, 1 H), 7.73 (dd, J = 9 Hz, 3 Hz, 1 H), 7.94 (s, 1 H). MS (DCI-NH3) m/z 383 (M+H)+, 400 (M+NH4)+ 246B. 2-.3-Chloro-4-fluorophenyl)-4-methoxy-5-bromo-3.2H)-pyridazinonB. The title compound is prepared according to the method of Example 194B, substituting 2-(3-chloro-4-fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone in place of 2-(4-fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (yield: 5.6 g, 84%). 1 H NMR (300 MHz, CDCI3) 4.32 (s, 3H), 7.22-7.30 (m, 1 H), 7.45-7.55 (m, 1 H), 7.64-7.74 (m, 1 H), 7.94 (d, J = 9 Hz, 1 H). MS (DCI-NH3) m/z 335 (M+H)+, 352 (M+NH4)+. 246C. 2-^3-Chloro-4-fluorophenvn-4-methoxy-5-[4-fmethylthio^phenyl]-3(2HV pyridazipope. The title compound is prepared according to the method of Example 6 starting with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-bromo-3(2H)-pyridazinone in place of 2-benzyl-5-methoxy-4-bromo-3(2H)-pyridazinone and substituting 3- methyl-4-(methylthio)benzeneboronic acid in place of 4-fluorobenzeneboronic acid (yield: 3.2 g, 63%). 1 H NMR (300 MHz, CDCI3) δ 2.53 (s, 3H), 4.13 (s, 3H), 7.25 (t, J = 9 Hz, 1 H), 7.35 (d, J = 9 Hz, 2H), 7.52 (d, J = 9 Hz, 2H), 7.55-7.64 (m, 1 H), 7.78 (dd, J = 9 Hz, 3 Hz, 1 H), 7.93 (s, 2H). MS (DCI-NH3) m/z 377 (M+H)+, 394 (M+NH4)+. 246D. 2-(3-Chloro-4-fluorophsnyl)-4-cvclohsxvl-5-[4-(mBthylthio.phBnyl]-3(2H)- pvridazinone The title compound is prepared starting with 2-(3-chloro-4-fluorophenyl)-4- methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone in place of 2-(4- fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone by treatment of the methoxy-sulfide compound with cyclohexylmagnesium chloride according to the method of Example 228 to provide the cyclohexyl sulfide compound. 246E. 2-(3-Chloro-4-fluorophenvh-4-cvclohexyl-5-[4- methylsulfonvnphenyl]- 3 ( 2H)-pvridazinona. The methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 150 mg, 53%). M.p. 180-181 °C. 1 H NMR (300 MHz, CDCI3) δ 1.02-1.36 (m, 2H), 1.49-1.68 (m, 4H), 1.75 (br d, J = 12 Hz, 2H), 2.28 (dq, J = 12 Hz, 3 Hz, 2H), 2.57 (tt, J = 12 Hz, 3 Hz, 1 H), 3.17 (s, 3H), 7.25 (t, J = 9 Hz, 1 H), 7.53 (d, J = 9 Hz, 1 H), 7.53-7.61 (m, 2H), 7.69 (s, 1 H), 7.78 (dd, J = 9 Hz, 3 Hz, 1 H), 8.12 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 461 (M+H)+, 478 (M+NH4)+. Anal. calc. for C23H22CIFN2O3S: C, 60.01 ; H, 4.78; N, 6.09. Found: C, 59.85; H, 4.97; N, 5.79. Example 247 2-(3-Chloro-4-fluorophenvh-4-^4-fluoro-3-methylphenvπ-5-[4- (methylsulfonyl)phenyl]-3 ( 2H.-pvridazinonθ 2-(3-Chloro-4-fluorophenyl)-4-(4-fluoro-3-methylphenyl)-5-[4-(methylthio)- phenyl]-3(2H)-pyridazinone was prepared according to the method of Example 228, starting with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone, prepared in Example 246D, and substituting 4-fiuoro-3- methylphenylmagnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 118 mg, 53.7%). M.p. 207-208 °C. 1 H NMR (300 MHz, CDCI3) δ 2.21 (br s, 3H), 3.08 (s, 3H), 6.81 -6.93 (m, 2H), 7.15-7.30 (m, 2H), 7.41 (d, J = 9 Hz, 2H), 7.60-7.68 (m, 1 H), 7.85 (dd, J = 9 Hz, 3 Hz, 1 H), 7.93 (d, J = 9 Hz, 2H), 7.99 (s, 1 H). MS (DCI-NH3) m/z 487 (M+H)+, 504 (M+NH4)+. Anal. calc. for C24H17CIF2N2O3S-0.25 H2O: C, 58.75; H, 3.52; N, 5.72. Found: C, 58.74; H, 3.60; N, 5.32. Example 248 2-f3-Chloro-4-fluorophenyl.-4-benzyl-5-r4-rmethylsulfonyl»phenyl]-3(2H)- pvridazinone 2-(3-Chloro-4-fluorophenyl)-4-benzyl-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone was prepared according to the method of Example 228, starting with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 246D, and substituting benzylmagnesium chloride in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 110 mg, 38.4%). M.p. 164-166 °C. 1 H NMR (300 MHz, CDCI3) δ 3.11 (s, 3H), 3.9g (s, 2H), 7.01 -7.06 (m, 2H), 7.17-7.28 (m, 4H), 7.53 (d, J = 9 Hz, 2H), 7.59-7.66 (m, 1 H), 7.81 (s, 1 H), 7.82 (dd, J = 6 Hz, 3 Hz, 1 H), 8.09 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 473 (M+H)+, 490 (M+NH4)+. Anal. calc. for C24H18CIFN2O3S: C, 61.54; H, 3.85; N, 5.99. Found: C, 61.40; H, 3.82; N, 5.54. Example 249 2-(3-Chloro-4-fluorophθnyl)-4-(3-fluorobenzyl)-5-[4-(msthylsulfonyl)phsnyη-3.2H ) - pvridazinone 2-(3-Chloro-4-fluorophenyl)-4-(3-fluorobenzyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone was prepared according to the method of Example 228, starting with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 246D, and substituting 3-fluorobenzylmagnesium chloride in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 33 mg, 15%). M.p. 101 -103 °C. H NMR (300 MHz, CDCI3) δ 3.15 (s, 3H), 3.95 (s, 2H), 6.73 (br d, J = 9 Hz, 1 H), 6.81 (br d, J = 9 Hz, 1 H), 6.88 (br t, J = 9 Hz, 1 H), 7.15-7.28 (m, 2H), 7.51 (d, J = 9 Hz, 2H), 7.53 (ddd, J = 9 Hz, 3 Hz, 1.5 Hz, 1 H), 7.83 (dd, J = 6 Hz, 3 Hz, 1 H), 7.83 (s, 1 H), 8.10 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 487 (M+H)+, 504 (M+NH4)+. Anal. calc. for C24H17CIF2N2O3S: C, 58.75; H, 3.52; N, 5.62. Found: C, 58.50; H, 3.65; N, 5.29. Example 250 2-(4-Fluorophenyl)-4-(3-fluoro-4-methylphBnyl)-5-[4-(mBthylsulfonyl)phsnyl]-3(2H)- pyrjdazinone 2-(4-Fluorophenyl)-4-(3-fluoro-4-methylphenyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone was prepared according to the method of Example 228, starting with 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 194C, and substituting 3-fluoro-4-methyl- phenylmagnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 540 mg, 73%). M.p. 245-248 °C. 1 H NMR (300 MHz, CDCI3) δ 2.22 (br s, 3H), 3.05 (s, 3H), 6.83 (dd, J = 9 Hz, 1.5 Hz, 1 H), 6.96 (dd, J = 9 Hz, 1.5 Hz, 1 H), 7.06 (t, J = 9 Hz, 1 H), 7.18 (t, J = 9 Hz, 2H), 7.41 (d, J = 9 Hz, 2H), 7.65-7.72 (m, 2H), 7.91 (d, J = 9 Hz, 2H), 7.95 (s, 1 H). MS (DCI-NH3) m/z 452 (M+H)+, 470 (M+NH4) + . Anal. calc. for C24H18F2N2O3S: C, 63.86; H, 3.99; N, 6.21. Found: C, 63.49; H, 4,13; N, 5.98. Example 251 2-(3-Chloro-4-fluorophenvn-4-f3.5-difluoro-4-methoxvphenvn-5-[4- (methvlsulfonvhDhenvl1-3f2HVpvridazinone 2-(3-Chloro-4-fluorophenyl)-4-{3,5-difluoro-4-methoxyphenyl)-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone was prepared according to the method of Example 228, starting with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone, prepared in Example 246D, and substituting 3,5-difluoro-4- methoxyphenylmagnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 500 mg, 65.7%). M.p. 195-197 °C. 1 H NMR (300 MHz, CDCI3) δ 3.10 (s, 3H), 4.12 (s, 3H), 6.81 (br d, J = 9 Hz, 2H), 7.27 (t, J = 9 Hz, 1 H), 7.43 (d, J = 9 Hz, 2H), 7.60-7.67 (m, 1 H), 7.83 (br d, J = 9 Hz, 1 H), 7.98 (d, J = 9 Hz, 2H), 7.98 (s, 1 H). MS (DCI-NH3) m/z 487 (M+H)+, 504 (M+NH4)+ Anal. calc. for C24H16CIF3N2O3S-0.5 H2O: C, 54.44; H, 3.12; N, 5.30. Found: C, 54.50; H, 3.12; N, 5.15. Example 252 2-f3-Chloro-4-fluorophenvh-4-(3-methvlbutvn-5-[3-fluoro-4-(methvlsulfonvnphenyl]- 3(2HVpvridazinone 2-(3-Chloro-4-fluorophenyl)-4-(3-methylbutyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone was prepared according to the method of Example 228, starting with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared in Example 246D, and substituting 1 -(3-methylbutyl)- magnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 425 mg, 54.4%). M.p. 102-104 °C. 1 H NMR (300 MHz, CDCI3) δ 0.85 (d, J = 9 Hz, 6H), 1.41-1.62 (m, 1 H), 2.50-2.63 (m, 2H), 3.30 (s, 3H), 7.22-7.38 (m, 3H), 7.57-7.64 (m, 1 H), 7.72 (br s, 1 H), 7.80 (br d, J = 6 Hz, 1 H), 8.15 (t, J = 9 Hz, 1 H). MS (DCI-NH3) m/z 467 (M+H)+, 484 (M+NH4)+. Anal. calc. for C22H2I CIF2N2O3S: C, 56.65; H, 4.51 ; N, 6.01. Found: C, 56.25; H, 4.49; N, 6.06. Example 253 2-<4-Fluorophenvπ-4-(3-fluorobenzvπ-5-[4-(aminosulfonvπphenyl]-3(2HV pyridazinone The methyl sulfide intermediate from Example 242 was oxidized to the methyl sulfoxide with one equivalent of meta-chloroperoxybenzoic acid according to the procedure in Example 69B to provide the sulfinyl compound. The sulfoxide was converted to the title sulfonamide according to the method of Example 68 (yield: 120 mg, 31 %). M.p. 199-202 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 3.02 (s, 2H), 6.85 (br t, J = 9 Hz, 2H), 6.99 (br t, J = 9 Hz, 1 H), 7.26 (q, J = 7 Hz, 1 H), 7.35 (t, J = 9 Hz, 2H), 7.50 (s, 2H), 7.62-7.71 (m, 4H), 7.95 (d, J = 9 Hz, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 454 (M+H)+, 471 (M+NH4)+. Anal. calc. for C23H17F2N3O3S: C, 60.86; H, 3.75; N, 9.27. Found: C, 60.99; H, 3.76; N, 9.02. Example 254 2-(3.4-Difluorophenvπ-4-fphenylethvnyn-5-[4-(methylsulfonvhphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 232 substituting phenylethynylmagnesium bromide in place of chloride (yield: 195 mg, 61 %). M.p. 211 -213 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 7.46 (m, 5H), 7.65 (m, 2H), 8.18 (t, 4H) ; 8.4 (s, 1 H). MS (DCI-NH3) m/z 463M+H)+, 480 (M+NH4)+. Anal, calc. for C25H16F2N2O3S: C, 64.56; H, 3.49; N, 6.06. Found: C, 64.49; H, 3.68; N, 5.86. Example 255 2-.3.4-DifluorophBnyl)-4-f3.4-difluorobBnzyl)-5-[4-(mBthylsulfonyl)phBnyl]-3(2H)- pvridazinone 3,4-Difluorobenzyl bromide (0.1 ml, 0.8 mmol) in ether (10 ml) was treated with magnesium turnings (19.4 mg, 0.81 mmol) and the reaction mixture was refluxed for 1 hour. The reaction mixture was cooled and added to a solution of 2- (3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (0.25 g, 0.7 mmol) in THF (10 ml) at -78 °C. The reaction mixture was stirred at room temperature for 18 hours. Water (50 ml) was added to the reaction mixture and extracted with ethyl acetate (50 ml). The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting crude residue was purified by flash chromatography (Siθ2, eluting with 9:1 hexanes:ethyl acetate) to provide 120 mg of desired product and some starting material. The methylthio compound (120 mg, 0.3 mmol) from above in CH2CI2 (10 ml) at 0 °C, was treated with CH3CO3H (0.3 ml, 1 mmol). The reaction was complete in 2 hours. The reaction mixture was diluted with CH2CI2 and washed with saturated NaHCO3 and brine respectively. The resulting crude residue was purified by flash chromatography (Siθ2, eluting with 1 :1 hexanes:ethyl acetate) to provide the desired product (yield: 44 mg, 13%). M.p. 177-179 °C. 1 H NMR (300 MHz, DMSO-d6) δ 3.3 (s, 3H), 3.9 (s, 2H), 6.85 (m, 1 H), 7.15 (m, 1 H), 7.25 (m, 2H), 7.6 (m, 7H), 8.15 (m, 3H). MS (DCI-NH3) m/z 489 (M+H)+, 506 (M+NH4) + . Anal. calc. for C24H16F4N2O3SO.25 H2O: C, 59.01 ; H, 3.30; N, 5.74. Found: C, 58.16; H, 3.56; N, 4.51. Example 256 2-(3.4-Difluorophenyl)-4-(3-methylbutvn-5-[4-(methylsulfonvnphenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 233, starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting 1 -bromo-3-methylbutane in place of 3,4-difluorobenzyl bromide (yield: 108 mg, 48%). M.p. 55-58 °C. 1 H NMR (300 MHz, DMSO-d6) δ 0.75 (d, 6H), 1.4, (m, 3H), 2.48 (m, 2H), 3.3 (s, 3H), 7.51 (m, 1 H), 7.65 (m, 1 H), 7.75 (d, J = 9 Hz, 2H), 7.81 (m, 1 H) 8.05 (s, 1 H), 8.12 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 433 (M+H)+, 450 (M+NH4)+ Anal. calc. for C22H22F2N2O3S-0.25 H2O: C, 61.10; H, 5.13; N, 6.48. Found: C, 61.09; H, 5.23; N, 6.36. Example 257 2-(3-Chloro-4-fluorophenvn-4-f3-methylbutvn-5-[4-(methylsulfonvnphenyl1-3(2HV pyridazinone The title compound was prepared according to the method of Example 233, procedure starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone with 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[4- (methylthio)phenyl]-3(2H)-pyridazinone and substituting 1 -bromo-3-methylbutane in place of 3,4-difluorobenzyl bromide (yield: 256 mg, 88%). M.p. 55-58 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (d, 6H), 1.4, (m, 3H), 2.48 (m, 2H), 3.3 (s, 3H), 7.62 (m, 2H), 7.75 (d, 2H), 7.93 (dd, 1 H), 8.05 (s, 1 H), 8.12 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 449 (M+H)+, 466 (M+NH4)+. Anal. calc. for C-22H22FN2O3SCI-0.25 H2O: C, 58.86; H, 4.04; N, 6.24 . Found: C, 50.23; H, 5.12; N, 6.00. Example 258 2-(3.4-Difluorophenyh-4-(3-methylbutylV5-[3-fluoro-4-(methylsulfonyl)phenyl]- 3(2HVpvridazinonB The title compound was prepared according to the method of Example 233, procedure starting with 2-(3,4-difluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-(3-chloro-4-fluorophenyl)-4-methoxy-5-[3- fluoro-4-(methylthio)phenyl]-3(2H)-pyridazinone and substituting 1 -bromo-3- methylbutane in place of 3,4-difluorobenzyl bromide (yield: 100 mg, 20%) . M.p. 119-121 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (d, 6H), 1.4, (m, 3H), 2.48 (m, 2H), 3.4 (s, 3H), 7.51 (m, 1 H), 7.8 (m, 2H), 7.81 (m, 2H). MS (DCI-NH3) m/z 451 (M+H)+, 468 (M+NH4)+. Ahal. calc. for C22H21 F3N2O3S: C, 58.66; H, 4.7; N, 6.22. Example 259 2-[4-Fluoro-3-(methylthio)phenyl]-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone To a stirred solution of 2-(3,4-difluorophenyl)-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (315 mg, 0.69 mmol) in DMF (10 ml) at room temperature was treated with sodium thiomethoxide (51 mg, 0.7 mmol). The reaction mixture was stirred at room temperature for 3.15 hours. The reaction was poured into water (75 ml) and extracted into ethyl acetate. The organic layer was washed two times with brine, dried over MgSO4, and concentrated in vacuo. The resulting crude residue was purified using flash chromatography (Siθ2, eluting with (15:1 CH2Cl2 * diethyl ether) to provide the desired product (yield: 30 mg, 8%) . M.p. 105-107 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.55 (s, 3H), 3.23 (s, 3H), δ 7.15 (m, 2H), 7.3 (m, 2H), 7.55 (m, 5H), 7.0 (d, 2H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 485 (M+H)+, 502 (M+NH4) + - Anal. calc. for C24H18F2N2O3S2: C, 59.49; H, 3.74; N, 5.78. Example 260 2-Benzyl-4-(4-fliJorophenvh-5-[4-(trifluoromethylsulfonvhphenyl]-3(2H pyridazinone: 260A. 2-Benzyl-4-^4-fluorophenvh-5-[4-(methylsulfinvnphenyl]-3(2H pyridazinone The title compound was prepared starting with 2-benzyl-4-(4-fluorophenyl)- 5-[4-(methylthio)phenyl]-3(2H)-pyridazinone and oxidizing the sulfide according to the procedure in example 69B. 260B. Bis(4-(5-(2-benzvl-4-f4-fluorophBnvl)-3r2H)-pyridazinonθ)phθnyl.disulfidB: A heterogeneous solution of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methyl- sulfinyl)phenyl]-3(2H)-pyridazinone (1.0 g, 2.30 mmol) in trifluoroacetic anhydride (10 mL, 70.8 mmol) was rapidly stirred at reflux for 2 hours with a bath temperature of 40-43 °C. The reaction solution was cooled to 23 °C, concentrated in vacuo, and azeotroped with toluene (2 x 5-7 mL). The resultant yellow/orange oil was cooled to 0 °C, and methanol/triethylamine (1 :1 , 6 mL) was slowly added, along the interior wall of the reaction vessel with rapid stirring. The bright red-orange solution was stirred for 10 minutes at 0 °C, the cooling bath removed, and the reaction mixture stirred an additional 1.5 hours warming to 23 °C. The mixture was cooled back to 0 °C, and a saturated NH4CI solution (200 mL) slowly added followed by enough aqueous 1 M HCl to adjust the solution to pH 1-2. The cooling bath was removed and the solution stirred overnight. The mixture was extracted with ethyl acetate. The ethyl acetate solution was washed with water and brine, and concentrated in vacuo. The resultant yellow/brown oil (0.89 g) was a mixture of predominantly the mono-sulfide and desired di-sulfide. Subsequent rapid stirring of a portion of the crude reaction mixture (360 mg) in benzene (100 mL) with I2 (648 mg, 2.55 mmol) at 23 °C for 30 minutes completed the conversion of the mono-sulfide to the di- sulfide. (Chem. Pharm. Bull., 1992, 40, 2842) The mixture was treated with a 0.1 M Na2S2θ3 solution to consume the excess I2. This solution was extracted with ethyl acetate, and the ethyl acetate layers dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in CH2Cl2/hexanes and concentrated in vacuo to provide the of product (yield: 347 mg, 90% for partial conversion). 1 H NMR (300 MHz, CDCI3) δ 5.38 (s, 4H), 6.91 (dd, J = 8.8, 8.8 Hz, 4H), 7.02 (d, J = 8.7 Hz, 4H), 7.11 -7.20 (m, 4H), 7.28-7.39 (m, 10H), 7.54 (dd, J = 6.9, 1.5 Hz, 4H), 7.83 (s, 2H). 260C. 2-Benzyl-4-f4-fluorophBnylV5-f4-.trifluoromBthylthio ) phθnyl]-3(2H)- pvridazinone: A rapidly stirred mixture of bis[4-{5-[2-benzyl-4-(4-fluorophenyl)-3(2H)- pyridazinone]}-phenyl]-disulfide (140 mg, 0.181 mmol), potassium trifluoroacetate (55 mg, 0.361 mmol), and sulfolane (1.5 mL) was immersed in a 180 °C pre-heated oil bath. The oil bath was heated to increase the temperature to 210 °C, and the reaction flask was promptly removed from the oil bath after 10 minutes from the point of first immersion. During the course of the reaction, the mixture changed from colorless and heterogeneous to deep, blood red and homogeneous. After cooling to 23 °C, the mixture was diluted with ethyl acetate and washed with aqueous 1 M HCl, water, and brine. The ethyl acetate solution was dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes 1 :4) to provide the product (yield: 17 mg, 41 %). {Tetrahedron Lett.., 1996, 37, 9057) " Η NMR (300 MHz, CDCI3) δ 5.41 (s, 2H), 6.94 (dd, J = 8.2, 8.2 Hz, 2H), 7.11 -7.20 (m, 4H), 7.31-7.42 (m, 3H), 7.52-7.61 (m, 4H), 7.86 (s, 1 H). MS (APCI+) m/z 457 (M+H)+ and m/z 474 (M+NH4)+. 260D. 2-Benzyl-4-(4-fluorophenvn-5-[4-rtrifluoromethylsulfonvnphenyl]-3f2H pvridazinone: A solution of 2-benzyl-4-(4-fluorophenyl)-5-[4-(thfluoromethylthio)phenyl]- 3(2H)-pyridazinone (100 mg, 0.219 mmol), 3-chloroperoxybenzoic acid (380 mg, 1.3 mmol, 57-86%), and methylene chloride (5 mL) was brought to reflux at a bath temperature of 55 °C. After 1.75 hours, 3.5 hours, 5 hours, and 6 hours, the reaction was not complete and additional 3-chloroperoxybenzoic acid (380 mg, 1.3 mmol, 57-86%) was added each time. With the reaction completed after 7.75 hours, the mixture was cooled to 23 °C and concentrated in vacuo. The residue was diluted with ethyl acetate and carefully shaken with a NaHSO3 solution, 3 times, for several minutes to consume the excess 3-chioroperoxybenzoic acid. The ethyl acetate solution was subsequently washed with a saturated Na2CO3 solution (3x), water, and brine and dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/methylene chloride/hexanes 1 :2:7) to provide of product (yield: 93 mg, 87%). (J. Med. Chem., 1990, 33, 2569) M.p. 80-115 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 5.36 (s, 2H), 7.1 1 (dd, J = 9.0, 0.0 Hz, 2H), 7.18-7.26 (m, 2H), 7.29-7.46 (m, 5H), 7.66 (d, J = 8.7 Hz, 2H), 8.10 (d, J = 8.7 Hz, 2H), 8.18 (s, 1 H). MS (APCI+) m/z 489 (M+H)+ and m/z 506 (M+NH4) + . Anal. calc. for C24H16F4N2O3S: C, 59.02; H, 3.30; N, 5.74. Found: C, 59.30; H, 3.48; N, 5.59. Example 261 2-(2.2.2-Trifluoroethvn-4-f2.2-dimBthylpropoxyV5-[4-(mθthylsulfonyl)phsnyl]-3.2H pvridazinone 2-(2,2,2-Trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (150 mg, 0.41 mmol), prepared in Example 1 Θ3E, and neopentyl alcohol (43 mg, 0.49 mmol) were dissolved in DMF (2 mL) and NaH (25 mg, 0.62 mmol, 60% in mineral oil) was added with shaking and left overnight. The reaction mixture was carefully quenched with saturated NH4CI solution, diluted with ethyl acetate and extracted with 1 N HCl, twice, then water, 3 times, and then dried over MgSO4. After filtration of the drying agent and concentration of the filtrate in vacuo, the residue was purified by chromatography on silica gel (Biotage 40S) eluted with 2:1 hexanes-ethyl acetate. The product fractions were combined and evaporated to provide the title compound (yield: 137 mg, 76%). M.p. 145-146 °C. 1 H NMR (300 MHz, DMSO-d6) δ 0.76 (s, 9H), 3.28 (s, 3H), 4.06 (s, 2H), 5.02 (q, J = 9 Hz, 2H), 7.88 (d, J = 8 Hz, 2H), 8.04 (d, J = 8 Hz, 2H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 419 (M+H)+, 436 (M+NH4)+. Anal. calc. for C18H21 F3N2O4S: C, 51.67; H, 5.06; N, 6.69. Found: C, 51.47; H, 5.12; N, 6.48. Example 262 2-.2.2.2-Trifluoroethyn-4-.4-mBthoxvphenoxv)-5-[4-(mBthylsulfonvl)phsnvl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 261 , substituting 4-methoxyphenol in place of neopentyl alcohol (yield: 130 mg, 54%). M.p. 194-195 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.24 (s, 3H), 3.26 (s, 3H), 5.00 (q, J = 9 Hz, 2H), 6.88 (d, J = 8 Hz, 2H), 7.09 (d, J = 8 Hz, 2H), 7.37 (d, J = 8 Hz, 2H), 8.03 (d, J = 8 Hz, 2H), 8.33 (s, 1 H). MS (ESI-) m/z 439 (M-H) ' . Anal. calc. for C-| gH-| 7F3N2θ4S: C, 54.7g; H, 3.91 ; N, 6.39. Found: C, 55.04; H, 4.00; N, 6.1 1. Example 263 2-f2.2.2-Trifluoroethvh-4-f2-fluoro-5-trifluoromethylphenoxy)-5-[4-(methylsulfonylV phenyl]-3(2H)-pyridazinope The title compound was prepared according to the method of Example 261 , substituting 2-fluoro-5-trifluoromethylphenol in place of neopentyl alcohol (yield: 155 mg, 8θ%). M.p. 133-135 °C. H NMR (300 MHz, DMSO-dβ) δ 3.28 (s, 3H), 5.03 (q, J = 0 Hz, 2H), 7.10-7.53 (m, 2H), 7.72 (dd, J = 1 Hz, 7 Hz 1 H), 7.92 (d, J = 8 Hz, 2H), 8.07 (d, J = 8 Hz, 2H), 8.38 (s, 1 H). MS (DCI-NH3) m/z 528 (M+NH4 Anal. calc. for C20H13F7N2O4S: C, 47.66; H, 3.09; N, 5.05. Found: C, 47.68; H, 2.95; N, 5.16. Example 264 2-(2.2.2-Thfluoroethvπ-4-(4-cvanophenoxy)-5-[4- methylsulfonvπphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 261 , substituting 4-cyanophenol in place of neopentyl alcohol (yield: 109 mg, 71 %). M.p. 179-181 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.26 (s, 3H), 5.02 (q, J = 9 Hz, 2H), 7.25 (d, J = 9 Hz, 2H), 7.81 (d, J = 9 Hz, 2H), 7.86 (d, J = 8 Hz, 2H), 8.03 (d, J = 8 Hz, 2H), 8.37 (s, 1 H). MS (DCI-NH3) m/z 467 (M+NH4 Anal. calc. for C20H14F3N3O4S: C, 53.45; H, 3.14; N, 9.35. Found: C, 53.19; H, 3.01 ; N, 9.09. Example 265 2-f2.2.2-Trifluoroethyl.-4-f3-pyridyloxy)-5-[4-(methylsulfonvhphenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 261 , substituting 3-hydroxypyridine in place of neopentyl alcohol (yield: 120 mg, 69%). M.p. 191 -193 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.26 (s, 3H), 5.01 (q, J = 9 Hz, 2H), 7.36 (dd, J = 3 Hz, 8 Hz, 1 H), 7.55 (ddd, J = 1 Hz, 3 Hz, 8 Hz, 1 H), 7.88 (d, J = 8 Hz, 2H), 8.04 (d, J = 8 Hz, 2H), 8.31 (dd, J = 1 Hz, 5 Hz, 1 H), 8.36 (s, 1 H), 8.38 (d, J = 3 Hz, 1 H). MS (DCI-NH3) m/z 426 (M+H) + , 443 (M+NH4)+. Anal. calc. for C18H14F3N3O4S: C, 50.82; H, 3.32; N, 0.88. Found: C, 50.95; H, 3.57; N, 9.71. Example 266 2-f2.2.2-Trifluoroethvh-4-f4-n-propylphenoxy)-5-[4-(methylsulfonyl.phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 261 , substituting 4-(n-propyl)phenol in place of neopentyl alcohol (yield: 147 mg, 77%). M.p. 152-153 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.87 (t, J = 7 Hz, 3H), 1.54 (h, J = 7 Hz, 2H), 3.25 (s, 3H), 5.00 (q, J = 9 Hz, 2H), 6.88 (d, J = 9 Hz, 2H), 7.09 (d, J = 9 Hz, 2H), 7.87 (d, J = 8 Hz, 2H), 8.02 (d, J = 8 Hz, 2H), 8.32 (s, 1 H). MS (DCI-NH3) m/z 484 (M+H)+. Anal. calc. for C22H2I F3N2O4S: C, 56.33; H, 4.54; N, 6.01. Found: C, 56.23; H, 4.75; N, 5.79. Example 267 2-(2.2.2-Trifluoroethyl)-4-f4-fmBthylsulfonvπphenoxy]-5-f4-. mathylsulfonyl -phenyll- 3(2H)-pyridazinone The title compound was prepared according to the method of Example 261 , substituting 4-(methylsulfonyl)phenol in place of neopentyl alcohol (yield: 115 mg, 56%). M.p. 212-213 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.21 (s, 3H), 3.27 (s, 3H), 5.03 (q, J = 9 Hz, 2H), 7.31 (d, J = 9 Hz, 2H), 7.83-7.89 (m, 4H), 8.04 (d, J = 8 Hz, 2H), 8.40 (s, 1 H). MS (DCI-NH3) m/z 520 (M+NH4)+. Anal. calc. for C20H17F3N2O6S2: C, 47.81 ; H, 3.41 ; N, 5.58. Found: C, 47.92; H, 3.18; N, 5.52. Example 268 2-(2.2.2-Trifluoroethvn-4-f4-phenylphenoxyV5-[4-(mBthylsulfonvhphenyl]-3f2HV pvridazinone The title compound was prepared according to the method of Example 261 , substituting 4-phenylphenol in place of neopentyl alcohol (yield: 105 mg, 51 %). M.p. 163-165 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.26 (s, 3H), 5.02 (q, J = 9 Hz, 2H), 7.10 (d, J = 8 Hz, 2H), 7.33 (br t, J = 7 Hz, 1 H), 7.44 (t, J = 7 Hz, 2H), 7.57-7.63 (m, 4H), 7.92 (d, J = 8 Hz, 2H), 8.04 (d, J = 8 Hz, 2H), 8.37 (s, 1 H). MS (DCI-NH3) m/z 518 (M+NH4)+. Anal. calc. for C25H19F3N2O4S: C, 60.00; H, 3.83; N, 5.60. Found: C, 60.18; H, 3.66; N, 5.52. Example 269 2-(2.2.2-Trifluoroethyl)-4-[2-(mBthylthio)Bthoxy]-5-[4-(mBthylsulfonyl)phBnyl]-3f2H pvridazinone The title compound was prepared according to the method of Example 261 , substituting 2-(methylthio)ethanol in place of neopentyl alcohol (yield: 105 mg, 61 %). M.p. 103-105 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.01 (s, 3H), 2.72 (t, J = 7 Hz, 2H), 3.20 (s, 3H), 4.50 (t, J = 7 Hz, 2H), 5.03 (q, J = 9 Hz, 2H), 7.91 (d, J = 8 Hz, 2H), 8.04 (d, J = 8 Hz, 2H), 8.15 (s, 1 H). MS (DCI-NH3) m/z 423 (M+H)+, 440 (M+NH4)+. Anal. calc. for C16H17F3N2O4S2: C, 45.40; H, 4.06; N, 6.33. Found: C, 45.83; H, 4.11 ; N, 6.42. Example 270 2-f2.2.2-Trifluoroethvn-4-(phBnvlmethoxvV5-[4-(methvlRulfonvnphenvl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 261 , substituting benzyl alcohol in place of neopentyl alcohol (yield: 137 mg, 76%). M.p. 121 -123 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.28 (s, 3H), 5.06 (q, J = 9 Hz, 2H), 5.48 (s, 2H), 7.20-7.25 (m, 2H), 7.27-7.81 (m, 3H), 7.76 (d, J = 8 Hz, 2H), 7.98 (d, J = 8 Hz, 2H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 456 (M+H)+. Anal. calc. for C20H17F3N2O4S: C, 54,79; H, 3.91 ; N, 6.39. Found: C, 55.10; H, 3.91 ; N, 6.13. Example 271 2-f2.2.2-Trifluoroethvn-4-(2-furylmethoxy 5-[4-(methylsulfonvπphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 261 , substituting 2-(hydroxymethyl)furan in place of neopentyl alcohol (yield: 101 mg, 58%). M.p. 113-115 °C. 1 H NMR (300 MHz, DMSO-dβ) 3.28 (s, 3H), 5.07 (q, J = 9 Hz, 2H), 5.52 (s, 2H), 6.41 (dd, J = 2 Hz, 3 Hz, 1 H), 6.45 (d, J = 4 Hz, 1 H), 7.62 (d, J = 2 Hz, 1 H), 7.69 (d, J = 8 Hz, 2H), 7.97 (d, J = 8 Hz, 2H), 8.13 (s, 1 H). MS (DCI- NH3) m/z 446 (M+NH4)+. Anal. calc. for C18H15F3N2O5S: C, 50.66; H, 3.80; N, 6.21. Found: C, 51.02; H, 3.71 ; N, 6.23. Example 272 2-(2.2.2-Trifluoroethvn-4-[2-(3.4-dimethoxyphenvnethoxy^-5-[4-(methylsulfonvn- phenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 261 , substituting 2-(3,4-dimethoxyphenyl)ethanol in place of neopentyl alcohol (yield: 118 mg, 56%). M.p. 133-134 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.82 (t, J = 7 Hz, 2H), 3.28 (s, 3H), 3.63 (s, 3H), 3.70 (s, 3H), 4.68 (t, J = 7 Hz, 2H), 5.01 (q, J = 9 Hz, 2H), 6.61 (dd, J = 2 Hz, 8 Hz, 1 H), 6.74 (d, J = 2 Hz, 1 H), 6.77 (d, J = 8 Hz, 1 H), 7.74 (d, J = 8 Hz, 2H), 7.93 (d, J = 8 Hz, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 530 (M+NH4)+. Anal. calc. for C23H23F3N2O6S: C, 53.90; H, 4.52; N, 5.47. Found: C, 53.87; H, 4.48; N, 5.45. Example 273 2-(2.2.2-Trifluoroethyl)-4-r2-f4-morpholino)ethoxy)]-5-[4-(mBthylsulfonvnphBnyl]- 3(2H)-pyridazinonB The title compound was prepared according to the method of Example 261 , substituting 4-(2-hydroxyethyl)morpholine in place of neopentyl alcohol (yield: 111 mg, 59%). M.p. 147-148 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.23 (m, 4H), 2.46 (t, J = 5 Hz, 2H), 3.28 (s, 3H), 3.40 (m, 4H), 4.60 (t, J = 5 Hz, 2H), 5.02 (q, J = 8 Hz, 2H), 7.96 (d, J = 8 Hz, 2H), 8.03 (d, J = 8 Hz, 2H), 8.17 (s, 1 H). MS (DCI-NH3) m/z 462 (M+H)+. Anal. calc. for C19H22F3N3O5S: C, 49.45; H, 4.81 ; N, 9.11. Found: C, 49.50; H, 4.80; N, 8.88. Example 274 2-f2.2.2-Trifluoroethvπ-4-[2-(1 -piperidinvhethoxy)]-5-[4-(methylsulfonvnphenyl]- 3(2H)-pyridazinonB The title compound was prepared according to the method of Example 261 , substituting 1 -(2-hydroxyethyl)piperidine in place of neopentyl alcohol (yield: 103 mg, 55%). M.p. 117-118 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.30 (br s, 6H), 2.20 (br s, 4H), 2.41 (t, J = 4 Hz, 2H), 3.28 (s, 3H), 4.60 (t, J = 5 Hz, 2H), 5.02 (q, J = 0 Hz, 2H), 7.97 (d, J = 8 Hz, 2H), 8.03 (d, J = 8 Hz, 2H), 8.15 (s, 1 H). MS (DCI-NH3) m/z 460 (M+H)+. Anal. calc. for C20H24F3N3O4S: C, 52.28; H, 5.26; N, 9.15. Found: C, 52.22; H, 5.08; N, 8.94. Example 275 2- ( 2.2.2-Trifluoroethyn-4-r4- ( carboxamido^phenoxy^-5-[4-(methylsulfonvnphenyl]- 3(2H ,-pyridazinone The title compound was prepared according to the method of Example 261 , substituting 4-hydroxybenzamide in place of neopentyl alcohol (yield: 50 mg, 26%). M.p. > 250 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.26 (s, 3H), 5.02 (q, J = 8 Hz, 2H), 7.08 (d, J = 9 Hz, 2H), 7.30 (s, 1 H), 7.82 (d, J = 9 Hz, 2H), 7.88 (d, J = 8 Hz, 2H), 7.02 (s, 1 H), 8.03 (d, J = 8 Hz, 2H), 8.47 (s, 1 H). MS (DCI-NH3) m/z 468 (M+H)+, 485 (M+NH4) + . Anal. calc. for C20H16F3N3O5S: C, 51.39; H, 3.45; N, 8.99. Found: C, 51.31 ; H, 3.28; N, 8.77. Example 276 2-r2.2.2-Trifluoroethyl)-4- -indanvloxy)-5-f4-fmθthvlsulfonvnphenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 261 , substituting 1 -indanol in place of neopentyl alcohol (yield: 84 mg, 44%). M.p. 113- 114 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.07-2.14 (m, 1 H), 2.22-2.35 (m, 1 H), 2.73 (dd, J = 5 Hz, 7 Hz, 2H), 3.24 (s, 3H), 5.00-5.22 (m, 2H), 6.48 (dd, J = 2 Hz, 6 Hz, 1 H), 7.12-7.24 (m, 2H), 7.21-7.28 (m, 2H), 7.44 (d, J = 8 Hz, 2H), 7.87 (d, J = 8 Hz, 2H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 482 (M+NH4)+. Anal. calc. for C22H19F3N2O4S: C, 57.10; H, 4.48; N, 5.80. Found: C, 57.36; H, 4.30; N, 5.78. Example 277 2-(2.2.2-Trifluoroethyl)-4-r4-(acBtamido)phsnoxy)]-5-[4-(mBthvlsulfonyl)phenyl]- 3(2H)-pvridazinone The title compound was prepared according to the method of Example 261 , substituting 4-acetamidophenol in place of neopentyl alcohol (yield: 45 mg, 23%). M.p. 215-216 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.02 (s, 3H), 3.26 (s, 3H), 5.02 (q, J = 8 Hz, 2H), 6.61 -6.65 (m, 1 H), 7.17-7.20 (m, 2H), 7.34 (br s, 1 H), 7.88 (d, J = 9 Hz, 2H), 8.03 (d, J = 8 Hz, 2H), 8.36 (s, 1 H), 9.97 (s, 1 H). MS (DCI-NH3) m/z 499 (M+NH4)+- Anal. calc. for C-21 H18F3N3O5S: C, 52.39; H, 3.77; N, 8.73. Found: C, 52.57; H, 4.02; N, 8.37. Example 278 2-(2.2.2-Trifluoroethyl)-4-f2-mθthylpropoxy)-5-[4-(mBthylsulfonyl)phenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 261 , substituting 2-methylpropanol in place of neopentyl alcohol (yield: 111 mg, 50%). M.p. 108-110 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.77 (d, J = 6.4 Hz, 6H), 1.52 (sept, J = 6.4 Hz, 1 H), 3.28 (s, 3H), 4.17 (d, J = 6 Hz, 2H), 5.02 (q, J = 9 Hz, 2H), 7.88 (d, J = 9 Hz, 2H), 8.04 (d, J = 9 Hz, 2H), 8.14 (s, 1 H). MS (DCI-NH3) m/z 405 (M+H)+, 422 (M+NH4) + . Anal. calc. for C17H19F3N2O4S: C, 50.49; H, 4.74; N, 6.93. Found: C, 50.69; H, 4.89; N, 6.75. Example 279 2- ( 2.2.2-ThfluoroethylV4- ( 1-methylcvclopropylmethoxyV5-[4-fmethylsulfonvh- phenvl]-3 2 -pvridazinone The title compound was prepared according to the method of Example 261 , substituting 1 -methylcyclopropanemethanol in place of neopentyl alcohol (yield: 360 mg, 75.5%). M.p. 08-99 °C. 1 H NMR (300 MHz, CDCI3) δ 0.35 (dt, J = 40 Hz, 5 Hz, 4H), 0.91 (s, 3H), 3.11 (s, 3H), 4.32 (s, 2H), 4.82 (q, J = 8.5 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.84 (s, 1 H), 8.06 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 417 (M+H)+, m/z 434 (M+NH4)+. Anal. calc. for C-| 8H-| F3N2θ4S: C, 51.92; H, 4.60; N, 6.73. Found: C, 51.87; H, 4.72; N, 6.69. Example 280 2-(2.2.2-Trifluoroethvh-4-(3.3-dimBthylbutoxyV5-f4-(mBthylsulfonyl.phBnyl]-3f2H)- pyridazinone The title compound was prepared according to the method of Example 261 , substituting 3,3-dimethyl-1 -butanol in place of neopentyl alcohol (yield: 270 mg, 67.4%). M.p. 83-85 °C. 1 H NMR (300 MHz, CDCI3) δ 0.88 (s, OH), 1.56 (t, J = 8 Hz, 2H), 4.60 (t, J = 8 Hz, 2H), 4.83 (q, J = 8.5 Hz, 2H), 7.73 (d, J = 8.5 Hz, 2H), 7.81 (s, 1 H), 8.05 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 433 (M+H)+, m/z 450 (M+NH4)+. Anal. calc. for C-| gH23F3N2θ4S: C, 52.77; H, 5.36; N, 6.48. Found: C, 52.g5; H, 5.2g; N, 6.35. Example 281 2-f3.4-Difluorophenyl)-4-(4-chlorophenoxy)-5-[4-(methylsulfonvhphenyl1-3f2HV pvridazinone A mixture of 2-benzyl-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (187 mg, 0.5 mmol), prepared in Example 78, p-chlorophenol (129 mg, 0.5 mmol) and NaH (60% oil suspension) (40 mg, 1 mmol) in THF (25 mL) was refluxed at 50 °C for 3 hours and then concentrated in vacuo. The residue was partitioned between water and ethyl acetate. The acetate layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed (silica gel, 1 :1 hexanes-ethyl acetate) to provide 2-benzyl-4-(4- chlorophenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 200 mg, 82%). The above derivative was dissolved in toluene (25 mL) and was treated with AIBr3 (400 mg, 1.5 mmol) for 20 minutes at 80 °C. The mixture was cooled to room temperature and poured into ice-10% citric acid-ethyl acetate. The organic layer was separated, dried over MgS04 and concentrated in vacuo to provide crude desbenzyl derivative. This compound was immediately dissolved in pyridine (50 mL) and was treated with 3,4-difluorobromobenzene (0.17 mL, 1.5 mmol), Cu (20 mg) and K2CO3 (100 mg, 1.5 mmol) at reflux for 16 hours. After the mixture was concentrated in vacuo, the residue was dissolved in ethyl acetate and was washed with water, 10% citric acid and brine. Purification by column chromatography (silica gel, 1 :1 hexanes-ethyl acetate) provided the title compound (yield: 73 mg, 30%). M.p. 192-194 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.22 (s, 3H), 7.13 (m, 2H), 7.35 (m, 2H), 7.50 (m, 1 H), 7.60 (m, 1 H), 7.75 (m, 1 H), 7.87 (d, J = 0 Hz, 2H), 8.05 (d, J = 9 Hz, 2H), 8.41 (s, 1 H). MS (APCI+) m/z 488 (M+H)+ and (APCI-) m/z 523 (M+CI) " . Example 282 2-(3.4-Difluorophenvπ-4-( , 4-bromophenoxyV5-[4-^methylsulfonvπphenyl]-3(2H)- pvridazinone. The title compound was prepared according to the method of Example 281 , substituting p-bromophenol in place of p-chlorophenol (yield: 54 mg, 20%). M.p. 196-199 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.25 (s, 3H), 7.09 (d, J = 9 Hz, 2H), 7.47 (d, J = 9 Hz, 2H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.78 (m, 1 H), 7.89 (d, J = 9 Hz, 2H), 8.05 (d, J = 9 Hz, 2H), 8.41 (s, 1 H). MS (APCI+) m/z 533 (M+H)+ and (APCI-) m/z 569 (M+CI) " . Example 283 2-(2.2.2-Trifluoroethvn-4-(cvclopθntylthioV5-[4-(methylsulfonvnphenyl]-3(2H pyridazinone To a solution of NaH (26 mg, 1.1 mmol) in acetonitrile (3.0 mL), under nitrogen, was added cyclopentyl mercaptan (120 μL, 1.1 mmol) dropwise via syringe. The resulting solution was flushed with nitrogen for a period of 20 minutes; after which 2-(thfluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone, prepared in Example 193E, (200 mg, 0.52 mmol) was added in one portion. The solution was stirred for an additional 20 minutes at which time, all the 4-bromo pyridazinone was consumed. The solution was analyzed by TLC (1 :1 , ethyl acetate-Hex). Water (5 mL) was carefully added and the reaction partitioned between ethyl acetate (125 mL) and saturated saline (50 mL). The organic layer is washed with saturated saline (50 mL), dried over MgSO4, and concentrated in vacuo. Silica gel chromatography (20% ethyl acetate-80% hexanes) provided a pale yellow solid (yield: 202 mg, 83.1 %). M.p. 149-151 °C. 1 H NMR (300 MHz, CDCI3) δ 1.40-1.34 (m, 2H), 1.62-1.54 (m, 4H), 1.93-1.88 (m, 2H), 3.13 (s, 3H), 4.40-4.35 (m, 1 H), 4.85 (q, J = 8.2 Hz, 2H), 7.58 (d, J = 8.5 Hz, 2H), 7.66 (s, 1 H), 8.06 (d, J = 8.4 Hz, 2H). MS (DCI-NH3) m/z 432 (M+H)+, (M+NH4)+. Anal. calc. for CI 8H1 ΘF3N2O3S2: C, 40.09; H, 4.43; N, 6.48. Found: C, 50.15; H, 4.30; N, 6.45. Example 284 2-(2.2.2-TrifluoroethylV4-f1 H-1.2.4-triazolB-3-ylthio 5-[4-fmethylsulfonylιphenyll- 3(2HVpyridazinone. The title compound was prepared according to the method of Example 283, substituting 1 H-1 ,2,4-triazole-3-thiol in place of cyclopentyl mercaptan (yield: 164 mg, 93%). M.p. 197-200 °C. 1 H NMR (300 MHz, CDCI3) δ 3.14 (s, 3H), 4.84 (q, J = 8.1 Hz, 2H), 7.41 (s, 1 H), 7.68 (d, J = 6.8 Hz, 2H), 7.83 (s, 1 H), 8.00 (d, J = 7.1 Hz, 2H), 8.05 (s, 1 H). MS (DCI-NH3) m/z 431 (M+H)+, (M+NH4)+. Anal. calc. for C15H-12F3N2O3S2: C, 41.76; H, 2.80 ; N, 16.23. Found: C, 41.68; H, 2.85; N, 15.99. Example 285 2-(2.2.2-Trifluoroethylι-4-phenylmBthylthio-5-[4- ( mθthylsulfonyl.phBnyl]-3(2Hι- pvridazinone. The title compound was prepared according to the method of Example 283, substituting benzyl mercaptan in place of cyclopentyl mercaptan (yield: 141 mg, 76%). M.p. 108-111 °C. 1 H NMR (300 MHz, CDCI3) δ 3.01 (s, 3H), 4.38 (s, 2H), 4.87 (q, J = Hz, 2H), 7.10-7.06 (m, 2H), 7.22-7.20 (m, 5H), 7.59 (s, 1 H), 7.95 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 454 (M+H)+, (M+NH4)+. Anal. calc. for C20H17F3N2O3S2, 0.75 EtOAc: C, 53.06; H, 4.45 ; N, 5.38. Found: C, 53.55; H, 4.16; N, 5.84. Example 286 2-(2.2.2-Trifluoroethvn-4-(4-fluorophBnylthio)-5-[4-(mBthylsulfonvhphsnyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 283, substituting 4-fluorophenylmethyl mercaptan in place of cyclopentyl mercaptan (yield: 184 mg, 73.5%). M.p. 182-185 °C. " Η NMR (300 MHz, CDCI3) δ 3.08 (s, 3H), 4.82 (q, J = 8.5 Hz, 2H), 6.87-6.81 (m, 2H), 7.19-7.11 (m, 2H), 7.48 (d, J = 9.0 Hz, 2H), 7.68 (s, 1 H), 7.93 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 458 (M+H)+, (M+NH4)+. Anal. calc. for C19H14F4N2O3S2: C, 49.78; H, 3.08 ; N, 6.11. Found: C, 49.89 ; H, 3.18 ; N, 5.86 Example 287 2- 2.2.2-Trifluoroethvn-4-(cvclohexylthioV5-[4-(methylsulfonvnphenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 283, substituting cyclohexyl mercaptan in place of cyclopentyl mercaptan (yield: 189 mg, 78%). M.p. 165-167 °C. 1 H NMR (300 MHz, CDCI3) δ 1.28-1.17 (m, 5H), 1.64-1.56 (m, 3H), 1.82-1.79 (m, 2H), 3.13 (s, 3H), 4.08-4.05 (m, 1 H), 4.86 (q, J = 8.5 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.67 (s, 1 H), 8.06 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 446 (M+H)+, (M+NH4)+. Anal. calc. for C-| gH2l F3N2O3S2: C, 51.11 ; H, 4.74 ; N, 6.27. Found: C, 51.39 ; H, 4.72 ; N, 5.91. Example 288 2-(2.2.2-Trifluoroethvn-4-(3-chloro-4-fluθrophenylthioV5-[4-(methylsulfonvnphenyl]- 3 2H ,-pvridazinone The title compound was prepared according to the method of Example 283, substituting 3-chloro-4-fluorothiophenol in place of cyclopentyl mercaptan (yield: 190 mg, 65%). M.p. 142-145 °C. 1 H NMR (300 MHz, CDCI3) δ 3.18 (s, 3H), 4.85 (q, J = 8.4 Hz, 2H), 6.96 (ov. t, J = 8.5 Hz, 1 H), 7.14-7.10 (m, 1 H), 7.18 (dd, J = 2.1 , 6.5 Hz, 1 H,), 7.53 (d, J = 8.4 Hz, 2H), 7.77 (s, 1 H), 7.96 (d, J = 8.0 Hz, 2H). MS (Cl) m/z 493 (M+1 )+, (M+NH4)+. Anal. calc. for C-| H-| 3CIF4N2θ3S2.0.25 C6Hβ-H2θ: C, 47.36 ; H, 2.02; N, 5.41. Found: C, 47.88 ; H, 2.g5; N, 5.24. Example 289 2-(2.2.2-Trifluoroθthvn-4-(2.2.2-trifluoroethylthioV5-[4-fmethylsulfonvhphenyl]- 3f2H ,-pyridazinone. The title compound was prepared according to the method of Example 283, substituting 2,2,2-trifluoroethyl mercaptan in place of cyclopentyl mercaptan (yield: 175 mg, 66%). M.p. 155-158 °C. 1 H NMR (300 MHz, CDCI3) δ 3.14 (s, 3H), 3.98 (q, J = 9.8 Hz, 2H), 4.86 (q, J = 8.1 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.75 (s, 1 H), 8.10 (d, J = 8.4 Hz, 2H). MS (DCI-NH3) m/z 446 (M+H)+, (M+NH4)+. Anal. calc. for C15H12F6N2O3S2: C, 40.36 ; H, 2.71 ; N, 6.28. Found: C, 40.50; H, 2.72; N, 6.01. Example 290 2- ( 2.2.2-TrifluoroethylV4- ( te f-butylthioV5-[4-(methylsulfonvnphenyl]-3f2HV pyridazinone. The title compound was prepared according to the method of Example 283, substituting tet -butyl mercaptan in place of cyclopentyl mercaptan (yield: 212 mg, 85%). M.p. 186-189 °C. 1 H NMR (300 MHz, CDCI3) δ 1.25 (s, OH), 3.13 (s, 3H), 4.87 (q, J = 8.1 Hz, 2H), 7.62 (d, J = 8.5 Hz, 2H), 7.67 (s, 1 H), 8.05 (d, J = 8.1 Hz, 2H). MS (ESI) m/z 420 (M+H)+, (M+Na)+. Anal. calc. for C17H19F3N2O3S2: C, 48.56 ; H, 4.55; N, 6.66. Found: C, 50.15; H, 4.39; N, 6.45. Example 291 2-(2.2.2-Trifluoroethyn-4-f4-acBtamidophBnvlthio)-5-[4-(mθthylsulfonvl)phsnvl]- 3f2HVpyridazinone. The title compound was prepared according to the method of Example 283, substituting 4-acetamidothiophenol in place of cyclopentyl mercaptan (yield: 100 mg, 37%). M.p. 191 -193 °C. 1 H NMR (300 MHz, CDCI3) δ 2.16 (s, 3H), 3.08 (s, 3H), 4.83 (q, J = 8.2 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.58 (s, 1 H), 7.78 (d, J = 8.1 Hz, 2H). MS (Cl) m/z 497 (M+H)+, (M+NH4) + . Anal. calc. for C2l H-| 8F3N3θ4S2-0.25H2θ, 0.25 CδHβ: C, 52.83; H, 4.06; N, 7.70. Found: C, 52.97; H, 3.85; N, 7.65. Example 292 2-(2.2.2-Trifluoroethyl)-4-(2-propylthio)-5-f4-fmBthylsulfonyl)phBnyl]-3r2H)- pyridazinone. The title compound was prepared according to the method of Example 283, substituting isopropyl mercaptan in place of cyclopentyl mercaptan (yield: 180 mg, 81%). M.p. 165-167 °C. H NMR (300 MHz, CDCI3) δ 1.17 (d, J = 6.8 Hz, 6H), 3.13 (s, 3H), 4.33 (p, J = 6.8 Hz, 1 H), 4.86 (q, J = 8.5 Hz, 2H), 6.59 (d, J = 8.5 Hz, 2H), 7.68 (s, 1 H), 8.07 (d, J = 8.1 Hz, 2H). MS (DCI-NH3) m/z 406 (M+H)+, (M+NH4)+. Anal. calc. for C16H17F3N2O3S2, 0.75H2O: C, 45.76 ; H, 4.4; N, 6.67. Found: C, 45.91 ; H, 3.98; N, 6.46. Example 293 2-r2.2.2-Trifluoroethyl)-4-f2-methylprop-1 -ylthio)-5-[4-(methylsulfonvhphenyl1- 3f2H)-pvridazinone. The title compound was prepared according to the method of Example 283, substituting 2-methyl-1 -propyl mercaptan in place of cyclopentyl mercaptan (yield: 100 mg, 83%). M.p. 135-138 °C. 1 H NMR (300 MHz, CDCI3) δ 0.87 (d, J = 6.4 Hz, 6H), 1.67-1.60 (m, 1 H), 3.00 (d, J = 6.7 Hz, 2H), 3.14 (s, 3H), 4.84 (q, J = 8.5 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.67 (s, 1 H), 8.08 (d, J = 8.5 Hz, 2H). MS (DCI-NH3) m/z 420 (M+H)+, (M+NH4) + - Anal. calc. for Ci 7H-| gF3N2θ3S2: C, 48.56 ; H, 4.55; N, 6.66. Found: C, 47.86; H, 4.57; N, 6.51. Example 294 2-(2.2.2-Trifluoroethyl)-4-amino-5-[4-(methylsulfonvhphenyl]-3(2HVpyridazinone 2-(2,2,2-Trifluoroethyl)-4-chloro-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone, prepared according to Example 193E, (500 mg, 1.36 mmol) was dissolved in DMF (10 mL) and treated with NaN3 (100 mg, 1.5 mmol). After 2 hours at room temperature, the reaction was diluted with ethyl acetate and washed with water, 4 times, and dried over MgSO4. After filtration of the drying agent and concentration of the filtrate in vacuo, the residue was purified by chromatography on silica gel (Biotage 40S) eluted with 2:1 hexanes-ethyl acetate. The product fractions were combined and evaporated to provide the azido intermediate, 2- (2,2,2-Trifluoroethyl)-4-azido-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (yield: 481 mg, 95%). The 4-azido-compound above (39 mg, 0.105 mmol) was dissolved in THF (3 mL) and MeOH (2 mL) and treated with excess NaBH4. After 15 minutes, the reaction was quenched with saturated NH4CI solution and the product was extracted into ethyl acetate. The organic layer was washed with water, 3 times, and dried over MgSO4. Filtration of the drying agent and evaporation of the solvent provided the title compound (yield: 26 mg, 71 %). M.p. > 260 °C. 1 H NMR (300 MHz, DMSO-d6) δ 3.26 (s, 3H), 4.03 (q, J = 9 Hz, 2H), 6.71 (s, 2H), 7.72 (s, 1 H), 7.76 (d, J = 8 Hz, 2H), 8.02 (d, J = 8 Hz, 2H). MS (ESI-) m/z 346 (M-H) " . Anal. calc. for C13H12F3N3O3S: C, 44.06; H, 3.48; N, 12.10. Found: C, 44.59; H, 3.52; N, 1 1.93. Example 295 2-(2.2.2-Trifluoroethvπ-4-(3-methoxypropylamino)-5-[4-(methylsulfonvπphenyl]- 3(2HVpyridazinone A solution of 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (200 mg, 0.546 mmol), prepared according to the method of Example 193E, and 3-methoxypropylamine (145 mg, 1.64 mmol) in pyridine (4 mL) was heated at 100 °C for 16 hours. The reaction mixture was cooled to room temperature, mixed with silica gel (2 g), and the solvent removed under reduced pressure. The adsorbed silica gel was layered over an Extract-Clean Cartridge® (Alltech, packing: 10 g silica gel) and the cartridge eluted with a hexanes/acetone step gradient consisting of 60 mL of each of the following mixtures: hexanes, 8:1 hexanes/acetone, 4:1 , 2:1 , and 1 :1. Fractions containing desired product were combined, concentrated, and further purified using HPLC (Technikrom Kromasil 60-5 sil silica column, 20 mm x 25 cm). The column was eluted with a linear gradient consisting of 30% ethyl acetate/hexanes to 100% ethyl acetate at 10 mL/min over 50 minutes. Fractions containing product were combined and concentrated under reduced pressure to provide the product as off-white crystals (yield: 215 mg, 05%). M.p. 110-113 °C. 1 H NMR (300 MHz, CDCI3) δ 8.02 (d, J = 18.0 Hz, 2H), 7.55 (d, 2H, J = 18.0 Hz), 7.48 (s, 1 H), 6.57 (br t, 1 H, J = 0.0 Hz), 4.81 (q, J = 17.4 Hz, 2H), 3.33 (t, J = 12.0 Hz, 2H), 3.28 (s, 3H), 3.12 (s, 3H), 2.76 (dt, J = 12.0, 12.0 Hz, 2H), 1.65 (tt, J = 12.0, 12.0, Hz, 2H). MS (DCI-NH3) m/z 420 (M+H)+, m/z 437 [M+NH4]+. Anal. calc. for C17H20F3N3O4S: C, 48.68; H, 4.81 ; N, 10.02. Found: C, 48.74; H, 4.69; N, 9.84. Example 296 2-f2.2.2-Trifluoroethvπ-4-(cvclopentylaminoV5-[4-fmethylsulfonvπphenyl]-3f2HV pyridazinone The product was prepared according to the method of Example 295, substituting cyclopentylamine in place of 3-methoxypropylamine to provide brown crystals (yield: 105 mg, 86%). M.p. 134-139 °C. 1 H NMR (300 MHz, CDCI3) δ 8.03 (d, J = 18.0 Hz, 2H), 7.56 (d, J = 18.0 Hz, 2H), 7.45 (s, 1 H), 6.12 (br d, J = 16.8 Hz, 1 H), 4.79 (q, J = 17.4 Hz, 2H), 3.33 (br m, 1 H), 3.12 (s, 3H), 1.64-1.23 (br m, 8H). MS (DCI-NH3) m/z 416 (M+H)+, m/z 433 (M+NH4) + - Anal. calc. for C18H20- F3N3O3S: C, 52.04; H, 4.85; N, 10.11. Found: C, 52.40; H, 4.93; N, 10.03. Example 297 2-(2.2.2-Trifluoroethyl)-4-(cyclobutvlamino)-5-[4-rmethylsulfonyl)phenyl1-3f2H)- pvridazinone The product was prepared according to the method of Example 205, substituting cyclobutylamine in place of 3-methoxypropylamine to provide an off- white solid (yield: 206 mg, 04%). M.p. 169-172 °C. 1 H NMR (300 MHz, CDCI3) δ 8.03 (d, J = 17.4 Hz, 2H), 7.54 (d, J = 17.4 Hz, 2H), 7.45 (s, 1 H), 6.28 (br d, J = 16.2 Hz, 1 H), 4.81 (q, J = 17.4 Hz, 2H), 3.42 (m, 1 H), 3.13 (s, 3H), 1.79 (m, 4H), 1.64 (m, 1 H), 1.39 (m, 1 H). MS (DCI-NH3) m/z 402 (M+H)+, m/z 419 (M+NH4)+. Anal calc. for C17H18F3N3O3S-0.25 CH3COCH3: C, 51.25; H, 4.72; N, 10.10; found: C, 51.38; H, 4.68; N, 10.25. Example 298 2-f2.2.2-Trifluoroethyl)-4-f3.4-dimethoxyphenethylamino)-5-[4-(methylsulfonvh- phenyl]-3f2Hι-pvridazinone The product was prepared according to the method of Example 205, substituting 3,4-dimethoxyphenethylamine in place of 3-methoxypropylamine to provide an off-white solid (yield: 206 mg, 94%). M.p. 163-165 °C. 1 H NMR (300 MHz, CDCI3) δ 8.02 (d, J = 18.0 Hz, 2H), 7.52 (d, J = 18.0 Hz, 2H), 7.45 (s, 1 H), 6.75 (d, J = 16.2 Hz, 1 H), 6.50 (m, 2H), 6.16 (br d, J = 11.4 Hz, 1 H), 4.79 (q, J = 17.4 Hz, 2H), 3.84 (s, 3H), 3.83 (s, 3H), 3.11 (s, 3H), 2.91 (dt, J = 12.6, 12.6 Hz, 2H), 2.60 (t, J = 13.8 Hz, 2H). MS (DCI-NH3) m/z 520 (M+NH4)+. Anal. calc. for C23H24F3N3O5S: C, 54.01 ; H, 4.73; N, 8.21. Found: C, 54.30; H, 4.69; N, 8.16. Example 299 2-(2.2.2-Trifluoroethvh-4-fcvclohexylamino)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The product was prepared according to the method of Example 295, substituting cyclohexylamine in place of 3-methoxypropylamine to provide an off- white solid (yield: 103 mg, 42%). 1 H NMR (300 MHz, CDCI3) δ 8.04 (d, J = 18.0 Hz, 2H), 7.58 (d, J = 18.0 Hz, 2H), 7.44 (s, 1 H), 6.06 (br d, J = 18.6 Hz, 1 H), 4.81 (q, J = 18.0 Hz, 2H), 3.11 (s, 3H), 2.70 (m, 1 H), 1.66-1.48 (m, 4H), 1.42 (m, 1 H), 1.07 (m, 3H), 0.76 (m, 2H). MS (DCI-NH3) m/z 430 (M+H)+, m/z 447 (M+NH4)+. Anal. calc. for C19H22F3N3O3S: C, 53.14; H, 5.16; N, 9.78. Found: C, 52.86; H, 5.06; N, 0.52. Example 300 2-(2.2.2-Trifluoroethyl)-4-[2-π -piperidinyl)ethylamino]-5-[4-.methylsulfonvnphenyl]- 3(2H)-pyridazinone The product was prepared according to the method of Example 295, substituting cyclopentylamine in place of 3-methoxypropylamine to provide an off- white solid (yield: 210 mg, 84%). 1 H NMR (300 MHz, CDCI3) δ 8.02 (d, J = 18.0 Hz, 2H), 7.56 (d, J = 18.0 Hz, 2H), 7.49 (s, 1 H), 6.91 (br, 1 H), 4.82 (q, J = 18.0 Hz, 2H), 3.13 (s, 3H), 2.64 (br, 2H), 2.32 (br, 4H), 1.58 (br, 6H), 1.42 (br, 2H). MS (DCI- NH3) m/z 450 (M+H)+. Anal. calc. for C-| gH22F3N3θ3S: C, 52.3g; H, 5.50; N, 12.22. Found: C, 52.64; H, 5.59; N, 12.00. Example 301 2-<2.2.2-Trifluoroethvπ-4-(2-tetrahvdrofurfurylaminoV5-[4-(methylsulfonvπphenyl]- 3f2HVpyridazinone The product was prepared according to the method of Example 295, substituting tetrahydrofurfurylamine in place of 3-methoxypropylamine to provide an off-white solid (yield: 150 mg, 64%). M.p. 128-129 °C. 1 H NMR (300 MHz, CDCI3) δ 8.03 (d, J = 18.0 Hz, 2H), 7.56 (d, J = 18.0 Hz, 2H), 7.47 (s, 1 H), 6.48 (br t, J = 9.0 Hz, 1 H), 4.81 (q, J = 18.0 Hz, 2H), 3.84 (m, 2H), 3.72 (m, 1 H), 3.12 (s, 3H), 2.83 (m, 1 H), 2.64 (m, 1 H), 1.84 (m, 3H), 1.34 (m, 1 H). MS (DCI-NH3) m/z 432 (M+H)+, m/z 440 (M+NH4)+. Anal. calc. for C18H20F3N3O3S: C, 50.11 ; H, 4.67; N, 9.74. Found: C, 50.25; H, 4.68; N, 9.68. Example 302 2-(2.2.2-Trifluoroethvn-4-(cvclopropylaminoV5-[4-(methylsulfonvnphenyl]-3(2HV pvridazinone The product was prepared according to the method of Example 295, substituting cyclopropylmethylamine in place of 3-methoxypropylamine to provide an off-white solid (yield: 130 mg, 59%). M.p. 145-146 °C. 1 H NMR (300 MHz, CDCI3) δ 8.01 (d, J = 18.0 Hz, 2H), 7.53 (d, J = 18.0 Hz, 2H), 7.48 (s, 1 H), 6.20 (br, 1 H), 4.82 (q, J = 18.0 Hz, 2H), 3.12 (s, 3H), 2.45 (br d, J = 13.2 Hz, 2H), 0.88 (m, 1 H), 0.51 (m, 2H), 0.10 (m, 2H). MS (DCI-NH3) m/z 402 (M+H)+, m/z 419 (M+NH4)+. Anal. calc. for C17H18F3N3O3S: C, 50.87; H, 4.52; N, 10.47. Found: C, 51.00; H, 4.52; N, 10.44. Example 303 2-(2.2.2-ThfluoroethylV4-f2.3-dihvdro-1 H-inden-1 -ylamino -5-[4-(methylsulfonvn- phenvl]-3(2H pvridazinone The product was prepared according to the method of Example 205, substituting 1 -indanylamine in place of 3-methoxypropylamine to provide an off- white solid (yield: 82 mg, 32%). M.p. 155-158 °C. " Η NMR (300 MHz, CDCI3) δ 8.04 (d, J = 18.0 Hz, 2H), 7.68 (d, J = 18.0 Hz, 2H), 7.49 (s, 1 H), 7.27-7.14 (m, 4H), 6.30 (br d, J = 18.0 Hz, 1 H), 4.81 (q, J = 18.0 Hz, 2H), 4.57 (m, 1 H), 3.09 (s, 3H), 2.89 (m, 1 H), 2.60 (m, 1 H), 1.85 (m, 1 H), 1.68 (m, 1 H). MS (ESI (-) m/z 462 (M-H)". Anal. calc. for C22H20F3N3O3S: C, 57.01 ; H, 4.35; N, 0.07. Found: C, 57.30; H, 4.45; N, 8.86. Example 304 2-(2.2.2-Trifluoroethvn-4-n -piperidinvn-5-[4-(methylsulfonvnphenyl]-3(2HV pvridazinonB The product was prepared according to the method of Example 295, substituting piperidine in place of 3-methoxypropylamine to provide an off-white solid (yield: 180 mg, 70%). M.p. 160-161 °C. " Η NMR (300 MHz, CDCl3) δ 8.04 (d, J = 18.0 Hz, 2H), 7.58 (s, 1 H), 7.46 (d, J = 18.0 Hz, 2H), 4.80 (q, J = 18.0 Hz, 2H), 3.13 (s, 3H), 2.06 (m, 4H), 1.65-1.52 (m, 6H). MS (DCI-NH3) m/z 416 (M+H)+. Anal. calc. for C18H20F3N3O3SΗ2O: C, 52.04; H, 4.85; N, 10.11. Found: C, 52.21 ; H, 5.02; N, 9.75. Example 305 2-(2.2.2-Trifluoroethyπ-4-(3-hydroxypropylamino)-5-[4-(methylsulfonyl)phenyl]- 3(2HVpvridazinone The product was prepared according to the method of Example 295, substituting 3-hydroxypropylamine in place of 3-methoxypropylamine to provide a white solid (yield: 109.6 mg, 50%). M.p. 152-154 °C. 1 H NMR (300 MHz, CDCI3) δ 8.02 (d, J = 18.0 Hz, 2H), 7.56 (d, J = 18.0 Hz, 2H), 7.48 (s, 1 H), 6.48 (br, 1 H), 4.79 (q, J = 17.4 Hz, 2H), 3.63 (t, J = 12.0 Hz, 2H), 3.12 (s, 3H), 2.81 (dt, J = 12.0, 12.0 Hz, 2H), 1.65 (tt, J = 12.0, 12.0 Hz, 2H). MS (DCI-NH3) m/z 406 (M+H)+, m/z 423 (M+NH4)+. Anal. calc. for C16H18F3N3O4S: C, 47.41 ; H, 4.48; N, 10.37. Found: C, 47.53; H, 4.33; N, 10.27. Example 306 2-(2.2.2-Trifluoroethvn-4-[3-(1 H-imidazol-1 -vnpropylamino]-5-[4-(methylsulfonvn- phenyl]-3(2H)-pyridazinone The product was prepared according to the method of Example 295, substituting (3-aminopropyl)imidazole in place of 3-methoxypropylamine. The reaction mixture was concentrated to dryness and the residue purified using RP- HPLC (Rainin Dynamax C-18 column, 60 Λ pore size, 21.4 mm i.d.). The column was eluted with a linear gradient consisting of 20% acetonitrile (containing 0.1 % TFA)/80% water (containing 0.1 % TFA) to 100% acetonitrile (containing 0.1 % TFA) at 15 mL/min over 70 minutes. The peak corresponding to the title product was collected and lyophilized to provide a tan hygroscopic foam (yield: 70.2 mg, 28%). 1 H NMR (300 MHz, DMSO) δ 8.95 (br s, 1 H), 7.97 (d, J = 16.8 Hz, 2H), 7.66 (d, J = 16.2 Hz, 2H), 7.61 (s, 1 H), 7.58 (d, J = 15.0 Hz, 2H), 6.99 (br t, 1 H, J = 13.2 Hz), 4.97 (dt, J = 18.0, 18.0 Hz, 2H), 3.97 (t, J = 13.2 Hz, 2H), 3.28 (s, 3H), 2.69 (m, 2H), 1.81 (tt, J = 13.2, 13.2 Hz, 2H). MS (DCI-NH3) m/z 456 (M+H)+. Anal. calc. for C-19H20F3N5O3S-1.4 CF3COOH: C, 42.57; H, 3.51 ; N, 11.30. Found: C, 42.78; H, 3.58; N, 11.24. Example 307 2-(2.2.2-Trifluoroethyl)-4-(2R-hydroxylpropylamino)-5-[4-(methylsulfonyl)phenyll- 3(2Hι-pvridazinone The product was prepared according to the method of Example 205, substituting (R)-(-)-2-propanolamine in place of 3-methoxypropylamine to provide an off-white solid (yield: 109.6 mg, 50%). M.p . = 140-142 °C. 1 H NMR (300 MHz, CDCI3) δ 8.04 (d, J = 18.0 Hz, 2H), 7.56 (d, J = 18.0 Hz, 2H), 7.49 (s, 1 H), 6.42 (br, 1 H), 4.79 (m, 2H), 3.80 (m, 1 H), 3.12 (s, 3H), 2.68 (m, 2H), 1.02 (d, J = 12.0 Hz, 3H). MS (DCI-NH3) m/z 406 (M+H)+, m/z 423 (M+NH4)+. Anal. calc. for C16H18F3N3O4S- C, 47.41 ; H, 4.48; N, 10.37. Found: C, 47.56; H, 4.41 ; N, 10.25. Example 308 2-(2.2.2-Trifluoroethyl)-4-f2-cyanoethylamino)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The product was prepared according to the method of Example 295, substituting 1 -cyanoethylamine in place of 3-methoxypropylamine to provide an off- white solid (yield: 27 mg, 12%). M.p. 172-174 °C. " Η NMR (300 MHz, CDCI3) δ 8.09 (d, J = 18.0 Hz, 2H), 7.63 (d, J = 18.0 Hz, 2H), 7.51 (s, 1 H), 6.08 (br t, 1 H), 4.87 (q, J = 18.0 Hz, 2H), 3.17 (dt, J = 13.2, 13.2 Hz, 2H), 3.13 (s, 3H), 2.39 (t, J = 13.2 Hz, 2H). MS (DCI-NH3) m/z 418 (M+NH4)+. Anal. calc. for C16H15F3N4O3S: C, 48.00; H, 3.78; N, 13.99. Found: C, 48.28; H, 3.77; N, 13.80. Example 309 2-(2.2.2-Trifluoro8thyl)-4-f4-cvanoanilinoV5-[4-(m9thylsulfonyl)phenyl]-3(2H)- pyridazinonθ A suspension of 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (300 mg, 0.820 mmol), prepared according to the method of Example 193E, 4-aminobenzonitrile (290 mg, 2.46 mmol), and silver oxide (760 mg, 3.28 mmol) in pyridine (1.5 mL) was stirred at 80 °C for 24 hours. The reaction was cooled to room temperature, adsorbed onto silica gel (2 g) and solvent removed under reduced pressure. The adsorbed silica gel was layered over an Extract-Clean Cartridge® (Alltech, packing: 10 g silica gel) and the cartridge eluted with a hexanes/acetone step gradient consisting of 60 mL of each of the following mixtures: hexanes, 8:1 hexanes/acetone, 4:1 , 2:1 , and 1 :1. Fractions containing desired product were combined, concentrated, and further purified using HPLC (Technikrom Kromasil 60-5sil column, 20 mm x 25 cm). The column was eluted with a linear gradient consisting of 30% ethyl acetate/hexanes to 100% ethyl acetate at 10 mL/min over 50 minutes. Fractions containing product were combined and concentrated under reduced pressure to provide the product as a tan solid (yield: 149.9 mg, 41 %). M.p.>230 °C. 1 H NMR (300 MHz, DMSO) δ 9.49 (s, 1 H), 8.00 (s, 1 H), 7.69 (d, J = 17.4 Hz, 2H), 7.43 (d, J = 16.8 Hz, 2H), 7.32 (d, J = 18.0 Hz, 2H), 6.78 (d, J = 18.0 Hz, 2H), 5.06 (q, J = 18.0 Hz, 2H), 3.13 (s, 3H), 2.68 (m, 2H), 1.02 (d, J = 12.0 Hz, 3H). MS (DCI-NH3) m/z 466 (M+NH4)+. Anal, calc. for C20H15F3N4O3S: C, 53.57; H, 3.37; N, 12.49. Found: C, 53.47; H, 3.49; N, 12.35. Example 310 2-(2.2.2-Trifluoroethyl)-4-[3-methoxy-5-ftrifluoromethyl)anilino]-5-[4-fmethyl- sulfonylιphenvl]-3.2H)-pvridazinone The product was prepared according to the method of Example 309 , substituting 3-methoxy-5-(thfluoromethyl)aniline in place of 4-aminobenzonitrile to provide a brown solid (yield: 226.5 mg, 80%). M.p. 206-208 °C. 1 H NMR (300 MHz, CDCI3) δ 7.90 (s, 1 H), 7.77 (s, 1 H), 7.71 (d, J = 18.0 Hz, 2H), 7.28 (d, J = 17.4 Hz, 2H), 6.61 (br s, 1 H), 6.46 (br s, 1 H), 6.31 (br s, 1 H), 4.00 (q, J = 17.4 Hz, 2H), 3.72 (s, 3H), 2.04 (s, 3H). MS (DCI-NH3) m/z 530 (M+NH4)+. Anal. calc. for C-21 H17F6N3O4S: C, 48.37; H, 3.29; N, 8.06. Found: C, 48.60; H, 3.33; N, 7.94. Example 311 2-(2.2.2-Trifluoroethyl)-4-anilino-5-[4-fmethylsulfonyl)phenyl]-3(2H)-pyridazinone The product was prepared according to the method of Example 309 , substituting aniline in place of 4-aminobenzonitrile to provide a tan solid (yield: 90 mg, 53%). M.p. 154-156 °C. 1 H NMR (300 MHz, CDCI3) δ 7.89 (br s, 1 H), 7.72 (s, 1 H), 7.62 (d, J = 18.0 Hz, 2H), 7.19 (d, J = 18.0 Hz, 2H), 7.96-7.82 (m, 3H), 6.61 (d, J = 14.4 Hz, 2H), 4.90 (q, J = 18.0 Hz, 2H), 2.94 (s, 3H). MS (DCI-NH3) m/z 424 (M+H)+, m/z 441 (M+NH4)+. Anal. calc. for C19H16F3N3O3S: C, 53.90; H, 3.81 ; N, 9.92. Found: C, 53.87; H, 3.73; N, 9.89. Example 312 2-(2.2.2-Trifluoroethvπ-4-f2.5-dimethoxyphenylaminot-5-[4-(methylsulfonv phenyl]- 3(2H pyhdazinone The product was prepared according to the method of Example 300 , substituting 2,5-dimethoxyaniline in place of 4-aminobenzonitrile to provide a tan solid (yield: 140 mg, 53%). M.p. 95-96 °C. 1 H NMR (300 MHz, CDCI3) δ 7.78 (br s, 1 H), 7.72 (s, 1 H), 7.63 (d, J = 18.0 Hz, 2H), 7.18 (d, J = 18.0 Hz, 2H), 6.54 (d, J = 18.0 Hz, 1 H), 6.38 (dd, J = 6.0, 18.0 Hz, 1 H), 4.80 (q, J = 18.0 Hz, 2H), 3.73 (s, 3H), 3.47 (s, 3H), 2.06 (s, 3H). MS (DCI-NH3) m/z 484 (M+H)+, m/z 501 (M+NH4)+. Anal. calc. for C21 H20F3N3O5S: C, 52.17; H, 4.17; N, 8.69. Found: C, 52.47; H, 4.17; N, 8.43. Example 313 2-(2.2.2-Trifluoroethvn-4-(3-fluoroanilinoV5-[4-(methylsulfonvnphenyl]-3(2HV pvridazinone The product was prepared according to the method of Example 300 , substituting 3-fluoroaniline in place of 4-aminobenzonitrile to provide a tan solid (yield: 151.3 mg, 42%). M.p. 156-158 °C. 1 H NMR (300 MHz, DMSO) δ 9.18 (s, 1 H), 7.91 (s, 1 H), 7.62 (d, J = 17.4 Hz, 2H), 7.36 (d, J = 17.4 Hz, 2H), 6.88 (dd, J = 15.0, 15.0 Hz, 1 H), 6.56 (m, 1 H), 6.49 (m, 2H), 5.04 (q, J = 18.0 Hz, 2H), 3.08 (s, 3H). MS (DCI-NH3) m/z 442 (M+H)+, m/z 459 (M+NH4)+, m/z 476 (M+2NH4-H)+. Anal. calc. for C19H15F4N3O3SO.5 CH3COCH3: C, 52.33; H, 3.85; N, 8.93. Found: C, 52.51 ; H, 3.58; N, 8.81. Example 314 2-(2.2.2-Trifluoroethvn-4-f2.4-difluoroanilinoV5-[4-,methylsulfonvhphenyl]-3f2HV pvridazinone The product was prepared according to the method of Example 309 , substituting 2,4-difluoroaniline in place of 4-aminobenzonitrile to provide a tan solid (yield: 63.1 mg, 17%). M.p. 170-175 °C. 1 H NMR (300 MHz, DMSO) δ 0.00 (s, 1 H), 7.80 (s, 1 H), 7.57 (d, J = 17.4 Hz, 2H), 7.26 (d, J = 17.4 Hz, 2H), 7.05 (m, 1 H), 6.75 (m, 2H), 5.05 (q, J = 18.0 Hz, 2H), 3.00 (s, 3H). MS (DCI-NH3) m/z 460 (M+H)+, m/z 477 (M+NH4)+. Anal. calc. for C19H14F5N3O3S: C, 4g.68; H, 3.07; N, 9.15; found: C, 50.00; H, 2.05; N, 0.10. Example 315 2-(2.2.2-Trifluoroathvh-4-r2.3.5-trifluoroanilino 5-[4-.methylsulfonvhphenvn-3r2HV pvridazinone The product was prepared according to the method of Example 300 , substituting 2,3,5-trifluoroaniline in place of 4-aminobenzonitrile to provide a pale purple solid (yield: 85.3 mg, 22%). M.p. 190-194 °C. 1 H NMR (300 MHz, DMSO) δ 9.27 (s, 1 H), 7.90 (s, 1 H), 7.70 (d, J = 17.4 Hz, 2H), 7.30 (d, J = 17.4 Hz, 2H), 7.03 (m, 1 H), 6.76 (m, 1 H), 5.06 (q, J = 18.0 Hz, 2H), 3.14 (s, 3H). MS (DCI-NH3) m/z 495 (M+NH4)+. Anal. calc. for Cι gH-| 3FβN3θ3S: C, 47.80; H, 2.74; N, 8.80. Found: C, 47.51 ; H, 2.55; N, 8.63. Example 316 2-(2.2.2-Trifluoroethyl»-4-r4-fluoroanilino)-5-[4-fmethylsulfonyl)phanyl]-3 2H)- pvridazinone The product was prepared according to the method of Example 309 , substituting 4-fluoroaniline in place of 4-aminobenzonitrile to provide a tan solid (yield: 15.8 mg, 4%). M.p. 158-160 °C. 1 H NMR (300 MHz, CDCI3) δ 7.80 (br s, 1 H), 7.69 (s, 1 H), 7.65 (d, J = 18.0 Hz, 2H), 7.18 (d, J =; 18.0 Hz, 2H), 6.63 (d, J = 3.6 Hz, 2H), 6.61 (s, 2H), 4.89 (q, J = 17.4 Hz, 2H), 2.96 (s, 3H). MS (DCI-NH3) m/z 459 (M+NH4)+. Anal. calc. for Cι gHi 5F4N3θ3S-1.25 H2O: C, 49.19; H, 3.80; N, 0.05. Found: C, 59.57; H, 3.53; N, 8.70. Example 317 2-Benzvl-4-f3-thienvl)-5-f4-fmethvlsulfonvl)phenvl]-3(2H)-pyridazinone 2-Benzyl-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone prepared in Example 78 (150 mg, 0.4 mmol), thiophene-3-boronic acid (66.5 mg, 0.52 mmol), CsF (145.8 mg, 0.96 mmol), and tetrakis-(triphenylphosphine)-palladium(0) (13.0 mg, 0.012 mmol) in DME (25 mL) were stirred at reflux for 6 hours TLC (1 CH 2 Cl2:1 hexanes:1.5 ethyl acetate) indicated that all starting materials were consumed. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over MgS04, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified using a silica gel column (0.5:2.5:0.5 CH2Cl2/hexanes/ethyl acetate). A yellow powder was obtained (yield: 50 mg, 31 %). 1 H NMR (300 MHz, CDCI3) δ 3.09 (s, 3H), 5.41 (s, 2H), 6.72 (dd, J = 1.5 Hz, 9 Hz, 1 H), 7.13 (dd, J = 3 Hz, 3 Hz, 1 H), 7.3-7.45 (m, 5H), 7.5-7.6 (m, 3H), 7.78 (s, 1 H), 7.02 (d, 0 Hz, 2H). MS (DCI-NH3) m/z 423 (M+H)+. Anal. calc. for C22 H18N2O3S2. 0.5 H2O: C, 6.23; H, 4.43; N, 6.40. Found C, 61.29; H, 4.40; N, 6.16. Example 318 2-Benzyl-4-f2-benzofuranvπ-5-[4-(methylsulfonvhphenyl]-3C2HVpyridazinone The title compound was prepared according to the method of Example 317, substituting 2-benzofuranboronic acid 3-thiopheneboronic acid (yield: 46 mg, 25%). 1 H NMR (300 MHz, CDCI3) δ 3.13 (s, 3H), 5.5 (s, 2 H,), 6.85-6.92 (m, 1 H), 7.15-7.25 (m, 3H), 7.3-7.42 (m, 3H), 7.45-7.7 (m, 5H), 7.79 (s, 1 H) 8.0 (d, J = 9 Hz, 2H), 8.08 (s, 1 H). MS (DCI-NH3), m/z 457 (M+H)+. Anal. calc. for C26H20 2O4SΗ2O: C, 65.80; H, 4.67; N, 5.90. Found C, 65.44; H, 4.42; N, 6.14. Example 319 2-Benzyl-4-(1.3-dihvdro-1 -oxo-5-isobenzofuranyπ-5-[4-(methylsulfonyl)phenyl]- 3(2HVpvridazinone The title compound was prepared according to the method of Example 221 , substituting 2-benzyl-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone, prepared in Example 78, in place of 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4- (methylsulfonyl)-phenyl]-3(2H)-pyridazinone (yield: 112 mg, 44%). M.p. > 250 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.20 (s, 3H), 5.34 (s, 2H), 5.36 (s, 2H), 7.30-7.44 (m, 6H), 7.48 (d, J = 8 Hz, 2H), 7.57 (s, 1 H), 7.73 (d, J = 8 Hz, 1 H), 7.85 (d, J = 8 Hz, 2H), 8.17 (s, 1 H). MS (DCI-NH3) m/z 473 (M+H)+, 400 (M+NH4)+. Anal. calc. for C26H20N2O5S: C, 65.46; H, 4.33; N, 5.87. Found: C, 65.56; H, 4.48; N, 5.75. Example 320 2-Benzyl-4-(5-chloro-2-thienylV5-[4-(methylsulfonvnphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 317, substituting 4-chloro-2-thiopheneboronic acid in place of 3-thiopheneboronic acid (yield: 21 mg, 17%). 1 H NMR (300 MHz, CDCI3) δ 3.15 (s, 3H), 5.45 (s, 2H), 6.51 (d, J = 4.5 Hz, 1 H), 6.7 (d, J = 4.5 Hz, 1 H), 7.3-7.4 (m, 3H), 7.5 = 7.6 (m, 4H), 7.6 (s, 1 H), 8.05 (d, J = 9 Hz, 2H). MS (DCI-NH3), m/z 457 (M+H)+. Anal. calc. for C18H15CIN2O3S: C, 57.68; H, 4.03; N, 7.47. Found C, 57.61 ; H, 3.84; N, 7.14. Example 321 2-Benzyl-4-(3-nitrophenvn-5-[4-fmethylsulfonvπphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 317, substituting 3-nitrobenzeneboronic acid in place of 3-thiopheneboronic acid (yield: 20 mg, 11 %). 1 H NMR (300 MHz, CDCI3) δ 3.0 (s, 3H), 5.93 (s, 2H), 7.6-7.8 (m, 9H), 7.8 (t, J = 4.5 Hz, 3H), 8.04 (s, 1 H), 8.15 (m, 1 H). MS (DCI-NH3), m/z 462 (M+H)+. Anal. calc. for C24 H-| gN3θ5S. 0.75 H2O: C, 60.68; H, 4.35; N, 8.84. Found C, 60.99; H, 3.97; N, 8.35. Example 322 2-Benzyl-4-(4-vinylphenvπ-5-[4-(methylsulfonvπphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 317, substituting 4-vinylbenzeneboronic acid in place of 3-thiopheneboronic acid (yield: 40 mg, 23%). 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 5.28 (d, J = 12 Hz, 1 H), 5.41 (s, 2H), 5.74 (d, J = 18 Hz, 1 H) 6.65 (dd , J = 12 Hz, 18 Hz, 1 H), 7.1 -7.6 (m, 11 H) 7.83 (d, J = 3 Hz, 2H), 7.85 (s, 1 H). MS (DCI-NH3), m/z 443 (M+H)+. Anal, calc. for C26 H22N2O3S: C, 70.57; H, 5.01 ; N, 6.33. Found C, 70.34; H, 4.67; N, 5.97. Example 323 2-Bsnzyl-4-(4-trifluormethylphenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 317, substituting 4-(trifluoromethyl)benzeneboronic acid in place of 3-thiopheneboronic acid (yield: 101 mg, 52%). 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 5.42 (s, 2H), 7.3-7.5 (m, 8H), 7.55-7.6 m, 3H), 7.85 (s, 2H), 7.0 (s, 1 H). MS (DCI-NH3) m/z 485 (M+H)+. Anal. calc. for C25H1 gF3N2θ3S-0.25 H2O: C, 61.40; H, 4.01 ; N, 5.72. Found C, 61.26; H, 4.01 ; N, 5.35. Example 324 2-Benzyl-4-(2-methoxyphenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 317, substituting 2-methoxybenzeneboronic acid in place of 3-thiopheneboronic acid (yield: 75 mg, 42%). 1 H NMR (300 MHz, CDCI3) δ 3.01 (s, 3H), 3.5 (s, 3H), 5.40 (dd, J = 12 Hz, 18 Hz, 2H), 6.76 (d, J = 0 Hz, 1 H), 6.85-6.05 (m, 1 H), 7.09 (dd, J = 1.5 Hz, 0 Hz, 1 H), 7.26-7.41 (m, 6H), 7.55 (dd, J = 1.5 Hz, 0 Hz, 2H), 7.82 (d, J = 9 Hz, 3H). MS (DCI-NH3) m/z 447 (M+H)+. Anal. calc. for C25H22N2O4S-0.5 H2O: C, 65.91 ; H, 5.08; N, 6.14. Found C, 65.86; H, 5.08; N, 5.58. Example 325 2-Bfinzvl-4-f3.4-dimethvlDhenvn-5-r4-(methvlsulfonvnphenvl]-3f2H pvridazinone 2-Benzyl-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (150 mg, 0.4 mmol) prepared in Example 78 was dissolved in anhydrous DME (10 mL) and heated to reflux with 3,4-dimethylbenzeneboronic acid in presence of CsF (146 mg, 0.06 mmol) and tetrakis(triphenylphosphine)palladium (14 mg, 0.012 mmol) for 6 hours. After cooling to room temperature the reaction mixture was diluted with water and extracted with ethyl acetate (100 mL). The organic layer was washed with brine, dried over MgSO4, and evaporated in vacuo. The compound was purified on a silica gel column, eluting with 30% ethyl acetate in pentanes, providing the desired compound (yield: 100 mg, 56%). 1 H NMR (300 MHz, CDCI3) δ 2.15, 2.20 (2s, 3H), 2.25, 2.30 (2s, 3H), 3.05, 3.08 (2s, 3H), 5.35, 5.40 (2s, 2H), 6.60-7.1 (m, 3H), 7.30-7.40 (m, 4H), 7.42-7.60 (m, 2H), 7.70-8, 02 (m, 4H). MS (DCI-NH3) m/z 445 (M+H)+. Anal. calc. for C26H24N2O3SΗ2O: C, 67.51 ; H, 5.66; N, 6.05. Found: C, 67.45;H, 5.56; N, 5.85. Example 326 2-BBnzyl-4-f3-fluoro-4-methoxyphsnvn-5-[4-(methylsulfonyl)phθnyη-3.2HV pvridazinone The title compound was prepared according to the method of Example 325, substituting 3-fluoro-4-methoxybenzeneboronic acid in place of 3,4-dimethyl- benzeneboronic acid (yield: 35 mg, 19%). 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 3.85 (s, 3H), 5.3, 5.4 (2s, 2H), 6.75-7.03 (m, 3H), 7.3-7.40 (m, 5H), 7.4-7.55 (dd, J = 1.5 Hz; 7.5 Hz, 2H), 7.8-7.05 (m, 3H). MS (DCI-NH3) m/z 465 (M+H)+. Anal. calc. for C25H21 N2O4SO.25 H2O: C, 64.02; H, 4.62; N, 5.07. Found: C, 63.93; H, 4.54; N, 5.43 Example 327 2-Benzyl-4-[3-f2-methoxypyridym-5-f4-fmBthylsulfonyl)phBnyl1-3(2HVpyridazinons The title compound was prepared according to the method of Example 325, substituting 2-methoxy-3-pyridylboronic acid in place of 3,4-dimethylbenzene- boronic acid (yield: 35 mg, 19%). 1 H NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 3.58 (s, 3H), 5.4 (dd, J = 15 Hz, 18 Hz; 2H), 6.88 (m, 1 H), 7.28-7.40 (m, 5H), 7.5-7.6 (dd, J = 1.5 Hz; 7.5 Hz, 3H), 7.82 (s, 1 H), 7.85 (d, J = 18 Hz, 2H), 8.15 (br s, 1 H). MS (DCI-NH3) m/z 448 (M+H)+. Anal. calc. for C24H21 N3O4S: C, 64.42; H, 4.73; N, 9.39. Found: C, 64.17; H, 5.11 ; N, 9.04 Example 328 2-Benzvl-4-(3-θthoxvphenvn-5-[4-fmethvlsulfonvπphenvl1-3f2HVpvridazinone The title compound was prepared according to the method of Example 325, substituting 3-ethoxybenzeneboronic acid in place of 3,4-dimethylbenzeneboronic acid (yield: 115 mg, 67%). " • H NMR (300 MHz, CDCI3) δ 1.31 (t, J = 7.5 Hz, 3H), 3.05 (s, 3H), 3.80 (q, J = 7.5 Hz, 2H), 5.14 (s, 2H), 6.65 (d, J = 0 Hz, 1 H), 6.72 (t, J = 1.5 Hz, 1 H), 6.8 (dd, J = 1.5 Hz, 9 Hz, 1 H), 7.15 (t, J = 9 Hz, 1 H), 7.3-7.4 (m, 5H), 7.5-7.6 (m, 2H), 7.85 (d, J = 9 Hz, 3H). MS (DCI-NH3) m/z 461 (M+H)+. Anal. calc. for C26H24N2O4S-0.5H2O: C, 66.50; H, 5.36; N, 5.06. Found: C, 66.30; H, 5.02; N, 5.77 Example 329 2-Benzvl-4-(4-fluorobenzvπ-5-[4-(methylsulfonvnphenyl]-(2HVpvridazinone 329A. 2-BBnzyl-4.5-dibromo-3(2H)-pyridazinone The title compound was prepared according to the method of Example 194A, substituting benzyl hydrazine hydrochloride in place of 4-fluorophenyl hydrazine hydrochloride (yield: 7.86 g, 60%). 1 H NMR (300 MHz, DMSO dβ) δ 5.27 (s, 2H), 7.26-7.41 (m, 5H), 8.19 (s, 1 H). MS (DCI-NH3) m/z 345 (M+H)+, 362 (M+H)+. 329B. 2-Bθnzvl-5-bromo-4-methoxy-3(2H)-pyridazinone The title compound was prepared according to the method described in Example 194B, substituting 2-benzyl-4,5-dibromo-3(2H)-pyridazinone for 2-(4- fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (yield: 2.877 g; 85%). 1 H NMR (300 MHz, DMSO-d6) δ 4.14 (s, 3H), 5.23 (s, 2H), 7.26-7.38 (m, 5H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 295 (M+H)+, 312 (M+NH4)+. 329C. 2-Benzyl-4-methoxy-5-[4-(methylthio)phenyl]-3(2H pyridazinone The title compound was prepared according to the method described in Example 6, substituting 2-benzyl-4-methoxy-5-bromo-3(2H)-pyhdazinone for 2- benzyl-4-methoxy-5-bromo-3(2H)-pyridazinone (yield: 3.705 g). 1 H NMR (300 MHz, DMSO-d6) δ 2.52 (s, 3H), 3.99 (s, 3H), 5.28 (s, 2H), 7.26-7.41 (m, 7H), 7.55 (m, 2H), 8.02 (s, 1 H). MS (DCI-NH3) m/z 330 (M+H)+, 356 (M+NH4) + . 329D. 2-Benzyl-4-f4-fluorobenzyl-5-[4-(methylsulfonvπphenyl]-3(2H -pyridazinone The title compound was prepared according to the method of Example 233, substituting 4-fluorobenzyl magnesium chloride in place of cyclohexylmagnesium chloride and 2-benzyl-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone was substituted in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone. 320C. 2-Benzyl-4-methoxy-5-[4-(methylsulfonvnphenyl]-3f2H pyridazinone The sulfide compound (Example 329D) was oxidized to the methyl sulfonyl compound according to the method of Example 10. M.p. 186-189 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.27 (s, 3H), 3.83 (s, 2H), 5.31 (s, 2H), 6.94-7.05 (m, 4H), 7.27-7.40 (m, 5H), 7.67 (m, 2H), 7.94 (s, 1 H), 8.03 (m, 2H). MS (DCI-NH3) m/z 449 (M+H)+, 466 (M+NH4) + - Anal. calc. for C25H21 FN2O3S: C, 66.95; H, 4.72; N, 6.25. Found: C, 66.68; H, 4.75; N, 6.14. Example 330 2-(te/ .-Butvπ-4-( , 3-methylbutoxy 5-[4-(methylsulfonvπphenyl]-3(2HVpyridazinone 330A. 2-(terf.-Butyl)-4.5-dichloro-3(2H)-pyridazinone A solution of mucochloric acid (33.8 g, 200 mmol) and ferf.-butylhydrazine hydrochloride (24.0 g, 200 mmol) in methanol (400 mL) was stirred at reflux overnight. Methanol was removed in vacuo and the residue was partitioned between ether and water. The organic layer was dried over MgSθ4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (silica gel, 100% hexanes). Product-containing fractions were combined and the title compound was crystallized from ether/hexanes (yield: 10.0 g, 22.6%). M.p. 63-64 °C. H NMR (300 MHz, CDCI3) δ 1.65 (s, 9H), 7.73 (s, 1 H). MS (DCI-NH3) m/z 221 (M+H)+, 238 (M+NH4)+. 330B. 2- ( fett.-ButylV4-(3-methylbutoxy 5-chloro-3(2H pyridazinone A stirred, room temperature solution of 3-methyl-1 -butanol (0.5 mL, 4.52 mmol) in tetrahydrofuran (10 mL) was treated with a 60% oil suspension of sodium hydride (0.24 g, 5.88 mmol). After 5 minutes, hydrogen gas evolution had subsided, so the dichloro-intermediate from Example 330A (1.0 g, 4.52 mmol) was added and the reaction mixture was stirred at room temperature for 20 hours. The reaction was quenched with 10% aqueous citric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 100% hexanes). The title compound was obtained as a pale yellow oil (yield: 0.7 g, 56.7%). 1 H NMR (300 MHz, CDCI3) δ 0.95 (d, J = 6 Hz, 6H), 1.63 (s, 9H), 1.64 (q, J = 6 Hz, 2H), 1.85 (nonet, J = 6 Hz, 1 H), 4.49 (t, J = 6 Hz, 2H), 7.64 (s, 1 H). MS (DCI-NH3) m/z 273 (M+H)+, 290 (M+NH4)+. 330C. 2-(tørt.-Butvn-4-f3-mBthylbutoxy>-5-r4-.mBthylthio)phsnvη-3(2HV pyridazinone A solution of the intermediate from Example 330B (700 mg, 2.57 mmol), 4- (methylthio)benzeneboronic acid (560 mg, 3.34 mmol), cesium carbonate (2.17 g, 6.67 mmol), and tetrakis(triphenylphosphine)palladium(0) (210 mg, 0.18 mmol) in dimethoxyethane (40 mL) was heated at reflux for 5 hours. The heat source was then removed and the reaction mixture was stirred at room temperature for 64 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo to provide a brown oil. This oil was purified by column chromatography twice (silica gel, 07:3 hexanes/ethyl acetate, then 96:4 hexanes/ethyl acetate) to provide a semi-solid product (yield: 270 mg, 29.2%). 1 H NMR (300 MHz, CDCI3) δ 0.81 (d, J = 6 Hz, 6H), 1.49 (q, J = 6 Hz, 2H), 1.63 (nonet, J = 6 Hz, 1 H), 1.69 (s, 9H), 2.52 (s, 3H), 7.32 (d, J = 9 Hz, 2H), 7.50 (d, J = 9 Hz, 2H), 7.73 (s, 1 H). MS (DCI) m/z 361 (M+H)+. 330D. 2-ftørf.-Butyl -f3-mBthylbutoxy)-5-[4-(mBthylsulfonyl)phBnyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 10, substituting 2-( et .-butyl)-4-(3-methylbutoxy)-5-[4-(methylthio)phenyl]-3(2H)- py dazinone for 4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (yield: 188 mg, 63.9%). M.p. 138-139°C. 1 H NMR (300 MHz, CDCI3) δ θ.81 (d, J = 6 Hz, 2H), 1.48 (q, J = 6 Hz, 2H), 1.48-1.68 (m, 1 H), 1.69 (s, 9H), 3.10 (s, 3H), 4.38 (t, J = 6 Hz, 2H), 7.71 (s, 1 H), 7.74 (d, J = 0 Hz, 2H), 8.03 (d, J = 9 Hz, 2H). MS (DCI-NH3) m/z 393 (M+H) + Anal. calc. for C20H28N2O4S: C, 61.20; H, 7.19; N, 7.14. Found: C, 61.13; H, 7.23; N, 6.89. Example 331 2-(3-ChloroDhanvn-4-methoxv-5-[4-(msthylsulfonvnphBnyl]-3.2Hi-pvridazinone The title compound was prepared according to the method of Example 10, substituting 2-(3-chlorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone (Example 207C) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methyl- thio)phenyl]-3(2H)-pyridazinone (yield: 3.31 g, 96%). M.p. 112-1 14 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.31 (m, 3H), 4.10 (m, 3H), 7.52-7.65 (m, 3H), 7.75 (m, 1 H), 7.90 (m, 2H), 8.07 (m, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 391 (M+H)+, 408 (M+NH4)+ Anal. calc. for: C-| 8H-| 5CIN2θ4S-0.25 H2O: C, 54.68; H, 3.95; N, 7.08. Found: C, 54.59; H, 3.65; N, 6.98. Example 332 2-(3-Chlorophenvn-4-hvdroxv-5-[4-(methylsulfonvl)phenyl]-3(2H)-pyridazinone A suspension of 2-(3-chlorophenyl)-4-(methoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone (6.26 g, 16 mmol) in 5% NaOH (54 mL) dioxane (39.4 mL) was heated at reflux and stirred for 1.5 hours. As the reaction proceeds, the solution becomes orange and homogeneous. The mixture was cooled and poured into 1 N HCl, with constant stirring. The resulting white solid was filtered and rinsed with H2O and left to dry overnight. The mostly dry product was taken up in CH2CI2 and azeotroped with toluene to remove any remaining H2O, to provide the desired product as a white solid (yield: 6.79 g, >100%). 1 H NMR (300 MHz, DMSO dβ) δ 2.27 (s, 3H), 7.51-7.62 (m, 2H), 7.68 (m, 1 H), 7.79 (m, 1 H), 8.03 (m, 4H), 8.24 (s, 1 H). MS (DCI-NH3) m/z 377 (M+H)+, 396 (M+NH4)+. Example 333 2-(3-Chlorophenvn-4-tosvloxv-5-f4-fmethvlsulfonynphBnvl]-3(2H)-pyridazinone To a 0 °C solution of 2-(3-chlorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone, prepared in Example 332, (6.79 g, 16 mmol) in pyridine (160 mL) was added p-toluenesulfonyl chloride (3.06 g, 16 mmol). The solution was left to warm slowly to room temperature with stirring under nitrogen. After 2.5 hours, the mixture was poured into H2O with constant stirring. The resulting off-white solid was filtered, rinsed with H2O and dried to provide the desired product (yield: 6.26 g, 79%). M.p. 198-200 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.35 (s, 3H), 3.28 (s, 3H), 7.20 (m, 2H), 7.52-7.64 (M, 5H), 7.70 (m, 3H), 7.89 (m, 2H), 8.32 (s, 1 H). MS APCI+ 531 (M+H)+, 548 (M+H2θ)+, APCI " 493 (M+35)\ Anal. calc. for C24H19CIN2O6S2: C, 54.29; H, 3.61 ; N, 5.28. Found: C, 54.55; H, 3.46; N, 5.57. Example 334 2-(3-Chlorophenvπ-4-chloro-5-[4-(methylsulfonvhphenyl]-3f2H pyridazinone A solution of 2-(3-chlorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone, prepared in Example 332, in POCI3 was heated to reflux for 3 hours while stirring under nitrogen. The mixture was cooled to room temperature and poured into ice with constant swirling. The resulting white solid was extracted with ethyl acetate. The combined organics were washed with H2O, dried over MgSO4, and concentrated to a solid. The crude product was purified using flash chromatography (Siθ2, eluting with 1 :1 ethyl acetate/hexanes) to provide the desired product (yield: 0.151 g, 29%). M.p. 203-204 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.29-3.36 (3H, obstructed by H2O), 7.60 (m, 3H), 7.76 (m, 1 H), 7.92 (m, 2H), 8.14 (m, 2H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 395 (M+H)+, 412 (M+NH4) + . Anal. calc. for C17H12CI2N2O3S: C, 51.66; H, 3.06; N, 7.00. Found: C, 51.67; H, 3.03; N, 6.93. Example 335 2-(3-Chlorophenvh-4-.2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone To a stirred suspension of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone, prepared in Example 333, (0.175 g, 0.33 mmol) in THF (3.3 mL) was added isobutanol (0.03 mL, 0.33 mmol), and NaH (0.0132 g, 0.33 mmol). The resulting solution was stirred under nitrogen for 1 hour. The reaction was poured into H2O and extracted with ethyl acetate. The combined organics were dried over MgSθ4 and concentrated in vacuo. The crude solid was purified using flash chromatography (Siθ2, 2:1 hexanes:ethyl acetate) to provide the desired product (yield: 0.1088 g 76%). M.p. 166-169 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.78 (d, J = 6 Hz, 6H), 1.84 (m, 1 H), 3.20 (s, 3H), 4.20 (d, J = 6 Hz, 2H), 7.51 -7.63 (m, 3H), 7.76 (m, 1 H), 7.92 (m, 2H), 8.07 (m, 2H), 8.21 (s, 1 H). MS (DCI- NH3) m/z 433 (M+H)+, 450 (M+NH4) + . Anal. calc. for C21 H21 CIN2O4S: C, 57.07; H, 5.01 ; N, 6.33. Found: C, 57.06; H, 4.78; N, 6.13. Example 336 2-(3-Chlorophenvn-4-(.-butoxyV5-[4-(methylsulfonvhphenyl1-3(2H pyridazinone The title compound was prepared according to the method of Example 335, substituting -butanol in place of isobutanol (yield: 0.003 g, 66%). M.p. 232-235 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.1 δ (s, 9H), 3.30 (s, 3H), 7.52-7.64 (m, 3H), 7.74 (m, 1 H), 7.92 (m, 2H), 8.08 (m, 2H), δ.20 (s, 1 H). MS (DCI-NH3) m/z 433 (M+H)+, 450 (M+NH4)+. Anal. calc. for C21 H21 CIN2O4S: C, 58.26; H, 4.89; N, 6.47. Found: C, 58.21 ; H, 4.δ8; N, 6.28. Example 337 2-(3-ChlorophenylV4-(cvclohexyloxyV5-[4-(methylsulfonvnphenyl]-3(2H - pvridazinone The title compound was prepared according to the method of Example 335, substituting cyclohexanol in place of isobutanol (yield: 0.130 g, 02%). semi-solid; 1 H NMR (300 MHz, CDCI3) δ 1.09-1.50 (m, 6H), 1.57 (m, 2H), 1.88 (m, 2H), 3.13 (s, 3H), 5.19 (m, 1 H), 7.38-7.48 (m, 2H), 7.59 (m, 1 H), 7.70 (m, 1 H), 7.83 (m, 2H), 7.92 (s, 1 H), 8.07 (m, 2H). MS APCI+ 450 (M+H)+, 476 (M+H2θ)+, APCI " 45δ (M) " , 493 (M+35)-. Anal. calc. for C23H23CIN2O4S O.25 H2O: C, 59.60; H, 5.11 ; N, 6.04. Found: C, 59.48; H, 4.86; N, 5.88. Example 338 2-(3-Chlorophenvπ-4-f2.2-dimθthylpropoxyV5-[4-fmethylsulfonvnphenyl]-3f2H)- pvridazinone The title compound was prepared according to the method of Example 335, substituting neopentyl alcohol in place of isobutanol (yield: 0.100 g, 74%). M.p. 151 -153 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.78 (s, 9H), 3.2g (s, 3H), 4.10 (s, 2H), 7.52-7.64 (m, 3H), 7.76 (m, 1 H), 7.02 (m, 2H), 8.07 (m, 2H), 8.20 (s, 1 H). MS (DCI-NH3) m/z 447 (M+H)+, 464 (M+NH4)+. Anal. calc. for C22H23CIN2O4S: C, 50.12; H, 5.19; N, 6.27. Found C, 59.40; H, 5.31 ; N, 5.00. Example 339 2- ( 3-ChlorophenylV4-f3-methylbutoxy 5-r4-(methylsulfonvnphenyl]-3(2HV pyridazinonθ The title compound was prepared according to the method of Example 335, substituting 3-methyl-1 -butanol was substituted in place of isobutanol (yield: 0.229 g, 80.5%). M.p. 134-135 °C. 1 H NMR (300 MHz, DMSO de) δ 0.79 (d, J = 6 Hz, 6H), 1.42-1.64 (m, 3H), 3.30 (s, 3H), 4.43 (t, J = 6 Hz, 2H), 7.52-7.65 (m, 3H), 7.76 (m, 1 H), 7.90 (m, 2H), δ.07 (m, 2H), 6.21 (s, 1 H). MS (DCI-NH3) m/z 447 (M+H)+, 464 (M+NH4)+. Anal. calc. for C22H23CIN2O4S: c, 50.12; H, 5.19; N, 6.27. Found: C, 58.91 ; H, 5.12; N, 6.01. Example 340 2-(3-ChloroDhenyl)-4-(3-octvn-1 -yloxyV5-[4-fmethylsulfonyl)phenyl]-3(2H)- pvridazinonθ The title compound was prepared according to the method of Example 335, substituting 3-octyn-1 -ol in place of isobutanol (yield: 0.128 g, 77%). Oil. 1 H NMR (300 MHz, CDCI3) δ 0.8δ (m, 3H), 1.25-1.44 (m, 4H), 2.05 (m, 2H), 2.52 (m, 2H), 4.68 (t, J = 6 Hz, 2H), 7.43 (m, 2H), 7.50 (m, 1 H), 7.70 (m, 1 H), 7.86 (m, 2H), 7.02 (s, 1 H). MS (DCI-NH3) m/z 4δ5 (M+H)+. Anal. calc. for C25H25CIN2O4S: C, 61.94; H, 5.20; N, 5.76. Found: C, 61.62; H, 4.00; N, 5.57. Example 341 2-(3-Chlorophenyl)-4-[2-(dimethylamino)ethoxy]-5-[4-(methylsulfonyl)phenyl]- 3(2H -pyridazinone The title compound was prepared according to the method of Example 335, substituting N,N-(dimethyl)ethanolamine in place of isobutanol (yield: 0.111 g, 75%). M.p. 110-113 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.20 (bs, 6H), 2.66 (bs, 2H), 4.68 (t, J = 5 Hz, 2H), 7.38-7.48 (m, 2H), 7.57 (m, 1 H), 7.68 (m, 1 H), 7.80 (m, 2H), 8.07 (m, 2H). MS (DCI-NH3) m/z 448 (M+H)+. Anal. calc. for C21 H22CIN3O4S-0.50 H2O: C, 55.19; H, 5.07; N, 0.10. Found: C, 55.24; H, 4.07; N, 9.07. Example 342 2-(3-ChlorophenylV4-[2-methyl-1 -(1 -methylethvπpropoxy]-5-f4-(methylsulfonvh- phenyl]-3(2HVpyridazinonθ The title compound was prepared according to the method of Example 335, substituting 2,4-dimethyl-3-pentanol in place of isobutanol (yield: 0.075 g, 48%). Semi-solid; 1 H NMR (300 MHz, DMSO dβ) δ 0.79 (m, 12H), 1.78-1.92 (m, J = 6 Hz, 2H), 3.29 (s, 3H), 5.40 (t, J = 6 Hz, 1 H), 7.57 (m, 3H), 7.72 (m, 1 H), 7.01 (m, 2H), 8.07 (m, 2H), 8.17 (m, 1 H). MS (DCI-NH3) m/z 475 (M+H)+, 492 (M+NH4)+. Anal. calc. for C24H27CIN2O4S (0.75 H2O): C, 59.00; H, 5.δδ; N, 5.78. Found: C, 58.83; H, 5.74; N, 5.52. Example 343 2-^3-ChlorophBnvπ-4-(phenoxyV5-[4-(methylsulfonvπphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 335, substituting phenol in place of isobutanol (yield: 0.053 g, 35%). M.p. 205-207 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.28 (s, 3H), 7.08 (m, 3H), 7.31 (m 2H), 7.50-7.64 (m, 3H), 7.73 (m, 1 H), 7.00 (m, 2H), 6.05 (m, 2H), 6.40 (s, 1 H). MS (DCI-NH3) m/z 453 (M+H)+, 470 (M+NH4)+. Anal. calc. for C23H17CIN2O4S: C, 60.99; H, 3.76; N, 6.19. Found: C, 60.79; H, 3.65; N, 5.87. Example 344 2-(3-Chlorophenvn-4-r3-fdimethylamino)phenvl]-5-[4-(methvlsulfonvl)phanvπ- 3f2H pyridazinone The title compound was prepared according to the method of Example 335, substituting 3-(dimethylamino)phenol in place of isobutanol (yield: 0.057 g, 60%). M.p. 191-193; 1 H NMR (300 MHz, DMSO dβ) δ 2.85 (s, 6H), 3.27 (s, 3H), 6.36 (m, 3H), 7.05 (m, 1 H), 7.51 -7.63 (m, 3H), 7.72 (m, 1 H), 7.00 (m, 2H), 8.05 (m, 2H), δ.39 (s, 1 H). MS APCI+ 495 (M+H)+, APCI " , 495 (M) ** , 590 (M+35) " . Anal. calc. for C25H22CIN3O4S: C, 60.54; H, 4.47; N, 8.47. Found: C, 60.04; H, 4.49; N, 8.26. Example 345 2-(3-Chlorophenyl)-4-(4-methoxyphenoxyV5-[4-fmethylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 335, substituting 4-methoxyphenol in place of isobutanol (yield: 0.080 g, 60%). M.p. 182-184 °C. H NMR (300 MHz, DMSO dβ) δ 3.27 (s, 3H), 3.70 (s, 3H), 6.84 (m, 2H), 7.00 (m, 2H), 7.56 (m, 3H), 7.72 (m, 1 H), 7.00 (m, 2H), 8.04 (m, 2H), δ.33 (s, 1 H). MS (DCI-NH3) m/z 463 (M+H)+, 500 (M+NH4)+. Anal. calc. for C24H19CIN2O5S: C, 5g.64; H, 3.97; N, 5.60. Found: C, 59.δ6; H, 3.94; N, 5.62. Example 346 2-(3.4-Difluorophenvn-4-f2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone (yield: 150 mg, 61 %) . M.p. 116-117 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.78 (d, 6H), 1.84, (m, 1 H), 3.3 (s, 3H), 4.2 (d, 2H), 7.54 (m, 1 H), 7.6 (m, 1 H), 7.82 (m, 1 H), 7.01 (d, 2H), 8.07 (d, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 435 (M+H)+, 452 (M+NH4)+- Anal. calc. for C21 F2H20N2O4S: C, 58.06; H, 4.64; N, 6.45. Example 347 2-(3.4-DifluoroDhBnyl)-4-.3-methyl-1 -butoxy)-5-[4-(methylsulfonyl)phenyl]-3.2H pvridazinonθ The title compound was prepared according to the method of Example 346 substituting 3-methyl-1 -butanol in place of isobutanol (yield: 63 mg, 23%). M.p. 121 -123 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.78 (d, 6H), 1.48, (m, 3H), 3.3 (s, 3H), 4.43 (t, 2H), 7.54 (m, 1 H), 7.6 (m, 1 H), 7.82 (m, 1 H), 7.01 (d, J = 9 Hz, 2H), 8.07 (d, J = 9 Hz, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 449 (M+H)+, 466 (M+NH4)+. Anal. calc. for C22H22F2N2O4S: C, 58.92; H, 4.94; N, 6.25. Found, C, 59.22; H, 4.97; N, 6.07. Example 348 2-(3.4-Difluorophenvπ-4-( , 4-fluorophenoxyV5-[3-fluoro-4-(methylsulfonvnphθnyl]- 3(2H)-pyridazinone The title compound was prepared according to the method of Example 346, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[3-fluoro-4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone in place of 2-(3-difluorophenyl)-4-tosyloxy-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone and substituting 4-fluorophenol in place of isobutanol M.p. 168-170 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.39 (s, 3H), 7.15 (d, 4H), 7.51 (m, 1 H), 7.6 (m, 1 H) 7.75 (m, 3H), 7.97 (t, 1 H); 8.4 (s, 1 H). MS (DCI-NH3) m/z 491 (M+H)+, 508 (M+NH4)+. Anal. calc. for C23H14F4N2O4S: C, 56.33; H, 2.88; N, 5.71. Found, C, 56.07; H, 2.94; N, 5.33. Example 349 2-(3.4-Difluorophenyl)-4-.2.2-dimBthylpropoxy)-5-[4-(mBthylsulfonyl)phBnyl]-3f2H)- pyridazinone The title compound was prepared according to the method of Example 346 substituting neopentyl alcohol in place of isobutanol (yield: 1.18 g, 94%). M.p. 126- 128 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.78 (s, 9H), 3.3 (s, 3H), 4.1 (s, 2H), 7.51 (m, 1 H), 7.6 (m, 1 H), 7.82 (m, 1 H), 7.91 (d, J = 9 Hz, 2H), 8.07 (d, J = 0 Hz, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 440 (M+H)+, 466 (M+NH4)+. Anal. calc. for C22H22F2N2O4S: C, 58.92; H, 4.94; N, 6.25. Found: C, 59.03; H, 5.03; N, 6.18. Example 350 2-f3.4-Difluorophenvπ-4-[2-M-sopropoxy ethoxy]-5-[4-(methylsulfonyhphenyl]-3f2HV pyridazinonθ The title compound was prepared according to the method of Example 346 substituting 2-(isopropoxy)ethanol in place of isobutanol (yield: 432 mg, 72%). M.p. 105-107 °C. 1 H NMR (300 MHz, DMSO-dβ) δ θ.95 (d, 6H), 3.3 (s, 3H), 3.43 (m, 1 H), 3.54 (m, 2H), 4.63 (m, 2H), 7.54 (m, 1 H), 7.6 (m, 1 H), 7.8 (m, 1 H), 8.01 (m, 4H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 465 (M+H)+, 482 (M+NH4)+- Anal. calc. for C22H22F2N2O5S: C, 56.80; H, 4.77; N, 6.03. Found, C, 57.03; H, 4.65; N, 5.83. Example 351 2-(3.4-Difluorophenvπ-4-(3-methylpentyloxyV5-[4-(mθthylsulfonvnphθnyl1-3(2HV pyridazinone The title compound was prepared according to the method of Example 346 substituting 3-methylpentyl-1 -ol in place of isobutanol (yield: 400 mg, 80%). M.p. 100-102 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (m, 6H), 1.05 (m, 1 H), 1.28 (m, 3H) 1.6 (m, 1 H), 3.3 (s, 3H), 4.45 (m, 2H), 7.5 (m, 1 H), 7.6 (m, 1 H), 7.8 (m, 1 H), 7.9 (d, J = 9 Hz, 2H) 8.05 (d, J = 0 Hz, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 463 (M+H)+, 480 (M+NH4) + - Anal. calc. for C23H24F2N2O4S: C, 50.73; H, 5.23; N, 6.06. Found, C, 59.78; H, 5.31 ; N, 6.00. Example 352 2- ( 3.4-Difluorophenvπ-4-(4-methyl-3-pentθn-1 -yloxy)-5-[4-(methylsulfonyπphenyl]- 5-3(2H ,-pvridazinone The title compound was prepared according to the method of Example 346 substituting 4-methyl-3-pentene-1 -ol in place of isobutanol (yield: 405 mg, 67.8%). M.p. 88-90 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.5 (d, 6H), 2.27 (m, 2H) 3.3 (s, 3H), 4.43 (t, 2H), 4.05 (m, 1 H), 7.5 (m, 1 H), 7.6 (m, 1 H), 7.8 (m, 1 H), 7.9 (d, 2H), 8.06 (d, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 461 (M+H)+, 478 (M+NH4)+. Anal. calc. for C23H22F2N2O4S: C, 50.09; H, 4.82; N, 6.08. Found, C, 50.88; H, 4.76; N, 5.84. -108- Example 353 2-.3.4-Difluorophenyn-4-f3-.mBthoxy)butoxy]-5-[4-fmθthylsulfonyl)phBnyl]-3.2H^- pyridazinone The title compound was prepared according to the method of Example 346 substituting 3-methoxybutyl-1 -ol in place of isobutanol (yield: 350 mg, 68%) . M.p. 99-101 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.07 (d, 3H), 1.7 (m, 2H), 3.05 (s, 3H), 3.2 (m, 1 H) 3.3 (s, 3H), 4.45 (m, 2H), 7.54 (m, 1 H), 7.6 (m, 1 H), 7.8 (m, 1 H), 7.9 (d, J = 9 Hz, 2H) 8.01 (d, J = 0 Hz, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 465 (M+H)+, 482 (M+NH4) + . Anal. calc. for C22H22F2N2O5S: C, 56.80; H, 4.77; N, 6.03. Found, C, 56.60; H, 4.83; N, 5.06. Example 354 2-(3-Chlorophenyl)-4-fΛ/-m6thylbθnzylamino)-5-[4-.mBthylsulfonyl)phBnyll-3f2H pvridazinonθ: To a rapidly stirred 0 °C mixture of Λ/-methylbenzylamine (67.5 mg, 0.56 mmol) and tetrahydrofuran (3.7 mL) was slowly added dropwise an n-BuLi solution (0.235 mL, 0.50 mmol, 2.5 M in hexanes). The reaction mixture was stirred for 10 minutes at 0 °C and 1 hour at 23 °C. The solution was cooled to -78 °C, and a tetrahydrofuran (10-15 mL) solution of the 2-(3-chlorophenyl)-4-methoxy-5-[4- (methylthio)phenyl]-3(2H)-pyridazinone (200 mg, 0.56 mmol) slowly added along the interior wall of the reaction vessel. This reaction mixture was stirred overnight, slowly warming to 23 °C as the cooling bath evaporated. The reaction was quenched with water and diluted with a large excess of ethyl acetate. The layers were separated, and the ethyl acetate layer washed with additional water and brine and dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes 1 :θ) to provide 2-(3- chlorophenyl)-4-(Λ/-methyl benzylamino)-5-[4-(methylthio)phenyl]-3(2H)- py dazinone (yield: 145 mg, 58%). The title compound was prepared according to the method of Example 10, substituting 2-(3-chlorophenyl)-4-(Λ/-methylbenzylamino)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylthio)- phenyl]-3(2H)-pyridazinone (yield: 143 mg, 95%). M.p. 60-85 °C. 1 H NMR (300 MHz, CDCI3) δ 2.46 (s, 3H), 3.00 (s, 3H), 4.63 (s, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.24- 7.2g (m, 2H), 7.32-7.48 (m, 5H), 7.60 (ddd, J = 7.2, 1.8, 1.8 Hz, 1 H), 7.67 (s, 1 H), 7.70 (dd, J = 1.8, 1.8 Hz, 1 H), 7.91 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 480 (M+H)+. -109- Example 355 2-<4-FluorophenylV4-( , 1 -pipθridinvπ-5-[4-(methylsulfonvπphenyl]-3(2HV pyridazinonθ To a slightly heterogeneous solution of piperidine (80.7 mg, 1.17 mmol) and toluene (8 mL) cooled to -78 °C was slowly added dropwise an n-BuLi solution (0.235 mL, 0.50 mmol, 2.5 M in hexanes). After stirring at -78 °C for 10 minutes, the cooling bath was removed and the mixture stirred an additional 1 hour at 23 °C. The 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (400 mg, 1.17 mmol) was dissolved in portions in toluene (3 x 6-7 mL aliquots) with a heat gun and cooled to 0 °C prior to transfer via syringe to the lithium amide solution (cooled to -78 °C). The addition was made slowly along the interior wall of the reaction vessel. This reaction mixture was stirred overnight, slowly warming to 23 °C as the cooling bath evaporated. The reaction was quenched with water and diluted with a large excess of ethyl acetate. The layers were separated, and the ethyl acetate layer washed with additional water and brine and dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes 1 :2) to provide 440 mg (05%) of 2-(4-fluorophenyl)-5-[4- (methylthio)phenyl]-4-piperidino-3(2H)-pyridazinone. The title compound was prepared according to the method of Example 10, substituting 2-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-4-piperidino-3(2H)- pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone (yield: 165 mg, 98%). M.p. 80-100 °C. 1 H NMR (300 MHz, CDCI3) δ 1.59 (br s, 6H), 2.59 (br s, 4H), 3.14 (s, 3H), 7.17 (dd, J = 8.7, 8.7 Hz, 2H), 7.51 (d, J = 8.7 Hz, 2H), 7.55-7.62 (m, 2H), 7.68 (s, 1 H), 8.06 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 428 (M+H)+. Powdered out in CH2CI2/C6H14. Anal. calc. for C22H22FN3O3S-0.25C6H14: C, 62.85; H, 5.72; N, 9.35. Found: C, 62.46; H, 5.77; N. 9.13. Example 356 2-.4-Fluorophenyl)-4-M -pyrrolidinyl)-5-f4-rmethylsulfonyl)phenvn-3.2HV pvridazinonfi The title compound was prepared according to the method of Example 355, substituting pyrrolidine for piperidine (yield: 107 mg, 82%). M.p. 102-195 °C. 1 H NMR (300 MHz, CDCI3) δ 1.71-1.80 (m, 4H), 3.13 (s, 3H), 3.40-3.40 (m, 4H), 7.16 (dd, J = 8.7, 8.7 Hz, 2H), 7.47-7.60 (m, 5H), 7.9g (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 414 (M+H)+. Anal. calc. for C-21 H20FN3O3S: C, 61.00; H, 4.87; N, 10.16. Found: C, 60.85; H, 4.04; N, 10.07. Example 357 2-(3-Chlorophenylι-4-f4-methylphenylthioV5-f4-fmethylsulfonyl)phenyl1-3f2Hι- pvridazinone To a stirred suspension of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone, prepared in Example 333, (0.0802 g, 0.15 mmol) in EtOH (1.5 mL) was added thiocresol (0.010 g, 0.15 mmol) and K2CO3 (0.0203 g, 0.15 mmol). The suspension was heated to 50 °C with stirring for 2.5 hours. The mixture was poured into H2O with constant stirring. The resulting precipitate was filtered, rinsed with H2O and dried to provide the desired product (yield: 0.060 g, 83%). M.p. 178-178 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.19 (s, 3H), 3.23 (s, 3H), 6.95 (m, 2H), 7.08 (m, 2H), 7.52-766 (m, 3H), 7.72 (m, 1 H), 7.88 (m, 2H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 483 (M+H)+, 500 (M+NH4)+. Anal. calc. for: C24Hι gCIN2θ3S2-075 H2O: C, 58.05; H, 4.16; N, 5.64. Found: C, 57.00; H, 3.60; N, 5.76. Example 358 2-(3-Chlorophenyl)-4-.2-pyridylthio ) -5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 357, substituting 2-mercaptopyhdine in place of thiocresol (yield: 0.061 g, 39%). M.p. 110-114 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.28 (s, 3H), 7.16 (m, 1 H), 7.37 (m, 1 H), 751 -771 (m, 5H), 7.81 (m, 2H), 8.03 (m, 2H), 8.27 (s, 1 H), 8.34 (m, 1 H). MS (DCI-NH3) m/z 470 (M+H)+. Anal. calc. for C22H16CIN3O3S2O.50 H2O: C, 55.16; H, 3.57; N, 8.77. Found: C, 54.88; H, 3.19; N, 8.59. Example 359 2-(3-Chlorophenyl)-4-(phenylmethylthioV5-[4-.methylsulfonvnphenyl]-3f2H)- pvridazinone To a stirred suspension of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone, prepared in Example 333, (0.175 g, 0.33 mmol) in THF (3.3 mL) was added benzyl mercaptan (0.04 mL, 0.33 mmol) and TEA (0.046 mL, 0.33 mmol). The resulting solution was stirred at room temperature under nitrogen for 1 hour. The mixture was poured into H2O and extracted with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo. The resulting crude product was purified using flash chromatography (Siθ2, 2:1 hexanes:ethyl acetate) to provide the desired product (yield: 0.136 g 85%). M.p. 142-145 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.31 (s, 3H), 4.36 (s, 2H), 7.17 (m, 2H), 7.21-7.33 (m, 3H), 7.51 (m, 2H), 757-764 (m, 3H), 7.74 (m, 1 H), 8.01 (m, 2H). MS (DCI-NH3) m/z 483 (M+H)+, 500 (M+NH4) + . Anal. calc. for C24H19CIN2O3S2: C, 5g.68; H, 3.96; N, 5.80. Found: C, 59.40; H, 4.11 ; N, 5.71. Example 360 2-(3-Chlorophenyl)-4-(2-furylmethylthio)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 359, substituting furfuryl mercaptan in place of benzyl mercaptan (yield: 0.162 g, 100%). M.p. 140-149 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.31 (s, 3H), 4.46 (s, 2H), 6.20 (m, 1 H), 6.37 (m, 1 H), 750-7.67 (m, 6H), 7.77 (m, 1 H), 8.03 (m, 2H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 473 (M+H)+, 400 (M+NH4) + . Anal. calc. for C22H17CIN2O4S2: C, 55.87; H, 3.62; N, 5.92. Found: C, 55.84; H, 3.61 ; N, 5.82. Example 361 2-(3-Chlorophenyl)-4-]2-(methylpropynthio]-5-[4-(methylsulfonvhphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 350, substituting 2-methyl-1 -propanethiol in place of benzyl mercaptan (yield: 0.134 g, 01 %). Oil. 1 H NMR (300 MHz, DMSO dβ) δ 0.61 (d, J = 6 Hz, 6H), 1.54-1.60 (m, 1 H), 2.91 (d, J = 6 Hz, 2H), 3.33 (s, 3H), 7.52-7.64 (m, 3H), 7.74 (m, 1 H), 7.79 (m, 2H), 8.04 (m, 3H). MS (DCI-NH3) m/z 449 (M+H)+, 466 (M+NH4) + . Anal. calc. for C-21 H21 CIN2O3S2 (0.50 H2O): C, 55.07; H, 4.84; N, 6.1 1. Found: C, 54.70; H, 4.64; N, 5.85. Example 362 2-(3-Chlorophenyl)-4-(cyclop8ntyl)-5-f4-(methylsulfonyhphenyl]-3(2H)- pyridazinone To a -78 °C solution of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyhdazinone, prepared in Example 333, (0.175 g, 0.33 mmol) in THF (3.3 mL) was added cyclopentyl magnesium chloride (0.17 mL, 1.0 M in diethyl ether). The resulting solution was stirred under nitrogen less than 1 our with warming to room temperature. The reaction was poured into water and extracted with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo. The resulting crude product was purified using flash chromatography (Siθ2, 2:1 ethyl acetate :hexanes) to provide the desired product (yield: 0.1328 g, 04%). M.p. 155-157 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.50 (m, 2H), 1.66 (m, 2H), 178 (m, 2H), 2.00 (m, 2H), 2.00 (m, J = 8 Hz, 1 H), 3.26-3.37 (3H, obstructed by H2O), 749-763 (m, 3H), 7.71 (m, 3H), 7.97 (s, 1 H), 8.10 (m, 2H). MS (DCI-NH3) m/z 429 (M+H)+, 446 (M+NH4)+. Anal. calc. for C22H21 CIN2O3S: C, 61.60; H, 4.93; N, 6.53. Found: C, 61.48; H, 4.81 ; N, 6.22. Example 363 2-(3-Chlorophenyl)-4-(3-methylpropyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound, an oil, was prepared according to the method of Example 362, substituting isobutyl magnesium chloride in place of cyclohexylmagnesium chloride, (yield: 0.132 g, 96%). 1 H NMR (300 MHz, CDCI3) δ 0.77 (d, J = 6 Hz, 6H), 2.08 (m, 1 H), 2.54 (d, J = 7 Hz, 2H), 736-7.46 (m, 2H), 7.56 (m, 2H), 7.62 (m, 1 H), 7.73 (m, 2H), 8.11 (m, 2H). MS (DCI-NH3) m/z 417 (M+H)+ , 434 (M+NH4)+. Anal. calc. for C-21 H21 CIN2O3S-0.50 H2O: C, 59.21 ; H, 5.20; N, 6.57 Found: C, 59.27; H, 5.40; N, 6.12. Example 364 2-.3-Chlorophenylι-4-.cvclohexylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinonθ The title compound, an oil, was prepared according to the method of Example 362, substituting cyclohexylmethyl magnesium bromide in place of cyclopentyl magnesium chloride (yield: 0.0579 g, 38%). 1 H NMR (300 MHz, DMSO dβ) δ 0.66 (m, 2H), 1.03 (m, 3H), 1.50 (m, 6H), 1.61 (m, 1 H), 2.46 (m, 1 H), 3.27-3.42 (3H, obstructed by H2O), 7.50-7.66 (m, .3H), 7.75 (m, 3H), 7.09 (s, 1 H), 8.10 (m, 2H). MS (DCI-NH3) m/z 457 (M+H)+, 474 (M+NH4)+. Anal. calc. for C24H25CIN2O3S: C, 63.08; H, 5.51 ; N, 6.13. Found: C, 63.08; H, 5.47; N, 6.04. Example 365 2-(3-Chlorophenyl)-4-(2-cvclohexylethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H.- pyridazinone The title compound was prepared according to the method of Example 362, substituting cyclohexylethyl magnesium bromide in place of cyclopentyl magnesium chloride (yield: 0.165 g, 94%). H NMR (300 MHz, DMSO dβ) δ 0.76 (m, 3H), 0.99-1.21 (m, 5H), 1.31-1.62 (m, 8H), 2.42-2.56 (1 H, obstructed by DMSO), 3.25-3.34 (2H, obstructed by H2O), 7.48-7.65 (m, 3H), 7.48-7.65 (m, 3H), 7.76 (m, 3H), 8.01 (s, 1 H), 8.10 (m, 2H). MS (DCI-NH3) m/z 471 (M+H)+, 488 (M+NH4) + - Anal. calc. for C25H27CIN2O3S: C, 63.75; H, 5.78; N, 5.95. Found: C, 63.48; H, 5.70; N, 5.67. Example 366 2-(3-Chlorophenyl)-4-(3-m9thylbutyl)-5-[4-(methylsulfonvhphenyl]-3(2H)- pvridazinonθ The title compound was prepared according to the method of Example 362, substituting 3-methylbutyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 0.0221 g, 16%). M.p. 60-65 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.75 (d, J = 7 Hz, 6H), 1.32-1.52 (m, 3H), 3.31 (s, 3H), 7.50-765 (m, 3H), 7.77 (m, 3H), 8.03 (s, 1 H), 8.11 (m, 2H). MS (DCI-NH3) m/z 431 (M+H)+, 448 (M+NH4)+. Anal. calc. for C22H23CIN2O3S-0.25 H2O: C, 60.68; H, 5.43; H, 6.43. Found C, 60.20; H, 5.60; N, 6.17. Example 367 2-f3-Chlorophenyl)-4-benzyl-5-[4-(methylsulfonyl)phenyl -3f2H)-pyridazinone The title compound was prepared according to the method of Example 362, substituting benzyl magnesium chloride in place of cyclohexylmagnesium chloride. M.p. 174-177 °C (yield: 25.9 g, 57%). " • H NMR (300 MHz, DMSO dβ) δ 3.30 (s, 3H), 3.91 (bs, 2H), 7.02 (m, 2H), 7.12-725 (m, 3H), 7.51 -764 (m, 3H), 7.72 (m, 3H), 8.07 (m, 2H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 451 (M+H)+, 468 (M+NH4)+. Anal. calc. for C24H19CIN2O3S: C, 63.92; H, 4.25; N, 6.21. Found: C, 63.69; H, 4.28; N, 6.02. Example 368 2-.3-ChlorophBnyn-4-cvclohexyl-5-[4-(methylsulfonyl.phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 362 substituting cyclohexylmagnesium chloride in place of cyclopentylmagnesium chloride (yield: 0.099 g, 68%). M.p. 85-90 °C. 1 H NMR (300 MHz, CDCI3) δ 1.01 - 1.30 (m, 3H), 1.48-1.69 (m, 3H), 1.75 (m, 2H), 2.28 (m, 2H), 2.57 (m, 1 H), 3.16 (s, 3H), 7.35-7.46 (m, 2H), 7.50-7.62 (m, 3H), 7.68 (m, 2H), 8.11 (m, 2H). MS (DCI- NH3) m/z 443 (M+H)+, 460 (M+NH4)+. Anal. calc. for C23H23CIN2O3S (1.25 H2O): C, 59.34; H, 5.52; N, 6.01. Found: C, 59.02; H, 5.24; N, 5.65. Example 369 2-(3-Ohlorophenyl)-4-f4-fluorobBnzyl)-5-[4-fmethylsulfonyl)phBnyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 228, substituting 4-fluorobenzyi magnesium chloride in place of cyclopentyl magnesium chloride (yield: 0.1895 g, 41 %). M.p. 183-185 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.25-3.36 (3H, obstructed by H2O), 3.80 (bs, 2H), 6.g7-7.0θ (m, 4H), 7.50-7.64 (m, 3H), 7.71 (m, 3H), 8.06 (m, 2H), 8.11 (s, 1 H). MS (DCI-NH3) m/z 460 (M+H)+, 486 (M+NH4)+. Anal. calc. for C24H18CIFN2O3S: C, 61.47; H, 3.87; N, 5.97. Found: C, 61.23; H, 3.84; N, 5.77. Example 370 2- 3-Chlorophenvn-4-(4-methylphenvn-5-[4-(methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 362 substituting p-tolylmagnesium bromide in place of cyclopentylmagnesium chloride (yield: 65 mg, 40.9%). M.p. 222-224 °C. 1 H NMR (300 MHz, DMSO-dε) δ 2.28 (s, 3H), 3.25 (s, 3H), 7.12 (t, 4H), 7.6 (m, 5H), 7.79 (t, 1 H) 7.9 (d, J = 9 Hz, 2H), 8.22 (s, 1 H). MS (DCI-NH3) m/z 451 (M+H)+, 468 (M+NH4)+. Anal. calc. for C24Hi gCIN2θ3S-0.25 H2O: C, 63.02; H, 4.25; N, 6.21. Found: C, 62.gg; H, 4.28; N. 5.85. Example 371 2-(3.4-Difluorophenyl)-4-(3-fluoro-4-mBthylphBnyl)-5-[4-(m6thylsulfonvπphBnyl]- 3(2H)-pyridazinone 2-(3,4-Difluorophenyl)-4-(3-fluoro-4-methylphenyl)-5-[4-(methylthio)phenyl]- 3(2H)-pyhdazinone was prepared according to the method of Example 362, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone and substituting 3-fluoro-4-methylphenylmagnesium bromide in place of cyclohexylmagnesium chloride to provide the methyl sulfide compound. The methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 265 mg, 85.4%). M.p. 204-206 °C. 1 H NMR (300 MHz, CDCI3) δ 2.25 (br s, 3H), 3.08 (s, 3H), 6.83 (dd, J = 9 Hz, 1.5 Hz, 1 H), 6.96 (dd, J = 9 Hz, 1.5 Hz, 1 H), 7.08 (t, J = 9 Hz, 1 H), 7.23-733 (m, 1 H), 7.41 (d, J = 9 Hz, 2H), 749-756 (m, 1 H), 7.61-7.69 (m, 1 H), 7.93 (d, J = 9 Hz, 2H), 7.9g (s, 1 H). MS (DCI-NH3) m/z 471 (M+H)+, 488 (M+NH4)+. Anal. calc. for C24H17F3N2O3S: C, 61.28; H, 3.62; N, 5.96. Found: C, 61.07; H, 3.95; N, 5.56. Example 372 2-(3-Chlorophenyl)-4-(phBnethyli-5-f4-.methylsulfonyliphenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 228, starting with 2-(3-chlorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]-3(2H)- py dazinone in place of 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone and substituting phenethyl magnesium chloride in place of cyclohexylmagnesium chloride then oxidizing by the method of Example 10 (yield: 0.100 g, 39%). M.p. 142-145 °C. 1 H NMR (300 MHz, DMSO dβ) δ 2.80 (m, 4H), 3.30 (s, 3H), 7.01 (m, 2H), 7.21 (m, 3H), 7.51-7.60 (m, 4H), 7.63 (m, 1 H), 7.78 (m, 1 H), 8.03 (m, 3H). MS (DCI-NH3) m/z 465 (M+H)+, 482 (M+NH4)+. Anal. calc. for C25H21 CIN2O3S: C, 64.58; H, 4.55; N, 6.02. Found: C, 64.24; H, 4.50; N, 5.00. Example 373 2-(3-Chlorophenyl)-4-(2-methylpropoxy)-5-[3-fluoro-4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinons 373A. 2-(3-ChlorophenylV4-f2-methylpropoxy)-5-bromo-3(2HVpyridazinone. The title compound is prepared according to the method of Example 1 Θ4B, starting with 2-(3-chlorophenyl)-4,5-dibromo-3(2H)-pyridazinone (Example 207A) in place of 2-(4-fluorophenyl)-4,5-dibromo-3(2H)-pyridazinone ans substituting 2- methyl-1 -propanol in place of methanol. 373B. 2-.3-Chlorophenv -4-(2-methvlpropoxy)-5-[3-fluoro-4-fmsthylthio)phθnyl]- 3.2H)-pyridazinonB The title compound is prepared according to the method of Example 6, starting with 2-(3-chlorophenyl)-4-(2-methylpropoxy)-5-bromo-3(2H)-pyhdazinone in place of 2-benzyl-4-bromo-5-methoxy-3(2H)-pyridazinone and substituting 3- fluoro-4-(methylthio)benzeneboronic acid (Example 72C) in place of 4- fluorobenzeneboronic acid. 373C. 2-f3-ChlorophBnyl)-4-(2-mBthylpropoxy -5-f3-fluoro-4-.mBthylsulfonyπ- phenvll-3(2HVpvridazinone The methyl sulfide compound was oxidized according to the method of Example 10 to provide the title compound (yield: 0.73 g, 100%). M.p. 180-183 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.82 (d, J = 6 Hz, 2H), 3.30-3.30 (3H, obstructed by H2θ) 4.25 (d, J = 6 Hz, 2H), 7.57 (m, 3H), 7.75 (m, 1 H), 7.85 (m, 1 H), 8.00 (m, 1 H), 8.23 (s, 1 H). MS (DCI-NH3) m/z 451 (M+H)+, 468 (M+NH4)+. Anal. calc. for C21 H20CIFN2O4S: C, 55.94; H, 4.47; N, 6.21. Found: C, 55.73; H, 4.58; N, 6.01. Example 374 2-(3-Chlorophenvn-4-.bBnzvloxy)-5-[4-(mBthylsulfonyl)phBnyl]-3(2H)-pyridazinone To a stirred solution of 2-(3-chlorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone (Example 332) (0.100 g, 0.28 mmol) in DMF (2.8 mL) was added benzyl chloride (0.32 mL, 0.28 mmol). The resulting solution was stirred with heating to 60 °C overnight. The solvent was removed in vacuo and the resulting residue partitioned between ethyl acetate and 10% citric acid. After extracting with ethyl acetate, the combined organics were dried over MgSO4 and concentrated in vacuo. The crude product was purified using flash chromatography (Siθ2, 1 :1 ethyl acetate :hexanes) to provide the desired product (yield: 0.006 g, 76%). M.p. 110-113 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.39 (s, 3H), 5.48 (s, 2H), 7.29 (m, 4H), 759-771 (m, 3H), 7.76 (m, 3H), 8.00 (m, 2H), 8.21 (s, 1 H). MS (DCI- NH3) m/z 467 (M+H)+, 484 (M+NH4)+. Anal. calc. for C24Hi gCIN2θ4S: C, 61.73; H, 4.10; N, 6.00. Found: C, 62.00; H, 4.18; N, 5.03. Example 375 2-(4-FluorophBnyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl1-3f2Hi- pvridazinone 2-(4-Fluorophenyl)-4-methoxy-5-bromo-3(2H)-pyridazinone (Example 104B) is converted into 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone according to the method of Example 194C followed by the oxidation method in Example 10. The methoxy compound is converted to the 2-(3- chlorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone, by treatment with NaOH according to the procedure of Example 332. The hydroxy compound is treated with p-toluenesulfonyl chloride according to the procedure of Example 333, to furnish 2-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-4-tosyloxy- 3(2H)-pyridazinone. The title compound was prepared according to the method of Example 335, starting with 2-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-4-tosyloxy-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-4- tosyioxy-3(2H)-pyridazinone substituting 3-methyl-1 -butanol in place of isobutanol (yield: 0.3932 g, 94%). M.p. 1 17-120 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.79 (d, J = 6 Hz, 6H), 1.41 -1.50 (m, 3H), 3.30 (s, 3H), 4.42 (d, J = 5 Hz, 2H), 7.36 (m, 2H), 7.65 (m, 2H), 7.00 (m, 2H), 8.06 (m, 2H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 431 (M+H)+, 448 (M+NH4)+. Anal. calc. for C22H23FN2O4S: C, 61.38; H, 5.39; N, 6.51. Found: C, 61.42; H, 5.30; N, 6.40. Example 376 2-f4-FluorophenylV4-(2-methylpropoxyV5-[4-( ' methylsulfonvπphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-4-tosyloxy-3(2H)- py dazinone (prepared as an intermediate in Example 375) in place of 2-(3- chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-4-tosyloxy-3(2H)-pyridazinone (yield: 0.486 g, 100%). M.p. 121 -128 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.78 (d, J = 7 Hz, 6H), 1.84 (m, 1 H), 3.30 (s, 3H), 4.20 (d, J = 6 Hz, 2H), 7.37 (m, 2H), 7.66 (m, 2H), 7.02 (m, 2H), 8.07 (m, 2H), 8.19 (s, 1 H). MS (DCI-NH3) m/z 417 (M+H)+, 434 (M+NH4)+. Anal. calc. for C21 H21 FN2O4S-0.50 H2O: C, 50.28; H, 5.21 ; N, 6.58. Found: C, 59.49; H, 4.97; N, 6.34. Example 377 2-(4-Fluorophenyl)-4-(4-fluorobBnzyl)-5-[4-(mθthylsulfonynphsnyl]-3f2H ) - pvridazinonθ The title compound was prepared according to the method of Example 62, starting with 4-(4-fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone and reacting with 1-iodo-4-fluorobenzene (yield: 0.0881 g, 78%). M.p. 175-177 °C. H NMR (300 MHz, DMSO dβ) δ 3.27-3.36 (3H, obstructed by H2O), 3.88 (bs, 2H), 6.08-7.00 (m, 4H), 7.34 (m, 2H), 7.65 (m, 2H), 7.71 (m, 2H), 8.06 (m, 3H). MS (DCI-NH3) m/z 453 (M+H)+, 470 (M+NH4)+. Anal. calc. for C24H18F2N2O3S: C, 63.71 ; H, 4.01 ; N, 6.19. Found: C, 63.61 ; H, 4.26; N, 6.03. Example 378 2-(4-Fluorophenvn-4-(3-methylbutvn-5-[4-(methylsulfonvhphenyll-3(2H)- pvridazinone The title compound was prepared according to the method of Example 228, substituting 3-methylbutyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 0.325 g, 69%). M.p. 151 -154 °C. 1 H NMR (300 MHz, DMSO d6) δ 0.75 (d, J = 7 Hz, 6H), 1.32-1.51 (m, 3H), 3.31 (s, 3H), 7.37 (m, 2H), 7.66 (m, 2H), 7.77 (m, 2H), 8.00 (s, 1 H), 8.10 (m, 2H). MS (DCI-NH3) m/z 415 (M+H)+, 432 (M+NH4) + . Anal. calc. for C22H23FN2O3S-0.50 H2O: C, 62.39; H, 5.71 ; N, 6.61. Found: C, 62.04; H, 5.78; N, 6.46. Example 379 2-fTetrahvdro-2H-Pyrano-2-ylV4-f4-fluorophenvn-5-[4-(methylsulfonvnphenyl]- 3(2HVpvridazinonθ To the solution of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone prepared according to Example 11 (172 mg, 0.5 mmol) and p- toluenesulfonic acid hydrate (10 mg, 0.1 mmol) in dioxane (10 mL) was added 2,3- dihydropyran (2 mL). The mixture was stirred at room temperature for 6 hours. The mixture was then poured into a solution of saturated NaHCO3 and extracted with ethyl acetate. The ethyl acetate was concentrated in vacuo and the residue was chromatographed (silica gel, 1 :1 hexanes-ethyl acetate) to provide the title compound (yield: 25 mg, 11 %). 1 H NMR (DMSO-dβ, 300 MHz) δ 1.54 (m, 2H), 174 (m, 2H), 2.00 (m, 1 H), 2.17 (m, 1 H), 3.23 (s, 3H), 3.62 (m, 1 H), 4.00 (m, 1 H), 5.98 (m, 1 H), 7.13 (7, J = 9 Hz, 2H), 7.23 (m, 2H), 7.47 (d, J = 9 Hz, 2H), 7.86 (d, J = 9 Hz, 2H), 8.12 (s, 1 H). MS (DCI-NH3) m/z 429 (M+H)+. Example 380 2-f3-(4-Fluorophenyl)phBnyl)-4-(4-fluorophBnvn-5-[4-(mθthylsulfonvnphBnyl]- 3(2HVpvridazinone The title compound was prepared according to the method of Example 4, starting with 2-(3-bromophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (Example 166) in place of 2-benzyl-4-bromo-5-[4-(methylthio)- phenyl]-3(2H)-pyridazinone and substituting cesium fluoride for sodium carbonate (yield: 0.62g, 62%). M.p. 222-225 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.24 (s, 3H), 7.16 (m, 2H), 7.36 (m, 3H), 7.53 (m, 2H), 7.64 (m, 2H), 773-781 (m, 3H), 7.93 (m, 3H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 515 (M+H)+, 532 (M+NH4)+. Anal. calc. for C29H20F2N2O3S-0.25 H2O: C, 67.10; H, 3.98; N, 5.35. Found: C, 66.93; H, 3.99; N, 5.17. Example 381 2-(2.2.2-Trifluoroethylι-4-f2.2-dimBthylpropoxyι-5-[3-fluoro-4- (aminosulfonyl)phθnvπ-3(2H)-pyridazinone 2-(2,2,2-Trifluoroethyl)-4-(2,2-dimethylpropoxy)-5-[3-fluoro-4-(methylthio)- phenyl]-3(2H)-pyridazinone was prepared according to the method of Example 261 , substituting 2-(2,2,2-thfluoroethyl)-4-chloro-5-[3-fluoro-4-(methylthio)phenyl]- 3(2H)-pyridazinone in place of 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone. The methyl sulfide was oxidized with one equivalent of mera-chioroperoxy- benzoic acid to give the methyl sulfoxide. The sulfoxide was converted to the title compound according to the method of Example 68 (yield: 196 mg, 28%). M.p. 144- 145 °C. 1 H NMR (300 MHz, CDCI3) δ 0.86 (s, OH), 4.23 (s, 2H), 4.82 (q, J = 8 Hz, 2H), 5.10 (s, 2H), 7.46 (s, 1 H), 7.48 (br s, 1 H), 7.70 (s, 1 H), 8.03 (t, J = 8 Hz, 1 H). MS (DCI-NH3) m/z 438 (M+H)+. Anal. calc. for Ci 7Hι gF3N3θ4S: C, 46.68; H, 4.38; N, 9.61. Found: C, 46.76; H, 4.30; N, 9.52. Example 382 2-(2.2.2-Trifluoroethvπ-4-(2-methylpropoxy 5-[3-fluoro-4-(aminosulfonvhphenyl1- 3(2H pyridazinonθ The title compound was prepared according to the method of Example 68 substituting 2-(2,2,2-trifluoroethyl)-4-(2-methylpropoxy)-5-[4-(methylsulfinyl)phenyl]- 3(2H)-pyridazinone in place of 2-(2,2,2-trifluoroethyl)-4-(4-fluorophenyl)-5-[4- (methylsulfinyl)phenyl]-3(2H)-pyhdazinone (yield: 260 mg, 26%). M.p. 163-164 °C. 1 H NMR (300 MHz, CDCI3) δ 0.86 (d, J = 6.6 Hz, 6H), 1.91 (septet, J = 6.6 Hz, 1 H), 4.34 (d, J = 6.6 Hz, 2H), 5.1 1 (br s, 2H), 7.43-7.52 (m, 2H), 7.80 (s, 1 H), 8.02 (t, J = 8 Hz, 1 H). MS (DCI-NH3) m/z 424 (M+H)+, m/z 441 (M+NH4)+- Anal. calc. for C16H17F4N3O4S: C, 45.39; H, 4.05; N, 9.92. Found: C, 59.89; H, 3.83; N, 8.61. Example 383 2-Benzyl-4-(4-fluorobenzvπ-5-f4- ( aminosulfonyl)phenyl]-3f2HVpyridazinone The title compound was prepared according to the method of Example 384, substituting 2-benzyl-4-(4-fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3,4-difluorophenyl)-4-(4-fluorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (yield: 0.5723 g 34%). M.p. 120-123 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.83 (bs, 2H), 5.30 (bs, 2H), 6.95-7.06 (m, 4H), 7.28- 7.40 (m, 5H), 7.48 (m, 2H), 7.60 (m, 2H), 7.91 (m, 2H), 7.95 (s, 1 H). MS (DCI-NH3) m/z 450 (M+H)+, 467 (M+NH4)+- Anal. calc. for C24H20FN3O3S: C, 64.13; H, 4.48; N, 9.35. Found: C, 63.76; H, 4.71 ; N, 9.02. Example 384 2-Benzyl-4-(4-fluorophenyl)-5-[4-(aminosulfonvπphenyl]-3(2H pyridazinone To a solution of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (130 mg, 0.3 mmol) and di-t-butylazodicarboxylate (DBAD) (69 mg, 0.3 mmol) in THF (30 mL) at -78 °C was added dropwise a 1 N solution of lithium 1 ,1 ,1 ,3,3,3-hexamethyldisilazide (0.0 mL, 0.9 mmol) in THF. After addition, the reaction was stirred an additional 45 minutes at -78 °C (or until the TLC indicated a disappearance of starting material). The reaction was quenched with a saturated solution of NH4CI and extracted with ethyl acetate. The acetate extract was dried over MgSO4 and concentrated in vacuo to obtain 220 mg of crude adduct. The above adduct was dissolved in THF (30 ML) and was treated at room temperature with 1 N NaOH (3 mL) for 5 hours. Sodium acetate (NaOAc-3 H2O, 1.38 g, 10 mmol) was added followed by addition of hydroxylamine-O-sulfonic acid (1.13 g, 10 mmol) and H2O (30 mL). The resulting mixture was stirred at room temperature for 18 hours and then extracted with ethyl acetate. The extract was washed with water, brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography (silica gel, 1 :1 hexanes-ethyl acetate) to provide the desired product (yield: 70 mg, 54%). M.p. 185-189 °C. 1 H NMR (DMSO-d6, 300 MHz) δ 5.33 (s, 2H), 7.11 (m, 2H), 7.22 (m, 2H), 7.40 (m, 7H), 7.83 (d, J = 9 Hz, 2H), 8.10 (s, 1 H). MS (DCI-NH3) m/z 436 (M+H)+. Anal. calc. for C23H18FN3O3S-0.75 H2O: C, 61.65; H, 4.26; N, 9.04. Found: C, 61.67; H, 4.61 ; N, 8.66. Example 385 2- (' 4-Fluorophenvπ-4-C4-fluorophenoxy 5-[4-faminosulfonvhphenyl1-3(2H)- pyridazinone The product from Example 108 was converted to the title sulfonamide according to the method of Example 384, (yield: 65 mg, 28.8%). M.p. 227-229 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 7.08-7.17 (m, 4H), 7.36 (t, J = 3 Hz, 2H), 7.47 (br s, 2H), 7.61 -769 (m, 2H), 7.83 (d, J = 9 Hz, 2H), 7.93 (d, J = 9 Hz, 2H), 8.40 (s, 1 H). MS (DCI-NH3) m/z 469 (M+H)+, 486 (M+NH4) + . Anal. calc. for C24H15 F2N3O4S: C, 58.02; H, 3.30; N, 9.24. Found: C, 57.84; H, 3.34; N, 9.01. Example 386 2-(3.4-Difluorophenvπ-4-C3-fluoro-4-methylphenvπ-5-[4-(aminosulfonvπphenyl]- 3(2 -pvridazinone The product from Example 371 was converted to the title sulfonamide according to the method of Example 384 (yield: 45 mg, 28%). M.p. 198-200 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 6.87 (dd, J = 9 Hz, 3 Hz, 1 H), 7.13 (dt, J = 9 Hz, 3 Hz, 1 H), 7.19 (t, J = 7 Hz, 1 H), 7.46 (d, J = 9 Hz, 2H), 7.47 (br s, 2H), 752-7.69 (m, 2H), 7.79 (d, J = 9 Hz, 2H), 782-789 (m, 1 H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 472 (M+H)+, 48g (M+NH4) + . Example 387 2-(4-Fluorophenyl)-4-(3-fluoro-4-mBthylphenyl)-5-[4-(aminosulfonyl)phsnyl]-3(2H)- pyridazipppe The product from Example 250 was converted to the title sulfonamide according to the method of Example 384 (yield: 185 mg, 46%). M.p. 187-188 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.22 (br s, 3H), 6.87 (dd, J = 9 Hz, 3 Hz, 1 H), 7.16 (q, J = 9 Hz, 2H), 7.38 (t, J = 9 Hz, 2H), 7.46 (br s, 2H), 7.47 (d, J = 9 Hz, 2H), 767- 7.73 (m, 2H), 7.77 (d, J = 9 Hz, 2H), 8.22 (s, 1 H). MS (DCI-NH3) m/z 454 (M+H)+, 471 (M+NH4)+. Anal. calc. for C23Hi7F2N3θ3S-0.25 H2O: C, 60.36; H, 3.87; N, 9.19. Found: C, 60.30; H, 4.26; N, 8.83. Example 388 2- ( 3.4-Difluorophenvπ-4-( , 4-fluorophenoxy 5-[4-(aminosulfonvπphenyl]-3(2HV pyridazinonθ The product from Example 100 was converted to the title sulfonamide according to the method of Example 384 (yield: 110 mg, 45.7%). M.p. 224-226 °C. 1 H NMR (300 MHz, CDCI3) δ 4.86 (br s, 2H), 6.89-7.03 (m, 4H), 7.19-7.30 (m, 1 H), 7.45-7.52 (m, 1 H), 7.56-7.66 (m, 1 H), 7.79 (d, J = 9 Hz, 2H), 8.04 (d, J = 9 Hz, 1 H), 8.08 (s, 1 H). MS (DCI-NH3) m/z 474 (M+H)+, 491 (M+NH4)+. Anal. calc. for C22H14 F3N3O4SO.25 H2O: C, 55.32; H, 2.93; N, 8.80. Found: C, 55.26; H, 3.11 ; N, 8.58. Example 389 2-(3-Chloro-4-fluorophenylV4-i ' 4-fluoro-3-methylphenyl)-5-f4- (aminosulfonyl)phBnvn-3f2H)-pyridazinonB The product from Example 247 was converted to the title sulfonamide according to the method of Example 384 (yield: 230 mg, 38%). M.p. 243-245 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.17 (br s, 3H), 6.94-7.00 (m, 2H), 7.25 (dd, J = 9 Hz, 3 Hz, 1 H), 7.41 -7.48 (m, 4H), 7.60 (t, J = 9 Hz, 1 H), 7.68-775 (m, 1 H), 7.77 (d, J = 9 Hz, 2H), 7.95 (dd, J = 6 Hz, 3 Hz, 1 H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 469 (M+H)+, 486 (M+NH4)+. Anal. calc. for C23H16CIF2N3O3S: C, 56.67; H, 3.29; N, 8.63. Found: C, 56.81 ; H, 3.35; N, 8.05. Example 390 2-f4-Fluorophenvπ-4-( , 4-fluoro-3-methylphenvπ-5-[4-faminosulfonvπphenyl1-3f2HV pvridazinone The methyl sulfone product of Example 245 was converted to the title sulfonamide according to the method of Example 384 (yield: 78 mg, 28.3%). M.p. 202-204 °C. 1 H NMR (300 MHz, CDCI3) δ 2.22 (s, 3H), 4.86 (s, 2H), 6.83-6.91 (m, 2H), 7.14-7.25 (m, 3H), 7.36 (d, J = 9 Hz, 2H), 7.65-772 (m, 2H), 7.91 (d, J = 9 Hz, 2H), 8.0 (s, 1 H). MS (DCI-NH3) m/z 454 (M+H)+, 471 (M+NH4)+. Anal. calc. for C23H17F2N3O3SO.25 H2O: C, 60.36; H, 3.77; N, 0.10. Found: C, 60.24; H, 3.03; N, 9.25. Example 391 2-f3-Chlorophenvn-4-f4-fluoro-3-msthylphBnvl.-5-f4-(aminosulfonvnphenyl]-3(2h)- pyridazinone The methyl sulfone product of Example 244was converted to the title sulfonamide according to the method of Example 384 (yield: 125 mg, 39%). M.p. 187-188 °C. 1 H NMR (300 MHz, CDCI3) δ 2.21 (s, 3H), 4.71 (s, 2H), 6.85-6.92 (m, 2H), 7.21 (d, J = 9 Hz, 1 H), 7.32-7.47 (m, 2H), 7.37 (d, J = 9 Hz, 2H), 7.64 (dt, J = 7 Hz, 3 Hz, 1 H), 7.77 (br s, 1 H), 7.01 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 470 (M+H)+, 487 (M+NH4) + . Anal. calc. for C23Hi 7CIFN3θ3S-0.25 H2O: C, 58.32; H, 3.65; N, 8.88. Found: C, 58.27; H, 3.01 ; N, 8.62. Example 392 2-(3-Chlorophenyl)-4-(3-mBthylbutyl)-5-[4-faminosulfonvlιphBnvl]-3f2H pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3-chlorophenyl)-4-(3-methylbutyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (Example 366) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyhdazinone (yield: 0.0756 g, 16%). M.p. 167-170 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.78 (d, J = 6 Hz, 6H), 1.47 (5H, obstructed by hexanes), 7.51 -765 (m, 4H), 7.68 (m, 2H), 7.75 (m, 1 H), 7.98 (m, 2H), 8.03 (s, 1 H), 8.60 (bs, 1 H). MS (DCI-NH3) m/z 432 (M+H)+, 449 (M+NH4)+. Anal. calc. for C21 H22CIN3O3S (0.25 H2O): C, 5779; H, 5.19; N, 9.62. Found: C, 57.78; H, 5.02; N, 9.40. Example 393 2-(3-Chlorophenyπ-4-(phenethyπ-5-[4-(aminosulfonyπphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3-chlorophenyl)-4-(phenethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (Example 372) in place of 2-benzyl-4-(4-fiuorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (yield: 0.075 g, 17%). semi-solid; 1 H NMR (300 MHz, DMSO dβ) δ 2.80 (m, 4H), 3.20-3.42 (3H, obstructed by H2O), 6.06 (m, 2H), 7.14-7.28 (m, 3H), 7.46-7.68 (m, 7H), 7.78 (m, 1 H), 7.02 (m, 2H), 8.01 (s, 1 H). MS (DCI-NH3) m/z 466 (M+H)+, 483 (M+NH4)+. Anal. calc. for C24H20CIN2O3S-0.25 H2O: C, 61.27; H, 4.30; N, 8.03. Found: 61.18; H, 4.68; N, 8.58. Example 394 2-(3-Chlorophenyl)-4-(3-mBthylbutoxy)-5-[4-(aminosulfonyl)phBnyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3-chlorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (Example 330) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyhdazinone (yield: 0.575 g, 18%). M.p. 137-130 °C. " I H NMR (300 MHz, DMSO dβ) δ 0.81 (d, J = 7 Hz, 6H), 1.40 (m, 2H), 1.57 (m, 1 H), 4.42 (t, J = 7 Hz, 2H), 7.44-7.65 (m, 5H), 7.76 (m, 1 H), 7.84 (m, 2H), 7.04 (m, 2H), 8.20 (s, 1 H). MS (DCI-NH3) m/z 448 (M+H)+, 465 (M+NH4)+. Anal. calc. for C-21 H22CIN3O4S: C, 56.31 ; H, 4.05; N, 0.38. Found C, 56.02; H, 4.82; N, 0.31. Example 395 2-(3-Chlorophenvl)-4-(2-methylpropoxy)-5-[4-.aminosulfonvl)phenvl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3-chlorophenyl)-4-(2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyhdazinonβ (Example 335) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyhdazinone (yield: 0.0458 g, 25%). M.p. 80-85 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.80 (d, J = 6 Hz, 6H), 174-1.92 (m, 3H), 4.20 (d, J = 6 Hz, 2H), 7.49-7.64 (m, 5H), 7.76 (m, 1 H), 7.85 (m, 2H), 7.95 (m, 2H), 8.21 (m, 1 H). MS (DCI-NH3) m/z 434 (M+H)+, 451 (M+NH4)+. Anal. calc. for C20H20CIN3O4S: C, 55.36; H, 4.65; N, 0.68. Found: C, 55.12; H, 4.58; N, 0.42. Example 396 2-(4-Fluorophenyl)-4-(3-methylbutylι-5-f4-faminosulfonyl)phenyl1-3(2H)- pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(4-fluorophenyl)-4-(3-methylbutyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (Example 378) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (0.090 g 21 %). M.p. 180-183 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.78 (d, J = 6 Hz, 6H), 1.49 (m, 5H), 7.36 (m, 2H), 7.53 (m, 2H), 7.62-773 (m, 4H), 7.98 (m, 3H). MS (DCI-NH3) m/z 416 (M+H)+, 433 (M+NH4)+. Anal. calc. for C21 H22FN3O3S: C, 60.71 ; H, 5.34; N, 10.11. Found: C, 60.37, H, 5.36, N, 9.84. Example 397 2-.4-Fluorophenvl)-4-(2-methvlpropoxy)-5-f4-(aminosulfonyl)phenyl]-3.2H)- pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(4-fluorophenyl)-4-(2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (Example 376) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 0.024 g, 6%). M.p. 132-136 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.79 (d, J = 6 Hz, 6H), 1.83 (m, 1 H), 4.19 (d, J = 6 Hz, 2H), 7.36 (m, 2H), 7.50 (m, 2H), 7.66 (m, 2H), 7.84 (m, 2H), 7.95 (m, 2H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 4 8 (M+H)+, 435 (M+NH4)+. Anal. calc. for C20H20FN3O4S: C, 57.54; H, 4.83; N, 10.07. Found C, 57.26; H, 5.00; N, 0.78. Example 398 2- 4-Fluorophenyπ-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pvridazinonθ The title compound was prepared according to the method of Example 384, substituting 2-(4-fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (Example 375) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 0.051 g, 18%). Yellow oil. 1 H NMR (300 MHz, DMSO dβ) δ 0.80 (d, J = 5 Hz, 6H), 1.47 (m, 3H), 4.42 (t, J = 6 Hz, 2H), 7.37 (m, 2H), 7.50 (m, 1 H), 7.65 (m, 2H), 7.83 (m, 2H), 7.93 (m, 2H), 8.18 (s, 1 H), 8.60 (bs, 1 H). MS (DCI-NH3) m/z 432 (M+H)+, 449 (M+NH4)+. Anal. calc. for C-21 H22FN3O4S: C, 58.46; H, 5.14; N, 9.74. Found: C, 58.16; H, 5.21 ; N, 9.57. Example 399 2-fι'-Butvπ-4-(3-methyl-1 -butoxy 5-[4-(aminosulfonvπphθnyl1-3( , 2H)-pyπdazinone 2-(?-Butyl)-4-(3-methyl-1 -butoxy)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone prepared in Example 330C was oxidized with one equivalent of mefa-chloroperoxybenzoic acid to the corresponding methyl sulfoxide. The sulfoxide was converted to the title sulfonamide by the method of Example 68 (yield: 1.25 g, 54%). M.p. 153-155°C. 1 H NMR (300 MHz, CDCI3) δ 0.82 (d, J = 6 Hz, 2H), 1.48 (q, J = 6 Hz, 2H), 1.49-1.69 (m, 1 H), 170 (s, 9H), 4.37 (t, J = 6 Hz, 2H), 4.32 (s, 2H), 7.70 (d, J = 0 Hz, 2H), 7.72 (s, 1 H), 8.01 (d, J = 0 Hz, 2H). MS (DCI- NH3) m/z 304 (M+H)+. Anal. calc. for C10H27N3O4S: C, 57.00; H, 6.01 ; N, 10.67. Found: C, 58.11 ; H, 6.71 ; N, 10.58. Example 400 2- ( 3.4-Difluorophenyl)-5-[4-faminosulfonyπphenyl]-4-(4-fluorophenyl)-3(2H)- pyridazinone The title compound was prepared according to Example 384 substituting 2- (3,4-difluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (Example 182) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (yield: 050 mg, 54%). M.p. 177-181 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 7.15 (t, 2H), 7.20 (m, 2H), 7.43 (s, 1 H), 7.45 (bs, 2H), 7.50 (m, 2H), 7.76 (d, J = 0 Hz, 2H), 7.85 (m, 1 H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 458 (M+H)+, 475 (M+NH4) + . Anal. calc. for C22H14F3N3O3S: C, 57.77; H, 3.08; N, 0.10. Found, C, 57.22; H, 3.28; N, 8.00. Example 401 2-(3-Chloro-4-fluorophenvπ-4-f4-fluorophθnvπ-5-[4-(aminosulfonvπphθnyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3-chloro-4-fluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 380 mg, 47%). M.p. 208-210 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 7.15 (t, 2H), 7.27 (m, 2H), 7.43 (s, 1 H), 7.45 (bs, 2H) 7.51 (d, J = 0 Hz, 4H), 7.6 (t, 1 H), 7.7 (m, 1 H), 7.75 (d, J = 0 Hz, 2H), 7.04 (dd, 1 H), 8.25 (s, 1 H). MS (DCI-NH3) m/z 474 (M+H)+, 401 (M+NH4)+. Anal. calc. for C22H14F2CI2N3O3S-0.5 H2O: C, 55.76; H, 2.08; N, 8.87. Found: C, 56.05; H, 3.42; N, 8.65. Example 402 2-(3.4-Difluorophenvπ-4-(4-fluoro-3-mθthylphenvπ-5-[4-(aminosulfonvπphenyl]- 3(2H)-pyridazinone The title compound was prepared according to the method of procedure Example 384, substituting 2-(3,4-difluorophenyl)-4-(4-fluoro-3-methylphenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fiuorophenyl)- 5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 105 mg, 27%). M.p. 243- 245 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.2 (s, 3H), 7.01 (m, 2H), 7.25 (m, 1 H), 7.45 (s, 1 H), 7.47 (bs, 2H), 7.6 (m, 2H), 7.77 (d, J = 0 Hz, 2H), 7.85 (m, 1 H), 8.26 (s, 2H). MS (DCI-NH3) m/z 472 (M+H)+, 480 (M+NH4)+. Anal. calc. for C24H17F3N2O3SO.5 H2O: C, 58.50; H, 3.42; N, 8.01. Found: C, 57; H, 4.23; N, 8.80. Example 403 2-(3.4-Difluorophenvπ-4-(2-mθthylpropoxyV5-[4-(aminosulfonyπphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3,4-difluorophenyl)-4-(2-methyipropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 35 mg, 42%). M.p. 160-171 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.78 (d, 6H), 1.84, (m, 1 H), 4.2 (d, 2H), 7.54 (m, 3H), 7.6 (m, 1 H), 7.82 (m, 3H), 7.01 (d, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 436 (M+H)+, 453 (M+NH4)+. Anal. calc. for C2θHl øF2N3θ4S-0.25 H2O: C, 55.17; H, 4.40; N, 0.65. Found: C, 54.10; H, 4.25; N, 0.35 Example 404 2-(3.4-Difluorophenyl)-4-.3-methylbutyl)-5-[4-(aminosulfonvnphenyl]-3.2H .- pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3,4-difluorophenyl)-4-(3-methylbutyl)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone in place of 2-benzyl-4-(4-fiuorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (yield: 58 mg, 52%). M.p. 171 -173 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (d, 6H), 1.4, (m, 3H), 2.48 (m, 2H), 3.3 (s, 3H), 7.51 (m, 1 H), 7.65 (m, 1 H), 7.75 (d, J = 0 Hz, 2H), 7.81 (m, 1 H) 8.05 (s, 1 H), 8.12 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 434 (M+H)+, 451 (M+NH4)+. Anal. calc. for C-21 H21 F2N3O3SO.25 H2O: C, 58.10; H, 4.88; N, 0.60. Found: C, 57.60; H, 5.01 ; N, 0.18. Example 405 2-(3-Chloro-4-fluorophenyl)-4-(3-mathylbutyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3-chloro-4-fluorophenyl)-4-(3-methylbutyl)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyhdazinone (yield: 102 mg, 61.8%). M.p. 154-156 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (d, 6H), 1.4, (m, 3H), 2.48 (m, 2H), 7.54 (s, 2H), 7.6 (m, 1 H), 7.60 (m, 2H), 7.03 (dd, 1 H), 8.05 (m, 2H). MS (DCI-NH3) m/z 450 (M+H)+, 468 (M+NH4) + - Anal. calc. for C22H22FN2O3SCIO.25 H2O: C, 58.86; H, 4.04; N, 6.24. Found: C, 50.23; H, 5.12; N, 6.00. Example 406 2-f3.4-Difluorophenyl)-4-f2.2-dimsthylpropoxy)-5-[4-raminosulfonyl.phenyl]-3(2HV pvridazinonB The title compound was prepared according to the method of Example 384 substituting 2-(3,4-difluorophenyl)-4-(2,2-dimethylpropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 310 mg, 38%). M.p. 173-175 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.8 (s, 0H), 3.3 (s, 3H), 4.1 (s, 2H), 7.51 (m, 3H), 7.6 (m, 1 H), 7.85 (m, 3H), 7.05 (d, J = 0 Hz, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 450 (M+H)+, 467 (M+NH4) + . Anal. calc. for C21 H21 F2N3O4S: C, 56.12; H, 4.71 ; N, 0.35. Found, C, 55.83; H, 4.73; N, 0.08. Example 407 2-f3.4-Difluorophenyl')-4-(4-fluorophenoxy 5-[3-fluoro-4-(aminosulfonvπphenyl]- 3r2HVpyridazinone The title compound was prepared according to the method of Example 400 substituting 2-(3,4-difluorophenyl)-4-(4-fluorophenoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[3-fluoro-4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 125 mg, 31 %). M.p. 224-226 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 7.15 (d, 4H), 7.51 (m, 1 H), 7.6 (m, 2H) 7.75 (m, 4H), 7.0 (t, 1 H); 8.4 (s, 1 H). MS (DCI-NH3) m/z 402 (M+H)+, 500 (M+NH4)+ Anal. calc. for C22H13F4N3O4S: C, 53.77; H, 2.67; N, 8.55. Found,; C, 53.33; H, 2.84; N, 8.22 Example 408 2-(3.3-Difluoro-2-propenvn]-4-f4-fluorophenvn-5-[3-fluoro-4- Caminosulfonvπphenyl]-3(2HVpyridazinone The intermediate, 2-benzyl-4-(4-fluorophenyl)-5-[3-fluoro-4-(methylthio)- phenyl]-3(2H)-pyridazinone prepared according to the method of Example 72, was oxidized with one equivalent of tnera-chloroperoxybenzoic acid to provide the methyl sulfoxide which was converted to the sulfonamide according to the method of Example 68. The sulfonamide material was N-debenzylated according to the method of Example 11 and N-alkylated according to the method of Example 127, substituting 1 ,3-dibromo-1 ,1 -difluoropropane in place of 3,4-difluorobenzyl bromide and employing 4 equivalents of potassium carbonate to provide the title compound (yield: 120 mg, 27%). M.p. 180-183 °C. 1 H NMR (300 MHz, CDCI3) δ 4.71 (dt, J = 15 Hz, 7.5 Hz, 2H), 4.75 (d, J __ 7.5 Hz, 2H), 5.06 (s, 2H), 7.02 (m, 2H), 7.10 (dd, J = 0 Hz, 6 Hz, 2H), 7.81 (s, 1 H), 7.87 (t, J = 7.5 Hz, 2H). MS (DCI-NH3) m/z 440 (M+H)+. Anal. calc. for Cι gHi 3F4N3θ3S: C, 51.93; H, 2.98; N, 9.56. Found: C, 51.71 ; H, 3.15; N, 9.28. Example 409 2-f3.4-Difluorophenvπ-4-[2-(2-propoxy^ethoxy]-5-[4-(aminosulfonvπphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 384, substituting 2-(3,4-difluorophenyl)-4-[2-(2-propoxy)ethoxy]-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (yield: 110 mg, 34%). M.p. 54-56 °C. 1 H NMR (300 MHz, DMSO-d6) δ 1.0 (d, 6H), 3.43 (m, 1 H), 3.54 (m, 2H), 4.63 (m, 2H), 75 (m, 3H), 7.6 (m, 1 H), 7.8 (m, 1 H), 7.05 (m, 4H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 466 (M+H)+, 483 (M+NH4)+. Anal. calc. for C21 H21 F2N3O5S: C, 54.10; H, 4.55; N, 0.03. Found, C, 54.20; H, 4.67; N, 8.05. Example 410 2-(3.4-Difluorophenyl)-4-(4-methyl-3-pentenyloxy)-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pvridazinone The title compound was prepared according to the method of Example 384 substituting 2-(3,4-difluorophenyl)-4-(4-methyl-3-pentenyloxy)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone. M.p. 70-73 °C. 1 H NMR (300 MHz, DMSO-d6) δ 1.5 (d, 6H), 2.27 (m, 2H) 4.43 (t, 2H), 4.5 (m, 1 H), 7.5 (m, 2H), 7.6 (m, 1 H), 7.8 (m, 2H), 7.02 (d, J = 2 H, 2H), 8.2 (s, 1 H). MS (DCI-NH3) m/z 462 (M+H)+, 470 (M+NH4)+. Anal. calc. for C22H21 F2N3O4S: C, 57.26; H, 4.50; N, 0.11. Found, : C, 56.96; H, 4.70; N, 9.01. Example 411 2-(3-Chlorophenyl)-4-(3-fluorophenoxy)-5-[4-(methylsulfonyl)phsnyl]-3(2H)- pvridazinonθ The title compound was prepared according to the method of Example 335, substituting 3-fluorophenol in place of isobutanol (yield: 0.034 g, 22%). M.p. 178- 180 °C. 1 H NMR (300 MHz, DMSO dβ) δ 3.27 (s, 3H), 6.88-7.00 (m, 2H), 7.10 (m, 1 H), 7.36 (m, 1 H), 7.59 (m, 3H), 7.74 (m, 1 H), 7.90 (m, 2H), 8.06 (m, 2H), 8.43 (s, 1 H). MS (DCI-NH3) m/z 488 (M+H)+. Anal. calc. for C23Hι βCIFN2θ4S-0.25 H2O: C, 58.10; H, 3.49; N, 5.89. Found C, 58.04; H, 3.59; N, 5.80. Example 412 P-(3-ChloroDhenyl>-4-.2-methylpropoxyi-5-[3-fluoro-4-^aminosulfonyl)phenvn- 3(PH ι-pvridazinone The title compound was prepared according to the method of Example 384 , substituting 2-(3-chlorophenyl)-4-(2-methylpropoxy)-5-[3-fiuoro-4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methyl- sulfonyl)phenyl]-3(2H)-pyridazinone (yield: 0.019 g, 10%). M.p. 157-159 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.81 (d, J = 6 Hz, 6H), 1.86 (m, 1 H), 4.24 (d, J = 6 Hz, 2H), 7.75 (m, 3H), 7.66 (m, 1 H), 7.73 (m, 2H), 7.83 (m, 2H), 7.91 (m, 1 H), 8.23 (s, 1 H). Anal. calc. for C2l Hι gCIFN3θ4S: C, 53.16; H, 4.24; N, 9.30. Found: C, 53.02; H, 4.43; N, 0.10. Example 413 P-(3-ChloroDhenvn-4-f4-m9thvlDentvloxvi-5-[4-rmethylsulfonyl)phenyl]-3.2H)- pvridazinone The title compound was prepared according to the method of Example 335, substituting 4-methyl-1 -pentanol in place of isobutanol (yield: 0.137 g, 00%). M.p. 130-140 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.74 (d, J = 6 Hz, 6H), 1.03 (m, 2H), 1.30 (m, 1 H), 1.54 (m, 2H), 3.20 (s, 3H), 4.40 (t, J = 5 Hz, 2H), 751 -7.60 (m, 3H), 7.75 (m, 1 H), 7.00 (m, 2H), 8.07 (m, 2H), 8.20 (s, 1 H). MS (DCI-NH3) m/z 461 (M+H)+, 478 (M+NH4)+. Anal. calc. for C23H25CIN2O4S: C, 50.05; H, 5.07; N, 6.08. Found: C, 50.62; H, 5.63; N, 5.86. Example 414 2-(4-Fluorophenyl)-4-(4-methylpentyloxy)-5-f4-(methylsulfonyl)phenyl1-3(2H)- pyridazinone The title compound was prepared according to the method of Example 335, starting with 2-(4-fluorophenyl)-4-tosyioxy-5-[4-(methyisulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone and substituting 4-methyl-1 -pentanol in place of isobutanol (yield: 0.128 g, 85%). M.p. 123-125 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.74 (d, J = 6 Hz, 6H), 1.03 (m, 2H), 1.30 (m, 1 H), 1.54 (m, 2H), 3.28 (s, 3H), 4.30 (t, J = 6 Hz, 2H), 7.37 (m, 2H), 7.66 (m, 2H), 7.01 (m, 2H), 8.07 (m, 2H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 445 (M+H)+. Anal. calc. for C23H25FN2O4S: C, 62.14; H, 5.67; N, 6.30. Found: C, 62.28; H, 5.50; N, 6.25. Example 415 2-(4-Fluorophenvπ-4-hvdroxy-5-[4-(methylsulfonvπphenyl]-3(2H pyridazinonθ The title compound was prepared according to the method of Example 332, substituting 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone for 2-(3-chlorophenyl)-4-methoxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (yield: 2.022 g, 07%). 1 H NMR (300 MHz, DMSO dβ) δ 3.28 (s, 3H), 738 (m, 2H), 7.70 (m, 2H), 8.03 (m, 4H), 8.22 (s, 1 H). MS (APCI-+Q1 MS) 361 (M+H)+, (-Q1 MS) 350 (M-H)T Example 416 2-f4-Fluorophenvh-4-cvclopropylmθthoxy-5-[4-(methylsulfonvπphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- py dazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyhdazinone and substituting cyclopropylmethanol in place of isobutanol (yield: 0.117 g, 83%). M.p. 166-167 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.22 (m, 2H), 0.46 (m, 2H), 1.10 (m, 1 H), 3.31 (s, 3H), 4.30 (d, J = 7 Hz, 2H), 7.36 (m, 2H), 7.66 (m, 2H), 7.06 (m, 2H), 8.07 (m, 2H), 8.20 (s, 1 H). MS (DCI-NH3) m/z 415 (M+H)+, 432 (M+NH4) + . Anal. calc. for C23H25CIN2O4S: C, 60.86; H, 4.62; N, 6.76. Found: C, 60.76; H, 4.72; N, 6.61. Example 417 2-(4-Fluorophenvh-4- ( 2-cvclopropyl-1 -ethoxyV5-[4-(methylsulfonvπphenyl]-3f2HV pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone and substituting 2-cyclopropane ethanol in place of isobutanol (yield: 0.1472 g, 100%). M.p. 11 1 -117 °C. 1 H NMR (300 MHz, DMSO dβ) δ -0.01 (m, 2H), 0.31 (m, 2H), 0.60 (m, 1 H), 1.40 (q, J = 6 Hz, 2H), 3.20 (s, 3H), 4.48 (t, J = 6 Hz, 2H), 7.37 (m, 2H), 7.65 (m, 2H), 7.01 (m, 2H), 8.06 (m, 2H), 8.17 (s, 1 H). MS (DCI-NH3) m/z 420 (M+H)+, 446 (M+NH4) + - Anal. calc. for C22H21 FN2O4S: C, 61.67; H, 4.04; N, 6.54. Found: C, 61.50; H, 5.02; N, 6.45. Example 418 2-(3-Chlorophenylι-4-cvclopropanθmθthoxy-5-[4- m9thylsulfonyl)phθnyl1-3.2H)- pyridazinone The title compound was prepared according to the method of Example 335, substituting cyclopropane methanol in place of isobutanol (yield: 0.0017 g, 64%). M.p. 158-161 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.22 (m, 2H), 0.46 (m, 2H), 1.13 (m, 1 H), 3.31 (s, 3H), 4.31 (d, J = 7 Hz, 2H), 7.57 (m, 3H), 7.75 (m, 1 H), 7.06 (m, 2H), 8.08 (m, 2H), 8.23 (s, 1 H). MS (DCI-NH3) m/z 431 (M+H)+, 448 (M+NH4)+. Anal, calc. for C-21 Hi 9CIN2O4SO.25 H2O: C, 57.02; H, 4.51 ; N, 6.43. Found: C, 57.86; H, 4.35; N, 6.27. Example 419 2- ( 3-Chlorophenvπ-4- ( 2-cvclopropane-1 -ethoxy -5-[4-(methylsulfonyl)phenyl]- 3r2H)-pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-cyclopropane ethanol in place of isobutanol (yield: 0.114 g, 78%). M.p. 124-128 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.00 (m, 2H), 0.32 (m, 2H), 0.61 (m, 1 H), 1.49 (q, J = 6 Hz, 2H), 3.30 (s, 3H), 4.50 (t, J = 6 Hz, 2H), 7.58 (m, 3H), 7.76 (m, 1 H), 7.91 (m, 2H), 8.07 (m, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 445 (M+H)+, 462 (M+NH4)+. Anal. calc. for C22H21 CIN2O4S: C, 59.3g; H, 4.76; N, 6.30. Found: C, 58.02; H, 4.g4; N; 6.15. Example 420 2-M-Fluorophenvπ-4-C4-methylpentvπ-5-[4-( , mθthylsulfonvπphenyl]-3(2HV pvridazinone The title compound was prepared according to the method of Example 362, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone and substituting 4-methylpentane-1 -magnesium bromide for cyclopropyl magnesium chloride (yield: 0.165 g, 99%). M.p. 1 12-115 °C. 1 H NMR (300 MHz, DMSO dβ) δ 0.75 (d, J = 7 Hz, 6H), 1.07 (q, J = 7 Hz, 2H), 1.32-1.53 (m, 3H), 2.45 (t, 2H), 3.31 (s, 3H), 7.37 (m, 2H), 7.66 (m, 2H), 7.76 (m, 2H), 8.00 (s, 1 H), 8.10 (m, 2H). MS (DCI-NH3) m/z 420 (M+H)+. 446 (M+NH4)+. Anal. calc. for C23H25FN2O3S: C, 64.47; H, 5.88; N, 6.54. Found: C, 64.44; H, 5.gθ; N, 6.4θ. Example 421 2-(3-Chlorophenvn-4-f4-methylpentvn-5-[4-fmθthylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 362, substituting 4-methylpentane-1 -magnesium bromide in place of cyclopropyl magnesium chloride (yield: 165 mg, 08%). oil. 1 H NMR (300 MHz, DMSO dβ) δ 0.76 (d, J = 6 Hz, 6H), 1.07 (m, 2H), 1.33-1.55 (m, 3H), 2.45 (m, 2H), 3.32 (s, 3H), 7.51 -7.65 (m, 4H), 7.76 (m, 2H), 8.03 (s, 1 H), 8.11 (m, 2H). MS (DCI-NH3) m/z 445 (M+H)+, 462 (M+NH4) + . Anal. calc. for C23H25CIN2O3S: C, 62.06; H, 5.66; N, 6.30. Found: C, 61.86; H, 5.64; N, 6.18. Example 422 2-(4-Fluorophenvn-4-r3-methyl-2-butBnoxyV5-[4-(mBthylsulfonvnphBnyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- py dazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone and substituting 3-methyl-2-buten-1 -ol in place of isobutanol (yield: 0.1284 g, 88%). M.p. 128-132 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.58 (s, 3H), 1.67 (s, 3H), 3.30 (s, 3H), 4.05 (d, J = 7 Hz, 2H), 5.31 (m, 1 H), 7.38 (m, 2H), 7.65 (m, 2H), 7.80 (m, 2H), 8.06 (m, 2H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 420 (M+H)+, 446 (M+NH4)+. Anal. calc. for C22H2I FN2O4S: C, 61.67; H, 4.04; N, 6.54. Found: C, 61.41 ; H, 4.05; N, 6.47. Example 423 2-(3-Chlorophenyl)-4-(3-methyl-2-butenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H pyridazinone The title compound was prepared according to the method of Example 335, substituting 3-methyl-2-buten-1 -ol in place of isobutanol (yield: 0.110 g, 81 %). M.p. 113-115 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.58 (s, 3H), 1.67 (s, 3H), 3.31 (s, 3H), 4.06 (m, 2H), 5.32 (m, 1 H), 7.58 (m, 3H), 7.75 (m, 1 H), 780 (m, 2H), 8.07 (m, 2H), 8.21 (s, 1 H). MS (APCI+Q1 MS) 445 (M+H)+, (APCI-Q1 MS) 470 (M+35) " . Anal. calc. for C22H21 CIN2O4S: C, 50.30; H, 4.76; N, 6.30. Found: C, 50.14; H, 4.66; N, 6.16. Example 424 2-(4-Fluorophenyl)-4-(4-methyl-3-pentenyloxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pvridazinone The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone and substituting 4-methyl-2-penten-1 -ol in place of isobutanol (yield: 0.1165 g, 77%). M.p. 111 -114 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.46 (s, 3H), 1.56 (s, 3H), 2.26 (m, 2H), 3.30 (s, 1 H), 4.43 (t, J = 7 Hz, 2H), 4.06 (m, 1 H), 7.37 (m, 2H), 7.65 (m, 2H), 7.01 (m, 2H), 8.06 (m, 2H), 8.18 (s, 1 H). MS (DCI-NH3) m/z 443 (M+H)+, 460 (M+NH4)+. Anal. calc. for C23H23FN2O4S: C, 62.43; H, 5.24; N, 6.33. Found: C, 62.32; H, 5.30; N, 6.25. Example 425 2-(4-Fluorophenyl)-4-(3-methyl-3-butenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3-chlorophenyl)-4-tosyioxy-5-[4- (methyisulfonyl)phenyl]-3(2H)-pyridazinone and substituting 3-methyl-3-butene-1 - ol in place of isobutanol (yield: 0.1327 g, 01 %). M.p. 100-111 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.61 (s, 3H), 2.32 (t, J = 7 Hz, 2H), 3.30 (s, 3H), 4.56 (t, J = 7 Hz, 2H), 4.63 (bs, 1 H), 4.68 (bs, 1 H), 7.37 (m, 2H), 7.66 (m, 2H), 7.00 (m, 2H), 8.05 (m, 2H), 8.10 (s, 1 H). MS (DCI-NH3) m/z 420 (M+H)+, 446 (M+NH4)+. Anal. calc. for C22H21 FN2O4S: C, 61.67; H, 4.04; N, 6.54. Found: C, 61.50; H, 5.00; N, 6.45. Example 426 2-(3-Chlorophenyl)-4-(4-methyl-3-pentenyloxy 5-f4-.methylsulfonyl)phenyl]-3(2H)- pyridazinone The title compound was prepared according to the method of Example 335, substituting 4-methyl-3-pentene-1 -ol in place of isobutanol (yield: 0.1140 g, 76%). M.p. 110-111 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.47 (s, 3H), 1.55 (s, 3H), 2.27 (m, 2H), 3.30 (s, 3H), 4.44 (t, J = 6 Hz, 2H), 4.06 (m, 1 H), 752-7.64 (m, 3H), 7.75 (m, 1 H), 7.01 (M, 2H), 8.06 (m, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 450 (M+H)+, 476 (M+NH4)+. Anal. calc. for C23H23CIN2O4S: C, 60.10; H, 5.05; N, 6.10. Found: C, 60.06; H, 4.00; N, 5.06. Example 427 P-(3-nhlorophenyl)-4-f3-methyl-3-butenoxy)-5-[4-fmethylsulfonyl)phenyl]-3.2H ) - pyridazinone The title compound was prepared according to the method of Example 335, substituting 3-methyl-3-butene-1 -ol in place of isobutanol (yield: 0.1150 g, 70%). M.p. 110-112 °C. 1 H NMR (300 MHz, DMSO dβ) δ 1.62 (s, 3H), 2.32 (t, J = 7 Hz, 2H), 3.30 (s, 3H), 4.57 (t, J = 6 Hz, 2H), 4.63 (bs, 1 H), 4.68 (bs, 1 H), 7.51-7.64 (m, 3H), 7.76 (m, 1 H), 7.00 (m, 2H), 8.05 (m, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 445 (M+H)+, 462 (M+NH4) + - Anal. calc. for C22H21 CIN2O4S: C, 50.30; H, 4.76; N, 6.30. Found: C, 50.27; H, 4.68; N, 6.18. Example 428 2-.4-Fluorophenvh-4-ι1 .5-hexadienyl-3-oxy.-5-r4-(methylsulfonyl)phenvπ-3.2H pyridazinone The title compound was prepared according to the method of Example 178, substituting 1 ,5-hexadien-3-ol in place of 2-ethyl-1 -hexanol (yield: 150 mg, 85%). M.p. 104-105 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.42 (m, 2H), 3.30 (s, 3H), 5.00 (m, 2H), 5.17 (m, 2H), 5,64 (m, 2H), 7.36 (t, J = 0 Hz, 2H), 7.64 (m, 2H), 7.02 (d, J = 0 Hz, 2H), 8.06 (d, J = 0 Hz, 2H), 8.10 (s, 1 H). MS (APCI+) m/z 441 (M+H)+; (APCI-) m/z 475 (M+CI) " . Anal. calc. for C23H21 FN2O4S: C, 62.71 ; H, 4.80; N, 6.35. Found: C, 62.06; H, 4.03; N, 5.85. Example 429 2- ( 4-Fluorophenvπ-4- ( 5-methyl-2-hexyloxyV5-[4-fmethylsulfonvnphenyl]-3(2HV pvridazinonθ The title compound was prepared according to the method of Example 178, substituting 5-methyl-2-hexanol in place of 2-ethyl-1 -hexanol (yield: 150 mg, 82%). M.p. 102-103 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.73 (d, J = 7 Hz, 6H), 1.04 (m, 2H), 1.14 (d, J = 7 Hz, 3H), 1.40 (m, 3H), 3.20 (s, 3H), 5.12 (m, 1 H), 7.36 (t, J = 9 Hz, 2H), 7.66 (m, 2H), 7.92 (d, J = 9 Hz, 2H), 8.07 (d, J = 0 Hz, 2H), 8.10 (s, 1 H). MS (APCI+) m/z 450 (M+H)+; (APCI-) m/z 403 (M+CI)-. Anal. calc. for C24H27FN2O4S: C, 62.86; H, 5.03; N, 6.10. Found: C, 62.83; H, 5.00; N, 6.07. Example 430 2-f4-Fluorophenvπ-4-f2-ethyl-1 -butoxy)-5-[4-(methylsulfonyl)phenyll-3(2H)- pvridazinone The title compound was prepared according to the method of Example 178, substituting 2-ethyl-1-butanol in place of 2-ethyl-1 -hexanol (yield: 140 mg, 80%). M.p. 107-108 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.73 (t, J = 7 Hz, 6H), 1.20 (quintet, J = 7 Hz, 4H), 1.40 (m, 1 H), 3.20 (s, 3H), 4.20 (d, J = 7 Hz, 2H), 7.37 (t, J = 0 Hz, 2H), 7.66 (m, 2H), 7.00 (d, J = 0 Hz, 2H), 8.07 (d, J = 0 Hz, 2H), 8.10 (s, 1 H). MS (APCI+) m/z 445 (M+H)+; (APCI-) m/z 470 (M+CI) " . Anal. calc. for C23H25FN2O4S: C, 62.14; H, 5.66; N, 6.30. Found: C, 62.05; H, 5.86; N, 6.30. Example 432 2-(4-Fluorophanyl)-4-(2-thioisopropyl-1 -ethoxy)-5-[4-(methylsulfonyl)phenyl1-3(2H)- pyridazjnope The title compound was prepared according to the method of Example 178, substituting 2-(isopropylthio)ethanol in place of 2-ethyl-1 -hexanol (yield: 138 mg, 74%). M.p. 137-130 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.13 (d, J = 7 Hz, 6H), 2.77 (t, J = 7 Hz, 2H), 2.88 (quintet, J = 7 Hz, 1 H), 3.20 (s, 3H), 4.58 (t, J = 7 Hz, 2H), 7.37 (t, J = 0 Hz, 2H), 7.66 (m, 2H), 7.92 (d, J = 9 Hz, 2H), 8.06 (d, J = 9 Hz, 2H), 8.18 (s, 1 H). MS (APCI+) m/z 463 (M+H)+. Anal. calc. for C22H23FN2O4S2: C, 57.12; H, 5.01 ; N, 6.05. Found: C, 56.82; H, 4.91 ; N, 5.99. Example 433 2-C4-Fluorophenvh-4-(3-mθthylthio-1 -hexyloxyV5-[4-( r methylsulfonvhphθnyl]-3( , 2HV pvridazinone The title compound was prepared according to the method of Example 178, substituting 3-(methylthio)-1 -hexanol in place of 2-ethyl-1 -hexanol (yield: 155 mg, 70%). M.p. 00-02 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.78 (t, J = 7 Hz, 3H), 1.30 (m, 4H), 1.76 (m, 2H), 2.82 (s, 3H), 2.38 (m, 1 H), 3.20 (s, 3H), 4.55 (m, 2H), 7.37 (t, J = 0 Hz, 2H), 7.66 (m, 2H), 7.02 (d, J = 0 Hz, 2H), 8.06 (d, J = 0 Hz, 2H), 8.18 (s, 1 H). MS (APCI+) m/z 401 (M+H)+; (APCI-) m/z 525 (M+CI) " . Anal. calc. for C24H27FN2O4S2: C, 58.75; H, 5.54; N, 5.70. Found: C, 58.66; H, 5.54; N, 5.66. Example 434 2-(4-Fluorophenyl)-4-(2-methyl-4-pentenyl-1 -oxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pvridazinone The title compound was prepared according to the method of Example 178, substituting 2-methyl-4-penten-1-ol in place of 2-ethyl-1 -hexanol (yield: 135 mg, 76%). M.p. 106-107 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.76 (d, J = 7 Hz, 3H), 1.78 (m, 2H), 2.00 (m, 1 H), 3.20 (s, 3H), 4.25 (m, 2H), 4.00 (m, 2H), 5.67 (m, 1 H), 7.37 (t, J = 0 Hz, 2H), 7.66 (m, 2H), 7.02 (d, J = 9 Hz, 2H), 8.06 (d, J = 0 Hz, 2H), 8.18 (s, 1 H). MS (APCI+) m/z 443 (M+H)+; (APCI-) m/z 477 (M+CI) " . Anal. calc. for C23H23FN2O4S: C, 62.42; H, 5.23; N, 6.33. Found: C, 62.13; H, 5.12; N, 6.22. Example 435 2-(3.4-DifluorophenylV4-f3-thfluoromθthyl-1 -butoxyV5-[4-(mθthylsulfonvπphenyl]- 3(2H)-pyridazinone To a solution of 2-(3,4-difluorophenyl)-4-hydroxy-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyidazinone (18θmg, 0.5 mmol), Ph3P (262 mg, 1 mmol) and 3-trifluoromethyl-1 -butanol (66 mg, 0.5 mmol) in THF (25 mL) was added dropwise a solution of DIAD (0.2 mL, 1 mmol) in THF (5 mL) and the resulting mixture was stirred at room temperature for 8 hours. The mixture was -220- concentrated in vacuo and the residue was chromatographed (silica gel, 1 :1 hexanes-ethyl acetate) to provide the desired product, (yield: 180 mg 71%). M.p. 126-128 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.96 (d, J = 7 Hz, 3H), 1.55 (m, 1 H), 1.97 (m, 1 H), 2.30 (m, 1 H), 3.29 (s, 3H), 4.46 (m, 2H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.00 (d, J = 0 Hz, 2H), 8.08 (d, J = 0 Hz, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 503 (M+H)+; (APCI-) m/z 537 (M+CI) " . Anal. calc. for C22H10F5N2O4S: C, 52.50; H, 3.81 ; N, 5.57. Found: C, 52.70; H, 3.73; N, 5.63. Example 436 2-(3.4-DifluorophenylV4-ethoxy-5-[4-(methylsulfonvπphθnyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 178, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinonβ in place of 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinonβ and substituting ethanol in place of 2-ethyl-1 -hexanol (yield: 25 mg, 12%). M.p. 121 -123 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.23 (t, J = 7 Hz, 3H), 3.30 (s, 3H), 4.51 (q, J = 7 Hz, 2H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.00 (d, J = 0 Hz, 2H), 8.08 (d, J = 0 Hz, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 407 (M+H)+; (APCI-) m/z 441 (M+CI) " . Anal. calc. for CιgHιβF2N2θ4S-0.25 H2O: C, 55.53; H, 4.04; N, 6.81. Found: C, 55.58; H, 4.21 ; N, 6.61. Example 437 2-(3.4-Difluorophenvπ-4- ( 4-mθthyl-1 -pentyloxy 5-[4-(methylsulfonvnphenyl]-3(2HV pyridazinone The title compound was prepared according to the method of Example 178, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone and substituting 4-methyl-1 -pentanol in place of 2-ethyl-1 - hexanol (yield: 120 mg, 52%). M.p. 08-00 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.73 (d, J = 7 Hz, 6H), 1.02 (m, 2H), 1.20 (m, 1 H), 1.54 (m, 2H), 3.30 (s, 3H), 4.40 (t, J = 7 Hz, 2H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.00 (d, J = 0 Hz, 2H), 8.08 (d, J = 0 Hz, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 463 (M+H)+; (APCI-) m/z 407 (M+CI)-. Anal. calc. for C23H24F2N2O4S: C, 50.72; H, 5.23; N, 6.05. Found: C, 50.57; H, 5.28; N, 6.01. Example 438 2-f3.4-Difluorophenyl -ι -mθthyl-2-pBntyloxyV5-f4- (msthylsulfonyl)phenyl]-3(2H)-pyridazinone The title compound was prepared according to the method of Example 178, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone and substituting 4-methyl-2-pentanol for 2-ethyl-1 -hexanol (yield: 115 mg, 50%). M.p. 132-133 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.80 (d, J = 7 Hz, 3H), 0.87 (d, J = 7 Hz, 3H), 1.10 (d, J = 7 Hz, 3H), 1.26 (m, 1 H), 1.50 (m, 1 H), 1.63 (m, 1 H), 3.30 (s, 3H), 5.31 (m, 1 H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.00 (d, J = 0 Hz, 2H), 8.08 (d, J = 0 Hz, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 463 (M+H)+; (APCI-) m/z 407 (M+CI) " . Anal. calc. for C23H24F2N2O4S: C, 50.72; H, 5.23; N, 6.05. Found: C, 50.44; H, 5.26; N, 5.00. Example 439 2-(3.4-Difluorophenyl)-4-(2-cyclopentyl-1 -ethoxy)-5-[4- (methylsulfonvπphenyr|-3(2H>-pyridazinone The title compound was prepared according to the method of Example 178, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone and substituting 2-cyclopentyl-1 -ethanol in place of 2-ethyl-1 - hexanol (yield: 115 mg, 60%). M.p. 100-101 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.00 (m, 2H), 1.38 (m, 2H), 1.57 (m, 7H), 3.30 (s, 3H), 4.42 (t, J = 7 Hz, 2H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.90 (d, J = 0 Hz, 2H), 8.08 (d, J = 0 Hz, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 475 (M+H)+; (APCI-) m/z 50Θ (M+CI) ' . Anal. calc. for C24H24F2N2O4S-0.25 H2O: C, 60.17; H, 5.15; N, 5.84. Found: C, 60.12; H, 5.14; N, 5.76. Example 440 2-(3.4-DifluoroDhenvli-4-f2-cvclopent-2-enyl-1 -ethoxy)-5-[4- (methylsulfonvnphenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 178, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone and substituting 2-cyclopent-2-enyl-1 -ethanol in place of 2- ethyl-1 -hexanol (yield: 05 mg, 48%). M.p. 126-127 °C. 1 H NMR (300 MHz, DMSO- dβ) δ 1.30 (m, 1 H), 1.57 (sextet, J = 7 Hz, 1 H), 1.60 (sextet, J = 7 Hz, 1 H), 1.87 (m, 2H), 2.57 (m, 1 H), 3.30 (s, 3H), 4.45 (m, 2H), 5.60 (m, 1 H), 5.68 (m, 1 H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.00 (d, J = 9 Hz, 2H), 8.08 (d, J = 9 Hz, 2H), 8.22 (s, 1 H). MS (APCI+) m/z 473 (M+H)+; (APCI-) m/z 507 (M+CI) " . Anal. calc. for C24H22F2N2O4S: C, 61.00; H, 4.69; N, 5.92. Found: C, 60.76; H, 4.65; N, 5.80. Example 441 2-(2-Hydroxy-2-phenylethyl)-4-(4-fluorophanyl)-5-[4-(methylsulfonyl)phenyl]-3.2H)- pvridazinone A mixture of the product from Example 46, 2-phenacyl-4-(4-fluorophenyl)-5- [4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (700 mg, 1.5 mmol), and sodium borohydride (60 mg, 1.8 mmol) in ethanol (200 mL), was stirred at 40 °C for 2 hours. The reaction mixture was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 2 N aqueous hydrochloric acid. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a pale yellow solid which was crystallized from ethyl acetate/hexanes to provide the title compound as white crystals (yield: 540 mg, 78%). M.p. 205-207 °C. 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 3.75 (br s, 1 H), 4.63-4.47 (m, 2H), 5.33 (dd, J = 0 Hz, 3 Hz, 1 H), 7.00 (t, J = 0 Hz, 2H), 7.20 (dd, J = 0 Hz, 3 Hz, 2H), 7.30-7.45 (m, 5H), 7.52 (d, J = 0 Hz, 2H), 7.01 (s, 1 H), 7.01 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 465 (M+H)+. Anal. calc. for C25H21 FN2O4S: C, 64.64; H, 4.55; N, 6.03. Found: C, 64.34; H, 4.66; N, 5.03. Example 442 2-C2-Methoxy-2-phenylethvh-4-f4-fluorophenvh-5-[4-(methylsulfonvhphenyl]-3(2H)- pyridazinone A mixture of the product from Example 441 , 2-(2-hydroxy-2-phenylethyl)-4- (4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (210 mg, 0.45 mmol), iodomethane (56 μL, 0.90 mmol), and an 80% oil dispersion of sodium hydride (18 mg, 0.59 mmol) in anhydrous DMF (16 mL) was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and 2 N aqueous hydrochloric acid. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a yellow oil which was purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate). Fractions containing product were combined and concentrated in vacuo , and the residue was triturated with hexanes to provide the title compound (yield: 75 mg, 34.7%). M.p. 135-137 °C. 1 H NMR (300 MHz, CDCI3) δ 3.07 (s, 3H), 3.26 (s, 3H), 4.33-4.52 (m, 2H), 4.01 (dd, J = 9 Hz, 3 Hz, 1 H), 6.99 (t, J = 9 Hz, 2H), 7.20 (dd, J = 0 Hz, 3 Hz, 2H), 7.31 -7.50 (m, 7H), 7.87 (s, 1 H), 7.80 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 470 (M+H)+. Anal. calc. for C26H23FN2O4S: C, 65.25; H, 4.84; N, 5.85. Found: C, 64.08; H, 4.83; N, 5.81. Example 443 2-f2-Methoxyimino-2-phenylethyπ-4-(4-fluorophenylV5-[4-(methylsulfonvπphenyl]- 3(2HVpvridazinone A mixture of the product from Example 46, 2-phenacyl-4-(4-fiuorophenyl)-5- [4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (220 mg, 0.476 mmol), methoxylamine hydrochloride (318 mg, 3.8 mmol), and sodium acetate (518 mg, 3.8 mmol) in methanol (100 mL) was stirred at reflux for 48 hours. The reaction mixture was concentrated in vacuo , and the residue was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was washed with brine then dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a brown oil which was purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate). Fractions containing product were combined and concentrated in vacuo . The residue was crystallized from methanol/water to provide the title compound as a mixture of E and Z oximes (yield: 82 mg, 35%). M.p. 05-00 °C. 1 H NMR (300 MHz, CDCI3) δ 3.03 (s, 3H), 4.07 (s, 3H), 5.57 (s, 2H), 6.04 (t, J = 0 Hz, 2H), 7.07 (dd, J = 0 Hz, 3 Hz, 2H), 7.24 (d, J = 0 Hz, 2H), 7.31 -7.37 (m, 3H), 760-7.67 (m, 2H), 7.74 (s, 1 H), 7.83 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 402 (M+H)+. Anal. calc. for C-26H22FN3O4S: C, 63.53; H, 4.51 ; N, 8.54. Found: C, 63.40; H, 4.51 ; N, 8.31. Example 444 2-(3.4-DifluorophenylV4-(4-mθthylpentvπ-5-[3-fluoro-4-(methylsulfonvπphenyll- 3(2H pyhdazinone The title compound was prepared according to the method of Example 255, substituting 1 -bromo-4-methylpentane in place of 3,4-difluorobenzyl bromide (yield: 145 mg, 58%). M.p. 111 -113 °C. 1 H NMR (300 MHz, DMSO-dδ) δ 0.75 (d, 6H), 1.00 (m, 2H), 1.4 (m, 3H), 2.48 (m, 2H), 3.4 (s, 3H), 7.61 (m, 2H), 7.75 (d, 2H), 7.81 (m, 1 H), 8.02 (s, 1 H), 8.1 (d, 2H). MS (DCI-NH3) m/z 447 (M+H)+, 464 (M+NH4) + - Anal. calc. for C23H24F2N2O3S: C, 61.87; H, 5.42; N, 6.27. Found: C, 6176; H, 5.55; N, 6.11. Example 445 2-(3.4-Difluorophenyl)-4-.3-methyl-1 -butoxy)-5-f4-(aminosulfonyl)phenyl1-3(2H)- pvridazinone The title compound was prepared as described in Example 384, -substituting 2-(3,4-difluorophenyl)-4-(3-methyl-1 -butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone (Example 347) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyhdazinone (yield: 248 mg, 42%). M.p. 140-151 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 0.8 (d, J = 6 Hz, 6H), 1.48 (m, 2H), 1.54 (m, 1 H), 4.4 (t, 2H), 7.51 (m, 3H), 7.6 (m, 1 H), 7.85 (m, 3H), 7.05 (d, J = 0 Hz, 2H), 8.21 (s, 1 H). MS (DCI-NH3) m/z 450 (M+H)+, 467 (M+NH4)+. Anal. calc. for C21 H21 F2N3O4S: C, 56.12; H, 4.71 ; N, 0.35. Found, C, 56.12; H, 4.67; N, 0.15. Example 446 2-(2.2.2-Trifluoroethyl)-4-(2.2-dimethylpropoxy ) -5-f4- ( aminosulfonyhphenyl]-3(2H)- pvridazinone The intermediate, 2-(2,2,2-trifluoroethyl)-4-hydroxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone prepared in Example ΘOC was reacted with 2,2-dimethyl- propanol to provide 2-(2,2,2-trifluoroethyl)-4-(2,2-dimethylpropoxy)-5-[4- (methylthio)phenyl]-3(2H)-pyridazinone according to the method of Example 0OD. The product was oxidized with one equivalent of me a-chloroperoxybenzoic acid to provide the methyl sulfoxide. The sulfoxide was converted to the title compound according to the method of Example 68, substituting 2-(2,2,2-trifluoroethyl)-4-(2,2- dimethylpropoxy)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone for 2-(2,2,2- trifluoroethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone (yield: 125 mg, 53%). M.p. 123-124 °C. 1 H NMR (300 MHz, CDCI3) δ 0.82 (s, ΘH), 4.18 (s, 2H), 4.82 (q, J = 0 Hz, 2H), 4.84 (s, 2H), 7.70 (d, J = 0 Hz, 2H), 7.81 (s, 1 H), 8.04 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 420 (M+H)+. Anal. calc. for C17H20F3N3O4S: C, 48.68; H, 4.80; N, 10.01. Found: C, 48.76; H, 4.77; N, 0.04. Example 447 2-(2.2.2-Trifluoroethyl)-4-(3-methylbutoxy)-5-[4-(msthylsulfonyl)phenyl]-3f2H)- pyridazinonθ The title compound was prepared according to the method of Example 83, substituting 3-methyl-1 -butanol in place of isopropanol (yield: 65 mg, 85%). M.p. 11 1 -113 °C. 1 H NMR (300 MHz, CDCI3) δ 0.84 (d, J = 6 Hz, 6H), 1.51 (m, 2H), 1.63 (m, 1 H), 3.11 (s, 3H), 4.54 (t, J = 6 Hz, 2H), 4.83 (q, J = 0 Hz, 2H), 7.73 (d, J = 0 Hz, 2H), 7.82 (s, 1 H), 8.05 (d, J = 0 Hz, 2H); MS (DCI-NH3) m/z 410 (M+H)+. Anal. calc. for C18H21 F3N2O4S: C, 51.66; H, 5.05; N, 6.60. Found: C, 51.01 ; H, 5.06; N, 6.56. Example 448 2-(2.2.2-Trifluoroethyl)-4-f3-methylbutoxy)-5-[4-(aminosulfonyl.phenyl]-3.2HV pvridazinone The intermediate, 2-(2,2,2-trifluoroethyl)-4-hydroxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone prepared in Example ΘOC was reacted with 3-methyl-1 -butanol to provide 2-(2,2,2-trifluoroethyl)-4-(3-methylbutoxy)-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone according to the method of Example ΘOD. The product was oxidized with one equivalent of mefa-chloroperoxybenzoic acid to provide the methyl sulfoxide. The sulfoxide was converted to the title compound according to the method of Example 68, substituting 2-(2,2,2-trifluoroethyl)-4-(3-methylbutoxy)-5- [4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone for 2-(2,2,2-trifluoroethyl)-4-(4- fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyhdazinone (yield: 65 mg, 50%). M.p. 123-124 °C. 1 H NMR (300 MHz, CDCI3) δ 0.84 (d, J = 6 Hz, 6H), 1.52 (q, J = 6 Hz, 2H), 1.60 (h, J = 7.5 Hz, 1 H), 4.52 (t, J = 6 Hz, 2H), 4.83 (q, J = 0 Hz, 2H), 4.00 (s, 2H), 7.60 (d, J = 0 Hz, 2H), 7.82 (s, 1 H), 8.04 (d, J = 0 Hz, 2H). MS (DCI-NH3) m/z 420 (M+H)+. Anal. calc. for C17H20F3N3O4S: C, 48.68; H, 4.80; N, 10.01. Found: C, 48.86; H, 4.83; N, 0.02. Example 449 2-(2.2.2-Thfluoroethvn-4-(2-methylpropoxyV5-[4-(aminosulfonvπphenyl]-3(2HV pyridazinone The intermediate, 2-(2,2,2-trifluoroethyl)-4-hydroxy-5-[4-(methylthio)phenyl]- 3(2H)-pyridazinone prepared in Example ΘOC was reacted with 2-methyl-1 - propanol to provide 2-(2,2,2-trifluoroethyl)-4-(2-methylpropoxy)-5-[4-(methylthio)- phenyl]-3(2H)-pyridazinone according to the method of Example 90D. The product was oxidized with one equivalent of mefa-chloroperoxybenzoic acid to provide the methyl sulfoxide. The sulfoxide was converted to the title compound according to the method of Example 68, substituting 2-(2,2,2-trifluoroethyl)-4-(2-methylpropoxy)- 5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone for 2-(2,2,2-trifluoroethyl)-4-(4- fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone (yield: 120 mg, 40%). M.p. 170-172 °C. 1 H NMR (300 MHz, CDCI3) δ 0.83 (d, J = 6 Hz, 6H), 1.0 (m, 1 H), 4.3 (m, 2H), 4.82 (s, 2H), 4.88 (m, 2H), 7.70 (d, J = 0 Hz, 2H), 7.70 (s, 1 H), 8.03 (d, J = 0 Hz, 2H); MS (DCI-NH3) m/z 406 (M+H)+. Anal. calc. for C16H18F3N3O4S: C, 47.4; H, 4.47; N, 10.36. Found: C, 47.48; H, 4.36; N, 10.25. Example 450 2- 2.3.3-Trifluoropropenvn-4-(4-fluorophenvn-5-[4-(aminosulfonvhphenvπ-3(2H)- pvridazinone The product of Example 4, 2-benzyl-4-(4-fluorophenyl)-5-[4- (methylthio)phenyl]-3(2H)-pyridazinone, was N-debenzylated by the method of Example 11 to provide 4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)- pyridazinone. The intermediate was mixed with one equivalent of 1 -methylsufonyl- oxy-2,3,3-thfluoro-2-propene, (Example 88A) in ethyl acetate, followed by one equivalent of cesium carbonate. The reaction mixture was heated to 50 °C for 5 hours. Aqueous work-up, followed by chromatography provided 2-(2,3,3-trifluoro- propenyl)-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone (650 mg, 63%). The product was oxidized with one equivalent of mefa-chloroperoxybenzoic acid to provide the methyl sulfoxide which was converted to the title compound according to the method of Example 68, substituting 2-(2,3,3-trifluoropropenyl)-4- (4-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone for 2-(2,2,2- trifluoroethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfinyl)phenyl]-3(2H)-pyridazinone (yield: 65 mg, 35%). M.p. 100-103°C. 1 H NMR (300 MHz, CDCI3) δ 5.07 (s, 2H), 5.10 (dt, J = 21 Hz, J = 3 Hz, 2H), 7.05 (m, 4H), 7.10 (dd, J = 0 Hz, J = 6 Hz, 2H), 7.84 (s, 1 H), 7.87 (t, J = 7.5 Hz, 1 H). MS (ESI-NH3) m/z 456 (M-H)+. Anal. calc. for Cι gHi 2FδN3θ3S: C, 40.80; H, 2.64; N, 0.18. Found: C, 40.80; H, 2.73; N, 0.03. Example 451 2-^4-Fluorophenvπ-4-( , 3-hvdroxy-3-methyl-1-butoxyV5-[4-fmethylsulfonvπphenyl]- 3f2H pyridazinone The title compound was prepared according to the method of Example 178, substituting 3-methyl-1 ,3-butandiol in place of 2-ethyl-1 -hexanol (yield: 110 mg, 61 %), M.p. 133-134 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.04 (s, 6H), 172 (t, J = 7 Hz, 2H), 3.20 (s, 3H), 4.32 (s, 1 H), 4.53 (t, J = 7 Hz, 2H), 7.37 (t, J = 0 Hz, 2H), 7.66 (m, 2H), 7.00 (d, J = 0 Hz, 2H), 8.07 (d, J = 0 Hz, 2H), 8.19 (s, 1 H). MS (APCI+) m/z 447 (M+H)+; (APCI-) m/z 481 (M+CI) ** . Anal. calc. for C22H23FN2O5S-0.25 H2O: C, 58.59; H, 5.25; N, 6.21. Found: C, 58.42; H, 5.00; N, 6.02. Example 452 2-f3.4-DifluorophenylV4-f2-hvdroxy-2-methyl-1 -propoxy)-5-[4- (methylsulfonyl)phenvl]-3f2H)-pyridazinone The title compound was prepared according to the method of Example 178, starting with 2-(3,4-difluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- py dazinone in place of 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone and substituting 2-methyl-1 ,2-propandiol in place of 2-ethyl-1 - hexanol (yield: 55 mg, 31 %). 1 H NMR (300 MHz, DMSO-dβ) δ 0.07 (s, 6H), 3.30 (s, 3H), 4.20 (s, 2H), 4.54 (s, 1 H), 7.52 (m, 1 H), 7.62 (m, 1 H), 7.81 (m, 1 H), 7.08 (d, J = 0 Hz, 2H), 8.05 (d, J = 0 Hz, 2H), 8.21 (s, 1 H). MS (APCI+) m/z 451 (M+H)+; (APCI-) m/z 485 (M+CI) " . Anal. calc. for C-21 H20F2N2O5S: C, 55.00; H, 4.47; N, 6.21. Found: C, 56.00; H, 4.48; N, 5.87. u Example 453 2-(3.4-Difluorophenyli-4-methoxy-5-[4-(mathylsulfonyl)phenyl]-3(2H.-pyridazinone The title compound was isolated from the reaction mixture in Example 233, as a product of oxidation of unreacted starting material (yield: 22 mg, 8%). M.p. 113-115 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.3 (s, 3H), 4.1 (s, 3H), 7.53 (m, 1 H), 7.63 (m, 1 H), 7.8 (m, 1 H), 8.15 (d, 2H), 8.2 (s, 2H). MS (DCI-NH3) m/z 303 (M+H)+, 410 (M+NH4)+. Anal. calc. for C18H14F2N2O4S: C, 55.10; H, 3.60; N, 7.14. Example 454 2-.2.3.4.5.6-Pentafluorobenzvn-4-(4-fluorophenyl)-5-[4-[fdimethylamino)- methvlane]aminosulfonvlphenyl]-3(2 -pvridazinone The title compound was isolated from the reaction mixture in Example 125, as a product resulting from a reaction with the solvent, N,N-dimethylformamide (yield: 53 mg, 16%). M.p. 104-106 °C. " Η NMR (300 MHz, CDCI3) δ 3.05 (s, 3H), 3.17 (s, 3H), 5.40 (s, 2H), 6.07 (t, J = 9 Hz, 2H), 7.18 (dd, J = 9 Hz, 6 Hz, 2H), 7.20 (d, J = 0 Hz, 2H), 7.81 (s, 1 H), 7.82 (d, J = 0 Hz, 2H), 8.14 (s, 1 H). MS (DCI-NH3) m/z 581 (M+H)+. Anal. calc. for C26H18F6N4O3S: C, 53.70; H, 3.12; N, 0.65. Found: C, 53.50; H, 3.24; N, 0.56. Example 455 2-(2.4-Difluorobenzvh-4-f4-fluorophenyl)-5-[4-[(dimethvlamino.methvlene1- aminosulfonylphBnyl]-3(2HVpyridazinonθ The title compound was isolated from the reaction mixture in Example 124, as a product resulting from a reaction with the solvent, N,N-dimethylformamide (yield: 55 mg, 18%). M.p. 103-105 °C. 1 H NMR (300 MHz, CDCI3) δ 3.03 (s, 3H), 3.16 (s, 3H), 5.43 (s, 2H), 6.88 (m, 2H), 6.05 (t, J = 0 Hz, 2H), 7.18 (dd, J = 0 Hz, 6 Hz, 2H), 7.20 (d, J = 0 Hz, 2H), 7.52 (m, 1 H), 7.81 (d, J = 0 Hz, 2H), 7.84 (s, 1 H), 8.13 (s, 1 H). MS (DCI-NH3) m/z 527 (M+H)+. Anal. calc. for C26H21 F3N4O3S: C, 50.30; H, 4.02; N, 10.64. Found: C, 50.08; H, 3.07; N, 10.48. Example 456 2-(4-Fluoroohenvli-5-[4-(methylselenonyl)phenyl]-3f2H)-pvridazinone 446A. 4-Bromosθl6noanisolθ Freshly crushed magnesium turnings (6.1 g, 0.25 mol) were suspended with vigorous stirring in a solution of diethyl ether (360 mL) and 1 ,4-dibromobenzene (10 g, 0.04 mol). The solution was brought to reflux for 30 minutes, without initiation. Several crystals of iodine were added which initiated the reaction to a self-sustained reflux. The reflux was maintained as the remainder of the 1 ,4- dibromobenzene (49 g, 0.21 mol) was slowly added. The reaction was refluxed for an additional 2 hours after addition of the 1 ,4-dibromobenzene was completed. When nearly all of the magnesium turnings had been consumed, the yellow/gray heterogeneous solution was cooled to 23 °C, and selenium (19 g, 0.24 mol) was added in small portions via spatula so as to maintain a gentle reflux. The selenium that became stuck to the sides of the flask was washed in with additional diethyl ether. After addition, the solution was stirred for 20 minutes at 23 °C and then was cooled to 0 °C. A diethyl ether (20 mL) solution of methyl iodide (35.5 g, 0.25 mol) was slowly added dropwise to the reaction mixture. Upon completion of addition, the cooling bath was removed, and the solution stirred for 3 hours at 23 °C. The reaction solution was slowly poured into ice water/1 M HCl , and then the biphasic solution filtered through a glass wool plug. The ethereal layer was separated and the aqueous phase extracted twice more with diethyl ether. The combined ethereal extracts were dried over MgSθ4, filtered, and concentrated in vacuo to provide a semi-viscous orange oil. On standing overnight at -20 °C, large yellow needles formed. The residual oil was drawn off via pipette to provide 17 g (27%) of crystalline product. (J. Org. Chem., 1983, 48, 4169) 1 H NMR (300 MHz, CDCI3) δ 2.46 (s, 3H), 7.12 (d, J = 8.7 Hz, 2H), 7.39 (d, J = 8.7 Hz, 2H). MS (APCI+) m/z 248 (Se7β M+H)+, m/z 250 (Se78 M+H)+, m/z 252 (Seso M+H)+, and m/z 254 (Se82 M+H)+. 446B. 2.4-Bis^4-fluorophenvn-5-[4-(methylselθno)phenyl]-3(2HVpyridazinone The title compound was prepared according to the method of Example 228, substituting 2-(4-fluorophenyl)-4-methoxy-5-[4-(methylseleno)phenyl]-3(2H)- pyridazinonβ [prepared according to the method of Example 1 Θ4C, substituting 4-(methylseleno)benzeneboronic acid, (prepared according to the method of Example 1 , substituting 4-bromoselenoanisole in place of 4-bromothioanisole) in place of 4-(methylthio)benzeneboronic acid] in place of 2-(4-fluorophenyl)-4- methoxy-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone and substituting 4- fluorophenyl magnesium bromide in place of cyclohexylmagnesium chloride (yield: 44 mg, 60%). 1 H NMR (300 MHz, CDCI3) δ 2.37 (s, 3H), 6.08 (dd, J = 8.8, 8.8 Hz, 2H), 7.05 (d, J = 8.7 Hz, 2H), 7.17 (dd, J = 8.7, 8.7 Hz, 2H), 7.23-7.31 (m, 2H), 7.32 (d, J = 8.7 Hz, 2H), 7.65-772 (m, 2H), 8.00 (s, 1 H). MS (APCI+) m/z 455 (M+H)+. 446C. 2.4-Bis(4-fluorophenvπ-5-[4-Cmethylselθnonvπphenyl]-3f2HVpyridazinone A stirred solution of the 2,4-bis(4-fluorophenyl)-4-(4-fluorophenyl)-5-[4- (methylseleno)phenyl]-3(2H)-pyhdazinone (40 mg, 88.1 mmol) in methylene chloride (2 mL) was treated with 3-chloroperoxybenzoic acid (100 mg, 342 mmol, 57-86%) at 23 °C. After 2 hours, the reaction appeared to be only slightly more than 50% completed. Additional 3-chloroperoxybenzoic acid (80 mg, 274 mmol, 57-86%) was added. The reaction ran to completion over the next 16 hours of stirring at 23 °C. The solution was diluted with ethyl acetate and carefully shaken with a NaHSO3 solution (two times) for several minutes to consume the excess 3- chloroperoxybenzoic acid. The ethyl acetate solution was subsequently washed with a saturated Na2C03 solution (two times), water, and brine and dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (flash silica gel, acetone/methylene chloride/hexanes 2:2:1 ) to provide the product (yield: 40 mg, 03%). (J. Chem. Soc, Chem. Commun., 1985, 569). M.p. 110-150 °C. 1 H NMR (300 MHz, CDCI3) δ 3.32 (s, 3H), 6.91 (dd, J = 8.7, 8.7 Hz, 2H), 7.14- 7.27 (m, 4H), 7.48 (d, J = 8.4 Hz, 2H), 7.65-773 (m, 2H), 7.97 (s, 1 H), 8.00 (d, J = 8.4 Hz, 2H). MS (APCI+) m/z 487 (M+H)+ and m/z 504 (M+NH4)+. Anal. calc. for C23Hl 6F2N2θ3Se-0.5 H2O: C, 55.88; H, 3.46; N, 5.66. Found: C, 55.60; H, 3.61 ; N, 5.29. Example 457 2-(3.4-Difluorophenyl)-4-f3-fluorophBnyl)-5-r4-(methylsulfonyl)phBnyl]-3(2H)- pvridazinonθ The title compound was prepared as described in Example 62, starting with 4-(3-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4- fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 3,4- difluorobromobenzene in place of 1 -bromo-4-fluorobenzene (yield: 185 mg, 46.5%). M.p. 182-185 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.23 (s, 3 H), 6.98 (d, J = 9 Hz, 1 H), 7.18 (m, 2H), 7.32 (m, 1 H), 7.52 (d, J = 9 Hz, 2 H), 7.6 (m, 2H), 7.85 (m, 1 H), 7.9 (d, J = 9 Hz, 2H), 8.3 (s, 1 H). MS (DCI-NH3) m/z 457 (M+H)+, 474 (M+NH4)+. Example 458 2-(4-Fluorophenvn-4-.3-fluorophBnyl)-5-[4-(mθthvlsulfonvl)phBnyl]-3(2H)- pyridazinone The title compound was prepared as described in Example 62, substituting 4-(3-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4- fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 135 mg, 34%). M.p. 100-201 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 3.24 (s, 3H), 6.08 (d, J = 0 Hz, 1 H), 7.18 (m, 2H), 7.32 (m, 1 H), 7.30 (t, 1 H), 7.54 (d, J = 0 Hz, 2 H), 7.71 (m, 2H), 7.01 (d, J = 0 Hz, 2 H), 8.27 (s, 1 H). MS (DCI-NH3) m/z 430 (M+H)+, 456 (M+NH4)+. Example 459 2-(3.4-Difluorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)- phsnyl]-3(2H)-pvridazinons 2-(3,4-Difluorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyhdazinone (Example 452) is converted to the title sulfonamide according to the method of Example 384. Example 460 2-(3.4-Difluorophenyl)-4-(2-oxo-1 -propoxv 5-[4-(mBthylsulfonyl)phsnyl]-3(2H)- pyridazinone A solution of 2-(3,4-difluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (378 mg, 1 mmol), Ph3P (524 mg, 2 mmol) and acetol (74 mg, 1 mmol) in THF (25 mL) at room temperature was treated dropwise with a solution of DIAD (0.4 mL, 2 mmol) in THF (5 mL). The mixture was stirred at room temperature for 6 hours and concentrated in vacuo. The residue was chromatographed (silica gel, 1 :1 hexanes-ethyl acetate) to provide the desired product (yield: 205 mg, 48%). M.p. 160-170 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 2.08 (s, 3H), 3.30 (s, 3H), 5.30 (s, 2H), 7.48 (m, 1 H), 7.62 (q, J = 10 Hz, 1 H), 7.75 (m, 1 H), 7.04 (d, J = 0 Hz, 2H), 8.05 (d, J = 9 Hz, 2H), 8.21 (s, 1 H). MS (APCI+) m/z 435 (M+H)+, (APCI-) m/z 469 (M+CI) " . Anal. calc. for C20H16F2N2O5SO.75H2O: C, 53.62; H, 3.93; N, 6.25. Found: C, 53.26; H, 3.61 ; N, 6.08. Example 461 2-r3.4-DifluorophBnyl)-4-[2- ( mBthoxyimino)propoxy]-5-[4-(mBthylsulfonyl)phBnyl]- 3(2HVpyhdazinonθ A mixture of 2-(3,4-difluorophenyl)-4-(2-oxo-1 -propoxy)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone from Example 460 (150 mg, 0.3 mmol) in H2O (10 mL) and dioxane (20 mL) was treated with methoxylamine hydrochloride (84 mg, 1 mmol) and sodium acetate trihydrate (138 mg, 1 mmol). The mixture was stirred at room temperature for 6 hours. The reaction mixture was extracted with ethyl acetate and purified by column chromatography (silica gel, 1 :1 hexanes-ethyl acetate) to provide the title compound (yield: 20 mg, 15%). M.p. 143-145 °C. 1 H NMR (300 MHz, DMSO-dβ) δ 1.63 (s, 3H), 3.30 (s, 3H), 3.74 (s, 3H), 4.03 (s, 2H), 7.54 (m, 1 H), 7.65 (q, J = 10 Hz, 1 H), 7.82 (m, 1 H), 7.02 (d, J = 0 Hz, 2H), 8.07 (d, J = 9 Hz, 2H), 8.24 (s, 1 H). MS (APCI+) m/z 464 (M+H)+; (APCI-) m/z 498 (M+CI) " . Anal. calc. for C21 H19F2N3O5S: C, 54.42; H, 4.13; N, 9.06. Found: C, 54.33; H, 3.03; N, 8.02. Example 462 (S)-2-f3.4-Difluorophenylι-4-(3-hydroxy-2-mBthylpropoxv>-5-f4-.mBthvl- sulfonyl.phenyl]-3(2H)-pyridazinone 462A (RV3-f-Butoxy-2-methyl-1 -propanol A solution of (S)-(+)-methyl 3-hydroxy-2-methylpropionate (1.18 g, 10 mmol) in t-butyl acetate (30 mL) was treated with 70% HCIO4 (0.1 mL), and the reaction mixture was left at room temperature in a tighthly closed flask for 24 hours. The mixture was poured into a saturated solution of sodium bicarbonate and extracted with diethyl ether. The ether was removed in vacuo and the residue was dissolved in THF (50 mL). To the resulting solution was added sodium borohydride (025 mg, 25 mmol) and at 55 °C dropwise methanol (10 mL). The reaction was continued at 55 °C for 1 hour, then cooled to room temperature, acidified with 10% citric acid to pH 5 and extracted with ethyl acetate. The acetate extract was washed with water, brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed (silica gel, 2:1 hexanes-ethyl acetate) to provide (R)-3-ι " -butoxy-2- methyl-1 -propanol (yield: 1 g, 68%). 1 H NMR (300 MHz, CDCI3) δ 0.85 (d, J = 7 Hz, 3H), 1.20 (s, ΘH), 2.03 (m, 1 H), 3.30 (t, J = 12 Hz, 1 H), 3.53 (dd, J = 12 Hz, 4.5 Hz, 1 H), 3.70 (m, 2H). MS (DCI-NH3) m/z 164 (M+NH4)+. 462B .S.-2-.3.4-DifluoroDhenyl.-4-.3-f-butoxy-2-msthylpropoxy)-5-[4- ■ methylsulphonyl)phenyl]-3(2H)-pyridazinone To a solution 2-(3,4-difluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone (378 mg, 1 mmol), Ph3P (524 mg, 2 mmol) and the above alcohol, (R)-3-f-butoxy-2-methyl-1 -propanol (146 mg, 1 mmol) in THF (25 mL) at room temperature was added dropwise a solution of DIAD (0.4 mL, 2 mmol) in THF (5 mL). The mixture was then stirred at room temperature for 6 hours and concentrated in vacuo. The residue was passed through a silica gel pad (hexanes- ethyl acetate as an eluent) to provide 550 mg of roughly purified (S)-2-(3,4- difluorophenyl)-4-(3-f-butoxy-2-methylpropoxy)-5-[4-(methylsulphonyl)phenyl]- 3(2H)-pyridazinone, still contaminated with reduced DIAD. MS (APCI+) m/z 507 (M+H)+; (APCI-) m/z 541 (M+CI) " . 462C fSV2-(3.4-Difluorophenvn-4-f3-hvdroxy-2-methylpropoxyV5-[4-(methyl- sulfonvnphenvl]-3(2HVpvridazinone A mixture of the above product (100 mg, -0.2 mmol) in TFA (5 mL) was stirred at room temperature for 24 hours and then concentrated in vacuo. The residue was neutralized with saturated NaHCO3 and extracted with ethyl acetate. Purification by column chromatography (silica gel, 1 :2 hexanes-ethyl acetate) provided the title compound (yield: 51 mg, 56%). 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (d, J = 7 Hz, 3H), 1.81 (septet, J = 7 Hz, 1 H), 3.21 (d, J = 6 Hz, 2H), 3.30 (s, 3H), 4.20 (dd, J = 12 Hz, 6 Hz, 1 H), 4.40 (dd, J = 12 Hz, 6 Hz, 1 H), 4.48 (br s, 1 H), 7.52 (m, 1 H), 7.61 (m, 1 H), 7.80 (m, 1 H), 7.01 (d, J = 0 Hz, 2H), 8.07 (d, J = 0 Hz, 2H), 8.20 (s, 1 H). MS (APCI+) m/z 451 (M+H)+; (APCI-) m/z 485 (M+CI) " . Anal. calc. for C-21 H20F2N2O5S: C, 55.99; H, 4.47; N, 6.21. Found: C, 55.65; H, 4.65; N, 5.92. Example 463 )-2-f3.4-Difluorophenvn-4-.3-hvdroxv-2-msthylpropoxv)-5-[4-(methylsulfonyl)- phenvl]pvridazinone The desired material was prepared according to the procedure of Example 462 starting with (R)-(-)-methyl 3-hydroxy-2-methylpropionate in place of (S)-(-)- methyl 3-hydroxy-2-methylpropionate (yield: 65 mg, 61 %). 1 H NMR (300 MHz, DMSO-dβ) δ 0.75 (d, J = 7 Hz, 3H), 1.81 (septet, J = 7 Hz, 1 H), 3.21 (t, J = 6 Hz, 2H), 3.30 (s, 3H), 4.20 (dd, J = 6 Hz and 12 Hz, 1 H), 4.40 (dd, J = 6 Hz and 12 Hz, 1 H), 4.40 (t, J = 6 Hz, 1 H), 7.52 (m, 1 H), 7.61 (m, 1 H), 7.80 (m, 1 H), 7.01 (d, J = 9 Hz, 2H), 8.07 (d, J = 0 Hz, 2H), 8.20 (s, 1 H). MS (APCI+) m/z 451 (M+H)+; (APCI-) m/z 485 (M+CI) " . Anal. calc. for C21 H20F2N2O5S: C, 55.00; H, 4.47; N, 6.21. Found: C, 55.62; H, 4.52; N, 6.06. Example 464 (S)-2-(3.4-Difluorophenyn-4-(3-hydroxv-2-methylpropoxy)-5-[4-(aminosulfonyl)- phenyl]-3(2H .-p y ridazinone To a solution of (S)-2-(3,4-difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5- [4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone from Example 462 (450 mg, -0.0 mmol) and DBAD (207 mg, 0.0 mmol) in THF (25 mL) at -78 °C was added dropwise 1 M lithium bis(trimethylsilyl)amide solution in THF (3 mL, 3 mmol). The resulting mixture was stirred at -78 °C for 2 hours. The mixture was warmed to room temperature and 1 N NaOH was added (5 mL, 5 mmol). After 12 hours, at room temperature, sodium acetate trihydrate (2.76 g, 20 mmol) and H2O (10 mL) followed by hydroxylamine-O-sulphonic acid (2 g, 15 mmol) were added and the mixture was stirred at room temperature for 5 hours. The product was extracted with ethyl acetate and purified by chromatography (silica gel, 1 :2 hexanes-ethyl acetate) to provide the desired intermediate (yield: 160 mg, 35%). MS (APCI+) m/z 508 (M+H)+; (APCI-) m/z 542 (M+CI) " . TFA (5 mL) was added to the above intermediate and the resulting solution was stirred at room temperature for 24 hours. The TFA was removed in vacuo, and the residue was neutralized with saturated NaHCO3 and extracted with ethyl acetate. The organic extract was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed (silica gel, 1 :2 hexanes-ethyl acetate) to provide the title compound (yield: 50 mg, 33%). 1 H NMR (300 MHz, DMSO-dβ) δ 0.76 (d, J = 7 Hz, 3H), 1.81 (sextet, J = 7 Hz, 1 H), 3.22 (t, J = 6 Hz, 2H), 4.28 (dd, J = 12 Hz, 6 Hz, 1 H), 4.40 (dd, J = 12 Hz, 6 Hz, 1 H), 4.50 (t, J = 6 Hz, 1 H), 7.51 (m, 3H), 7.61 (m, 1 H), 7.80 (m, 1 H), 7.84 (d, J = 0 Hz, 2H), 7.05 (d, J = 0 Hz, 2H), 8.20 (s, 1 H). MS (APCI+) m/z 452 (M+H) + ; (APCI-) m/z 486 (M+CI) " . Example 465 (R)-2-(3.4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)- phenvl]-3(2HVpvhdazinone The title compound was prepared according to the procedure of Example 464 starting with (R)-2-(3,4-difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyhdazinone in place of (S)-2-(3,4-difluorophenyl)- 4-(3-hydroxy-2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 30 mg, 20%). 1 H NMR (300 MHz, DMSO-dβ) δ 0.76 (d, J = 7 Hz, 3H), 1.81 (sextet (J = 7 Hz, 1 H), 3.22 (t, J = 6 Hz, 2H), 4.28 (dd, J = 6 Hz and 12 Hz, 1 H), 4.40 (dd, J = 6 Hz and 12 Hz, 1 H), 4.50 (t, J = 6 Hz, 1 H), 7.51 (m, 3H), 7.61 (m, 1 H), 780 (m, 1 H), 7.84 (d, J = 0 Hz, 2H), 7.05 (d, J = 0 Hz, 2H), 8.20 (s, 1 H). MS (APCI+) m/z 452 (M+H)+; (APCI-) m/z 486 (M+CI)-. Anal. calc. for C20HI ΘF2N3O5S: C, 53.21 ; H, 4.24; N, 0.30. Found: C, 53.45; H, 5.53; N, 0.50. Example 466 2-f4-Fluorophenyl)-4-(4-hydroxy-3-methylbutoxy -5-[4-(methylsulphonvπphenyl]- S HVpyridazinonθ. The title compound was prepared according to the method of Example 178, substituting 2-methyl-1 ,4-butanediol in place of 2-ethyl-1 -hexanol and separating the regioisomeric products by preparative TLC using Silica Gel with ethyl acetate:hexanes (4/1 ). 1 H NMR (300 MHz, CDCI3) δ 0.87 (d, J = 8.1 Hz, 3H), 1.48- 1.87 (m, 4H), 3.13 (s, 3H), 3.41 (dd, J = 6.3, 13.5 Hz, 1 H), 3.46 (dd, J = 6.3, 13.5 Hz, 1 H), 4.48-4.63 (m, 2H), 7.15-7.24 (m, 2H), 7.58-766 (m, 2H), 7.70 (d, J=10.5 Hz, 2H), 7.01 (s, 1 H), 8.07 (d, J = 10.5 Hz, 2H). MS (APCI+) m/z 447 (M+H)+. Example 467 2-f3.4-difluorophenyl)-4-(3-oxobutoxy)-5-[4-(methylsulfonvnphenyl]-3.2H)- pvridazinone The title compound is prepared according to the method of Example 460 β substituting 4-hydroxy-2-butanone in place of acetol. (yield: 05.0 mg, 21 %). M.p. 134-135 °C. 1 H NMR (300 MHz, CDCI3) δ 2.06 (s, 3H), 2.81 (t, J = 0 Hz, 2H), 3.13 (s, 3H), 4.75 (t, J = 0 Hz, 2H), 7.30 (m, 1 H), 7.45 (m, 1 H), 7.58 (m, 1 H), 7.73 (d, J = 0 Hz, 2H), 7.80 (s, 1 H), 8.05 (d, J = 9 Hz, 2H) . MS (DCI-NH3) m/z 440 (M+H)+, 466 (M+NH4) + . Anal. calc. for C21 H18F2N2O5S: C, 56.25; H, 4.02; N, 6.25. Found: C, 55.07; H, 4.17; N, 6.11. Example 468 2-(4-Fluorophenvn-4-(3-oxobutoxy)-5-[4-(methylsulfonyl.phenyl]-3(2H)- pyridazinone The title compound is prepared according to the method of Example 460 starting with 2-(4-fluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone in place of 2-(3,4-difluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyhdazinone and substituting 4-hydroxy-2-butanone in place of acetol. (yield: 85.0 mg, 20%). M.p. 133-136 °C. 1 H NMR (300 MHz, CDCI3) δ 2.04 (s, 3H), 2.80 (t, J = 0 Hz, 2H), 3.13 (s, 3H), 4.76 (t, J = 0 Hz, 2H , 7.20 (t, J = 0 Hz, 2H), 7.55 (m, 2H), 7.75 (d, J = 0 Hz, 2H), 7.01 (s, 1 H), 8.05 (d, J = 0 Hz, 2H) . MS (DCI-NH3) m/z 431 (M+H)+, 448 (M+NH4)+. Anal. calc. for C-21 Hi gFN2θδS: C, 58.60; H, 4.42; N, 6.52. Found: C, 58.87; H, 4.55; N, 6.51. Prostaglandin Inhibition Determination Compound Preparation and Administration For oral administration, test compounds were suspended on the day of use in 100% polyethyleneglycol (PEG 400) with a motorized homogenizer equipped with a Teflon-coated pestle (TRI-R Instrument, Jamaica, NY). To compare the mean responses of the treatment groups, analysis of variance was applied. Percent inhibition values were determined by comparing the individual treatment mean values to the mean of the control group. Linear regression was used to estimate ICso's/EDso's in appropriate assays. EIA Determination of Prostaglandins EIA reagents for prostaglandin determination were purchased from Perseptive Diagnostics, (Cambridge, MA). Prostaglandin E2 (PGE2) levels in lavage fluids were determined after the samples were dried under nitrogen and reconstituted with assay buffer. PGE2 levels in enzyme assays or cell culture media were measured against standards prepared in the same milieu. The immunoassays were conducted as recommended by the manufacturer. The EIA was conducted in 06 well microtiter plates (Nunc Roskilde, Denmark) and optical density was measured using a microplate reader (Vmax, Molecular Devices Corp., Menlo Park, CA). Recombinant Human PGHS-1 and PGHS-2 Enzyme Assays Inhibition of prostaglandin biosynthesis in vitro was evaluated using recombinant human Cox-1 (r-hu Cox1 ) and Cox-2 (r-hu Cox2) enzyme assays. Representative compounds dissolved in DMSO (3.3% v/v) were preincubated with microsomes from recombinant human PGHS-1 or PGHS-2 expressed in the baculovirus/Sfø cell system (Gierse, J. K., Hauser.S. D., Creely, D. P., Koboldt, C, Rangwala, S., H., Isakson, P. C, and Seibert, K. Expression and selθctivθ inhibition of the constituitive and inducible forms of cyclooxygenase , Biochem J. 1005, 305: 470.), together with the cofactors phenol (2 mM) and hematin (1 μM) for 60 minutes prior to the addition of 10 μM arachidonic acid. The reaction was allowed to run for 2.5 minutes at room temperature prior to quenching with HCl and neutralization with NaOH. PGE2 production in the presence and absence of the drug was determined by EIA analysis. The EIA was conducted in 06 well microtiter plates (Nunc Roskilde, Denmark) and optical density was measured using a microplate reader (Vmax, Molecular Devices Corp., Menlo Park, CA). EIA reagents for prostaglandin determination were purchased from Perseptive Diagnostics (Cambridge, MA). PGE2 levels were measured against standards prepared in the same milieu. The immunoassays were conducted as recommended by the manufacturer. The data illustrating the inhibition of prostaglandin biosynthesis in vitro by compounds of this invention is shown in Table 1. The compounds are designated by the Example Number. Column 2 shows Cox-1 percent inhibition at the particular micromolar dose level and Column 3 shows Cox-2 percent inhibition at the particular nanomolar dose level. Values for Cox-2 inhibition that are parenthetical indicate IC50 values. SEE ATTACHED TABLE Table 1 -240- -250- IL-1 B Induced PGE2 Production in WISH Cells Human amnionic WISH cells were grown to 80% confluence in 48 well plates. Following removal of the growth medium and two washings with Gey's Balanced Salt Solutn, 5 ng IL-1 β/ml (UBI, Lake Placid, NY) was added to the cells with or without test compound in DMSO (0.01 % v/v) in Neuman-Tytell Serumless Medium (GIBCO, Grand Island, NY). Following an 18 hour incubation to allow for the maximal induction of PGHS-2, the conditioned medium was removed and assayed for PGE2 content by EIA analysis as described above. Monocyte UΘ37 (ATCC, Rockville, MD) cells were grown in a similar fashion to the WISH cells. After incubation, the conditioned medium was removed and assayed for Cox-1 content by EIA analysis as described above. The data illustrating the inhibition of prostaglandin biosynthesis in vitro by compounds of this invention is shown in Table 2. U037 values indicate Cox-1 percent inhibition at the particular micromolar dose level while partenthetical values indicate IC50 values. WISH cell values indicate percent inhibition at the particular micromolar dose level while parenthetical values indicate IC50 values. Human Whole Platelet Cyclooxygenase-1 Assay (HWCX) Blood from normal healthy volunteers is collected into tubes containing ACD (acid citrate dextrose) as the anticoagulant. This blood is centrifuged at 175 x g to prepare platelet rich plasma. The platelet rich plasma is then centrifuged at 100 x g to pellet the white blood cells, leaving the platelets in the supernatant. The supernatant is layered on a cushion of 0.7 mL of 10% bovine serum albumin in Tyrodes solution (Gibco; Grand Island, NY) and then centrifuged at 1000 x g. The resulting supernatant from this centrifugation is then removed and 11 mL of Tyrodes solution is added to the remaining pellet of platelets. The platelets are then aliquoted at 120 μl into a 06 well plate. Experimental compounds are added and allowed to pre-incubate for 10 minutes. At the end of this pre-incubation period, the calcium ionophore A23187 is added to a final concentration of 8.8 μM and the incubation is continued for ten minutes. The reaction is stopped by adding cold 6 mM EDTA, the incubation mixture is centrifuged at 220 x g, and the supematants are then analyzed for thromboxane using a commercial kit from Cayman Chemical (Ann Arbor, Ml). SEE ATTACHED TABLE Table 2 Carrageenan Induced Paw Edema (CPE) in Rats Hindpaw edema was induced in male rats as described by Winter et al., Proc. Soc. Exp. Biol. Med., 1962, 111, 544. Briefly, male Sprague-Dawley rats weighing between 170 and 190 g were administered test compounds orally 1 hour prior to the subplantar injection of 0.1 ml of 1 % sodium carrageenan (lambda carrageenan, Sigma Chemical Co., St Louis, MO) into the right hindpaw. Right paw volumes (ml) were measured immediately following injection of carrageenan for baseline volume measurements using a Buxco plethysmograph (Buxco Electronics, Inc., Troy, NY). Three hours after the injection of carrageenan, right paws were remeasured and paw edema calculated for each rat by subtracting the zero time reading from the 3 hour reading. Data are reported as mean percent inhibition +/- SEM. Statistical -260- significance of results was analyzed by Dunnetts multiple comparison test where p< 0.05 was considered statistically significant. Rat Carrageenan Pleural inflammation (CIP) Model Pleural inflammation was induced in male adrenaiectomized Sprague- Dawley rats following the method of Vinegar et al., Fed. Proc. 1976, 35, 2447- 2456. Animals were orally dosed with experimental compounds, 30 minutes prior to the intrapleural injection of 2% lambda carrageenan (Sigma Chemical Co., St. Louis MO). Four hours later the animals were euthanized and the pleural cavities lavaged with ice cold saline. The lavage fluid was then added to two volumes of ice cold methanol (final methanol concentration 66%) to lyse cells and precipitate protein. Eicosanoids were determined by EIA as described above. The data illustrating the inhibition of prostaglandin biosynthesis in vivo by the compounds of this invention is shown in Table 3. Values reported are percent inhibition at 10 milligrams per kilogram body weight. Carrageenan induced air pouch prostaglandin biosynthesis model (CAP) Air pouches are formed in the backs of male Sprague Dawley rats by injecting 20 mL of sterile air on day 0. Three days later the pouch was reinflated with an additional 10 mL of sterile air. On day 7, 1 mL of saline containing 0.2 % lambda carrageenan (Sigma Chemical Co.) is injected into the pouch to induce the inflammatory reaction that is characterized by the release of prostaglandins. Test compounds are dosed at 0.1 to 10 mg/kg 30 minutes prior to carrageenan. Four hours after the carrageenan injection the pouch is lavaged and levels of prostaglandins are determined by enzyme immuno-assay using commercially available kits. Percent inhibitions are calculated by comparing the response in animals which have received vehicle to those which received compound. Values for Cox-2 inhibition that are parenthetical indicate ED50 values. The data illustrating the inhibition of prostaglandin biosynthesis in vivo by the compounds of this invention is shown in Table 3. Values reported are percent inhibition at 10 milligrams per kilogram body weight for CIP and CPE tests and at 3 milligrams per kilogram body weight for CAP testing. See attached table Table 3 Pharmaceutical Compositions The present invention also provides pharmaceutical compositions which comprise compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. As used herein, the term "pharmaceutically acceptable carrier" means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the procedures and judgements well known to one skilled in the art. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracistemally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray. The compounds of the present invention may be potentially useful in the treatment of several illness or disease states such as inflammatory diseases, dysmennorhea, asthma, premature labor, adhesions and in particular pelvic adhesions, osteoporosis, and ankylosing spondolitis. Current Drugs Ltd, ID Patent Fast Alert, AG16, May 0, 1097. The compounds of the present invention may also be potentially useful in the treatment of cancers, and in particular, colon cancer. Proc. Natl. Acad. Sci., 94, pp. 3336-3340, 1007. The compounds of the present invention may be useful by providing a pharmaceutical composition for inhibiting prostaglandin biosynthesis comprising a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, ester, or prodrug thereof, and a pharmaceutically acceptable carrier. The compounds of the present invention may be useful by providing a pharmaceutical composition for inhibiting prostaglandin biosynthesis comprising a therapeutically effective amount of a compound of formula II or a pharmaceutically acceptable salt, ester, or prodrug thereof, and a pharmaceutically acceptable carrier. The compounds of the present invention may be useful by providing a pharmaceutical composition for inhibiting prostaglandin biosynthesis comprising a therapeutically effective amount of a compound of formula III or a pharmaceutically acceptable salt, ester, or prodrug thereof, and a pharmaceutically acceptable carrier. In addition, the compounds of the present invention may be useful by . providing a method for inhibiting prostaglandin biosynthesis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, ester, or prodrug thereof. The compounds of the present invention may be useful by providing a method for inhibiting prostaglandin biosynthesis comprising administering to a mammal in need of such treatment a therapeutically effective amount a compound of formula II or a pharmaceutically acceptable salt, ester, or prodrug thereof. The compounds of the present invention may be useful by providing a method for inhibiting prostaglandin biosynthesis comprising administering to a mammal in need of such treatment a therapeutically effective amount compound of formula III or a pharmaceutically acceptable salt, ester, or prodrug thereof. In addition, the compounds of the present invention may be useful by providing a method for treating pain, fever, inflamation, rheumatoid arthritis, osteoarthritis, adhesions, and cancer comprising administering to a mammal in need of such teratment a therapeutically effective amount of a compound of formula I. In addition, the compounds of the present invention may be useful by providing a method for treating pain, fever, inflamation, rheumatoid arthritis, osteoarthritis, adhesions, and cancer comprising administering to a mammal in need of such teratment a therapeutically effective amount of a compound of formula II. In addition, the compounds of the present invention may be useful by providing a method for treating pain, fever, inflamation, rheumatoid arthritis, osteoarthritis, adhesions, and cancer comprising administering to a mammal in need of such teratment a therapeutically effective amount of a compound of formula III. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3- butylene glycol, dimethylformamide, oils (such as, for example, cottonseed, groundnut, corn, germ, olive, castor, sesame oils, and the like), glycerol, tetrahydrofurfuryl alcohol, poly-ethyl-ene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Injectable preparations, such as, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, such as, for example, a solution in 1 ,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, isotonic sodium chloride solution, and the like. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectable preparations. The injectable formulations can be sterilized by any method known in the art, such as, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsulated matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides) Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and thus melt in the rectum or vaginal cavity and release the active compound. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is usually mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as, for example, sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as, for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as, for example, glycerol, d) disintegrating agents such as, for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as, for example, paraffin, f) absorption accelerators such as, for example, quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as, for example, kaolin and bentonite clay, and) lubricants such as, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients such as, for example, lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using excipients such as, for example, lactose or milk sugar as well as high molecular weight polethylene glycols and the like. The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulation art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as, for example, sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such as, for example, magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as, for example, animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, poly- ethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the compounds of this invention, excipients such as, for example, lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chloro- fluorohydrocarbons. Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in a suitable medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. According to the methods of treatment of the present invention, a patient, such as a human or mammal, is treated by administering to the patient a therapeutically effective amount of a compound of the invention, in such amounts and for such time as is necessary to achieve the desired result. By a "therapeutically effective amount" of a compound of the invention is meant a sufficient amount of the compound to provide the relief desired, at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. The total daily dose of the compounds of this invention administered to a human or other mammal in single or in divided doses can be in amounts, for example, from 0.001 to about 1000 mg/kg body weight daily or more preferably from about 0.1 to about 100 mg/kg body weight for oral administration or 0.01 to about 10 mg/kg for -270- parenteral administration daily. Single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. 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. The reagents required for the synthesis of the compounds of the invention are readily available from a number of commercial sources such as Aldrich Chemical Co. (Milwaukee, WI, USA); Sigma Chemical Co. (St. Louis, MO, USA); and Fluka Chemical Corp. (Ronkonkoma, NY, USA); Alfa Aesar (Ward Hill, MA 01835-0053); Eastman Chemical Company (Rochester, New York 14652- 3512); Lancaster Synthesis Inc. (Windham, NH 03087-0077); Spectrum Chemical Manufacturing Corp. (Janssen Chemical) (New Brunswick, NJ 08001 ); Pfaltz and Bauer (Waterbury, CT. 06708). Compounds which are not commercially available can be prepared by employing known methods from the chemical literature.

Claims: CLAIMS We Cairn: 1. A compound of formula !: where X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NR^R 0 , wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, heterocyclic, heterocyclic alkyl, and arylalkyl; and R a , R ; and R c are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, alkoxy, alkoxyalkyl, carboxy, carboxyalkyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, arylhaloalkyl, arylhydroxyalkyl, aryloxy, aryloxyhydroxyalkyl, aryloxyhaloalkyl, arylcarbonylalkyl, haloalkoxyhydroxyalkyl, heterocyclic, heterocyclic alkyl, heterocyclic alkoxy, heterocyclic oxy, -C(O)R 5 - -(CH2)nC(O)R 5 , -R6-R 7 , -(CH2) n CH(OH)R5, -(CH2) n CH(ORd)R5, -(CH2) n C(NORd)R5, -(CH2) n C(NRd)R5 j -(CH2) n CH(NORd)R5, -(CH2) n CH(NRdRe)R5 f -(CH 2 )nC≡C-R7, -(CH 2 )n[CH(CX'3)]m-(CH2)n-CX' 3 , -(CH 2 )n(C X'2)m-(CH 2 ) n -CX'3, -(CH 2 )n[CH(CX'3)]m-(CH 2 )n -R 8 , -(CH 2 )n(C X ' 2)m-(CH 2 )n R 8 , -(CH 2 )n(CHX') m -(CH 2 )n - CX' 3 , -(CH 2 )n(CHX') m -(CH2) n -R 8 , and - (CH 2 ) n -R20, wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic, and heterocyclic alkyl; wherein R 6 is alkylene or alkenylene, or halo-substituted alkylene halo-substituted alkenylene; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; Rd and R Θ are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, and m is 0 to about 5; at least one of R1 , R 2 and R 3 is where X 1 is selected from the group consisting of -SO2-, -SO^Rl )., -SO-, - Seθ2-, PO(ORl )-, and -PO(NR 2 R " l 3 )-, R9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, -NHNH2, -N=CH(N RI OR 1 "1 ), dialkylamino, alkoxy, thiol, alkylthiol, protecting groups, and protecting groups attached to X 1 by an alkylene; X 2 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, and alkynyl; R "1 0, R 1 1 , R "1 2 , and R 13 are independently selected from the group consisting of hydrogen, alkyl, and cycloalkyl, or R 2 and R 1 3 can be taken together, with the nitrogen to which they are attached, to form a heterocyclic ring having from 3 to 6 atoms. The remaining two of the groups of R 1 , R 2 , and R 3 , are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyalkylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, haloalkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, cycloalkylidenealkyl, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic(alkyl) amino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxy, hydroxyalkyl, hydroxyalkylamino, hydroxyalkoxy, hydroxyalkylthio, mercaptoalkoxy, oxoalkoxy, cyano, nitro, and -Y-RI 4 , wherein Y is selected from the group consisting of -O-, -S-, -C(R 1 6 ) (R 17 )-, -C(O)NR l R 22 -, -O )-, -C(O)O-, -NH-, -NC(O)-, -N=C R 21 R 22 , N- R 21 R 22 , and -NR 1 9-. R14 j s selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyciic(alkyl), R "1 6 , R "1 7 , and R 1 9 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 2. A compound having the formula \l. II wherein Z is a group having the formula: where X 1 is selected from the group consisting of -SO2-, -SO-, -Seθ2- ,SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, -NHNH2, dialkylamino, alkoxy, thiol, alkylthiol, protecting groups, and protecting groups attached to X 1 by an alkylene; R10 is selected from the group consisting of hydrogen, alkyl, and cycloalkyl; X 2 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, and alkynyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, alkoxy, alkoxyalkyl, carboxy, carboxyalkyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, arylhaloalkyl, arylhydroxyalkyl, aryloxy, aryloxyhydroxyalkyl, aryloxyhaloalkyl, arylcarbonylalkyl, haloalkoxyhydroxyalkyl, heterocyclic, heterocyclic alkyl, heterocyclic alkoxy, heterocyclic oxy, -C(0)R > -(CH2)nC(O)R 5 , -R 6 -R 7 , -(CH2) n CH(OH)R5, -(CH2) n CH(ORd)R5, -(CH2) n C(NORd)R5, -(CH2) n C(NRd)R5, -(CH2) n CH(NOR d )R5 ι -(CH2) n CH(NR d Re)R5 ( -(CH 2 )nCΞ_C-R7 -(CH2)n[CH(CX'3)]m-(CH 2 )n-CX'3, -(CH 2 )n(C X'2)m-(CH2)n -CX ' 3, -(CH2)n[CH(CX'3)] m -(CH2)n -R 8 , -(CH 2 )n(C X'2)rτr(CH 2 )n R 8 , -(CH2)n(CHX ' ) m -(CH2)n - CX'3 , -(CH 2 )n(CHX')m-(CH2)n -R 8 , and - (CH 2 ) n -R 20 , wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic, and heterocyclic alkyl; wherein R is alkylene or alkenylene, or halo-substituted alkylene halo-substituted alkenylene; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; Rd and R Θ are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, and m is 0 to about 5; R1 , and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyalkylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, halolkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic(alkyl) amino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxy, hydroxyalkyl, hydroxyalkylamino, hydroxyalkoxy, mercaptoalkoxy, oxoalkoxy, cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of -O-, -S-, -C(R 1 6 ) (R 17 )-, -C(O)NR 2 1 R 22 -, -C(O)-, -C(O)O-, -NH-, -NC(O)-, -N=C R 2" ! R 22 , N- R 21 R 22 , and -NR "1 9-. R14 j s selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), R 1 6 , R 1 7 , and R19 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 2" ! and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 3. A compound having the formula HI: III wherein X, χ1 , X 2 , R, R 1 , R 3 , and R 9 are as defined in claim 1 ; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 4. A compound of claim 3 wherein X 1 is selected from the group consisting of -SO2-, -SO-, -Seθ2-, and -SO(NR 1 °)-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbRC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, heterocyclic, heterocyclic alkyl, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, carboxyalkyl, cyanoalkyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkenyl, arylalkynyl, heterocyclic, heterocyclic alkyl, arylalkyl, -(CH2)nC(O)R 5 > -(CH2)nC=C- R 7 ' -(CH2)n[CH(CX'3)]m(CH2)n- R 8 , and -(CH 2 )n-R 0; wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl; R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl, R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; X' is halogen; n is from 0 to about 10, m is from 0 to about 5; R^ and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkoxyalkyl, amido, amidoalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, amino, aminocarbonyl, aminocarbonylalkyl, alkylamino, dialkylamino, arylamino, arylalkylamino, diarylamino, aryl, aryloxy, heterocyclic, heterocyclic alkyl, cyano, nitro, and -Y-RI 4 , wherein Y is selected from the group consisting of, -O-, -S-, -C(R 1 6) (Rl 7) . f _C(O)NR 2 1 R 22 -, -C(O)-, - C(O)O-, -NH-, -NC(O)-, -N=C R 21 R 22 , N- R 2" ! R 22 , and -NR " ! 9-. R14 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), R 1 6 , RI 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 5. A compound of claim 3 wherein χ1 is selected from the group consisting of -SO2-, -SO-, -Seθ2-, and -SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbR C , wherein R 4 is selected from the group consisting of alkyl, alkenyl, cyclo- alkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, carboxyalkyl, cyanoalkyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkenyl, arylalkynyl, heterocyclic, heterocyclic alkyl, arylalkyl, -(CH2)nC(O)R 5 > and - wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl; R 20 is selected from the group consisting of alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic, and heterocyclic alkyl; n is from 0 to about 10; R 1 and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkylthioalkyl, aryloxyalkyl, arylthioalkyl, amido, amidoalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, amino, aminocarbonyl, aminocarbonylalkyl, alkylamino, alkylaminoalkyl, dialkylamino, arylamino, arylalkylamino, diarylamino, aryl, heterocyclic, heterocyclic(alkyl), cyano, nitro, and -Y-R 1 4 , wherein Y is selected from the group consisting of, -O-, -S-, -C(R 1 6 ) (R 1 7 )-, -C(0)NR 1 R 22 -, -C(O)-, -C(0)0-, -NH-, -NC(O)-, and -NR19-. R14 J S selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl), and R 1 6, R17, and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; R 2" ! and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 6. A compound of claim 3 wherein X 1 is selected from the group consisting of -SO2-, -SO-, -Seθ2-, and-SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbRC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, carboxyalkyl, cyanoalkyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkenyl, arylalkynyl, heterocyclic, heterocyclic alkyl, arylalkyl, and -(CH2)nC(O)R 5 >; wherein R 5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, haloalkyl, heterocyclic, and heterocyclic alkyl; and n is from 0 to about 10; R 1 and R 3 are independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkylthioalkyl, aryloxyalkyl, arylthioalkyl, amido, amidoalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, amino, aminocarbonyl, aminocarbonylalkyl, alkylamino, alkylaminoalkyl, dialkylamino, arylamino, arylalkylamino, diarylamino, aryl, heterocyclic, heterocyclic(alkyl), cyano, nitro, and -Y-R 14 , wherein Y is selected from the group consisting of, -0-, -S-, -C(R 1 6 ) (R 17 )-, -C(0)NR 2 1 R 22 -, -C(0)-, -C(0)O-, -NH-, -NC(O)-, and -NR19-. R14 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic(alkyl); R15, R 1 6 , R 1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl or cyano; -280- R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 7. A compound of claim 3 wherein χ1 is selected from the group consisting of -SO2-, -SO-, -Seθ2-, and -SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbRC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from alkyl, haloalkyl, aryl, heterocyclic, heterocyclic alkyl, and - (CH2)n-R 20 where is R 20 is substituted and unsubstituted aryl wherein the substituted aryl compounds are substituted with halogen; n is from 0 to about 10; R 1 is selected from the group consisting of alkoxy, alkenyloxy, hydroxyalkoxy, aryloxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, and -Y-R 1 4 , wherein Y is selected from the group consisting of, -O-, -S-, -C(R 1 6 ) (R 17 )-, -C(O)-, - C(O)O-, -NH-, -NC(O)-, and -NR 1 9-. RI 4 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxy, cycloalkyl, cycloalkenyl, amino, cyano, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl, R 3 is hydrogen; R 1 5 , R 1 6 , R 1 7 , and R 1 9 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; and R 21 and R 22 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, or cyano; -200- or a pharmaceutically acceptable salt, ester, or prodrug thereof. 8. A compound of claim 3 wherein X 1 is selected from the group consisting of -SO2-, -SO-, and -SO(NR 1 0 )-, and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NR RC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; R is selected from alkyl, haloalkyl, aryl, heterocyclic, heterocyclic alkyl, and - (CH2)n-R 20 where is R 20 is substituted and unsubstituted aryl wherein the substituted aryl compounds are substituted with halogen; n is from 0 to about 10; R 1 is selected from the group consisting of alkoxy, alkenyloxy, hydroxyalkoxy, aryloxy, aryl, arylalkyl, heterocyclic, and heterocyclic alkyl; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 0. A compound of claim 3 wherein X 1 is -SO2- and and R 9 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, amino, alkylamino, or dialkylamino; X 2 is selected from the group consisting of hydrogen and halogen; X is selected from the group consisting of O, S, NR 4 , N-OR a , and N-NRbRC, wherein R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, alkylcycloalkenyl, aryl, heterocyclic, and arylalkyl; and R a , Rb, and R c .are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, and arylalkyl; -201 R is selected from haloalkyl, aryl, heterocyclic, heterocyclic alkyl, and -(CH2)n-R 20 where is R 20 is substituted and unsubstituted aryl wherein the substituted aryl compounds are substituted with halogen; n is from 0 to about 10; R 1 is selected from the group consisting of unsubstituted aryl, and substituted aryl with one, two, or three substituents selected from the group consisting of fluorine and chlorine including, but not limited to, p-chlorophenyl, p- fluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-fluoro-phenyl, and the like; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 10. A compound of claim 3 wherein X 1 is -Sθ2-,and R 9 is selected from the group consisting of alkyl and amino; X 2 is selected from the group consisting of hydrogen and halogen; X is O; R is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, and arylalkyl; R 1 is selected from the group consisting of alkoxy, aryl, alkenyloxy, hydroxyalkoxy, haloalkoxy, arylalkyl, alkyl, and aryloxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 1 1. A compound of claim 3 wherein X 1 is -SO2-, and R 9 is selected from the group consisting of alkyl and amino; X 2 is selected from hydrogen and fluorine; R is selected from haloalkyl, aryl, and alkyl; n is from 0 to about 10; R 1 is selected from the group consisting of isobutyloxy, isopentyloxy, 1 -(3-methyl-3-butenyl)oxy, 2-hydroxy-2-methyl-propyloxy, 3-hydroxy-3-methyl- butyloxy, neopentyloxy, isopentyl, aryloxy including 4-fluorophenoxy, unsubstituted -202- aryl, and substitued aryl with one, two, or three substituents selected from the group consisting of fluorine and chlorine including, , 4-fluorophenyl, 4-chlorophenyl, 3- chloro-4-fluoro-phenyl4-chloro-3-fluoro-phenyl; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 12. A compound of claim 3 wherein X 1 is selected from the group consisting of -SO2-, and -SO(NR 1 0)-, and R 9 is alkyl, X 2 is selected from the group consisting of hydrogen and fluorine; X is O; R is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, and arylalkyl; R 1 is selected from the group consisting of alkoxy, aryl, alkenyloxy, hydroxyalkoxy, alkyl, and aryloxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 13. A compound of claim 3 wherein X 1 is -SO2-, R 9 is amino; X 2 is selected from the group consisting of hydrogen and fluorine; X is O; R is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, aryl, and arylalkyl; R 1 is selected from the group consisting of alkoxy, aryl, alkenyloxy, hydroxyalkoxy, alkyl, and aryloxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 14. A compound of claim 3 wherein X 1 is -SO2-, and R 9 is methyl; X 2 is selected from the group consisting of hydrogen; -203- X is O; R is selected from the group consisting t-butyl, 3-chlorophenyl, 3,4- difluorophenyl, 4-fluorophenyl, 4-chloro-3-fluoro-phenyl, 3-chloro-4-fluoro-phenyl, and CF 3 CH 2 -, ; R is selected from the group consisting of aryloxy, isobutyloxy, isopentyloxy, 1 -(3-methyl-3-butenyl)oxy, 2-hydroxy-2-methyl-propyloxy, 3-hydroxy- 3-methyl-butyloxy, neopentyloxy, isopentyl, 4-fluorophenyl, 4-chlorophenyl, 4- chloro-3-fluoro-phenyl, 4-fluorophenoxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 15. A compound of claim 3 wherein X 1 is -SO2-, and R 9 is amino; X 2 is selected from the group consisting of hydrogen; X is O; R is selected from the group consisting t-butyl, 3-chlorophenyl, 3,4- difluorophenyl, 4-fluorophenyl, 4-chloro-3-fluoro-phenyl, 3-chloro-4-fluoro-phenyl and CF 3 CH 2 -, ; R 1 is selected from the group consisting of aryloxy, isobutyloxy, isopentyloxy, 1 -(3-methyl-3-butenyl)oxy, 2-hydroxy-2-methyl-propyloxy, 3-hydroxy- 3-methyl-butyloxy, neopentyloxy, isopentyl, 4-fluorophenyl, 4-chlorophenyl, 4- chloro-3-fluoro-phenyl, 4-fluorophenoxy; and R 3 is hydrogen; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 16. A compound according to claim 3, selected from the group consisting of: 2-(2,2,2-Trifluoroethyl)-4-(4-chiorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; -204- 2-(3-Chlorophenyl)-4-(3-methyl-3-butenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(4-chloro-3-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone; 2-(4-fluorophenyl)-4-(4-flurophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-hydroxy-2-methyl-1 -propoxy)-5-[4- (methylsulfonyl)phenyl]-3(2H)-pyridazinone; 2-(4-Fluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone; 2-(f-Butyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)-pyridazinone; 2-( -Butyl)-4-(3-methylbutoxy)-5-[4-(methyisulfonyl)phenyl]-3(2H)-pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(2,2-dimethylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; -205- 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3-Chlorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(4-fluorophenoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(4-fluorophenoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(2,2-dimethylpropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; -206- 2-(4-Chloro-3-fluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(4-fluorophenoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)- -4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]- 3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinonβ; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2,4-Bis(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)-pyhdazinone; 2-(4-fluorophenyl)-4-(4-flurophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; and 2-(3,4-Difluorophenyl)-4-(2-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]- 3(2H)-pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-oxopropoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methoxy-imino-propoxy)-5-[4-(methylsulfonyl)phenyl]- 3(2H)-pyridazinone; (R)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone; (S)- 2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(methylsulfonyl)- phenyl]-3(2H)-pyridazinone; -207- (R)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)- phenyl]-3(2H)-pyridazinone; (S)- 2-(3,4-Difluorophenyl)-4-(3-hydroxy-2-methylpropoxy)-5-[4-(aminosulfonyl)- phenyl]-3(2H)-pyridazinone; 2-(3,4-Difluorophenyl)-4-(3-oxo-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-oxo-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; and 2,4-Bis(4-Flurophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone; or a pharmaceutically acceptable salt, ester, or prodrug thereof. 17. A compound of claim 16 selected from the group consisting of 2-Phenyl-4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)-pyhdazinone; 2-(2,2,2-Trifluoroethyl)-4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)- pyridazinone; 2-(2,2,2-Trifluoroethyl)-4-(4-chlorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)- pyridazinone; 2-(4-Fluorophenyl)-4-(3-methylbutoxy)-5-[4-(methylsulfonyl)phenyl]-3(2H)- pyridazinone; 2-(3,4-Difluorophenyl)-4-(2-methylpropoxy)-5-[4-(aminosulfonyl)phenyl]-3(2H)- pyridazinone; and 2,4-Bis(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-3(2H)-pyridazinone; or a pharmaceutically acceptable salt, ester, or prodrug thereof. -208- 18. A pharmaceutical composition for inhibiting prostaglandin biosynthesis comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier. 10. A pharmaceutical composition for inhibiting prostaglandin biosynthesis comprising a therapeutically effective amount of the compound of claim 2 and a pharmaceutically acceptable carrier. 20. A pharmaceutical composition for inhibiting prostaglandin biosynthesis comprising a therapeutically effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier. 21. A method for inhibiting prostaglandin biosynthesis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1. 22. A method for inhibiting prostaglandin biosynthesis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 2. 23. A method for inhibiting prostaglandin biosynthesis comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 3. 24. A method for treating pain, fever, inflamation, rheumatoid arthritis, osteoarthritis, adhesions, and cancer comprising administering to a therapeutically effective amount of a compound of claim 1. -200- 25. A method for treating pain, fever, inflamation, rheumatoid arthritis, osteoarthritis, adhesions, and cancer comprising administering to a therapeutically effective amount of a compound of claim 2. 26. A method for treating pain, fever, inflamation, rheumatoid arthritis, osteoarthritis, adhesions, and cancer comprising administering to a therapeutically effective amount of a compound of claim 3. 27. A method for the preparation of a compound of claim 3 , or a pharmaceutically acceptable salt, ester, or prodrug thereof having the formula : III wherein X, X 1 , X 2 , R, R 1 , R 3 , and R 9 are as defined in claim 1 ; comprising the step of reacting a compound having formula LU, where R is hydrogen, with an alkylating agent. 28. The method according to claim 27 wherein the alkylating agent has the formula R99-Q where Q is a leaving group and R 99 js selected from the group consisting of methyl, ethyl, 1 ,1 ,1 -trifluoroethyl, cyclopropylmethyl, 3-(2-methyl)- propenyl, 4-(2-methyl)but-2-enyl, 1 ,1 -dichloropropen-3-yl, 2,2-dimethyl-3-oxo- 4-butyl, 2,3,3,4,4,4-hexafluoro-n-buten-1 -yl, propargyl, phenylpropargyl, phenyl, phenethyl, 1 -phenylpropen-3-yl, benzyl, α-methyl-4-fluorobenzyl, 2,3,4,5,6-pentafluorobenzyl, 4-trifluomethoxyphenacyl, 4-fluorobenzyl, 4-fluorophenyl, 2-trifluoromethylbenzyl, 2,4-difluorobenzyl, 2,4-difluorophenacyl, 4-trifluomethylphenacyl, phenacyl, 4-carboxyphenacyl, 4-chlorophenacyl, 4-cyanophenacyl, 4-diethylaminophenacyl, 3-thienylmethyl, 5-methylthien- 2-ylmethyl, 5-chiorothien-2-ylmethyl, 2-benzo[b]thienylmethyl, 3-benzothienacyl, 5-chlorothiazol-2-ylmethyl, 5-methylthiazol-2-ylmethyl, 2-pyhdylmethyl, 3-pyridyl- methyl, 4-pyridylmethyl, quinolin-2-ylmethyl, and fluoroquinolin-2-ylmethyl. 20. The method according to claim 27 wherein the alkylating agent has the formula R99-Q where Q is a leaving group and R99 JS selected from the group consisting of methyl, ethyl, 1 ,1 ,1 -trifluoroethyl, cyclopropylmethyl, 3-(2-methyl)- propenyl, 4-(2-methyl)but-2-enyl, 1 ,1 -dichloropropen-3-yl, 2,3,3,4,4, 4-hexafluoro-n- buten-1 -yl, propargyl, phenylpropargyl, phenyl, phenethyl, 1 -phenylpropen-3-yl, benzyl, -methyl-4-fluorobenzyl, 2,3,4,5,6-pentafluorobenzyl, 4-trifluomethoxy- phenacyl, 4-fluorobenzyl, 4-fluorophenyl, 2,4-difluorobenzyl, 2,4-difluorophenacyl, 4-trifluomethylphenacyl, phenacyl, 4-carboxyphenacyl, 4-chlorophenacyl, 4-cyanophenacyl, 4-diethylaminophenacyl, 3-thienylmethyl, 5-methylthien-2-yl- methyl, 5-chlorothien-2-ylmethyl, 2-benzo[b]thienylmethyl, and 3-benzothienacyl. 30. The method according to claim 27 wherein the alkylating agent has the formula R99-Q where Q is a leaving group and R Q 9 js selected from the group consisting of 1 ,1 ,1 -trifluoroethyl, 3-(2-methyl)propenyl, 4-(2-methyl)but-2-enyl, 1 ,1 -dichloropropen-3-yl, 2,3,3,4,4,4-hexafluoro-n-buten-1-yl, propargyl, phenylpropargyl, phenyl, benzyl, α-methyl-4-fluorobenzyl, 2,3,4,5,6-pentafluorobenzyl, 4-fluorobenzyl, 4-fluorophenyl, 2,4-difluorobenzyl, 3-thienylmethyl, 5-methylthien- 2-ylmethyl, 5-chlorothien-2-ylmethyl, and 2-benzo[b]thienylmethyl. 31. The method according to claim 27 wherein the alkylating agent has the formula R99.Q where Q is a leaving group and R Q 9 is selected from the group consisting of 1 ,1 ,1 -trifluoroethyl, phenyl, benzyl, α-methyl-4-fluorobenzyl, 4-fluorobenzyl, 4-fluorophenyl, and 2,4-difluorobenzyl. 32. The method according to claim 27 wherein the alkylating agent has the formula R99-Q where Q is a leaving group and R g 9 js selected from the group consisting of 1 ,1 ,1 -trifluoroethyl, benzyl, and 4-fluorophenyl. 33. A method for regioselectively preparing a 4,5- substituted pyridazone comprising the steps of a) reacting a compound with the formula where R is an alkyl or aryl group, and X is a leaving group with a nucleophilic agent to displace the X group; b) converting the -OR98 to a leaving group; and c) reacting the compound with a second nucleophilic agent to provide the 4,5- substituted pyridazone. 34. The method according to claim 33 wherein the benzyl group is removed using a Lewis acid. 35. A method for regioselectivly preparing a 4,5- substituted pyridazone comprising the steps of treating a compound having the formula with a hydrazine having the formula RNHNH2 to furnish the pyridazone having the formula: III wherein X, X 1 , X 2 , R, R , R 3 , and R 9 are as defined in claim 1 ; or a pharmaceutically acceptable salt, ester, or prodrug thereof.

Inventors: BASHA ANWER, BLACK LAWRENCE A, KOLASA TEODOZYJ, KORT MICHAEL E, LIU HUAQING, MCCARTY CATHERINE M, PATEL MEENA V, ROHDE JEFFREY J, BASHA, ANWER, BLACK, LAWRENCE, A., KOLASA, TEODOZYJ, KORT, MICHAEL, E., LIU, HUAQING, MCCARTY, CATHERINE, M., PATEL, MEENA, V., ROHDE, JEFFREY, J.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1998
Main classification: C07D237
IPC codes: C07D237, C07D401, C07D403, C07D405, C07D409, C07D417