SUBSTITUTED SPIRO COMPOUNDS FOR THE TREATMENT OF INFLAMMATION

Abstract: A class of substituted spiro compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (III), wherein n is a number selected from 0, 1 and 2; wherein R<6> is selected from hydrido and halo; wherein R<7> is selected from hydrido and halo; wherein R<8> is selected from hydrido, halo, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, and hydroxyl; wherein R<9> is selected from hydrido, halo, and lower alkyl; or wherein R<8> and R<9> together form methylenedioxy; and wherein R<11> is selected from lower alkyl and amino; or a pharmaceutically-acceptable salt thereof.

Description: SUBSTITUTED SPIRO COMPOUNDS FOR THE TREATMENT OF INFLAMMATION FIELD OF THE INVENTION This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating inflammation and inflammation-associated disorders, such as arthritis. BACKGROUND OF THE INVENTION Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG2, PGH2 and PGE 2 , has been a common target of antiinflammatory drug discovery. However, common non-steroidal antiinflammatory drugs (NSAIDs) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAIDs can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAIDs is the use of corticosteroids, which have even more drastic side effects, especially when long term therapy is involved. Previous NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX) . The recent discovery of an inducible enzyme associated with inflammation (named "cyclooxygenase-2 (COX-2)" or "prostaglandin G/H synthase II") provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects. The substituted spiro compounds disclosed herein preferably selectively inhibit cyclooxygenase-2 over cyclooxygenase-1 and relieve the effects of inflammation. These compounds, in addition, do not display substantial inhibition of cyclooxygenase-1 and produce a reduced amount of side effects. Diarylcycloalkenes have been made and used for a variety of utilities. For example, Offenlegungsschrift 4,212,628, published Oct. 21, 1993, describes l,2-bis(4- alkylphenyl) cyclohex-1-ene compounds as having anti-tumor activity. 2,3-Bis- (4-hydroxyphenyl) -2-cyclopenten-l-one has been identified from the knot resin powder of Argaucaria angustifolia [H. Ohash, et al. , Phvtochemistrv. 31, 1371-73 (1992)] . Substituted 1,2-diphenylcyclopentenes have been synthesized for use in studies of their rotational behavior, and specifically, 1- (2, 4-dimethylphenyl) -2- phenylcyclopentene [D. y. Curtin, et al. , J. Orσ. Chem. , !£., 565-72 (1971)] . 1,2-Di- (2 ' -methoxyphenyl) -Δ 1 - cyclopentene has been identified as an impurity in the synthesis of cannabinoids [O.P. Malik, et al., Ind. J. Chem.. 14B, 975-78 (1976)]. 1- (Substitutedphenyl) -2-phenylcyclopentenes have been synthesized to study their photochemical reactions into phenanthrene derivatives. Compounds with meta substituents, such as 1- (3-chlorophenyl) -2- phenylcyclopentene, are described in Somers, et al., J. Photochem. Photobiol. , 48A. 353-74 (1989) . Para substituents, including specifically 1- (4-fluorophenyl) - 2-phenylcyclopentene, are described in aarhoven, Pure & ADDI. Chem.. 5L, 1225-40 (1984) . U.S. Patent No. 3,214,470 to Grogan describes aminospiroalkanes as having anesthetic properties. The synthesis of 7, 8-diphenyl-l, 4- dioxaspiro[4.4]non-7-ene is described as an intermediate for forming 1, 5-diphenylbicyclo[3.1.0]hexan-3-ol [E. J. Corey, et al., J. Amer. Chem. Soc.. 85, 1788-1792 (1963)]. U.S. Patent No. 3,728,404 to Kubicek describes a method to make spiro compounds, and specifically 1,1- dichloro-2,2, 5-triphenylspiro[2.4]hept-5-ene. The invention's spiro compounds are found to show usefulness in vivo as antiinflammatory agents with minimal side effects. DESCRIPTION OF THE INVENTION A class of substituted spiro compounds useful in treating inflammation-related disorders is defined by Formula I: wherein A is selected from wherein each of R through R.10, if present, is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylamino, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl; and wherein n is a number selected from 0, 1, 2 and 3; or a pharmaceutically-acceptable salt thereof. Compounds of Formula I would be useful for, but not limited to, the treatment of inflammation in a subject, and for treatment of other inflammation-associated disorders, such as, as an analgesic in the treatment of pain and headaches, or as an antipyretic for the treatment of fever. For example, compounds of Formula I would be useful to treat arthritis, including but not limited to rheumatoid arthritis, spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis. Such compounds of Formula I would be useful in the treatment of asthma, bronchitis, menstrual cramps, tendinitis, bursitis, and skin related conditions such as psoriasis, eczema, burns and dermatitis. Compounds of Formula I also would be useful to treat gastrointestinal conditions such as inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome and ulcerative colitis and for the prevention of colorectal cancer. Compounds of Formula I would be useful in treating inflammation in such diseases as vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodgkin's disease, sclerodoma, rheumatic fever, type I diabetes, myasthenia gravis, sarcoidosis, nephrotic syndrome, Behcet ' s syndrome, polymyositiε, gingivitis, hypersensitivity, conjunctivitis, swelling occurring after injury, myocardial ischemia, and the like. The compounds are useful as anti¬ inflammatory agents, such as for the treatment of arthritis, with the additional benefit of having significantly less harmful side effects. The present invention also includes compounds which selectively inhibit cyclooxygenase-2 over cyclooxygenase-1 and do not significantly inhibit one or more other arachidonic pathway steps, such as thromboxane B 2 (TXB2) production. The present compounds may also be used in co-therapies, partially or completely, in place of other conventional antiinflammatories, such as together with steroids, NSAIDs, 5-lipoxygenase inhibitors, LTB 4 inhibitors and LTA 4 hydrolase inhibitors. More preferably, the compounds also have a selectivity ratio of cyclooxygenaεe-2 inhibition over cyclooxygenase-1 inhibition of at least 50, and preferably of at least 100. Even more preferably, the compounds have a cyclooxygenase-1 IC 5 0 of greater than about 0.5 μM, and more preferably of greater than 5 μM. Such preferred selectivity may indicate an ability to reduce the incidence of common NSAlD-induced side effects, such as ulcers. A preferred class of compounds consists of those compounds of Formula I wherein, if present, each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; and wherein R 3 is selected from lower alkylsulfonyl, lower haloalkylsulfonyl and aminosulfonyl, and R 8 , if present, is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylamino, hydroxyl and mercapto; or wherein further R 8 and R 9 , if present, together form methylenedioxy; or wherein further, R 3 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylamino, hydroxyl and mercapto, and R 8 is selected from lower alkylsulfonyl, lower haloalkylsulfonyl and aminosulfonyl; or wherein further R 3 and R 4 , if present, together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. A class of compounds of particular interest consists of those compounds of Formula I wherein, if present, each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethy1, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is selected from methylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl and aminosulfonyl, and R 8 , if present, is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n- propyl, isopropyl, butyl, terfc-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methylamino, N,N- dimethylamino, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; or wherein further R 8 and R 9 , if present, together form methylenedioxy; or wherein further R 3 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl, and R 8 is selected from methylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl and aminosulfonyl; or wherein further R 3 and R 4 , if present, together form methylenedioxy; or a pharmaceutically- acceptable salt thereof. Within Formula I there is a subclass of compounds of high interest represented by Formula II: wherein each of R 1 through R 10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylamino, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl; and wherein n is a number selected from 0, 1, 2 and 3; or a pharmaceutically-acceptable salt thereof. A preferred class of compounds consists of those compounds of Formula II wherein n is a number selected from 0, 1 and 2; wherein each of R 1 , R 2 and R 4 through R 10 is independently selected from hydrido, halo, lower alkyl, lower alkylamino, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower alkoxy, hydroxyl, mercapto, lower hydroxyalkyl and lower alkoxyalkyl; and wherein R 3 is selected from lower alkylsulfonyl, lower haloalkylsulfonyl and aminosulfonyl; or wherein R 8 and R 9 together form methylenedioxy; or a pharmaceutically-acceptable ' salt thereof. A class of compounds of particular interest consists of those compounds of Formula II wherein each of R 1 , R 2 and R 4 through R 10 is independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methylamino, N,N- dimethylamino, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is selected from methylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl and aminosulfonyl; or wherein R 8 and R 9 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. A family of specific compounds of particular interest within Formula II consists of compounds and pharmaceutically-acceptable salts thereof as follows: 5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5- yl] -1,3-benzodioxole; 2, 6-dichloro-4- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5- yl]phenol 5- (4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 4- [6- (4-trifluoromethoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (2, 4-difluorophenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (2, 4-dichlorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-methylphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-methyl-4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-chloro-4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 4- [6- (3-methyl-4- trifluoromethoxyphenyl) spiro [2.4]hept-5-en-5- yl]benzenesulfonamide; 4-[6-(3-chloro-4- trifluoromethoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5-phenyl-6- [4- (methylsulfonyl) henyl] spiro[2.4]hept- 5-ene; 5- (4-fluorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-chlorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- (4-bromophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- 4-iodophenyl) -6-[4- (methylsulfonyl)phenyl] spiro [2.4] ept-5-ene; 4-methylphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- 4-ethylphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2 .4]hept-5-ene; 5- 4-methoxγphenyl) -6- [4- (methylsulfonyl) phenyl]spiro[2.4]hept-5-ene; 5- 4-methylthiophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4] ept-5-ene; 5- 4-cyanophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2. ]hept-5-ene; 5- 4-trifluoromethylphenyl) -6-[4- (methylsulfonyl) phenyl]spiro[2.4]hept-5-ene; 5- 4-hydroxymethylphenyl) -6- [4- (methylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 4-methoxymethylpheny1) -6- [4- (methylsulfonyl) phenyl]spiro [2 .4]hept-5-ene; 4-hydroxyphenyl) -6- [4- (methylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 5- 4-mercaptophenyl) -6- [4- (methylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 4- (N-methylamino)phenyl] -6-[4- (methylsulfonyl) phenyl]spiro[2.4]hept-5-ene; 5- 4- (N,N-dimethylamino) henyl] -6- [4- (methylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 4- 6-phenylspiro[2.4]hept-5-en-5-yl) benzenesulfonamide; 6- ( -fluorophenyl)spiro [2 .4]hep -5-en-5-yl] benzenesulfonamide; 4- 6- (4-chlorophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 6- (4-bromophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 6- (4-iodophenyl)spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- 6- (4-methylphenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-ethylphenyl) spiro [2 .4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-methoxyphenyl) spiro[2.4]hep -5-en-5-yl] benzenesulfonamide; 4- [6- (4-methylthiophenyl) spiro [ 2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-cyanophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-trifluoromethylphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (4-hydroxymethylphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (4-methoxymethylphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (4-hydroxypheny1) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-mercaptophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- [4- (N-methylamino)phenyl] spiro [2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- [4- (N,N-dimethylamino)phenyl] spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 6-phenyl-7- [4- (methylsulfonyl)phenyl] spiro[3.4] oct- 6-ene; 6- (4-fluorophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-chlorophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-bromopheny1) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-iodophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-methylphenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-ethylphenyl) -7-[4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-methoxyphenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-methylthiophenyl) -7- [4- (me hylsulfonyl) henyl] spiro[3.4]oct-6-ene; 6- (4-cyanophenyl) -7- [4- (methylsulfonyl) henyl] spiro[3.4]oct-6-ene; 6- (4-trifluoromethylphenyl) -7- [4- (methylsulfonyl) phenyl]spiro[3.4]oct-6-ene; 6- (4-hydroxymethylphenyl) -7- [4- (methylsulfonyl) phenyl] spiro[3.4]oct-6-ene; 6- (4-methoxymethylphenyl) -7- [4- (methylsulfonyl) phenyl] spiro[3.4]oct-6-ene; 6- (4-hydroxyphenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-mercaptophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 4- (7-phenylspiro[3.4]oct-6-en-6-yl) benzenesulfonamide; 4- [7- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-chlorophenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-bromophenyl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-iodophenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-methylphenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-ethylphenyl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-methoxyphenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-methylthiophenyl) spiro[3.4] oct-6-en-6-yl] benzenesuIfonamide; 4- [7- (4-cyanophenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-trifluoromethylphenyl) spiro [3.4]oct-6-en-6- yl]benzenesulfonamide; 4- [7- (4-hydroxymethylphenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-methoxymethylphenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4-[7- (4-hydroxypheny1) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-mercaptophenyl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 2-phenyl-3- [4- (methylsulfonyl)phenyl] spiro[4.4]non- 2-ene; 2- (4-fluorophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-chlorophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-bromophenyl) -3-[4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-iodophenyl) -3- [4- (methylsulfonyl) henyl] spiro[4.4]non-2-ene; 2- (4-methylphenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-ethylphenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-methoxypheny1) -3- [4- (methylsulfonyl) henyl] spiro[4.4]non-2-ene; 2- (4-methylthiophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-cyanophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-trifluoromethylphenyl) -3- [4- (methylsulfonyl) phenyl]spiro[4.4]non-2-ene; 2- (4-hydroxymethylphenyl) -3- [4- (methylsulfonyl) phenyl] spiro[4.4]non-2-ene; 2- (4-methoxymethylphenyl) -3- [4- (methylsulfonyl) phenyl]spiro[4.4]non-2-ene; 2- (4-hydroxypheny1) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; (4-mercaptophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; (3-phenylspiro[4.4]non-2-en-2-yl) benzenesulfonamide; - [3- ( -fluorophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; - [3- (4-chlorophenyl) spiro[ .4]non-2-en-2-yl] benzenesulfonamide; - [3- (4-bromophenyl)spiro[4.4]non-2-en-2-y1] benzenesulfonamide; - [3- (4-iodophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; - [3- (4-me hylphenyl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; [3- (4-ethylphenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; [3- (4-methoxyphenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; - [3- (4-methylthiophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; [3- (4-cyanophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; [3- ( -trifluoromethylphenyl)spiro[4.4]non-2-en-2- yl]benzenesulfonamide; [3- (4-hydroxymethylphenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; - [3- (4-methoxymethylphenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; [3- (4-hydroxyphenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; [3- (4-mercaptophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; (3-trifluoromethyl-4-methylphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; (3-trifluoromethyl-4-fluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; - (3-1rifluoromethyl-4-chloropheny1) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl- -bromophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-fluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-chlorophenyl) - 6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-bromophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-trifluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methy1-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-fluoro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-bromo-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3, 4, 5, 6-pentafluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-methoxy-2, 3,5, 6-tetrafluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3, 5, 6-tetrafluoro-4-trifluoromethylphenyl) - 6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 5-difluoro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 5-dichloro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3,5-dibromo-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3,4-trifluoro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3, 4-trichloro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3,4-tribromo-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2 ,4, 5-trifluoro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,4, 5-trichloro-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2, 4, 5-tribromo-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4-dimethoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4,5-trimethoxypheny1) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- [3 , 4-bis (trifluoromethyl)phenyl] - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 ,4-dimethylphenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4-difluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4-dichlorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 ,4-dibromophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-fluorophenyl) - 6- [4- (methylsulfonyl) henyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-bromophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-chloro-3-fluorophenyl) - 6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-chloro-3-bromophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-methylphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-fluorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-chlorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-bromophenyl) -6-[4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-fluorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-methyl-4-chlorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-bromophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-trifluorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methy1-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-fluoro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-bromo-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (2, 3, 4, 5, 6-pentafluorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-methoxy-2,3 , 5, 6-tetrafluorophenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3,5, 6-tetrafluoro-4-trifluoromethylphenyl) -6- [4- (fluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3 , 5-difluoro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 5-dichloro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3,5-dibromo-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2 ,3, 4-trifluoro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2, 3 ,4-trichloro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (2,3,4-tribromo-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 2,4, 5-trifluoro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; - 2,4, 5-trichloro-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 2,4, 5-tribromo-4-methoxyphenyl) -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; - 3 , 4-dimethoxyphenyl) -6- [4- (fluoromethylsulfonyl) phenyl]spiro[2.4]hept-5-ene; - 3,4, 5-trimethoxyphenyl) -6- [4- (fluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 3 , 4-bis (trifluoromethyl)phenyl] -6- [4- (fluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 3 , 4-dimethylphenyl) -6- [4- (fluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 3 , 4-difluorophenyl) -6- [4- (fluoromethylsulfonyl) phenyl]spiro[2.4]hept-5-ene; 3 , 4-dichlorophenyl) -6- [4- (fluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; - 3 ,4-dibromophenyl) -6-[4- (fluoromethylsulfonyl) phenyl] spiro[2.4]hep -5-ene;. - 3-chloro-4-fluorophenyl) -6- [4- (fluoromethylsulfonyl) phenyl] spiro[2.4] ep -5-ene; 3-chloro-4-bromophenyl) -6- [4- (fluoromethylsulfonyl) phenyl]spiro[2.4]hept-5-ene; 4-chloro-3-fluorophenyl) -6- [4- (fluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; - 4-chloro-3-bromophenyl) -6-[4- (fluoromethylsulfonyl) phenyl]spiro[2.4]hept-5-ene; - 3-trifluoromethyl-4-methylphenyl) -6- [4- (difluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; - 3-trifluoromethyl-4-fluorophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; - 3-trifluoromethy1-4-chlorophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 3-trifluoromethyl-4-bromophenyl) -6- [4- (difluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 3-methyl-4-fluorophenyl) -6- [4- (difluoromethylsulfonyl) henyl]spiro[2.4] ept-5-ene; 5- (3-methyl-4-chlorophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-bromophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-trifluorophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-fluoro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-bromo-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3, 4, 5, 6-pentafluorophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hep -5-ene; 5- (4-methoxy-2,3 ,5, 6-tetrafluorophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3 , 5, 6-tetrafluoro-4-trifluoromethylphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 ,5-difluoro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 5-dichloro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 ,5-dibromo-4-methoxyphenyl) -6-[4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3, 4-trifluoro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2,3, 4-trichloro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (2,3 , 4-tribromo-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2, 4, 5-trifluoro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2, 4, 5-trichloro-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (2, 4, 5-tribromo-4-methoxyphenyl) -6- [4- (difluoromethylsulfonyl) henyl]spiro[2.4]hept-5-ene; 5- (3 , 4-dimethoxyphenyl) -6- [4- (difluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4, 5-trimethoxyphenyl) -6- [4- (difluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 5- [3 ,4-bis (trifluoromethyl)phenyl] -6- [4- (difluoromethylsulfonyl) henyl] spiro[2.4]hept-5-ene; 5- (3 , 4-dimethylphenyl) -6- [4- (difluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4-difluorophenyl) -6- [4- (difluoromethylsulfonyl) phenyl] spiro[2.4]hept-5-ene; 5-(3,4-dichlorophenyl)-6-[4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3 , 4-dibromophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-fluorophenyl) -6- [4- (difluoromethylsulfonyl) henyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-bromophenyl) -6- [4- (difluoromethylsulfonyl)phenyl] spiro[2.4] ept-5-ene; 5- (4-chloro-3-fluorophenyl) -6- [4- (difluoromethylsulfonyl) henyl] spiro[2.4]hept-5-ene; 5- (4-chloro-3-bromophenyl) -6- [4- (difluoromethylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-methylphenyl) -6- [4- (trifluoromethy1sulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-trifluoromethy1-4-fluorophenyl) -6- [4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept-5- ene; 5- (3-trifluoromethyl-4-chlorophenyl) -6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-trifluoromethy1-4-bromophenyl) -6- [4- (trifluoromethy1sulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-methyl-4-fluorophenyl) -6- [4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept-5- ene; 5- (3-methyl-4-chlorophenyl) -6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-methyl-4-bromophenyl) -6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-methyl-4-trifluorophenyl) -6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-trifluoromethyl-4-methoxyphenyl) -6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept-5- ene; 5- (3-methy1-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3-fluoro-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3-chloro-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3-bromo-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept- 5-ene; 5-(2,3,4,5,6-pentafluorophenyl) - 6-[4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept- 5-ene; 5- (4-methoxy-2, 3,5, 6-tetrafluorophenyl) - 6-[4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (2,3, 5, 6-tetrafluoro-4-trifluoromethylphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3,5-difluoro-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept- 5-ene, • 5- (3 ,5-dichloro-4-methoxyphenyl) - 6-[4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3 , 5-dibromo-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (2,3 ,4-trifluoro-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (2,3,4-trichloro-4-methoxyphenyl) - 6- [4- ( rifluoromethylsulfonyl)phenyl]spiro[2.4]hept- 5-ene; 5- (2,3 ,4-tribromo-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (2, 4, 5-trifluoro-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (2, 4,5-trichloro-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept- 5-ene; 5- (2 , 4, 5-tribromo-4-methoxyphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl]spiro[2.4] ept- 5-ene; 5- (3 ,4-dimethoxyphenyl) - 6-[4- (trifluoromethylsulfonyl)phenyl]spiro[2.4]hept- 5-ene; 5- (3 ,4, 5-trimethoxypheny1) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- [3 , 4-bis (trifluoromethyl)phenyl] - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3 , 4-dimethylphenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3 , 4-difluorophenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3 , 4-dichlorophenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3 , 4-dibromophenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (3-chloro-4-fluorophenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4] ept- 5-ene; 5- (3-chloro-4-bromophenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (4-chloro-3-fluorophenyl) - 6- [4- (trifluoromethylsulfonyl)phenyl] spiro[2.4]hept- 5-ene; 5- (4-chloro-3-bromophenyl) - 6- [4- (trifluoromethylsulfonyl) henyl] spiro[2.4] hept-5-ene; 4- [6- (3-methyl-4-fluorophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-methyl-4-chlorophenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-methyl-4-bromophenyl) spiro[2.4]hept- 5-e -5-yl]benzenesulfonamide; 4- [6- (3-methyl-4-trifluoromethylphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4-[6- (3-methyl-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-trifluoromethyl-4-fluorophenyl) spiro[2.4]hept- 5-en-5-y1]benzenesulfonamide; 4- [6- (3-trifluoromethyl-4-chlorophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-trifluoromethyl-4-bromophenyl) spiro[2.4]hept- 5-en-5-y1]benzenesulfonamide; 4- [6- (3-trifluoromethyl-4-methylphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-trifluoromethyl-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-fluoro-4-methoxyphenyl) spiro[2.4]hep - 5-en-5-y1]benzenesulfonamide; 4- [6- (3-chloro-4-methoxyphenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-bromo-4-methoxyphenyl) spiro [2.4]hept- 5-en-5-yl]benzenesulfonamide; 4-[6-(2,3,4,5, 6-pentafluorophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (4-methoxy-2,3, 5, 6-tetrafluorophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (2,3 ,5, 6-tetrafluoro-4- trifluoromethylphenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3, 5-difluoro-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3 , 5-dichloro-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4-[6- (3,5-dibromo-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (2,3, 4-trifluoro-4-methoxyphenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (2,3, 4-trichloro-4-methoxyphenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (2,3, 4-tribromo-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-y1]benzenesulfonamide; 4- [6- (2, 4, 5-trifluoro-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (2, 4, 5-trichloro-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (2,4, 5-tribromo-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3 , 4-dimethoxypheny1) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3 , 4, 5-trimethoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6-[3 ,4-bis (trifluoromethyl)phenyl]spiro[2.4]hept- 5-en-5-yl]benze esulfonamide; 4- [6- (3 , 4-dimethylpheny1) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3, 4-difluorophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3 ,4-dibromophenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-chloro-4-fluorophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- [6- (3-chloro-4-bromophenyl) spiro[2.4]hept- 5-en-5-y1]benzenesulfonamide; 4-[6- (4-chloro-3-fluorophenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; and 4- [6- (4-chloro-3-bromophenyl) spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide. Within Formula I there is a second subclass of compounds of high interest represented by Formula III: wherein n is a number selected from 0, 1 and 2; wherein R 6 is selected from hydrido and halo; wherein R 7 is selected from hydrido and halo; wherein R 8 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, and hydroxyl; wherein R 9 is selected from hydrido, halo, and lower alkyl; or wherein R 8 and R 9 together form methylenedioxy; and wherein R 11 is selected from lower alkyl and amino; or a pharmaceutically-acceptable salt thereof. A class of compounds of particular interest consists of those compounds of Formula III wherein R 6 is selected from hydrido, fluoro, chloro, bromo, and iodo; wherein R 7 is selected from hydrido, fluoro, chloro, bromo, and iodo; wherein R 8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n- propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, and trifluoromethoxy; wherein R 9 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, ϋert-butyl, and isobutyl; or where R 8 and R 9 together form methylenedioxy; and wherein R 11 is methyl or amino; and or a pharmaceutically-acceptable salt thereof. A family of specific compounds of particular interest within Formula III consists of compounds and pharmaceutically-acceptable salts thereof as follows: 5- (3-chloro-4-methoxyphenyl)-6-[4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 4- [6- (3-chloro-4-methoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (3-fluoro-4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 4- [6- (3-fluoro-4-methoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (3 , 4-difluorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5- yl] -1,3-benzodioxole; 4- [6- (3 ,4-difluorophenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 2,6-dichloro-4-[6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5- yl]phenol 5- (4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- (3-bromo-4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 4- [6- (4-methoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (3-bromo-4-methoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (4-trifluoromethylphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 5- (3 , 5-dichloro-4-methoxy-phenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 4-[6- (4-trifluoromethoxyphenyl)spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (3-chloro-4-fluorophenyl) -6- [4- (methylsulfonyl) henyl] spiro[2.4]hept-5-ene; 5- (2,4-difluorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- (2, 4-dichlorophenyl) -6- [4- (methylεulfonyl)phenyl]spiro[2.4]hept-5-ene; 4- [6- (4-trifluoromethylphenyl) spiro [2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (3-chloro-4-fluorophenyl) spiro [2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (3,4-dichlorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- (4-chlorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 4- [6- (3, 4-dichlorophenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (4-chlorophenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (3-chloro-4-methylphenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3,4-dimethylphenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4- ethylpheny1) -6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3-methyl-4-trifluoromethoxyphenyl) -6- [4- (methylεulfonyl)phenyl] εpiro [2.4]hept-5-ene; 5- (3-chloro-4-trifluoromethoxyphenyl) -6- [4- (methylεulfonyl)phenyl] εpiro [2.4]hept-5-ene; 4- [6- (3,5-dichloro-4-methoxyphenyl) spiro[2.4]hept-5- en-5-yl]benzenesulfonamide; 4-[6-(3-methyl-4- trifluoromethoxyphenyl) spiro [2.4]hept-5-en-5- yl]benzenesulfonamide; 4-[6-(3-chloro-4- trifluoromethoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (4-fluorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 4- [6- (4-fluorophenyl) spiro[2.4]hept-5-en-5- yl]benzeneεulfonamide; 6- (4-fluorophenyl) -7- [4- (methylεulfonyl)phenyl] εpiro[3.4]oct-5-ene; 4- [7- (4-fluorophenyl) εpiro[3.4]oct-6-en-6-yl] benzenesulfonamide; and 2- (4-fluorophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-5-ene. Within Formula I there is a third εubclaεε of compoundε of high interest represented by Formula IV: wherein n is a number selected from 0, 1, 2 and 3; and wherein each of R 1 through R 5 and R 7 through R 10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, alkylamino, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof. A preferred claεs of compounds consistε of thoεe compoundε of Formula IV wherein n is a number selected from 0, 1 and 2; wherein each of R 1 , R 2 , R 4 , R 5 , R 7 , R 9 and R 10 is independently selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; and wherein R 3 is selected from lower alkylsulfonyl and aminosulfonyl and R 8 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower haloalkoxy, lower hydroxyalkyl, lower alkylamino, mercapto, hydroxyl, lower alkoxyalkyl, cyano and lower haloalkyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower haloalkoxy, lower alkylamino, lower hydroxyalkyl, hydroxyl, mercapto, lower alkoxyalkyl, cyano and lower haloalkyl, and R 8 is selected from lower alkylsulfonyl and aminosulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. A class of compounds of particular interest consiεts of those compounds of Formula IV wherein each of R 1 , R 2 , R 4 , R 5 , R 7 , R 9 and R 10 is hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methylamino, N,N- dimethylamino, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is methylsulfonyl or aminosulfonyl, and R 8 is εelected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, iεopropyl, butyl, tert-butyl, iεobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylamino, N,N-dimethylamino, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 iε selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, and R 8 is methylsulfonyl or aminosulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. A family of εpecific compounds of particular interest within Formula IV consists of compounds and pharmaceutically-acceptable salts thereof as follows: 2- [6- [4- (methylsulfonyl)phenyl] εpiro[2.4]hept-5-en- 5-yl]pyridine; 5-fluoro-2- [6- [4- (methylεulfonyl)phenyl] spiro [2.4]hept-5-en-5-y1]pyridine; 5-chloro-2- [6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-en-5-yl]pyridine; 5-methyl-2-[6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-en-5-yl]pyridine; 5-methoxy-2-[6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-en-5-yl]pyridine; 5-methylthio-2- [6- [4- (methylsulfonyl) henyl]spiro [2.4]hept-5-en-5-yl]pyridine; 5-cyano-2- [6- [4- (methylsulfonyl)phenyl] spiro [2.4] e t-5-en-5-y1]pyridine; 5-trifluoromethyl-2- [6- [4- (methylsulfonyl) phenyl] spiro[2.4]hept-5-en-5-yl]pyridine; 4- [6- (pyridin-2-yl) εpiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (5-fluoropyridin-2-yl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [ 6- ( 5-chloropyridin-2 -yl ) spiro [2 . 4 ] hept-5-en-5-yl ] benzenesulfonamide; 4-[6- (5-methylpyridin-2-yl)spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4-[6- (5-methoxypyridin-2-yl)spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4-[6- (5-methylthiopyridin-2-yl)spiro[2.4]hept-5-en- 5-y1]benzenesulfonamide; 4-[6- (5-cyanopyridin-2-yl)spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4-[6- (5-trifluoromethylpyridin-2-yl)spiro[2.4]hept- 5-en-5-yl]benzene ulfonamide; 2-[7-[4-(methylsulfonyl)phenyl]spiro[3.4]oct-6-en-6- yl]pyridine; 5-fluoro-2-[7-[4- (methylsulfonyl) phenyl]spiro[3.4]oct-6-en-6-yl]pyridine; 5-chloro-2-[7-[4- (methylεulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 5-methyl-2-[7-[4-(methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 5-methoxy-2-[7-[4-(methylsulfonyl)phenyl] spiro[3.4] oct-6-en-6-yl]pyridine; 5-methylthio-2-[7-[4-(methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 5-cyano-2-[7-[4- (methylsulfonyl) henyl] spiro[3.4]oct-6-en-6-yl]pyridine; 5-trifluoromethyl-2-[7-[4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 4-[7- (pyridin-2-yl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4-[7- (5-fluoropyridin-2-yl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4-[7-(5-chloropyridin-2-yl)εpiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4-[7- (5-methylpyridin-2-yl)εpiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4-[7- (5-methoxypyridin-2-yl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (5-methylthiopyridin-2-yl) spiro[3.4]oct-6-en-6- yl]benzeneεulfonamide; 4- [7- (5-cyanopyridin-2-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (5-trifluoromethylpyridin-2-yl)spiro[3.4]oct-6- en-6-yl]benzenesulfonamide; 2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2- yl]pyridine; 5-fluoro-2-[3-[4- (methylsulfonyl)phenyl]spiro[4.4] non-2-en-2-yl]pyridine; 5-chloro-2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4] non-2-en-2-yl]pyridine; 5-methy1-2-[3- [4- (methylsulfonyl)phenyl] spiro[4.4] non-2-en-2-yl]pyridine; 5-methoxy-2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4] non-2-en-2-yl]pyridine; 5-methylthio-2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl]pyridine; 5-cyano-2- [3- [4- (methylεulfonyl)phenyl]εpiro[4.4] non-2-en-2-yl]pyridine; 5-trifluoromethyl-2- [3- [4- (methylεulfonyl)phenyl] εpiro[4.4]non-2-en-2-yl]pyridine; 4- [3- (pyridin-2-yl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (5-fluoropyridin-2-yl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (5-chloropyridin-2-yl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (5-methylpyridin-2-yl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4-[3- (5-methoxypyridin-2-yl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (5-methylthiopyridin-2-yl) spiro[4.4]non-2-en-2- yl]benzenesulfonamide; 4- [3- (5-cyanopyridin-2-yl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- (5-trifluoromethylpyridin-2-yl) spiro[4.4]non-2- en-2-yl]benzeneεulfonamide; 2- 6- phenylεpiro[2.4]hept-5-en-5-yl) -5- (methylεulfonyl)pyridine; 2- 6- (4-fluorophenyl) εpiro[2.4]hept-5-en-5-yl] -5- (methylεulfonyl)pyridine; 2- 6- (4-chlorophenyl) εpiro[2.4]hept-5-en-5-yl] -5- (methylsulfonyl)pyridine; 6- (4-methylphenyl) spiro[2.4]hept-5-en-5-yl] -5- (methylεulfonyl)pyridine; 6- (4-methoxyphenyl) εpiro[2.4]hept-5-en-5-yl] -5- (methylεulfonyl)pyridine; 2- (4-methylthiophenyl) spiro[2.4]hept-5-en-5-yl] - 5- (methylsulfonyl) yridine; 2- (4-cyanophenyl) εpiro[2.4]hept-5-en-5-yl] -5- (methylεulfonyl)pyridine; 6- (4-trifluoromethylphenyl) εpiro [2.4]hept-5-en-5- yl] -5- (methylεulfonyl) yridine; 2- 6-phenylεpiro[2.4]hept-5-en-5-yl] -5- pyridinesulfonamide; 6- (4-fluorophenyl) spiro[2.4]hept-5-en-5-yl] -5- pyridineεulfonamide; 2- 6- (4-chlorophenyl)εpiro[2.4]hept-5-en-5-yl] -5- pyridinesulfonamide; 2- 6- (4-methylphenyl) spiro[2.4]hept-5-en-5-yl] -5- pyridineεulfonamide; 2- 6- (4-methoxyphenyl) εpiro[2.4]hept-5-en-5-yl] -5- pyridineεulfonamide; 2- 6- (4-methylthiophenyl) spiro[2.4]hept-5-en-5-yl] - 5-pyridinesulfonamide; (4-cyanophenyl) spiro[2.4]hept-5-en-5-yl] -5- pyridineεulfonamide; 2- 6- (4-trifluoromethylphenyl) εpiro[2.4]hept-5-en-5- yl] -5-pyridinesulfonamide; 2- 7-phenylspiro[3.4] oct-6-en-6-yl) -5- (methylεulfonyl)pyridine; 2- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-chlorophenyl)spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-methylphenyl)spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-methoxyphenyl) spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2-[7- (4-methylthiophenyl) spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-cyanophenyl) spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-trifluoromethylphenyl) spiro [3.4]oct-6-en-6- yl] -5- (methylsulfonyl)pyridine; 2- (7-phenylspiro[3.4]oct-6-en-6-yl) -5- pyridinesulfonamide; 2- [7- (4-fluorophenyl)spiro[3.4]oct-6-en-6-yl] -5- pyridinesulfonamide; 2- [7- (4-chlorophenyl)spiro[3.4]oct-6-en-6-yl] -5- pyridineεulfonamide; 2-[7-(4-methylphenyl)spiro[3.4]oct-6-en-6-yl]-5- pyridineεulfonamide; 2- [7- (4-methoxyphenyl) spiro[3.4]oct-6-en-6-yl] -5- pyridinesulfonamide; 2- [7- (4-methylthiophenyl) spiro[3.4] oct-6-en-6-yl] -5- pyridinesulfonamide; 2- [7- (4-cyanophenyl) spiro[3.4]oct-6-en-6-yl] -5- pyridineεulfonamide; 2- [7- (4-trifluoromethylphenyl)εpiro[3.4]oct-6-en-6- yl] -5-pyridineεulfonamide; 2- (3-phenylspiro[4.4]non-2-en-2-yl) -5- (methylεulfonyl)pyridine; 2-[3- (4-fluorophenyl) spiro[4.4]non-2-en-2-yl] -5- (methylεulfonyl)pyridine; 2- [3- (4-chlorophenyl) εpiro[4.4]non-2-en-2-yl] -5- (methylεulfonyl)pyridine; 2- [3- (4-methylphenyl) εpiro[4.4]non-2-en-2-yl] -5- (methylεulfonyl)pyridine; 2- [3- (4-methoxyphenyl) spiro[4.4]non-2-en-2-yl] -5- (methylεulfonyl) yridine; 2- [3- (4-methylthiophenyl) spiro[4.4]non-2-en-2-yl] -5- (methylεulfonyl)pyridine; 2-[3- (4-cyanophenyl) εpiro[4.4]non-2-en-2-yl] -5- (methylsulfonyl) yridine; 2- [3- (4-trifluoromethylphenyl)spiro[4.4]non-2-en-2- yl] -5- (methylsulfonyl)pyridine; 2- (3-phenylspiro[4.4]non-2-en-2-yl) -5- pyridinesulfonamide; 2- [3- (4-fluorophenyl) spiro[4.4]non-2-en-2-yl] -5- pyridinesulfonamide; 2- [3- (4-chlorophenyl) spiro[4.4]non-2-en-2-yl] -5- pyridinesulfonamide; 2- [3- (4-me hylphenyl)spiro[4.4]non-2-en-2-yl] -5- pyridinesulfonamide; 2- [3- (4-methoxyphenyl) spiro[4.4]non-2-en-2-yl] -5- pyridineεulfonamide; 2- [3- (4-cyanophenyl) spiro[4.4]non-2-en-2-yl] -5- pyridinesulfonamide; and 2- [3- (4-trifluoromethylphenyl) spiro [4.4]non-2-en-2- yl] -5-pyridinesulfonamide. Within Formula I there is a fourth subclass of compounds of high interest represented by Formula V: wherein n is a number selected from 0, 1, 2 and 3; and wherein each of R 1 through R 6 and R 8 through R 10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylamino, alkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof. A preferred clasε of compoundε consistε of thoεe compoundε of Formula V wherein n iε a number εelected from 0, 1 and 2; wherein each of R 1 , R 2 , R 4 , R 5 , R 6 , R 9 and R 10 iε independently εelected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; and wherein R 3 is selected from lower alkylsulfonyl and aminosulfonyl and R 8 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower haloalkoxy, lower hydroxyalkyl, mercapto, hydroxyl, lower alkoxyalkyl, cyano and lower haloalkyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower haloalkoxy, lower hydroxyalkyl, hydroxyl, lower alkoxyalkyl, cyano and lower haloalkyl, and R 8 iε selected from lower alkylsulfonyl and aminoεulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable εalt thereof. A claεs of compounds of particular interest consists of those compounds of Formula V wherein each of R 1 , R 2 , R 4 , R 5 , R 6 , R 9 and R 10 is hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is methylsulfonyl or aminosulfonyl, and R 8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylamino, N,N-dimethylamino, hydroxyl, methylthio, ethylthio, cyano, mercapto, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, hydroxyl, methylamino, N,N- dimethylamino, methylthio, ethylthio, cyano, mercapto, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, and R 8 is methylsulfonyl or aminosulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. A family of specific compounds of particular interest within Formula V consistε of compounds and pharmaceutically-acceptable salts thereof as follows: 5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en- 5-yl]pyridine; 2-fluoro-5- [6- [4- (methylsulfonyl)phenyl] εpiro[2.4] hept-5-en-5-yl]pyridine; 2-chloro-5- [6- [4- (methylεulfonyl)phenyl]εpiro[2.4] hept-5-en-5-yl]pyridine; 2-methyl-5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4] hept-5-en-5-yl]pyridine; 2-methoxy-5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4] hept-5-en-5-yl]pyridine; 2-methylthio-5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5-yl]pyridine; 2-cyano-5- [6- [4- (methylsulfonyl)phenyl] spiro[2.4] hept-5-en-5-yl]pyridine; 2-trifluoromethyl-5- [6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-en-5-y1]pyridine; 4- [6- (pyridin-5-yl) spiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4- [6- (2-fluoropyridin-5-yl)spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (2-chloropyridin-5-yl) εpiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4- [6- (2-methylpyridin-5-yl) εpiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4-[6- (2-methoxypyridin-5-yl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (2-methylthiopyridin-5-yl) spiro[2.4]hept-5-e - 5-y1]benzenesulfonamide; 4- [6- (2-cyanopyridin-5-yl)εpiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4- [6- (2-trifluoromethylpyridin-5-yl) εpiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 5- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6- yl]pyridine; 2-fluoro-5-[7- [4- (methylsulfonyl)phenyl] εpiro[3.4]oct-6-en-6-yl]pyridine; 2-chloro-5- [7- [4- (methylεulfonyl) henyl] εpiro[3.4]oct-6-en-6-yl]pyridine; 2-methyl-5- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 2-methoxy-5- [7- [4- (methylsulfonyl)phenyl] spiro [3.4]oct-6-en-6-yl]pyridine; 2-methylthio-5- [7- [4- (methylsulfonyl)phenyl] spiro [3.4]oct-6-en-6-yl]pyridine; 2-cyano-5- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 2-trifluoromethy1-5- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-en-6-yl]pyridine; 4-[7-(pyridin-5-yl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-fluoropyridin-5-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-chloropyridin-5-yl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-methylpyridin-5-yl)spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-methoxypyridin-5-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-methylthiopyridin-5-yl) spiro[3.4]oct-6-en-6- yl]benzenesulfonamide; 4- [7- (2-cyanopyridin-5-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-trifluoromethylpyridin-5-yl) spiro [3.4]oct-6- en-6-yl]benzenesulfonamide; 5- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2- yl]pyridine; 2-fluoro-5- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl]pyridine; 2-chloro-5- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl]pyridine; 2-methyl-5- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl]pyridine; 2-methoxy-5-[3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl]pyridine; 2-methylthio-5- [3- [4- (methylsulfonyl)phenyl] spiro [4.4]non-2-en-2-yl]pyridine; 2-trifluoromethyl-5- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl]pyridine; 4- [3- (pyridin-5-yl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (2-fluoropyridin-5-yl) εpiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (2-chloropyridin-5-yl) εpiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4-[3- (2-methylpyridin-5-yl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (2-methoxypyridin-5-yl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (2-methylthiopyridin-5-yl) spiro[4.4]non-2-en-2- yl]benzenesulfonamide; 4- [3- (2-cyanopyridin-5-yl) εpiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (2-trifluoromethylpyridin-5-yl) εpiro[4.4]non-2- en-2-y1]benzeneεulfonamide; 5- (6-phenylspiro[2.4]hept-5-en-5-yl) -2- (methylsulfonyl)pyridine; 5- [6- (4-fluorophenyl)spiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-chlorophenyl) spiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-methylphenyl) spiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-methoxyphenyl) εpiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-methylthiophenyl) spiro[2.4]hept-5-en-5-yl] - 2- (methylsulfonyl)pyridine; 5- [6- (4-cyanophenyl)spiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-trifluoromethylphenyl) spiro [2.4]hept-5-en-5- yl] -2- (methylsulfonyl)pyridine; 5-(6-ρhenylspiro[2.4]hept-5-en-5-yl)-2- pyridineεulfonamide; 5- [6- (4-fluorophenyl) εpiro[2.4]hept-5-en-5-yl] -2- pyridinesulfonamide; 5- [6- (4-chlorophenyl)spiro[2.4]hept-5-en-5-yl] -2- pyridineεulfonamide; 5- [6- (4-methylphenyl)spiro[2.4]hept-5-en-5-yl] -2- pyridinesulfonamide; 5-[6- (4-methoxyphenyl) spiro[2.4]hept-5-en-5-yl] -2- pyridinesulfonamide; 5-[6- (4-methylthiophenyl)spiro[2.4]hep -5-en-5-yl] - 2-pyridinesulfonamide; 5-[6- (4-cyanophenyl) εpiro[2.4]hept-5-en-5-yl] -2- pyridineεulfonamide; 5- [6- (4-trifluoromethylphenyl) εpiro [2.4]hept-5-en-5- yl] -2-pyridinesulfonamide; 5- (7-phenylspiro[3.4]oct-6-en-6-yl) -2- (methylsulfonyl)pyridine; 5- [7- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5- [7- (4-chlorophenyl) spiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5-[7-(4-methylphenyl)spiro[3.4]oct-6-en-6-yl]-2- (methylεulfonyl)pyridine; 5- [7- (4-methoxyphenyl) εpiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5- [7- (4-methylthiophenyl) εpiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5- [7- (4-cyanophenyl) εpiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl) yridine; 5- [7- (4-trifluoromethylphenyl) spiro[3.4]oct-6-en-6- yl] -2- (methylsulfonyl)pyridine; 5- (7-phenylspiro[3.4] oct-6-en-6-yl) -2- pyridineεulfonamide; 5- [7- (4-fluorophenyl) εpiro[3.4]oct-6-en-6-yl] -2- pyridinesulfonamide; 5- [7- (4-chlorophenyl) spiro[3.4]oct-6-en-6-yl] -2- pyridinesulfonamide; 5- [7- (4-methylphenyl) spiro[3.4]oct-6-en-6-yl] -2- pyridineεulfonamide; 5- [7- (4-methoxyphenyl) spiro[3.4]oct-6-en-6-yl] -2- pyridineεulfonamide; 5- [7- (4-cyanophenyl) spiro[3.4]oct-6-en-6-yl] -2- pyridineεulfonamide; 5- [7- (4-trifluoromethylphenyl) spiro[3.4]oct-6-en-6- yl] -2-pyridinesulfonamide; 5- (3-phenylspiro[4.4]non-2-en-2-yl) -2- (methylsulfonyl)pyridine; 5- [3- (4-fluorophenyl)spiro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5- [3- (4-chlorophenyl) spiro[4.4]non-2-en-2-yl] -2- (methylεulfonyl)pyridine; 5- [3- (4-methylphenyl) piro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5-[3- (4-methoxyphenyl) spiro[4.4]non-2-en-2-yl] -2- (methylεulfonyl)pyridine; 5- [3- (4-methylthiophenyl) spiro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5- [3- (4-cyanophenyl) spiro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5- [3- (4-trifluoromethylphenyl) spiro[4.4]non-2-en-2- yl] -2- (methylsulfonyl) yridine; 5- (3-phenylspiro[4.4]non-2-en-2-yl) -2- pyridinesulfonamide; 5- [3- (4-fluorophenyl) εpiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide; 5- [3- (4-chlorophenyl)spiro[4.4]non-2-en-2-yl]-2- pyridinesulfonamide; 5- [3- (4-methylphenyl) spiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide; 5- [3- (4-methoxyphenyl) εpiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide; 5-[3- (4-methylthiophenyl) εpiro[4.4]non-2-en-2-yl] -2- pyridineεulfonamide; 5-[3- (4-cyanophenyl)εpiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide; and 5- [3- (4-trifluoromethylphenyl) spiro [4.4]non-2-en-2- yl] -2-pyridinesulfonamide. Within Formula I there iε a fifth subclass of compounds of high intereεt represented by Formula VI: wherein n is a number selected from 0, 1, 2 and 3; and wherein each of R 1 through R 7 , R 9 and R 10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylamino, alkylεulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof. A preferred class of compounds consistε of thoεe compounds of Formula VI wherein n is a number selected from 0, 1 and 2; wherein each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently- selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower haloalkoxy, lower hydroxyalkyl, hydroxyl, lower alkoxyalkyl, mercapto, cyano and lower haloalkyl; and wherein R 3 is selected from lower alkylsulfonyl and aminosulfonyl; or a pharmaceutically- acceptable salt thereof. A class of compounds of particular interest consiεts of those compounds of Formula VI wherein each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylthio, ethylthio, cyano, hydroxyl, mercapto, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is methylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof. A family of specific compoundε of particular interest within Formula VI consists of compounds and pharmaceutically-acceptable salts thereof as follows: 4- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en- 5-yl]pyridine; 4- [6- (4-pyridinyl) spiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4- [7- [4- (methylsulfonyl) henyl] spiro[3.4] oct-6-en-6- yl]pyridine; 4- [7- (4-pyridinyl) εpiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4-[3-[4- (methylεulfonyl)phenyl]spiro[4.4]non-2-en-2- yl]pyridine; and 4- [3- (4-pyridinyl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide. Where the term "alkyl" is used, either alone or within other terms such as "haloalkyl", "alkylsulfonyl", "alkoxyalkyl" and "hydroxyalkyl", embraces linear or branched radicals having one to about twenty carbon atoms or, preferably, one to about twelve carbon atoms. More preferred alkyl radicals are "lower alkyl" radicals having one to about ten carbon atoms. Most preferred are lower alkyl radicals having one to about six carbon atoms. Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert- butyl, pentyl, iso-amyl, hexyl and the like. The term "hydrido" denotes a single hydrogen atom (H) . This hydrido radical may be attached, for example, to an oxygen atom to form a "hydroxyl" radical, to a sulfur atom to form a "mercapto" radical, or two hydrido radicals may be attached to a carbon atom to form a methylene (-CH 2 -) radical. The term "halo" means halogens such as fluorine, chlorine, bromine or iodine. The term "haloalkyl" embraces radicals wherein any one or more of the alkyl carbon atoms is subεtituted with halo as defined above. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either an iodo, bromo, chloro or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more of the same halo atoms or a combination of different halo radicals. The term "hydroxyalkyl" embraces linear or branched alkyl radicals having one to about ten carbon atoms any one of which may be subεtituted with one or more hydroxyl radicalε. The terms "alkoxy" and "alkoxyalkyl" embrace linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms. More preferred alkoxy radicals are "lower alkoxy" radicals having one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy and tert-butoxy. The term "alkoxyalkyl" also embraces alkyl radicals having two or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. The "alkoxy" or "alkoxyalkyl" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "haloalkoxy" or "haloalkoxyalkyl" radicals. The term "alkylamino" embraceε amino radicalε having one or more alkyl radicalε attached to the nitrogen atom, that iε, to form N- alkylamino and N,N-dialkylamino radicals. The term "alkylthio" embraces radicals containing a linear or branched alkyl radical, of one to about ten carbon atoms attached to a divalent sulfur atom, such as a methythio radical, (CH 3 -S-). The term "sulfonyl", whether used alone or linked to other terms such as alkylsulfonyl, denotes respectively divalent radicals -S0 2 -. "Alkylsulfonyl" embraces alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. The "alkylsulfonyl" radicals may be further subεtituted with one or more halo atomε, εuch aε fluoro, chloro or bromo, to provide "haloalkylεulfonyl" radicalε. The termε "aminoεulfonyl" "εulfamyl" and "εulfonamidyl" denoteε a εulfonyl radical εubεtituted with an amine radical, forming a sulfonamide (-SO 2 NH 2 ) . The present invention comprises a pharmaceutical composition comprising a therapeutically- effective amount of a compound of Formula I in association with at least one pharmaceutically-acceptable carrier, adjuvant or diluent. The present invention also comprises a method of treating inflammation or inflammation-asεociated diεorderε in a εubject, the method comprising administering to the subject having such inflammation or disorder a therapeutically-effective amount of a compound of Formula I. Also included in the family of compounds of Formula I are the pharmaceutically-acceptable saltε thereof. The term "pharmaceutically-acceptable εalts" embraces salts commonly used to form alkali metal saltε and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically-acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula I may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phoεphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, example of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, meεylic, εalicyclic, salicyclic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic) , methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, tolueneεulfonic, 2-hydroxyethaneεulfonic, εulfanilic, εtearic, cyclohexylaminoεulfonic, algenic, β -hydroxybutyric, εalicyclic, galactaric and galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula I include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic saltε made from N,N'- dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N- methylglucamine) and procaine. All of these saltε may be prepared by conventional meanε from the correεponding compound of Formula I by reacting, for example, the appropriate acid or baεe with the compound of Formula I. GENERAL SYNTHETIC PROCEDURES The compounds of the invention can be synthesized according to the following procedures of Schemes I-XIX, wherein the R 1 -R 11 substituents are as defined for Formula I, above, except where further noted. Scheme I Cl-CO-OCH 2 CH(CH 3 ) 2 , THF, 0 °C, N(C 2 H 5 ) 3 HN(CH 3 )OCH. 3 HC1, N(C 2 H 5 ) 3 CH 3 MgBr, THF, 0 °C Synthetic Scheme I shows the three step procedures used to prepare the bromoacetophenones 4 and the phenyl silyl enol ethers 5 from commercially available benzoic acids 1. In step one, a THF solution at 0°C of the benzoic acids 1 and two equivalents of triethyla ine are sequentially treated with isobutyl chloroformate and N-hydroxymethyl-N-methylamine hydrochloride to give the Weinreb amides 2 [see: S. Nahm and S. M. Weinreb, Tetrahedron Let .. 21, 3815 (1981)]. In step two, the amides 2 are reacted with methylmagnesium bromide to give the corresponding acetophenones 3. In step three, the acetophenones 3 are either treated with bromine in acetic acid to give the corresponding bromoacetophenones 4 or chlorotrimethylsilane in acetonitrile in the presence of triethylamine and sodium iodide to give the corresponding phenyl silyl enol ethers 5. Scheme II Cl-CO-OCH 2 CH(CH 3 ) 2 , THF, 0 °C, N(C 2 H 5 ) 3 HN(CH 3 )OCH 3 HCl, N(C 2 H 5 ) 3 CH 3 MgBr , THF, 0 °C Synthetic Scheme II shows the three step procedures used to prepare the bromoacetophenones 9 and the phenyl silyl enol ethers 10 from commercially available benzoic acids 6. In step one, a THF solution at 0°C of the benzoic acids 6 and two equivalents of triethylamine are sequentially treated with isobutyl chlorofor ate and N-hydroxymethyl-N-methylamine hydrochloride to give the Weinreb amides 7. In step two, the amides 7 are reacted with methylmagnesium bromide to give the corresponding acetophenones 8. In step three, the acetophenones 8 are either treated with bromine in acetic acid to give the corresponding bromoacetophenones 9 or chlorotrimethylsilane in acetonitrile in the presence of triethylamine and sodium iodide to give the corresponding phenyl silyl enol ethers 10. Scheme III Cl-CO-OCH 2 CH(CH 3 ) 2 , THF, 0 °C, N(C 2 H 5 ) 3 HN(CH 3 )OCH 3 HCl, N(C 2 H 5 ) 3 12 CH 3 MgBr, THF, 0 °C ) 3 Synthetic Scheme III shows the three step procedures used to prepare the 2- (bromoacetyl)pyridines 14 and the 2-pyridinyl silyl enol ethers 15 from commercially available picolinic acids 11. In step one, a THF solution at 0°C of the picolinic acids 11 and two equivalents of triethylamine are sequentially treated with isobutyl chlorofor ate and N-hydroxymethyl-N-methylamine hydrochloride to give the Weinreb amides 12. In step two, the amides 12 are reacted with methylmagnesium bromide to give the corresponding 2-acetylpyridines 13. In step three, the 2-acetylpyridines 13 are either treated with bromine in acetic acid to give the corresponding 2- (bromoacetyl)pyridines 14 or chlorotrimethylsilane in acetonitrile in the presence of triethylamine and sodium iodide to give the corresponding 2-pyridinyl silyl enol ethers 15. Scheme IV 16 Cl-CO-OCH 2 CH(CH 3 ) 2 , THF, 0 °C, N(C 2 H 5 ) 3 HN(CH 3 )OCH 3 HCl, N(C 2 H 5 ) 3 17 CH 3 MgBr, THF, 0 °C 19 20 Synthetic Scheme IV shows the three step procedures used to prepare the 3- (bromoacetyl)pyridines 19 and the 3-pyridinyl silyl enol ethers 20 from commercially available nicotinic acids 16. In step one, a THF solution at 0°C of the nicotinic acids 16 and two equivalents of triethylamine are sequentially treated with isobutyl chloroformate and N-hydroxymethyl-N-methylamine hydrochloride to give the Weinreb amides 17. In step two, the amides 17 are reacted with methylmagnesium bromide to give the corresponding 3-acetylpyridines 18. In step three, the 3-acetylpyridines 18 are either treated with bromine in acetic acid to give the corresponding 3- (bromoacetyl)pyridines 19 or chlorotrimethylsilane in acetonitrile in the presence of triethylamine and sodium iodide to give the corresponding 3-pyridinyl silyl enol ethers 20. Scheme V 21 Cl-CO-OCH 2 CH(CH 3 ) 2 , THF, 0 °C, N(C 2 H 5 ) 3 HN(CH 3 )OCH 3 HCl, N(C 2 H 5 ) 3 22 CH 3 MgBr, THF, 0 °C 24 25 Synthetic Scheme V shows the three step procedures used to prepare the 4- (bro oacetyl)pyridines 24 and the 4-pyridinyl silyl enol ethers 25 from commercially available isonicotinic acids 21. In step one, a THF solution at 0°C of the isonicotinic acids 21 and two equivalents of triethylamine are sequentially treated with isobutyl chloroformate and N-hydroxymethyl-N-methylamine hydrochloride to give the Weinreb amides 22. In step two, the amides 22 are reacted with methylmagnesium bromide to give the corresponding 4-acetylpyridines 23. In step three, the 4-acetylpyridines 23 are either treated with bromine in acetic acid to give the corresponding 4- (bromoacetyl)pyridines 24 or chlorotrimethylsilane in acetonitrile in the presence of triethylamine and sodium iodide to give the corresponding 4-pyridinyl silyl enol ethers 25. Scheme VI 29 3 0 31 Synthetic Scheme VI shows the two step procedures which can be used to prepare the phenylacetic acids 28, 2-pyridinylacetic acids 31, 3-pyridinylacetic acids 34, and 4-pyridinylacetic acids 37 from commercially available toluenes 26, 2-picolines 29, 3-picolines 32, and 4-picolines 35, respectively. In step one,, toluenes 26, 2-picolines 29, 3-picolines 32, and 4-picolines 35 are sequentially treated with N-bromosuccinimide (NBS) in carbon tetrachloride at reflux in the presence of a free radical initiater, e.g., 2,2'-azobis(2- methyIpropionitrile) (AIBN) , and potassium cyanide in DMF to give the corresponding phenylacetonitriles 27, 2- pyridinylacetonitriles 30, 3-pyridinylacetonitriles 33, and 4-pyridinylacetonitriles 36, respectively. In step two, phenylacetonitriles 27, 2-pyridinylacetonitriles 30, 3-pyridinylacetonitriles 33, and 4-pyridinylacetonitriles 36 are hydrolyzed with aqueous sodium hydroxide; acidification provides the phenylacetic acids 28, 2- pyridinylacetic acids 31, 3-pyridinylacetic acids 34, and 4-pyridinylacetic acids 37, respectively. Scheme VII S0C1 2 , DMF, 5 °C Synthetic Scheme VII shows the four step procedures used to prepare the cis-2, 3-diaryl-l,4- dichloro-2-butenes 41 from the bromoacetophenones 4 (prepared in Synthetic Scheme I) and the phenylacetic acids 28 (prepared in Synthetic Scheme VI) . In step one, bromoacetophenones 4 are reacted with phenylacetic acids 28 in acetonitrile in the presence of triethylamine to give the corresponding esters 38. In step two, the esters 38 are cyclized to the corresponding furanones 39 on treatment with p-toluenesulfonic acid (PTSA) and triethylamine in the presence of 4 A molecular sieves in acetonitrile at reflux. In step three, the furanones 39 are reacted with diisobutylaluminum hydride (DIBAL) to give the corresponding cis-diols 40. In step four, the cis-diols 40 are reacted with thionyl chloride in DMF at 5°C to give the corresponding cis-2, 3-diaryl-l, 4-dichloro- 2-butenes 41. Scheme VIII 42 JTsCl, pyridine Zn°,NaI, DMF, 150 °C 45 Synthetic Scheme VIII shows the four step procedure used to prepare the 5,6-diarylspiro[2.4]hept-5- enes 45 from the cis-2,3-diaryl-l,4-dichloro-2-butenes 41 (prepared in Synthetic Scheme VII) . In step one, the cis- 2,3-diaryl-l,4-dichloro-2-butenes 41 are reacted with dimethyl malonate in DMF in the presence of two equivalents of lithium hydride to give the corresponding 4,4-dicarbomethoxycyclopentenes 42. In step two, the 4,4- dicarbomethoxycyclopentenes 42 are reacted with DIBAL in THF to give the corresponding 4,4- di (hydroxymethyl)cyclopentenes 43. In step three, the 4,4-di (hydroxymethyl)cyclopentenes 43 are reacted with p- toluenesulfonyl chloride (TsCl) in pyridine to give the corresponding 4,4-ditosylates 44. In step four, the 4,4- ditosylates 44 are reacted with metallic zinc and sodium iodide in DMF at 150°C to give the 5,6- diarylspiro[2.4]hept-5-ene antiinflammatory agents 45 of this invention. Scheme IX SOCl 2 , DMF, 5 ' Synthetic Scheme IX shows the four step procedure used to prepare the cis-2- (2-pyridinyl) -3-aryl- 1,4-dichloro-2-butenes 49 from the bromoacetophenones 4 (prepared in Synthetic Scheme I) and the 2-pyridinylacetic acids 31 (prepared in Synthetic Scheme VI) . In step one, bromoacetophenones 4 are reacted with 2-pyridinylacetic acids 31 in acetonitrile in the presence of triethylamine to give the corresponding esters 46. In step two, the esters 46 are cyclized to the corresponding furanones 47 on treatment with p-toluenesulfonic acid (PTSA) and triethylamine in the presence of 4 A molecular sieves in acetonitrile at reflux. In step three, the furanones 47 are reacted with diisobutylaluminum hydride (DIBAL) to give the corresponding cis-diols 48. In step four, the cis-diols 48 are reacted with thionyl chloride in DMF at 5°C to give the corresponding cis-2- (2-pyridinyl) -3-aryl- 1,4-dichloro-2-butenes 49. Scheme X 53 Synthetic Scheme X shows the four step procedure used to prepare the 5- (2-pyridinyl) -6-arylspiro [2.4]hept- 5-enes 53 from the cis-2- (2-pyridinyl) -3-aryl-l,4- dichloro-2-butenes 49 (prepared in Synthetic Scheme IX) . In step one, the cis-2- (2-pyridinyl) -3-aryl-l, 4-dichloro- 2-butenes 49 are reacted with dimethyl malonate in DMF in the preεence of two equivalents of lithium hydride to give the corresponding 4, 4-dicarbomethoxycyclopentenes 50. In step two, the 4, 4-dicarbomethoxycyclopentenes 50 are reacted with DIBAL in THF to give the corresponding 4,4- di (hydroxymethyl) cyclopentenes 51. In step three, the 4, 4-di (hydroxymethyl) cyclopentenes 51 are reacted with p- toluenesulfonyl chloride (TsCl) in pyridine to give the corresponding 4,4-ditosylates 52. In step four, the 4,4- ditosylates 52 are reacted with metallic zinc and sodium iodide in DMF at 150°C to give the 5- (2-pyridinyl) -6- arylspiro[2.4]hept-5-ene antiinflammatory agents 53 of this invention. Scheme XI N(C 2 H 5 ) 3 , PTSA, 4 A mol sieves, CH 3 CΝ, Δ S0C1 2 , DMF, 5 Synthetic Scheme XI shows the four step procedure used to prepare the cis-2-(3-pyridinyl)-3-aryl- 1,4-dichloro-2-buteneε 57 from the bromoacetophenoneε 4 (prepared in Synthetic Scheme I) and the 3-pyridinylacetic acidε 34 (prepared in Synthetic Scheme VI) . In εtep one, bromoacetophenones 4 are reacted with 3-pyridinylacetic acids 34 in acetonitrile in the presence of triethylamine to give the corresponding esters 54. In step two, the esters 54 are cyclized to the corresponding furanones 55 on treatment with p-toluenesulfonic acid (PTSA) and triethylamine in the presence of 4 A molecular sieves in acetonitrile at reflux. In step three, the furanones 55 are reacted with diisobutylaluminum hydride (DIBAL) to give the corresponding cis-diols 56. In step four, the cis-diols 56 are reacted with thionyl chloride in DMF at 5°C to give the corresponding cis-2- (3-pyridinyl)-3-aryl- 1,4-dichloro-2-buteneε 57. SchemeXII 61 Synthetic Scheme XII εhows the four step procedure used to prepare the 5- (3-pyridinyl) -6- arylεpiro[2.4]hept-5-eneε 61 from the cis-2- (3- pyridinyl) -3-aryl-l, 4-dichloro-2-butenes 57 (prepared in Synthetic Scheme XI). In step one, the cis-2- (3- pyridinyl)-3-aryl-l,4-dichloro-2-butenes 57 are reacted with dimethyl malonate in DMF in the presence of two equivalents of lithium hydride to give the corresponding 4, 4-dicarbomethoxycyclopentenes 58. In step two, the 4, 4-dicarbomethoxycyclopentenes 58 are reacted with DIBAL in THF to give the corresponding 4,4- di (hydroxymethyl) cyclopentenes 59. In step three, the 4, 4-di (hydroxymethyl) cyclopentenes 59 are reacted with p- tolueneεulfonyl chloride (TsCl) in pyridine to give the correεponding 4, 4-ditoεylateε 60. In εtep four, the 4,4- ditoεylateε 60 are reacted with metallic zinc and sodium iodide in DMF at 150°C to give the 5- (3-pyridinyl) -6- arylεpiro[2.4]hept-5-ene antiinflammatory agentε 61 of this invention. SchemeXIII N(C 2 H 5 ) 3 , PTSA, 4 A mol sieves, CH 3 CN, Δ SOCl 2 , DMF, 5 °C Synthetic Scheme XIII shows the four step procedure used to prepare the cis-2- (4-pyridinyl) -3-aryl- 1,4-dichloro-2-butenes 65 from the bromoacetophenones 4 (prepared in Synthetic Scheme I) and the 4-pyridinylacetic acids 37 (prepared in Synthetic Scheme VI) . In step one, bromoacetophenones 4 are reacted with 4-pyridinylacetic acids 37 in acetonitrile in the presence of triethylamine to give the corresponding esterε 62. In εtep two, the eεters 62 are cyclized to the corresponding furanones 63 on treatment with p-toluenesulfonic acid (PTSA) and triethylamine in the preεence of 4 A molecular εieves in acetonitrile at reflux. In step three, the furanones 63 are reacted with diisobutylaluminum hydride (DIBAL) to give the corresponding cis-diols 64. In step four, the cis-diols 64 are reacted with thionyl chloride in DMF at 5°C to give the corresponding cis-2- (4-pyridinyl) -3-aryl- 1,4-dichloro-2-butenes 65. Scheme XIV 69 Synthetic Scheme XIV εhowε the four step procedure used to prepare the 5- (4-pyridinyl)-6- arylspiro[2.4]hept-5-enes 69 from the cis-2-(4- pyridinyl)-3-aryl-l,4-dichloro-2-butenes 65 (prepared in Synthetic Scheme XIII). In εtep one, the ciε-2-(4- pyridinyl)-3-aryl-l,4-dichloro-2-buteneε 65 are reacted with dimethyl malonate in DMF in the preεence of two equivalentε of lithium hydride to give the correεponding 4,4-dicarbomethoxycyclopenteneε 66. In εtep two, the 4,4-dicarbomethoxycyclopenteneε 66 are reacted with DIBAL in THF to give the correεponding 4,4- di (hydroxymethyl)cyclopentenes 67. In step three, the 4,4-di (hydroxymethyl)cyclopentenes 67 are reacted with p- toluenesulfonyl chloride (TsCl) in pyridine to give the corresponding 4,4-ditosylates 68. In step four, the 4,4- ditoεylateε 68 are reacted with metallic zinc and sodium iodide in DMF at 150°C to give the 5- (4-pyridinyl) -6- arylεpiro[2.4]hept-5-ene antiinflammatory agents 69 of thiε invention. Scheme XV Synthetic Scheme XV shows the two step procedures which can be used to prepare the dialkylated compounds 71, 72, 73, and 74. In step one, dimethyl malonate and potassium carbonate in THF (or sodium hydride in DMF) is reacted with the bromoacetophenones 4 (prepared in Synthetic Scheme I) to give the monoalkylated compounds 70. In step two, the monoalkylated compounds 70 are reacted with the bromoacetophenones 9 (prepared in Synthetic Scheme II), the 2- (bromoacetyl)pyridines 14 (prepared in Synthetic Scheme III), the 3- (bromoacetyl)pyridines 19 (prepared in Synthetic Scheme IV), and the 4- (bromoacetyl)pyridines 24 (prepared in Synthetic Scheme V) in THF in the presence of potasεium carbonate (or εodium hydride in DMF) to give the dialkylated compoundε 71, 72, 73, and 74, reεpectively. Scheme XVI Synthetic Scheme XVI showε alternative procedures which can be used to prepare the 4,4- dicarbomethoxycyclopenteneε 42, 50, 58, and 66 from the dialkylated compoundε 71, 72, 73, and 74, respectively (prepared in Synthetic Scheme XV) . The dialkylated compounds 71, 72, 73, and 74 are reacted with metallic zinc and titanium(III) chloride [or titanium(IV) chloride] in DME (or THF) to give the 4,4- dicarbomethoxycyclopentenes 42, 50, 58, and 66, respectively. By procedures outlined in Schemes VIII, X, XII, and XIV, 42, 50, 58, and 66 can be converted to the 5,6-diarylspiro[2.4]hept-5-ene antiinflammatory agentε 45, 5- (2-pyridinyl)-6-arylspiro[2.4]hept-5-ene antiinflammatory agents 53, 5- (3-pyridinyl) -6- arylεpiro[2.4]hept-5-ene antiinflammatory agentε 61, and 5-(4-pyridinyl) -6-arylεpiro[2.4]hept-5-ene antiinflammatory agents 69, respectively, of this invention. Scheme XVII Synthetic Scheme XVII shows the three step procedures used to prepare the cycloalkyldiketones 77, 78, 79 and 80 from the phenyl silyl enol ethers 5 (prepared in Synthetic Scheme I) and cycloalkanones (n = 1,2). In step one, the silyl enol ethers 5 are reacted with cycloalkanones (n = 1,2) in methylene chloride in the presence of titanium(IV) chloride to give the corresponding cycloalkanols 75. In εtep two, the cycloalkanolε 75 are dehydrated with trifluoroacetic anhydride and triethylamine in methylene chloride at 0°C to give the correεponding conjugated exocyclic olefinε 76. In step three, the olefins 76 are reacted with the phenyl εilyl enol ethers 10 (prepared in Synthetic Scheme II) , 2-pyridinyl silyl enol ethers 15 (prepared in Synthetic Scheme III) , 3-pyridinyl silyl enol ethers 20 (prepared in Synthetic Scheme IV) , and 4-pyridinyl silyl enol ethers 25 (prepared in Synthetic Scheme V) to give the cycloalkyldiketones (n = 1,2) 77, 78, 79 and 80, respectively. Scheme XVIII Synthetic Scheme XVIII showε the procedures used to prepare 6,7-diarylspiro[3.4]oct-6-enes 81 (n = 1) and 2,3-diarylspiro[4.4]non-2-enes 81 (n = 2), 6- (2- pyridinyl) -7-arylspiro[3.4]oct-6-enes 82 (n = 1) and 2- (2-pyridinyl) -3-arylεpiro[4.4]non-2-eneε 82 (n = 2), 6- (3-pyridinyl) -7-arylspiro[3.4]oct-6-enes 83 (n = 1) and 2- (3-pyridinyl) -3-arylspiro [4.4]non-2-enes 83 (n = 2), and 6- (4-pyridinyl) -7-arylspiro[3.4] oct-6-enes 84 (n = 1) and 2- (4-pyridinyl) -3-arylspiro[4.4]non-2-enes 84 (n = 2) from cycloalkyldiketones (n = 1,2) 77, 78, 79 and 80, respectively (prepared in Synthetic Scheme XVII) . The cycloalkyldiketones (n = 1,2) 77, 78, 79 and 80 are reacted metallic zinc and titanium(IV) chloride in THF to give the 6,7-diarylspiro[3.4]oct-6-ene antiinflammatory agents 81 (n = 1) and 2,3-diarylεpiro[4.4]non-2-ene antiinflammatory agents 81 (n = 2), 6- (2-pyridinyl) -7- arylspiro[3.4] oct-6-ene antiinflammatory agentε 82 (n = 1) and 2- (2-pyridinyl) -3-arylεpiro[4.4]non-2-ene antiinflammatory agents 82 (n = 2), the 6- (3-pyridinyl) - 7-arylεpiro[3.4]oct-6-ene antiinflammatory agentε 83 (n = 1) and 2- (3-pyridinyl) -3-arylεpiro[4.4]non-2-ene antiinflammatory agents 83 (n = 2), and the 6- (4- pyridinyl) -7-arylspiro[3.4]oct-6-ene antiinflammatory agents 84 (n = 1) and 2- (4-pyridinyl) -3- arylεpiro[4.4]non-2-ene antiinflammatory agents 84 (n = 2), respectively, of this invention. SchemeXIX o o A J ^ττ 1. RMgX,THF,-78°C II Ar-S-CH 3 2 -: : *- Ar-S-NH 2 H 2. B(R Δ II O 3. H 2 NO 3 SO 3 H, O NaOAc,H 2 O Synthetic Scheme XIX shows the three step procedure used to prepare sulfonamide antiinflammatory agents from their corresponding methyl sulfoneε. In εtep one, a THF εolution of the methyl εulfones at -78°C is treated with a grignard reagent (RMgX) , e.g. methylmagneεium bromide, propylmagneεium chloride, etc., or an alkyllithium reagent, e.g., methyllithium, n- butyllithium, etc. In step two, the anions generated in step one is treated with an organoborane, e.g., triethylborane, tributylborane, etc., at -78°C then allowed to warm to ambient temperature prior to stirring at reflux. In step three, an aqueous solution of sodium acetate and hydroxyamine-O-sulfonic acid is added to provide the corresponding sulfonamide antiinflammatory agents of this invention. The following examples contain detailed descriptions of the methods of preparation of compounds of Formula I-VI. These detailed descriptions fall within the scope, and serve to exemplify, the above described General Synthetic Procedures which form part of the invention. These detailed descriptions are presented for illustrative purposes only and are not intended as a restriction on the scope of the invention. All parts are by weight and temperatures are in Degrees centigrade unless otherwise indicated. Example 1 5- (4-Fluorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hep -5-ene Step 1: Preparation of 4- (methylthio)acetophenone To a stirred solution of 50 g (340 mmol) of 4- (methylthio)benzonitrile in 2 L of THF at -78°C under an atmosphere of nitrogen was added 282 mL (390 mmol) of methyllithium (1.4 M in diethyl ether) over a period of ten minutes. The solution was stirred at -78°C for one hour, and then the dry ice bath waε removed. After five hourε, 100 mL of water followed by 200 mL of 3N hydrochloric acid were added to the reaction mixture and it waε stirred overnight. Concentration n vacuo gave a residue which was partitioned between ethyl acetate and water. The water layer was extracted with three portionε of ethyl acetate and the combined ethyl acetate layers were dried (MgSC. 4 ) . Concentration in vacuo gave 58 g of crude (4-methylthio)acetophenone as a solid: NMR (CDCI 3 ) δ 2.52 (s, 3H) , 2.57 (ε, 3H) , 7.26 (d, * ∑ = 9 Hz, 2H) , 7.87 (d, 3_ = 9 Hz, 2H) . Step 2: Preparation of 4- (methylεulfonyl)acetophenone To a solution of 11.73 g (71.1 mmol) of 4- (methylthio)acetophenone (prepared in Step 1) in 500 mL of methylene chloride at ambient temperature was added 61.14 g (177 mmol) of m-chloroperoxybenzoic acid (50%) (MCPBA) in portions over 20 minutes. The reaction was stirred for two hourε, quenched εlowly with aqueous sodium bisulfite, washed with three 100 mL portions of saturated sodium bicarbonate, dried (MgSC. 4 ) , and concentrated in vacuo to give 11.91 g (91%) of (4- methylεulfonyl)acetophenone aε a colorless solid: NMR (CDCI 3 ) δ 2.67 (s, 3H) , 3.08 (ε, 3H) , 8.06 (d, £ = 9 Hz, 2H) , 8.14 (d, J = 9 Hz, 2H) . Step 3: Preparation of 2-bromo-4 ' - (methylεulfonyl) acetophenone To a εtirred εolution of 11.91 g (60.5 mmol) of 4- (methylεulfonyl)acetophenone (prepared in Step 2) in 133 mL of glacial acetic acid and 0.11 mL of hydrochloric acid at ambient temperature was added a solution of 8.22 g (51.4 mmol) of bromine in 9.3 mL of glacial acetic acid over a period of three hours. The reaction mixture was diluted with 500 mL of water and extracted with chloroform. The combined extracts were dried (MgS0 4 ) and concentrated in vacuo to give 15.7 g of crude 2-bromo- . (4 ' -methylsulfonyl)acetophenone as a solid: NMR (CDCI 3 ) δ 3.10 (s, 3H) , 4.45 (s, 2H) , 8.08 (d, J = 9 Hz, 2H) , 8.17 (d, J = 9 Hz, 2H) . Step 4: Preparation of 2- (4-fluorophenyl) -1- \2- .4- (methylεulfonyl)phenyll -2-oxoethoxylethanone To a stirred solution of 4.45 g (28.9 mmol) of 4-fluorophenylacetic acid in 3.26 g (31.8 mmol) of triethylamine and 275 mL of acetonitrile was added 8.9 g (28.9 mmol) of 2-bromo-4'- (methylsulfonyl)acetophenone (prepared in Step 3) at ambient temperature. The reaction mixture was εtirred for 30 minutes, concentrated in vacuo, and partitioned between ethyl acetate and water. The organic phase was dried (MgSC< 4 ) and concentrated in vacuo. Purification by silica gel chromatography with ethyl acetate/hexane (1:1) gave 6.87 g (68%) of 2- (4-fluorophenyl) -1- [2- [4- (methylεulfonyl)phenyl] -2-oxoethoxy]ethanone as a colorlesε εolid: NMR (CDCI3) δ 3.08 (ε, 3H) , 3.79 (s, 2H) , 5.35 (s, 2H) , 7.06 (s, t, ∑ * = 9 Hz, 2H) , 7.32 (dd, .J = 6 and 9 Hz, 2H) , 8.06 (s, 4H) . Step 5: Preparation of 3- (4-fluorophenyl) -4-f (4- methylsulfonyl) henyl1 -5H-furan-2-one Under nitrogen, 4.10 g (11.7 mmol) of 2- (4- fluorophenyl) -1- [2- [4- (methylsulfonyl)phenyl] -2- oxoethoxy]ethanone (prepared in Step 4), 6.52 mL (46.8 mmol) of triethylamine, 4.89 g (25.7 mmol) of p- tolueneεulfonic acid, and 12 g of 4A molecular sieves were added to 117 mL of acetonitrile and stirred at reflux for 16 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between methylene chloride and water. The methylene chloride layer was dried (MgS0 4 ) and reconcentrated in vacuo. Recrystallization from hexane/ethyl acetate (2:1) gave 3.65 g (94%) of 3- (4-fluorophenyl) -4- [(4- methylsulfonyl)phenyl] -5H-furan-2-one as a solid: mp 166- 167°C; NMR (CDC1 3 ) δ 3.08 (s, 3H) , 5.19 (ε, 2H) , 7.10 (t, J = 9 Hz, 2H) , 7.42 (dd, J = 6 and 9 Hz, 2H) , 7.52 (d, J = 9 Hz, 2H) , 7.97 (d, *∑ = 9 Hz, 2H) . HRMS Calc'd for C 17 H 13 FO 4 S: 332.0519. Found: 332.0501. Anal. Calc'd for C 17 H 13 FO 4 S: C, 61.44; H, 3.94; 0, 19.26. Found: C, 61.11; H, 4.06; 0, 19.32. Step 6: Preparation of 2- (4-fluorophenyl) -3- \ (4- methylsulfonvDphenyll -1, 4-dihvdroxy-2-butene To a solution of 3.08 g (9.28 mmol) of 3- (4- fluorophenyl) -4- [ (4-methylsulfonyl)phenyl] -5H-furan-2-one (prepared in Step 5) in 93 mL of tetrahydrofuran (THF) at -78°C under an atmoεphere of nitrogen waε added 20 mL (30 mmol) of diiεobutylaluminum hydride (DIBAL) (1.5 M in THF) over a 10 minute period. The εolution waε stirred at -78°C for 20 minutes, allowed to warm to ambient temperature, and stirred overnight. An additional 15 mL (22 mmol) aliquot of DIBAL was added and stirring was continued for 2 hours. The reaction was cooled to -78°C, treated dropwiεe with 25 mL of acetone, warmed to room temperature, and slowly treated with 25 mL of water. The mixture was stirred for 30 minutes prior to the careful addition of 35 mL of 1.2 N sodium hydroxide. The mixture was extracted with ethyl acetate, washed with 1 N hydrochloric acid followed by brine, dried (MgSθ4) , and concentrated in vacuo to give 3.8 g of crude 2- (4- fluorophenyl) -3- [ (4-methylsulfonyl)phenyl] -1,4-dihydroxy- 2-butene as a colorless oil: NMR (CDC1 3 ) δ 2.98 (s, 3H) , 4.60 (d, J = 6 Hz, 4H) , 6.8 (t, J = 9 Hz, 2H) , 6,94-7.02 (m, 2H) , 7.22 (d, 0. = 9 Hz, 2H) , 7.65 (d, J = 9 Hz, 2H) . Step 7: Preparation of 2- (4-fluorophenyl) -3- . (4- methylsulfonvDphenyll -1.4-dichloro-2-butene To a solution of 3.5 g (7.62 mmol) of crude 2- (4-fluorophenyl) -3- [ (4-methylsulfonyl)phenyl] -1, 4- dihydroxy-2-butene (prepared in Step 6) in 58 mL of N,N- dimethylformamide (DMF) at 5°C under an atmosphere of nitrogen was added dropwise 1.52 mL (20.84 mmol) of thionyl chloride. The reaction waε εtirred at 5°C for 22 hours, stirred at ambient temperature for an additional 8 hours, and concentrated in vacuo. The residue was partitioned between ethyl acetate and water; the ethyl acetate phase was dried (MgSC. 4 ) and concentrated in vacuo to give crude 2- (4-fluorophenyl) -3- [ (4- methylεulfonyl)phenyl] -1, 4-dichloro-2-butene as a solid: NMR (CDCI 3 ) δ 3.0 (s, 3H) , 4.55 (d, 1 * = 3.4 Hz, 4H) , 6.86 (t, £ = 9 Hz, 2H) , 6.75 (d, J = 8.3 Hz, 2H) , 7.45 (d, J = 9 Hz, 2H) . Step 8, A: Preparation of 1- \2- (4-fluorophenyl) -4, 4- dicarbomethoxycvclopenten-1-vn -4- ( ethylεulfonyl)benzene To a solution of 1.2 mL (10.5 mmol) of dimethyl malonate in 10 mL of DMF under an atmosphere of nitrogen was added 215 mg (26.9 mmol) of lithium hydride in portions. The resulting suspenεion was stirred at ambient temperature for 20 minutes prior to the addition of a solution of crude 2- (4-fluorophenyl) -3- [ (4- methylsulfonyl)phenyl] -1, 4-dichloro-2-butene (prepared in Step 7) in 10 mL of DMF. The reaction was stirred at ambient temperature for 15 hours, treated with another 150 mg (18.8 mmol) of lithium hydride, and stirred for another 4 hours. The mixture was concentrated in vacuo and partitioned between ethyl acetate and water; the organic phase was dried (MgSC. 4 ) , and concentrated in vacuo. The residue was chromatographed on silica gel to give 1.1 g (34%) of 1- [2- (4-fluorophenyl) -4,4- dicarbomethoxycyclopenten-1-yl] -4- (methylsulfonyl)benzene as an oil: NMR (CDCI 3 ) δ 3.03 (s, 3H) , 3.55 (s, 4H) , 3.79 (s, 6H) , 6.93 (t, 1 * = 9 Hz, 2H) , 7.11 (dd, £= 6 and 9 Hz, 2H) , 7.32 (d, J. = 9 Hz, 2H) , 7.77 (d, £ = 9 Hz, 2H) . Step 8, B: Preparation of 1- \2- (4-fluorophenyl) -4, 4- dicarbomethoxycvclopenten-1-vπ -4- (methylεulfonyl)benzene To a solution of 7.18 mL (63 mmol) of dimethyl malonate in 160 mL of DMF at 0°C under an atmosphere of nitrogen was added 3.0 g (75 mmol) of sodium hydride (60% suspenεion in oil) . The reaction was stirred at ambient temperature for 15 minutes (or until the gas evolution has ceased), cooled to -20°C, and treated with 15 g (69 mmol) of 2-bromo-4 ' -fluoroacetophenone (Aldrich) in one portion. The mixture was εtirred at ambient temperature for 1 hour and then cooled to 0°C; another 75 mmol of sodium hydride was added and the resulting mixture stirred at ambient temperature for 15 minutes (or until the gas evolution has ceased) . The reaction was recooled to -20°C and treated with 19.1 g (69 mmol) of 2-bromo-4'- (methylεulfonyl) acetophenone (prepared in Step 3). The reaction was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was partitioned between water and ethyl acetate; the ethyl acetate phase was dried (MgSC. 4 ) and reconcentrated in vacuo. The residue was chromatographed on silica gel to give 13.8 g (51%) of dimethyl 2- [2- (4-fluorophenyl) -2-oxoethyl] -2- [2- [4- (methylεulfonyl)phenyl] -2-oxoethyl]propanedioate as an oil: NMR (CDCI 3 ) δ 3.06 (s, 3H) , 3.76 (s, 6H) , 4.03 (ε, 2H) , 4.08 (ε, 2H) , 7.13 (t, Q_ = 8.6 Hz, 2H) , 7.97-8.05 [m with d at 8 . 03 (2= 8 . 7 Hz ) , 4H] , 8 . 14 (d, I = 8 . 5 Hz , 2H) . To a vigorously stirred mixture of 50.4 g (771 mmol) of zinc dust in 640 mL of THF at -78°C under an atmosphere of nitrogen was added dropwise 60.4 mL (551 mmol) of titanium(IV) chloride. The reaction was warmed to ambient temperature with a water bath and then stirred at reflux for 1 hour. To the resulting dark mixture under reflux was added a solution of 15 g (32.3 mmol) of dimethyl 2-[2-(4-fluorophenyl)-2-oxoethyl]-2-[2-[4- (methylεulfonyl)phenyl]-2-oxoethyl]propanedioate (prepared above) in 20 mL of THF. The resulting mixture was stirred at ambient temperature for 16 hours, filtered through a pad of Celite®, rinεed with ethyl acetate, and concentrated in vacuo. The reεidue waε partitioned between water and ethyl acetate; the organic phase was washed with brine, dried ( gS0 4 ) , and concentrated in vacuo. The residue was chromatographed on silica gel to give 6.26 g (44%) of 1-[2- (4-fluorophenyl)-4,4- dicarbomethoxycyclopenten-1-yl]-4-(methylsulfonyl)benzene which waε identical to the material prepared in Step 8, Method A. Step 9: Preparation of 1- \2- (4-fluorophenyl) -4,4- di(hvdroxymethyl)cvclopenten-1-yll-4- (methylεulfonyl)benzene Under nitrogen, a εolution of 1.01 g (2.34 mmol) of 1-[2-(4-fluorophenyl)-4,4- dicarbomethoxycyclopenten-1-yl]-4-(methylsulfonyl)benzene (prepared in Step 8) in 1.5 mL of THF at -78°C was treated with 11.6 mL (11.6 mmol) of DIBAL (1.0' M in THF). The reaction was stirred at ambient temperature for 1.5 hours, quenched with acetone and aqueous NaOH, extracted with ethyl acetate, dried (MgS0 4 ), and concentrated in vacuo to give 840 mg of crude 1-[2-(4-fluorophenyl) -4,4- di (hydroxymethyl) cyclopenten-1-yl] -4- (methylεulfonyl)benzene aε a colorleεs oil: NMR (CDCI 3 ) δ 2.82 (d, £ = 5 Hz, 4H) , 3.04 (s, 3H) , 3.86 (d, J= 5 Hz, 4H) , 6.94 (t, il = 9 Hz, 2H) , 7.11 (dd, J = 5 and 9 Hz, 2H) , 7.33 (d, J = 9 Hz, 2H) , 7.77 (d, ∑ * = 9 Hz, 2H) . Step 10: Preparation of 1- \2 - (4-fluorophenyl) -4, - di (tosylmethyl) cvclopenten-l-yll -4- (methylεulfonyl)benzene Under nitrogen, a solution of 2.34 mmol of the crude 1-[2- (4-fluorophenyl) -4,4- di (hydroxymethyl) cyclopenten-1-yl] -4- (methylεulfonyl)benzene (prepared in Step 9) in 8 mL of pyridine at ambient temperature waε treated with 1.2 g (6.3 mmol) of p-tolueneεulfonyl chloride (tosyl chloride) . The resulting solution was εtirred at room temperature for 17 hours, concentrated in vacuo, and chromatographed on silica gel to give 1.06 g (66% overall yield from Step 9) of 1- [2- (4-fluorophenyl) -4, 4- di (tosylmethyl) cyclopenten-1-yl] -4- (methylsulfonyl)benzene as a colorlesε εolid: NMR (CDCI 3 ) δ 2.46 (s, 6H) , 2.73 (s, 3H) , 3.04 (s, 3H) , 4.05 (s, 4H) , 6.85-7.0 (m, 4H) , 7.20 (d, J = 8 Hz, 2H) , 7.34 (d, J = 8 Hz, 4H) , 7.75 (d, * ∑ = 8 Hz, 6H) . Step 11: Preparation of 5- (4-fluorophenyl) -6- .4- (methylsulfonylphenyll spiro .2.41hept-5-ene Under nitrogen, a solution of 1.02 g (1.49 mmol) of 1- [2- (4-fluorophenyl) -4, 4- di (tosylmethyl) cyclopenten-1-yl] -4- (methylεulfonyl)benzene (prepared in Step 10) in 24 mL of DMF waε treated with 3.23 g (21.55 mmol) of sodium iodide and 1.61 g (24.63 mmol) of zinc dust. The reaction was stirred at 150°C for 1.5 hour, concentrated in vacuo, and partitioned between water and ethyl acetate. The organic phase was washed with sodium sulfite, water, brine, dried (MgS0 4 ) , and concentrated in vacuo. The residue waε chromatographed on εilica gel to give 437 mg (86%) of 5- (4-fluorophenyl)-6-[4- (methylεulfonyl)phenyl]εpiro[2.4]hept-5-ene aε a colorleεε εolid: mp 140.5-142.0°C; NMR (CDCI 3 ) δ 0.69 (ε, 4H) , 2.92 (ε, 4H) , 3.04 (ε, 3H) , 6.93 (t, J = 9 Hz, 2H) , 7.10 (dd, .I = 5 and 9 Hz, 2H) , 7.32 (d, J = 8 Hz, 2H) , 7.76 (d, = 8 Hz, 2H) . HRMS Calc'd for C 20 H 19 FO 2 S: 342.1090. Found: 342.1126. Anal. Calc'd for C 20 H 19 FO 2 S: C, 70.15; H, 5.59; F, 5.55; S, 9.36. Found: C, 70.10; H, 5.69; F, 5.50; S, 9.60. Example 2 4- [6- (4-Fluorophenyl)spiro [2.4]hept-5- en-5-yl]benzenesulfonamide Under nitrogen, a εolution of 90 mg (0.248 mmol) of 5-(4-fluoro phenyl)-6-[4- (methylεulfonyl)phenyl]εpiro[2.4]hept-5-ene (the title compound of Example 1) in 1 mL of THF at -78°C waε treated with 0.21 mL (0.27 mmol) of methyllithium (1.3 M in ether) over a period of 2 minutes. The reaction was stirred at ambient temperature for 25 minutes, cooled to -78°C, and treated with 0.3 mL (0.3 mmol) of tributylborane (1.0 M in THF). The resulting dark brown solution was stirred at ambient temperature for 20 minutes and then at reflux for 16 hours prior to the addition of 350 mg (4.27 mmol) of sodium acetate, 2 mL of water, and 250 mg (2.21 mmol) of hydroxyamine-O-sulfonic acid. The resulting light orange mixture was εtirred at ambient temperature for 3 hourε and the aqueouε phaεe extracted with ethyl acetate. The combined extracts were washed with water, brine, dried (MgSC. 4 ) , and concentrated in vacuo. The residue was chromatographed on silica gel to give 24 mg (27%) of 4- [6- (4-fluoro phenyl) spiro[2.4]hept-5-en-5-yl]benzenesulfonamide aε a colorleεs solid: mp 131.0-133.0°C; NMR (CDCI 3 ) δ 0.68 (s, 4H) , 2.90 (s, 3H) , 4.81 (ε, 2H) , 6.92 (t, J = 9 Hz, 2H) , 7.11 (dd, J = 6 and 9 Hz, 2H) , 7.27 (d, J = 9 Hz, 2H) , 7.74 (d, J = 9 Hz, 2H) . HRMS Calc'd for CigHisFNC^S: 344.1121. Found: 344.1122. Anal. Calc'd for [Cι 9 H 18 FN0 2 S + 0.1 CH 3 CO2CH 2 CH 3 ] : C, 66.16; H, 3.98; S, 9.11. Found: C, 65.86; H, 5.52; N, 3.92; S, 9.57. Example 3 6- (4-Fluorophenyl) -7- [4- (methylsulfonyl) phenyl] spiro [3.4] oct-6-ene Step 1: Preparation of 1-methylthio-4- Tl- r (trimethylεilyl)oxyl ethenv11benzene Under nitrogen, 11.0 g (66.2 mmol) of 4- (methylthio)acetophenone (prepared in Step 1 of Example 1) and 13.8 mL (99 mmol) of triethylamine in 50 mL of acetonitrile was treated with 12.6 mL (99.3 mmol) of chlorotrimethylsilane at ambient temperature and allowed to stir for 20 minutes prior to the slow addition of a suspension of 14.9 g (99.4 mmol) of sodium iodide in 60 mL of acetonitrile. The reaction was stirred for 3 hours, poured into ice/water, and extracted with hexane. The extracts were combined, dried (K 2 CO 3 ), and concentrated in vacuo to give 16 g of crude 1-methylthio- 4- [1 [ (trimethylsilyl)oxy]ethenyl]benzene as an oil: NMR (CDCI 3 ) δ 0.26 (ε, 9H) , 2.48 (s, 3H) , 4.39 (d, ∑ * = 2 Hz, 1H) , 4.87 (d, J I= 2 Hz, 1H) , 7.20 (d, J= 8 Hz, 2H) , 7.50 (d, J I= 8 Hz, 2H) . Step 2: Preparation of 1-fluoro-4- fl- r (trimethylsilyl)oxyl ethenyllbenzene Under nitrogen, 17.7 g (128 mmol) of 4- fluoroacetophenone (Aldrich) and 20.7 mL (192 mmol) of triethylamine at ambient temperature was treated with 24.4 mL (192.3 mmol) of chlorotrimethylsilane and allowed to stir of 20 minutes prior to the slow addition of a suεpenεion of 30 g (200 mmol) of sodium iodide in 200 mL of acetonitrile. The extracts were combined, dried (K 2 CO 3 ), and concentrated in vacuo to give 27 g of crude 1-fluoro-4- [1[ (trimethylsilyl)oxy]ethenyl]benzene as an oil: NMR (CDCI 3 ) δ 0.28 (s, 9H) , 4.41 (d, ιl= 2 Hz, 1H) , 4.84 (d, 8 Hz, 2H) , 7.53-7.60 (m, 2H) . Step 3: Preparation of 1- (4-fluorophenyl) -2- (1- hvdroxycvclobutan-l-yl)ethan-l-one Under nitrogen, 11.0 g (100 mmol) of titanium(IV) chloride in 140 mL of methylene chloride at 0°C was slowly treated with a solution of 8.2 mL (110 mmol) of cyclobutanone in 30 mL of methylene chloride prior to the dropwise addition of a solution of 21.1 g (100 mmol) of l-fluoro-4- [1[ (trimethylsilyl)oxy]ethenyl]benzene (obtained from Step 2 ) in 15 mL of methylene chloride. The reaction was stirred for 15 minutes and then poured into 200 mL of ice/water; the phases were separated. The aqueous phase was extracted twice with 30 mL of methylene chloride and combined with the original methylene chloride phase. The combined extracts were washed 3 times with 120 mL of saturated sodium carbonate/water (1:1) and once with brine, dried (MgSC- 4 ) , and concentrated in vacuo to give 20.4 g (98%) of crude 1- (4-fluorophenyl) -2- (1- hydroxycyclobutan-1-yl)ethan-1-one as an oil: NMR (CDCI 3 ) δ 1.53-1.70 (m, 1H) , 1.80-1.94 (m, 1H) , 1.99-2.10 (m, 2H) , 2.17-2.31 (m, 2H) , 3.31 (s, 2H) , 7.10-7.19 ( , 2H) , 7.95-8.03 (m, 2H) . Step 4: Preparation of 1- (4-fluorophenyl) -2- (cvclobutanyliden-1-yl) ethan-1-one Under nitrogen, 20.3 g (98 mmol) of l-(4- fluorophenyl) -2- (1-hydroxycyclobutan-l-yl)ethan-1-one (prepared in Step 3), 37 mL (260 mmol) of triethylamine, and 50 mg of 4-dimethylaminopyridine (DMAP) in 80 mL of methylene chloride at 0°C was slowly treated with a solution of 16.6 mL (118 mmol) of trifluoroacetic anhydride (TFAA) in 40 mL of methylene chloride. The reaction was allowed to stir for 3 hours at 0°C and warmed to ambient temperature to stir for an additional 3 hours prior to the addition of 200 mL of saturated sodium carbonate/water (1:1) and 300 mL of ether. The phases were separated and the aqueous phase was extracted twice with 100 mL of ether. The ether extracts were combined with the original ether/methylene chloride phase, washed with brine, dried (MgS0 4 ) , and concentrated in vacuo. Purification by silica gel chromatography (Waterε Prep- 500A) with ethyl acetate/hexane (2:98) gave 12.1 g (65%) of 1- (4-fluorophenyl) -2- (cyclobutanyliden-1-yl) ethan-1- one aε an oil: NMR (CDCI 3 ) δ 2.11-2.24 (m, 2H) , 2.95 (t, J= 8 Hz, 2H) , 3.19-3.29 (m, 2H) , 2.68-2.74 (m, 1H) , 7.05- 7.16 ( , 2H) , 7.84-7.97 (m, 2H) . Step 5: Preparation of 1- (4-fluorophenyl) -2- .1- \2- .4- (methylthio) henyl1 -2-oxoethyl1 cvclobutan-1-yll ethan-1-one Under nitrogen, 7.2 mL (70.2 mmol) of titanium(IV) chloride in 100 mL of methylene chloride at -78°C waε εlowly treated with a εolution of 12.1 g (63.8 mmol) of 1- (4-fluorophenyl) -2- (cyclobutanyliden-1- yl) ethan-1-one (prepared in Step 4) in 30 mL of methylene chloride. The mixture was stirred for 10 minutes, then 16.7 g (70.2 mmol) of the silyl enol ether (from Step 1) in 40 mL of methylene chloride was added dropwise. The reaction was stirred at -78°C for 1 hour, poured into a solution of 22 g of sodium carbonate in 160 mL of water, and filtered through Celite®. The phases were separated and the aqueouε phase extracted twice with 40 mL of methylene chloride. The extracts were combined with the original methylene chloride phase and washed with brine, dried (MgSθ 4 ) , and concentrated in vacuo. Purification by silica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane (10:90) gave 1- (4-fluorophenyl) -2- [1- [2-[4- (methylthio)phenyl] -2-oxoethyl] cyclobutan-1- yl]ethan-l-one aε an oil: NMR (CDC1 3 ) δ 1.91-2.04 (m, 2H) , 2.11 (t, J Z= 8 Hz, 4H) , 2.49 (ε, 3H) , 3.48 (ε, 2H) , 3.49 (ε, 2H) , 7.08 (t, £= 8 Hz, 2H) , 7.23 (t, J= 8 Hz, 2H) , 7.84 (d, J I= 9 Hz, 2H) , 7.91-7.99 (m, 2H) . Step 6: Preparation of 1- (4-fluorophenyl) -2- TI- \ 2 - f4- (methylsulfonyl)phenyl1 -2-oxoethyll cvclobutan- 1-yll ethan-1-one A solution of 18.3 g (51.4 mmol) of l-(4- fluorophenyl) -2- [l-[2- [4- (methylthio)phenyl] -2- oxoethyl] cyclobutan-1-yl]ethan-1-one (prepared in Step 5) in 200 mL of chloroform at 10°C was slowly treated with 35.6 g (ca. 103 mmol) of εolid in-chloroperbenzoic acid (50-60%) . The reaction was allowed to stir for 30 minutes and treated with aqueous sodium bisulfite. The chloroform was removed in vacuo and the residue partitioned between ethyl acetate and water. The ethyl acetate extracts were washed 3 times with εaturated εodium bicarbonate and once with brine, dried (MgS0 4 ) , and concentrated in vacuo to give 19.27 g (97%) of l-(4- fluorophenyl) -2- [1- [2- [4- (methylεulfonyl)phenyl] -2- oxoethyl]cyclobutan-1-yl]ethan-1-one aε an oil: NMR (CDC1 3 ) δ 1.95-2.06 (M, 2H) , 2.11 (t, J= 7 Hz, 4H) , 3.05 (s, 3H) , 3.52 (s, 2H) , 3.59 (s, 2H) , 7.09 (t, £= 9 Hz, 2H) , 7.92-8.04 (m, 4H) , 8.19 (d, £= 9 Hz, 2H) . Step 7: Preparation of 6- (4-fluorophenyl) -7- F4- (methylsulfonyl)phenyl1εpiro \ 3 .41oct-6-ene Under nitrogen, 16.3 mL (149 mmol) of titanium(IV) chloride was slowly added to a suspension of 19.5 g (298 mmol) of zinc dust in 500 mL of anhydrous THF at -78°C. The resulting mixture was allowed to warm to ambient temperature and then to stir at reflux for 45 minutes. The reaction waε cooled to ambient temperature prior to the addition of 19.27 g (49.6 mmol) of neat 1- (4-fluorophenyl) -2- [1- [2- [4- (methylsulfonyl)phenyl] -2- oxoethyl] cyclobutan-1-yl]ethan-1-one (prepared in Step 6) by syringe. The reaction was allowed to stir at ambient temperature overnight, filtered through Celite®, and concentrated in vacuo. The residue was partitioned between ethyl acetate and water; the ethyl acetate phase was washed with brine, dried (MgSC. 4 ) , and concentrated in vacuo. Purification by silica gel chromatography (Waters Prep-500A) with ethyl acetate/hexane (20:80) gave 13.5 g (76%) of 6- (4-fluorophenyl) -7- [4- (methylεulfonyl)phenyl] εpiro[3.4] oct-6-ene aε a colorless solid: mp 123-124°C; NMR (CDCI 3 ) δ 1.85-1.98 (m, 2H) , 2.08 (t, J= 7 Hz, 4H) , 2.98 (s, 4H) , 3.04 (ε, 3H) , 6.92 (t, * ∑= 9 Hz, 7.05-7.13 (m, 2H) , 7.30 (t, J= 8 HZ, 2H) , 7.75 (t, J= 8 Hz, 2H) . MS (FAB) m/e 357 (M+H) . Anal. Calc'd for C 2l H 2 ιF0 2 S: C, 70.76; H, 5.94; F, 5.53; S, 8.99. Found: C, 70.76; H, 6.10; F, 5.20; S, 8.96. Example 4 4- [7- ( 4-Fluorophenyl) spiro[3.4]oct- 6-e -6-yl]benzenesulfonamide Following a procedure similar to the one described in Example 2, 1.76 g (4.94 mmol) of 6- (4-fluorophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene (the title compound of Example 3) was converted to 1.61 g of crude sulfonamide. Purification by εilica gel chromatography with ethyl acetate/hexane (20:80) and subsequent recrystallization from chloroform/hexane gave 970 mg (55%) of 4- [7- (4-fluorophenyl) εpiro[3.4]oct-6-en-6- yl]benzeneεulfonamide as a colorless solid: mp 118-119°C; NMR (CDC1 3 ) δ 1.92 (m, J= 8 Hz, 2H) , 2.08 (t, J= 7 Hz, 4H) , 2.97 (s, 3H) , 4.74 (s, 2H) , 6.92 (t, £= 9 Hz, 2H) , 7.06-7.13 (m, 2H) , 7.23-7.30 (m, 2H) , 7.74 (t, J= 8 Hz, 2H) . MS (El) m/e (rel intensity) 357 (100), 329 (48), 248 (66), 233 (44), 109 (32) . Ana Calc'd for C 20 H 20 FNO 2 S: C, 67.21; H, 5.64; N, 3.93; F, 5.32; S, 8.97. Found: C, 66.83; H, 5.89; N, 3.83; F, 4.96; S, 9.03. Example 5 2- (4-Fluorophenyl) -3- [4- (methylsulfonyl ) phenyl] spiro [4.4] non-2-ene Following a procedure similar to the one described in Example 3 with the subεtitution of cyclopentanone for cyclobutanone, 23 mg of 2- (4- fluorophenyl) -3- [4- (methylεulfonyl)phenyl]εpiro[4.4]non- 2-ene was obtained as a colorlesε solid: mp 142-143°C; NMR (CDCI 3 ) δ 1.72 (s, 8H) , 2.83 (s, 4H) , 3.04 (s, 3H) , 6.93 (t, J 2= 9 Hz, 2H) , 7.10 (dd, * ∑= 5 and 9 Hz, 2H) , 7.31 (d, J= 9 Hz, 2H) , 7.76 (d, £= 9 Hz, 2H) . HRMS Calc'd for C 22 H 23 FO 2 S: 370.1403. Found: 370.1411. Anal. Calc'd for C 22 H 23 O 2 S: C, 71.32; H, 6.26; F, 5.13; S, 8.65. Found: C, 71.66; H, 6.36; F, 4.91; S, 9.13. Example 6 5 - ( 3 -Chloro- -methoxyphenyl ) - 6 - [ 4 - ( ethyl sul fonyl ) phenyl ] spiro [2 .4 ] ept -5 -ene Step 1 : Preparation of 4- (methylthio) acetophenone To a stirred solution of 98.93 g (0.63 mol) of 4- (methylthio)benzonitrile in 1.2 L of THF under nitrogen at -78 °C waε added 568 mL (0.795 mol) of methyllithium (1.4 M in ethyl ether) . The reεulting dark red solution was warmed to room temperature, and stirred for another 2.5 hourε. The reaction waε εlowly quenched with 400 mL of 3 N HCl, and the reεulting mixture was stirred overnight at room temperature. The mixture was concentrated in vacuo to about 500 mL, diluted with ethyl acetate and washed with saturated NaHCC. 3 , brine, dried (MgSC. 4 ) and concentrated i vacuo to give 108.5 g (98.5%) of 4- (methylthio)acetophenone as a yellow solid: NMR (CDCI 3 ) δ 2.52 (s, 3H) , 2.56 (s, 3H) , 7.28 (d, £ = 8.6 Hz, 2H) , 7.86 (d, J = 8.6 Hz, 2H) . Step 2: Preparation of 4- (methylsulfonyl)acetophenone To a solution of 108.5 g (0.653 mol) of 4- (methylthio)acetophenone (prepared in Step 1) in 3 L of methylene chloride at 0 °C was added in portions 414 g (68%, 1.63 mol) of MCPBA over a period of one hour. The mixture was stirred at room temperature overnight. To the cooled white suεpension was added slowly a εolution of 124 g (0.653 mol) of meta biεulfite in 300 mL of water and the mixture waε εtirred at room temperature for one hour, then filtered. The filtrate waε concentrated in vacuo to about 1 L, and repeatedly washed carefully with saturated NaHCC. 3 to remove 3-chlorobenzoic acid. The extract was dried (MgS0 4 ) and concentrated in vacuo to give 117.33 g (91%) of 4- (methylεulfonyl)acetophenone as a bright yellow solid: NMR (CDCI 3 ) δ 2.67 (s, 3H) , 3.08 (ε, 3H) , 8.05 (d, J = 8.5 Hz, 2H) , 8.14 (d, J = 8.5 Hz, 2H) . Step 3: Preparation of 2-bromo-4 ' - (methylεulfonyl) acetophenone To a solution of 117 g (0.593 mol) of 4- (methylsulfonyl)acetophenone (prepared in Step 2) in 1 L of glacial acetic acid was added 1 mL of concentrated HCl. To the resulting solution was added dropwise a solution of 94.75 g (0.593 mol) of bromine in 100 mL of glacial acetic acid over a period of about 45 minutes, and the resulting light orange solution waε poured onto about 2 L of ice. The reεulting yellow precipitate was collected by filtration, washed with 2 L of water and dried (MgSθ 4 ) to give 161 g (87% pure by 1 H NMR analysis, 86% calculated yield) of 2-bromo-4'- (methylεulfonyl)acetophenone as a yellow solid: NMR (CDC1 3 ) δ 3.10 (s, 3H) , 4.45 (ε, 2H) , 8.08 (d, J = 8.7 Hz, 2H) , 8.17 (d, J Z = 8.6 Hz, 2H) . Step 4: Preparation of dimethyl keto malonate Under nitrogen, 161.8 g (0.508 mol) of 2-bromo-4'- (methylsulfonyl) acetophenone (prepared in Step 3) was added to a suspension of 133.44 g (1.01 mol) of dimethyl malonate, 350.5 g (2.54 mol) of potassium carbonate (Aldrich) , and 38.1 g (0.254 mol) of potassium iodide in 450 mL of THF, and the resulting suspension was stirred at room temperature for 6 hours (exothermic, temperature reached 40 °C in 30 minutes) . The mixture was filtered, concentrated in vacuo. and the residue was recrystallized from ethyl acetate. The mother liquor was concentrated in vacuo and purified by silica gel chromatography (Prep- 500, Waters), eluted with 15% of ethyl acetate in methylene chloride, to give a total of 100 g (63.3 %) of dimethyl keto malonate as a white solid: 1 H NMR (CDCI 3 ) δ 3.07 (s, 3H) , 3.64 (d, £ = 7.05 Hz, 2H) , 3.78 (s, 6H) , 4.09 (t, J = 7.04 Hz, 1H) , 8.05 (d, J = 8.7 Hz, 2H) , 8.15 (d, J = 8.7 Hz, 2H) . Step 5: Preparation of 3-chloro-4-methoxybenzamide To a solution of 132.5 g (0.71 mol) of 3- chloro-4-methoxybenzoic acid in 514 mL (7.05 mol) of thionyl chloride was added in portions 2.5 mL of DMF, and the resulting εolution waε stirred under reflux for 4 hourε. The mixture waε concentrated in vacuo and dissolved in 600 mL of methylene chloride. To the resulting solution was added 83.1 g (0.85 mol) of N,0- dimethylhydroxyamine (HCl salt) and cooled to 0 °C. To the suspension was added εlowly 198 mL (1.4 mL) of triethylamine, and the mixture waε stirred at room temperature overnight. The resulting solution was washed twice with 1 N KHSO 4 , NaHCC. 3 , brine, dried (MgSC- 4 ) and concentrated in vacuo to give 163.2 g (quantitative) of 3-chloro-4-methoxybenzamide as a light brown oil: 1 H NMR (CDCI 3 ) δ3.35 (s, 3H) , 3.56 (s, 3H) , 3.94 (s, 3H) , 6.93 (d, = 8.7 Hz, 1H) , 7.68 (dd, = 2.2, 8.7 Hz, 1H) , 7.82 (d, J = 2.1 Hz, 1H) . Step 6: Preparation of 3-chloro-4-methoxyacetophenone To a stirred solution of 64.7 g (0.28 mol) of 3-chloro-4-methoxybenzamide (prepared in Step 5) in 1 L of THF under nitrogen at -78 °C was added 110 mL (3 M in ethyl ether, 0.3 mol) of methylmagnesium bromide. The resulting solution was warmed to room temperature, and stirred for another 3 hours. The reaction was slowly quenched with 3 N HCl, diluted with ethyl acetate and waεhed with εaturated NaHCU 3 , brine, dried (MgSC> 4 ) and concentrated in vacuo to give 51.7 g (99%) of 3-chloro-4- methoxyacetophenone aε a off-white solid: ^ NMR (CDCI 3 ) δ 2.55 (s, 3H) , 3.97 (ε, 3H) , 6.96 (d, J= 8.5 Hz, 1H) , 7.86 (dd, J= 2.2, 8.7 Hz, 1H) , 7.98 (d, J = 2.2 Hz, 1H) . Step 7: Preparation of 2-bromo- (3 ' -chloro-4' - methoxy)acetophenone To a solution of 51.7 g (0.28 mol) of 3-chloro- 4-methoxyacetophenone (prepared in Step 6) in 103 mL of glacial acetic acid was added 1 mL of concentrated HCl. To the resulting solution was added dropwiεe a solution of 14.5 mL (0.28 mol) of bromine in 20 mL of glacial acetic acid over a period of about 1.5 hours, and the resulting dark solution was εtirred at room temperature for 2 hourε. The precipitate waε collected by filtration and waεhed with water. More εolid waε collected from the filtrate. The combined εolid waε dried to give 65 g (88%) of 2-bromo- (3 ' -chloro-4'-methoxy)acetophenone aε a yellow εolid: NMR (CDCI 3 ) δ 3.99 (ε, 3H) , 4.37 (ε, 2H) , 6.99 (d, J = 8.7 Hz, 1H) , 7.91 (dd, ∑ * = 2.4, 8.7 Hz, 1H) , 8.03 (d, J = 2.2 Hz, 1H) . Step 8: Preparation of dimethyl diketo malonate Under nitrogen, 30 g (0.114 mol) of 2-bromo- (3 ' -chloro-4' -methoxy) acetophenone (prepared in Step 7) waε added in three portions over 24 hours to a stirred suspenεion of 24 g (0.077 mol) of dimethyl keto malonate (prepared in Step 4), 42 g (0.3 mol) of potassium carbonate (Aldrich) , and 6 g (0.04 mol) of potassium iodide in 85 mL of THF. The mixture was filtered through a silica gel plug, eluted with ethyl acetate/hexane (1:1) and concentrated in vacuo. The residue was purified by silica gel chromatography (Prep-500, Waters) , eluted with 33% of ethyl acetate in hexane, to give 27.8 g (73%) of dimethyl diketo malonate as a white solid. Step 9 : Preparation of diaryl cvclooentenyl diester To a vigorouεly εtirred εuspension of 38.4 g (0.249 mol) of titanium(III) chloride in 400 mL of DME under nitrogen was added 14 g (0.214 mol) of zinc dust (Aldrich) , and the resulting mixture was stirred under reflux for one hour. To the dark solution at reflux was added 27.8 g (0.054 mol) of dimethyl diketo malonate (prepared in Step 8), and the resulting mixture was stirred under reflux for one hour. The mixture was filtered, concentrated in vacuo, diluted with ethyl acetate, washed with water, saturated NaHC0 3 , brine, dried (MgS0 4 ) and concentrated in vacuo. The residue was purified by silica gel chromatography to give 13 g (50%). of diaryl cyclopentenyl diester as a pale yellow solid: 1 H NMR (CDC1 3 ) δ 3.04 (s, 3H) , 3.5-3.6 (m, 4H) , 3.80 (ε, 6H) , 3.88 (ε, 3H) , 6.77 (d, J = 8.7 Hz, 1H) , 6.95 (dd, ∑ * = 2.2, 8.7 Hz, 1H) , 7.19 (d, J Z = 2.0 Hz, 1H) , 7.35 (dd, £ = 1.8, 6.9 Hz, 2H) , 7.79 (dd, J = 1-8, 6.8 Hz, 2H) . Step 10: Preparation of diaryl cvclopentenyl diol To a solution of 13 g (27.2 mmol) of cyclopentenyl diester (prepared in Step 9) in 200 mL of THF under nitrogen at -78 °C was added 100 mL (150 mmol) of DIBAL (1.5 M in toluene) over a period of 30 minutes. The resulting solution was stirred at -78 °C for 15 minuteε, then at room temperature overnight. The reaction mixture waε carefully quenched sequentially with 15 mL of acetone, 30 mL of water (caution: exothermic) and 90 mL of 10% NaOH. The aqueous layer was extracted with ethyl acetate, and the combined extracts were washed with εaturated NaHC0 3 , 1 N HCl, water, and brine. The extract waε dried (MgS0 4 ) and concentrated in vacuo to give 11.8 g of colorleεs oil which was uεed directly in Step 11: ^-H NMR (CDCI 3 ) δ 2.35 (ε, 2H) , 2.78 (d, J = 10.5 Hz, 4H) , 3.04 (ε, 3H) , 3.83 (ε, 4H) , 3.87 (ε, 3H) , 6.76 (d, £ = 8.7 Hz, 1H) , 6.95 (dd, 2.2, 8.7 Hz, 1H) , 7.18 (d, * ∑ = 2.1 Hz, 1H) , 7.34 (d, iZ = 1.8, 6.8 Hz, 2H) , 7.77 (dd, 2 * = 1.8, 6.6 Hz, 2H) . Step 11: Preparation of diaryl cvclopentenyl ditoεylate To a solution of 11.8 g (26.8 mmol) of crude diaryl cyclopentenyl diol (prepared in Step 10) in 92 mL of pyridine under nitrogen at 0 °C was added 23 g (120 mmol) of p-tolueneεulfonyl chloride in portions (exothermic) and the resulting dark solution was εtirred at room temperature overnight. The mixture waε concentrated in vacuo to remove pyridine, and the reεidue waε dissolved in ethyl acetate. The solution was washed with water, 1 N HCl, NaHCC< 3 , brine, dried (MgSθ 4 ) and concentrated in vacuo. The residue was chromatographed to give 11.6 g (59% from diester) of diaryl cyclopentenyl ditosylate as a tan solid: ^-H NMR (CDCI 3 ) δ 2.46 (s, 6H) , 2.70 (d, J = 15.1 Hz, 4H) , 3.04 (ε, 3H) , 3.88 (ε, 3H) , 4.03 (s, 4H) , 6.74 (d, -Z = 8.7 Hz, 1H) , 6.85 (dd, >Z = 2.2, 8.7 Hz, 1H) , 7.00 (d, -Z = 2.0 Hz, 1H) , 7.19 -7.25 (m, 2H) , 7.35 (d, J = 8.1 Hz, 4H) , 7.7-7.82 (m, 6H) . Step 12: Preparation of 5- (3-chloro-4-methoxyphenyl) -6- T4- (methylsulfonyl)phenyl! spiror2.41hept-5-ene Under nitrogen, a solution of 11.6 g (15.9 mmol) of diaryl cyclopentenyl ditosylate (prepared in Step 11) in 260 mL of DMF was treated with 34.7 g (231 mmol) of sodium iodide and 17.2 g (263 mmol) of zinc dust. The resulting mixture was stirred at 150 °C for 3 hours, and concentrated in vacuo. The residue waε diεsolved in ethyl acetate, and the solid was filtered off. The filtrate was washed with sodium sulfite, water, brine, dried (MgSC- 4 ) , and concentrated in vacuo. The residue waε chromatographed on silica gel to give 5.32 g (86%) of pale yellow solid The solid was recrystallized to give 2.32 g of 5- (3-chloro-4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene as a white solid: mp 140.0-140.5 °C; X H NMR (CDCI 3 ) δ 0.68 (s, 4H) , 2.84-2.95 (m, 4H) , 3.04 (s, 3H) , 3.88 (s, 3H) , 6.76 (d, * = 8.5 Hz, 1H) , 6.95 (dd, = 2,0, 8.5 Hz, 1H) , 7.18 (d, = 2.0 Hz, 1H) , 7.35 (dd, J = 1.6, 6.7 Hz, 2H) , 7.77 (dd, J = 1.8, 6.6 Hz, 2H) . HRMS (El) Calc'd for C 21 H 21 CIO3S: 388.0900. Found: 388.0909. Anal. Calc'd for C 2 ιH 2 ιC10 3 S: C, 64.93; H, 5.45; S, 8.24. Found: C, 64.77; H, 5.65; S, 8.53. The mother liquor from the recrystallization described above was concentrated in vacuo to give 3.0 g of pale yellow εolid which waε used directly in the preparation of the title compound of Example 7. Example 7 4- [6- (3-Chloro-4-methoxyphenyl) spiro [2.4]hept-5- en-5-yl]benzenesulfonamide Under nitrogen, a solution of 3.6 g (9.26 mmol) of 5-(3-chloro-4-methoxyphenyl) -6-[4- (methylεulfonyl)phenyl]εpiro[2.4]hept-5-ene (the title compound of Example 6) in 10 mL of THF at 0 °C waε treated with 6.3 mL (10.08 mmol) of propylmagneεium chloride (1.6 M in ether) . The reaction mixture waε εtirred at ambient temperature for 25 minutes, cooled to 0 °C, and treated with 16.5 mL (1.0 M in THF, 16.5 mmol) of tributylborane (or triethylborane) . The resulting solution was stirred at ambient temperature for 15 minutes and then at reflux for 18 hours prior to the addition of 7 g (85 mmol) of sodium acetate, 18 mL of water, and 4 g (35 mmol) of hydroxyamine-O-sulfonic acid at 0 °C. The resulting light orange mixture was stirred at ambient temperature for 3.5 hours and the aqueous phase was extracted with ethyl acetate. The combined extracts were waεhed with water, brine, dried (MgS0 4 ) , and concentrated in vacuo. The residue was chromatographed on silica gel to give 2.5 g (59%) of 4- [6- (3-chloro-4-methoxyphenyl) εpiro[2.4]hept-5- en-5-yl]benzeneεulfonamide aε a white εolid: mp 191.0- 192.0 °C; i H NMR (CDCI 3 ) δ 0.63 (s, 4H) , 2.84 (s, 4H) , 3.83 (ε, 3H) , 5.74 (br s, 2H) , 6.72 (d, = 8.5 Hz, 1H) , 6.92 (dd, J = 2.0, 8.5 Hz, 1H) , 7.15 (d, J = 2.2 Hz, 1H) , 7.24 (dd, iZ = 2.0, 6.9 Hz, 2H) , 7.72 (dd, J = 1.8, 6.7 Hz, 2H) . HRMS (El) Calc'd for C 20 H 20 CINO 3 S: 389.0852. Found: 389.0869. Anal. Calc'd for [C 20 H 20 CINO 3 S + 0.05 CH 2 C1 2 ] : C, 61.61; H, 5.17; N, 3.59; S, 8.22. Found: C, 61.06; H, 5.25; N, 3.51; S, 8.24. Example 8 5- ( 3 -Fluoro- 4 -methoxyphenyl ) -6 - [4- ( methyl sul fonyl ) phenyl] spiro [2.4] hept -5 -ene Following a procedure similar to the one described in Example 6, with the substitution of 3'- f luoro-4 ' -methoxyacetophenone (Aldrich) for 3 ' -chloro-4 ' - methoxyacetophenone (Example 6, Step 7), 5- (3-f luoro-4- methoxyphenyl ) -6- [4- (methylsulfonyl) phenyl] εpiro [2.4] hept - 5-ene was -prepared as a white solid: mp 110.5-111.5 °C; 1 H NMR (CDCI 3 ) δ 0.68 (s, 4H) , 2.85-2.95 (m, 4H) , 3.05 (ε, 3H) , 3.87 (ε, 3H) , 6.77-6.94 (m, 3H) , 7.35 (d, J = 8.4 Hz, 2H) , 7.78 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 21 H 21 FO 3 S: 372.1192. Found: 372.1187. Anal. Calc'd for C 21 H 21 FO 3 S: C, 67.72; H, 5.68; F, 5.10; S, 8.61. Found: C, 67.31; H, 5.68; F, 5.16; S, 8.62. Example 9 4- [6- (3 -Fluoro -4 -methoxyphenyl) spiro [2.4 ] hept -5- en-5-yl ] benzenesulfonamide Following a procedure similar to the one described in Example 7, 1.40 g (3.76 mmol) of 5-(3-fluoro- 4 -methoxyphenyl) -6- [4- (methylsulfonyl) phenyl] spiro [2.4]hept-5-ene (the title compound of Example 8) was converted to crude εulf onamide. Purification by εilica gel chromatography gave 0.88 g (63%) of 4- [6- (3-fluoro-4-methoxyphenyl) εpiro [2.4]hept-5- en-5-yl] benzeneεulf onamide aε a white solid: mp 153.0- 154.0 °C; 1 H NMR (CDCl 3 ) δ 0.68 (s, 4H) , 2.89 (s, 4H) , 3.87 (s, 3H) , 4.79 (ε, 2H) , 6.75-6.93 (m, 3H) , 7.31 (d, J = 8.7 Hz, 2H) , 7.77 (d, JZ = 8.4 Hz, 2H) . HRMS (El) Calc'd for C 20 H 20 FNO3S: 373.1148. Found: 373.1172. Anal. Calc'd for C 20 H 20 FNO3S: C, 64.33; H, 5.40; N, 3.75; F, 5.09. Found: C, 64.28; H, 5.49; N, 3.77; F, 5.23. Example 10 5- ( 3 , 4 -Dif luorophenyl ) -6- [4- ( methyl sul fonyl ) phenyl] spiro [2.4 ] hept -5 -ene Following a procedure similar to the one described in Example 6 with the subεtitution of 3 ',4'- difluroacetophenone (Aldrich) for 3 ' -chloro-4' - methoxyacetophenone (Example 6, Step 7), 5- (3, 4- dif luorophenyl) -6- [4- (methylsulfonyl) phenyl] spiro [2.4]hept-5-ene was obtained as a white solid: mp 113-114 °C. MS (FAB): m/z 367 (M+Li) , HRMS Calc'd for C2 0 H 18 F 2 O 2 S: 360.0996, found 360.1014. l H NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.90 (s, 2H) , 2.92 (s, 2H) , 3.06 (ε, 3H) , 6.80-6.87 (m, 1H) , 6.91-7.07 (m, 2H) , 7.33 (d, ∑ * = 8 Hz, 2H) , 7.79 (d, «Z = 8 Hz, 2H) . Anal. Calc'd for C 20 H 18 F 2 O 2 S: C, 66.65; H, 5.03. Found: C, 66.50; H, 5.02. Example 11 5- [6- [4- (Methylsulfonyl)phenyl] spiro[2.4]hept-5- en-5-yl] -1, 3-benzodioxole Following a procedure similar to that described in Example 6, with the substitution of 3',4'- (methylenedioxy)acetophenone [prepared by the addition of methyllithium to piperonylonitrile (Aldrich) , see Example 6, Step 1] for 3'-chloro-4'-methoxyacetophenone (Example 6, Step 7), 5-[6-[4- (methylεulfonyl)phenyl]spiro[2.4]hept- 5-en-5-yl]-1,3-benzodioxole was prepared aε a white εolid: mp 110.5-111.5 °C; X H NMR (CDCl 3 ) δ 0.67 (ε, 4H) , 2.89 (br d, = 2.4 Hz, 4H) , 3.05 (ε, 3H) , 5.94 (ε, 2H) , 6.55-6.67 (m, 2H) , 6.70 (d, £ = 8.1 Hz, 1H) , 7.36 (d, J = 8.5 Hz, 2H) , 7.76 (d, J Z = 8.5 Hz, 2H) . HRMS (El) Calc'd for C 21 H 20 O 4 S: 368.1082. Found: 368.1077. Anal. Calc'd for C 21 H 2 0O 4 S: C, 68.46; H, 5.47; S, 8.70. Found: C, 68.13; H,5.65; S, 8.81. Example 12 4- [6- (3, 4-Difluorophenyl ) spiro [2.4 ]hept-5-en-5- yl]benzenesulfonamide Following a procedure similar to the one described in Example 7, 880 mg (2.44 mmol) of 5- (3,4- difluorophenyl) -6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene (the title compound of Example 10) was converted to crude εulfonamide. Purification by silica gel chromatography (MPLC) with ethyl acetate/hexane (1:5) as the eluent followed by recrystallization from methylene chloride/hexane gave 370 mg (42%) of 4- [6- (3, 4- difluorophenyl) spiro[2.4]hept-5-en-5-yl]benzenesulfonamide as a white solid: mp 136-137 °C. MS (FAB): m/z 362 (M+H) ; HRMS Calc'd for C 19 H 17 F 2 NO 2 S: 361.0948, found: 361.0952. --H NMR (CDCI3) δ 0.68 (s, 4H) , 2.89 (s, 2H) , 2.90 (s, 2H) , 4.79 (ε, 2H) , 6.81-6.87 (m, 1H) , 6.91-7.06 (m, 2H) , 7.28 (d, ∑ * = 8 Hz, 2H) , 7.78 (d, . = 8 Hz, 2H) . Anal. Calc'd for [C 19 H 17 F 2 NO 2 S + 0.29 CH 2 C1 2 ] : C, 60.00; H, 4.59; N, 3.63; F, 9.84; S, 8.30. Found: C, 59.96; H, 4.57; N, 3.50; F, 10.05; S, 8.35. Example 13 2 , 6 -Dichloro- 4 - [ 6 - [ 4 - ( me thy l s l fonyl ) phenyl ] spiro [ 2 . 4 ] hept - 5 - en- 5 - yl ] phenol Step 1: Preparation of 3.5-dichloro-4-methoxybenzoic acid Under nitrogen, a mixture of 41.4 g (0.200 mol) of 3-chloro-4-hydroxybenzoic acid, 75 mL (1.2 mol) of iodomethane, and 81.5 g (0.25 mol) of potassium carbonate in 250 mL of DMF was stirred at 55 °C for 18 hours. The reaction mixture was filtered and concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with water, brine, dried (MgSθ 4 ) and concentrated in vacuo. The residue was dissolved in 84 mL of methanol and 84 mL of 2.5 N NaOH, and the resulting mixture was stirred at reflux for 4 hours. The reaction was concentrated in vacuo. The residue was disεolved in 600 mL of water, and pH waε adjusted to 2 with concentrated HCl. The solution was extracted with ethyl acetate, and the combined extractε were washed with brine, dried (MgSθ 4 ) and concentrated in vacuo to give 38.12 g (89%) of 3 , 5-dichloro-4-methoxybenzoic acid as a white solid: 1 H NMR (CDCI 3 ) δ 3.95 (s, 3H) , 7.98 (ε, 2H) Step 2: Preparation of 2 , 6-dichloro-4- f6- [4- (methylsulfonyl)phenyll spiro \2 .41hept-5-en-5- yllphenol Following a procedure similar to the one described in Example 6, with the substitution of 3,5- dichloro-4-methoxybenzoic acid (prepared in Step 1) for 3- chloro-4-methoxybenzoic acid (Example 6, Step 5), 2,6- dichloro-4- [6- [4- (methylsulfonyl)phenyl] spiro[2 ,4]hept-5- en-5-yl]phenol was isolated instead of the expected 5- (3,5-dichloro-4-methoxy-phenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene. The title product compound was recrystallized as a white solid: mp 163.5-164.5 °C; --Ε NMR (CDC1 3 ) δ 0.68 (s, 4H) , 2.88 (br d, J = 12.5 Hz, 4H) , 3.05 (s, 3H) , 5.83 (s, 2H) , 7.02 (ε, 2H) , 7.35 (d, J = 8.4 Hz, 2H) , 7.81 (d, J = 8.4 Hz, 2H) . HRMS (El) Calc'd for C 20 H 18 CI 2 O 3 S: 408.0354. Found: 408.0349. Anal. Calc'd for C 20 H 18 I 2 O 3 S: C, 58.69; H, 4.43; Cl, 17.32; S, 7.83. Found: C, 58.47; H, 4.55; Cl, 17.24; S, 7.65 Example 14 6- [4- (Methylsulfonyl)phenyl] -5- (4- trifluoromethoxyphenyl) spiro [2 .4]hept-5-ene Following a procedure εimilar to the one deεcribed in Example 6, with the substitution of 4'- trifluoromethoxyacetophenone (Aldrich) for 3 ' -chloro-4' - methoxyacetophenone (Example 6, Step 7), 6- [4- (methylsulfonyl)phenyl] -5- (4- trifluoromethoxyphenyl) spiro [2.4]hept-5-ene was prepared as a white solid: mp 126.0-127.0 °C; λ E NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.93 (s, 4H) , 3.05 (s, 3H) , 7.08 (d, J = 8.7 Hz, 2H) , 7.16 (d, J I = 8.7 Hz, 2H) , 7.33 (d, J = 8.4 Hz, 2H) , 7.78 (d, J = 8.1 Hz, 2H) . HRMS (El) Calc'd for C 21 H 19 F 3 O 3 S: 408.1007. Found: 408.1017. Anal. Calc'd for [C 21 H1 9 F 3 O 3 S + 0.12 H 2 0] : C, 61.43; H, 4.72; F, 13.88; S, 7.81. Found: C, 61.54; H, 4.76; F, 13.32; S, 7.98 Example 15 5- (4 -Methoxyphenyl) -6- [4- ( methyl sul fonyl ) phenyl] spiro [2.4 ] hept -5 -ene Following a procedure similar to the one described in Example 6, with the subεtitution of 2-bromo- 4 ' -methoxyacetophenone (Aldrich) for 2-bromo-3 ' -chloro-4 ' - methoxyacetophenone (Example 6, Step 8), 5- (4- methoxyphenyl ) -6- [4- (methylεulfonyl) phenyl] εpiro [2.4] hept- 5 -ene was prepared as a white εolid: mp 170.2-173.0 °C; 1 H NMR (CDCI 3 ) δ 0.67 (ε, 4H) , 2.91 (ε, 4H) , 3.04 (s, 3H) , 3.79 (s, 3H) , 6.77 (d, J = 8.9 Hz, 2H) , 7.07 (d, £ = 8.9 Hz, 2H) , 7.35 (d, sZ = 8.5 Hz, 2H) , 7.75 (d, £ = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 21 H 22 O 3 S: 354.1290. Found: 354.1317. Anal. Calc'd for C 21 H 22 O 3 S: C, 71.16; H, 6.26; S, 9.04. Found: C, 70.92; H, 6.20; S, 8.96. Example 16 5- ( 3 -Bromo -4 -methoxyphenyl ) -6- [4 - (methylsulfonyl ) phenyl] spiro [2.4 ] hept -5 -ene Following a procedure similar to the one described in Example 6, with the substitution of 3'-bromo- 4 ' -methoxyacetophenone [prepared by the addition of methylmagnesium bromide to 3-bromo-4-methoxybenzaldehyde (Aldrich) , followed by Mnθ 2 oxidation of the resulting alcohol] for 3 ' -chloro-4 ' -methoxyacetophenone (Example 6, Step 7), 5- (3 -bromo -4 -methoxyphenyl) -6- [4- (methylsulfonyl) phenyl] spiro [2.4]hept-5-ene was prepared as a white solid: mp 89.5-91.8 °C; X H NMR (CDCI 3 ) δ 0.68 (s, 4H) , 2.85-2.93 (m, 4H) , 3.04 (s, 3H) , 3.87 (s, 3H) , 6.73 (d, J = 8.7 Hz, 1H) , 6.97 (dd, j∑ = 2,5, 7.5 Hz, 1H) , 7.3-7.4 (m, 3H) , 7.78 (d, J. = 8.5 Hz, 2H) . HRMS (El) Calc'd for C 2 iH ιBr0 3 S: 432.0395. Found: 432.0375. Anal. Calc'd for [C 2 ιH 2 ιBr0 3 S + 0.64 CH 2 Cl 2 ] : C, 53.31; H, 4.61; Br, 16.39. Found: C, 53.12; H, 4.54; Br, 16.74. Example 17 4- [6- (4-Methoxyphenyl)spiro[2.4]hept-5-en-5 yl]benzenesulfonamide Following a procedure similar to the one described in Example 7, 200 mg (0.564 mmol) of 5- (4- methoxyphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept- 5-ene (the title compound of Example 15) was converted to crude sulfonamide. Purification by silica gel chromatography gave 96 mg (48%) of 4- [6- (4- methoxyphenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide as a white solid: 3 -H NMR (CDCI 3 ) δ 0.67 (s, 4H) , 2.90 (s, 4H) , 3.78 (s, 3H) , 4.86 (br s, 2H) , 6.76 (d, £ = 8.9 Hz, 2H) , 7.08 (d, 0. = 8.9 Hz, 2H) , 7.30 (d, J = 8.5 Hz, 2H) , 7.73 (d, J = 8.5 Hz, 2H) . HRMS (El) Calc'd for C 20 H 21 NO 3 S: 355.1242. Found: 355.1250. Anal. Calc'd for [C 20 H 21 NO 3 S + 0.6 H 2 0] : C, 65.60; H, 6.11; N, 3.82. Found: C, 65.59; H, 5.85; N, 3.66. Example 18 4- [6- (3-Bromo-4-methoxyphenyl) spiro [2.4]hept-5-en- 5-yl] enzenesulfonamide Following a procedure similar to the one described in Example 7, 3 g (6.92 mmol) of 5- (3-bromo-4- methoxyphenyl) -6- [4- (methylsulfonyl)phenyl]εpiro[2.4]hept- 5-ene (the title compound of Example 16) waε converted to crude sulfonamide. Purification by silica gel chromatography gave 1.32 g (44%) of 4- [6- (3-bromo-4- methoxyphenyl) spiro[2.4]hept-5-en-5-yl]benzenesulfonamide as a white solid: mp 187.5-189.8 °C; 1 H NMR (CDCI 3 ) δ 0.67 (s, 4H) , 2.89 (s, 4H) , 3.87 (s, 3H) , 4.76 (br s, 2H) , 6.73 (d, J = 8.5 Hz, 1H) , 7.0 (dd, *∑ = 2.1, 8.5 Hz, 1H) , 7.30 (d, = 8.7 Hz, 2H) , 7.37 (dd, J. = 2.1 Hz, 1H) , 7.76 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 2θ H 2θ BrN0 3 S: 433.0347. Found: 433.0310. Anal. Calc'd for C 2 oH 2θ BrN0 3 S: C, 55.31; H, 4.64; N, 3.22. Found: C, 55.31; H, 4.77; N, 2.93. Example 19 6- [4- (Methylsulfonyl)phenyl] -5- (4- trifluoromethylphenyl ) spiro [2.4] hept-5-ene Following a procedure similar to the one described in Example 6, with the substitution of 4- trifluoromethylacetophenone [prepared by the addition of methyllithium to α,α,α-trifluoro-p-tolunitrile (Aldrich), see Example 6, Step 1] for 3 ' -chloro-4' - methoxyacetophenone (Example 6, Step 7), 6-[4- (methylsulfonyl)phenyl] -5- (4- trifluoromethylphenyl) spiro[2.4]hept-5-ene was prepared as a white solid: mp 170.0-170.8 °C; λ H NMR (CDC1 3 ) δ 0.70 (ε, 4H) , 2.95 (ε, 4H) , 3.05 (ε, 3H) , 7.24 (d, £ = 8.4 Hz, 2H) , 7.31 (d, JI = 8.3 Hz, 2H) , 7.49 (d, = 8.1 Hz, 2H) , 7.78 (d, iZ = 8.2 Hz, 2H) . HRMS (El) Calc'd for C 21 H 19 F 3 O 2 S: 392.1058. Found: 392.1080. Anal. Calc'd for C 21 H 19 F 3 O 2 S: C, 64.27; H, 4.88; F, 14.52; S, 8.17. Found: C, 63.98; H, 4.90; F, 14.65; S, 8.33. Example 20 5- (3, 5-Dichloro-4-methoxyphenyl) -6- [4- (methylsulfonyl )phenyl] spiro [2.4 ]hept-5-ene Under nitrogen, a mixture of 0.2 g (0.49 mmol) • of 2,6-dichloro-4-[6-[4- (methylεulfonyl)phenyl] εpiro [2.4]hept-5-en-5-yl]phenol (the title compound of Example 13), 91 μL (1.5 mmol) of iodomethane and 0.32 g (1 mmol) of cesium carbonate in 6 mL of DMF was stirred at 25 °C for 16 hourε. The reaction mixture was diluted in ethyl acetate, washed with water, brine, dried (MgS0 4 ) and concentrated in vacuo. The reεidue was recrystallized to give 0.18 g (90%) of 5- (3,5- dichloro-4-methoxyphenyl) -6- [4- (methylεulfonyl)phenyl] εpiro [2.4]hept-5-ene aε a white εolid: mp 107.0-108.0 °C; --Η. NMR (CDC1 3 ) δ 0.69 (s, 4H) , 2.89 (d, J = 14 Hz, 4H) , 3.05 (ε, 3H) , 3.89 (s, 3H) , 7.04 (s, 2H) , 7.34 (d, = 8.7 Hz, 2H) , 7.82 (d, J = 8.4 Hz, 2H) . HRMS (El) Calc'd for C 21 H 20 CI 2 O 3 S: 422.0510. Found: 422.0513. Anai ^ Calc'd for [C 21 H 20 CI 2 O 3 S + 0.67 H 2 0] : C, 57.92; H, 4.94; Cl, 16.28; S, 7.36. Found: C, 57.79; H, 4.73; Cl, 16.68; S, 7.31. Example 21 4- [6- ( 4 -Trif luoromethoxyphenyl ) spiro [2.4 ] hept -5 - en-5-yl ] benzenesulfonamide Following a procedure similar to the one described in Example 7, 1.80 g (4.4 mmol) of 6- [4- (methylsulfonyl) phenyl] -5- (4- trif luoromethoxyphenyl) spiro [2.4] hept -5 -ene (the title compound of Example 14) was converted to crude sulf onamide. Purification by silica gel chromatography gave 0.73 g (40%) of 4-[6-(4- trif luoromethoxyphenyl) spiro [2.4]hept-5-en-5- yl] benzeneεulf onamide aε a white εolid: mp 144.0-145.0 °C; X H NMR (CDC1 3 ) δ 0.69 (s, 4H) , 2.92 (s, 4H) , 4.78 (br s, 2H) , 7.08 (d, = 8.9 Hz, 2H) , 7.16 (d, J. = 9.0 Hz, 2H) , 7.28 (d, J Z = 8.7 Hz, 2H) , 7.76 (d, = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 20 H 18 F 3 NO 3 S : 409.0960. Found: 409.0974. Anal. Calc'd for [C 20 H1 8 F 3 NO 3 S + 0.29 C 3 H 6 0 ] : C, 58.17; H, 4.62; N, 3.25; F, 13.23; S, 7.44. Found: C, 58.57; H, 4.47; N, 3.29; F, 12.62; S, 7.92. Example 22 5- ( 3 -Chloro -4 -fluorophenyl) -6- [4- ( methyl sul fonyl ) phenyl ] spiro [2.4] hept -5 -ene Following a procedure similar to the one described in Example 6, with the subεtitution of 3'- chloro-4' -fluoroacetophenone (Lancaster) for 3 ' -chloro-4' - methoxyacetophenone (Example 6, Step 7), 5- (3-chloro-4- • fluorophenyl) -6- [4- (methylsulfonyl) phenyl] spiro [2.4] hept - 5-ene was prepared as a white solid: mp 128.0-130.0 °C; 1 H NMR (CDC1 3 ) δ 0.69 (s, 4H) , 2.91 (d, J = 3.6 Hz, 4H) , 3.05 (ε, 3H) , 6.9-7.02 (m, 2H) , 7.19 (d, ∑ * = 7.5 Hz, 1H) , 7.33 (d, £ = 8.4 Hz, 2H) , 7.79 (d, = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 2 oHi 8 ClF0 2 S: 376.0700. Found: 376.0710. Anal. Calc'd for C 2 oHi 8 ClF0 2 S: C, 63.74; H, 4.81; F, 5.04; Cl, 9.41; S, 8.51. Found: C, 63.61; H, 4.85; F, 4.70; Cl, 9.58; S, 8.66. Example 23 5- ( 2, 4 -Dif luorophenyl ) -6- [4- ( me thy lsul fonyl ) phenyl] spiro [2.4 ] hept -5 -ene Following a procedure εimilar to the one described in Example 6, with the substitution of 2-chloro- 2 ' , 4 ' -difluoroacetophenone (Aldrich) for 2-bromo-(3'- chloro- 4 ' -methoxy) acetophenone (Example 6, Step 8), 5- (2, 4 -dif luorophenyl) -6- [4- (methylsulfonyl) phenyl] spiro [2.4]hept-5-ene was prepared as a white solid: mp 116.0-117.5 °C; 1 H NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.89 (ε, 2H) , 2.94 (s, 2H) , 3.03 (ε, 3H) , 6.78 (t, J = 8.4 Hz, 2H) , 7.05 (q, J = 6.6 Hz, 2H) , 7.28 (d, ∑ i = 8.1 Hz, 2H) , 7.74 (dd, £ = 1.8, 6.9 Hz, 2H) . HRMS (El) Calc'd for C 20 H 18 F2O 2 S: 360.0996. Found: 360.1010. Anal. Calc'd for [C 2 oHi 8 F 2 0 2 S+ 0.22 H 2 0] : C, 65.93; H, 5.10; S, 8.80. Found: C, 66.18; H, 5.16; S, 8.97. Example 24 ' 5- (2, 4-Dichlorophenyl) -6- [4- ( methyl sul fonyl ) phenyl] spiro [2.4 ] hept -5 -ene Following a procedure similar to the one described in Example 6, with the substitution of 2,2' 4'- trichloroacetophenone (Aldrich) for 2-bromo- (3 ' -chloro-4 ' - methoxy) acetophenone (Example 6, Step 8), 5-(2,4- dichlorophenyl ) - 6 - [ 4 - (methylsulfonyl) phenyl] spiro [2.4]hept-5-ene was prepared as a white εolid: mp 90.0-91.5 °C; λ H NMR (CDC1 3 ) δ 0.69 (s, 4H) , 2.85 (s, 2H) , 2.95 (ε, 2H) , 3.01 (ε, 3H) , 7.02 (d, J = 8.1 Hz, 1H) , 7.16 (d, * ∑ = 2.1 Hz, 1H) , 7.20 (d, ∑ * = 8.4 Hz, 2H) , 7.42 (d, *∑ = 2.1 Hz, 1H) , 7.72 (d, * ∑ = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 20 H 18 I 2 O 2 S: 392.0405. Found: 392.0423. Anal. Calc'd for [C 20 H 18 CI 2 O 2 S + 0.36 H 2 0 + 0.05 C 6 Hι ] : C, 60.31; H, 4.84; Cl, 17.56; S, 7.94. Found: C, 60.33; H, 4.53; Cl, 17.21; S, 8.32. Example 25 4- [6- ( -Trif luoromethylphenyl )spiro[2.4 ]hept-5-en- 5-yl ] benzenesulfonamide Following a procedure εimilar to the one described in Example 7, 1.81 g (4.6 mmol) of 6- [4- (methylεulfonyl) phenyl] -5- (4- trif luoromethylphenyl) εpiro [2.4] hept-5 -ene (the title compound of Example 19) waε converted to crude εulf onamide. Purification by silica gel chromatography gave 1.20 g (66%) of 4-[6-(4- trif luoromethylphenyl) spiro [2.4]hept-5-en-5- yl] benzenesulfonamide as a white solid: mp 157.2-188.8 °C; ^ NMR (CDC1 3 ) δ 0.70 (s, 4H) , 2.94 (ε, 4H) , 4.80 (ε, 2H) , 7.21-7.30 (m, 4H) , 7.48 (d, *∑ = 8.5 Hz, 2H) , 7.77 (d, J = 8.3 Hz, 2H) . HRMS (El) Calc'd for C 20 H 18 F 3 NO 2 S: 393.1010. Found: 393.1045. Anal. Calc'd for [C 20 H 18 F3NO 2 S + 0.07 CH 2 C1 2 ] : C, 60.38; H, 4.58; N, 3.51; S, 8.03. Found: C, 60.30; H, 4.69; N, 3.50; S, 8.44. 4- [6- (3-Chior0-4-fluorophenyl) spiro [2.4]hept-5-en- 5-yl]benzenesulfonamide Following a procedure similar to the one described in Example 7, 1.0 g (2.65 mmol) of 5-(3-chloro- 4-fluorophenyl) -6-[4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene (the title compound of Example 22) was converted to crude sulfonamide. Purification by silica gel chromatography gave 0.19 g (19%) of 4-[6-(3-chloro-4- fluorophenyl)εpiro[2.4]hept-5-en-5-yl]benzeneεulfonamide aε a white εolid: mp 163.0-165.0 °C; X H NMR (CDC1 3 ) δ 0.69 (s, 4H) , 2.90 (d, £ = 2.7 Hz, 4H) , 4.75 (br s, 2H) , 6.70- 7.05 (m, 2H) , 7.18-7.24 (m, 1H) , 7.24-7.32 (m, 3H) , 7.78 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 19 H 17 CIFNO 2 S: 377.0652. Found: 377.0639. Anal. Calc'd for [C 19 H 1 7CIFNO 2 S + 0.018 CH 2 C1 2 ] : C, 60.21; H, 4.53; N, 3.69; F, 5.01; Cl, 9.68; S, 8.45. Found: C, 60.49; H, 4.63; N, 3.50; F, 4.91; Cl, 9.86; S, 8.61. Example 27 5- ( 3 , 4-Dichlorophenyl ) -6- [4- ( methyl sul fonyl ) phenyl] spiro [2.4 ] ept -5 -ene Following a procedure similar to the one described in Example 6, with the substitution of 2-bromo- (3 ', 4' -dichloro) acetophenone (Lancaster) for 2 -bromo- (3 ' - chloro-4' -methoxy) acetophenone (Example 6, Step 8), 5- (3,4-dichlorophenyl)-6-[4- (methylεulfonyl)phenyl]εpiro[2.4]hept-5-ene waε prepared as a white solid: mp 107.5-108.5 °C; λ H NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.91 (d, i = 3.0 Hz, 4H) , 3.05 (ε, 3H) , 6.90 (dd, J = 1.9, 8.7 Hz, 1H) , 7.24 (d, ∑ * = 2,1 Hz, 1H) , 7.27 (d, J = 8.7 Hz, 1H) , 7.33 (d, J = 8.4 Hz, 2H) , 7.80 (d, J = 8.4 Hz, 2H) . MS (FAB): m/z 399 (100, M+Li) . Anal. Calc'd for [C 20 H 18 CI 2 O 2 S + 0.08 C 6 Hι ] : C, 61.45; H, 4.81; Cl, 17.72; S, 8.02. Found: C, 61.28; H, 4.73; Cl, 17.33; S, 8.30. Example 28 5- (4-Chlorophenyl) -6- [4- (methylsulfonyl )phenyl] spiro [2.4]hept-5-ene Following a procedure similar to the one described in Example 6, with the substitution of 2-bromo- 4' -chloroacetophenone (Aldrich) for 2-bromo- (3 ' -chloro-4' - methoxy)acetophenone (Example 6, Step 8), 5-(4- chlorophenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept- 5-ene was prepared as a white solid: mp 143.0-145.0 °C; 1 H NMR (CDC1 3 ) δ 0.69 (s, 4H) , 2.92 (s, 4H) , 3.05 (ε, 3H) , 7.07 (d, J = 8.7 Hz, 2H) , 7.21 (d, £ = 8.7 Hz, 2H) , 7.33 (d, = 8.4 Hz, 2H) , 7.77 (dd, J = 8.7 Hz, 2H) . MS (FAB): m/z 365 (100, M+Li) Anal. Calc'd for C 20 H 19 CIO 2 S: C, 66.94; H, 5.36; Cl, 9.88; S, 8.93. Found: C, 66.34; H, 5.38; Cl, 9.96; S, 9.01. Example 29 4- [ 6- ( 3 , 4 -Dichlorophenyl ) spiro [2.4 ] hept -5 -en- 5- yl ] enzenesulfonamide Following a procedure similar to the one described in Example 7, 5.20 g (13.2 mmol) of 5- (3,4- dichlorophenyl) -6- [ 4- (methylsul fonyl) phenyl] spiro [2.4] hept-5 -ene (the title compound of Example 27) was converted to crude sulf onamide. Purification by εilica gel chromatography gave 1.40 g (27%) of 4-[6-(3,4- dichlorophenyl) εpiro [2.4 ] hept -5 -en- 5 -yl] benzenesulfonamide as a white solid: mp 162.0-163.0 °C; R NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.90 (d, J =2.1 Hz, 4H) , 4.77 (s, 2H) , 6.92 (dd, >Z = 2.1, 8.4 Hz, 1H) , 7.23-7.32 (m, 4H) , 7.78 (d, £ = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 19 H 17 CI 2 NO 2 S: 393.0357. Found: 393.0354. Anal. Calc'd for [C 19 H 17 CI 2 ΝO 2 S+ 0.035 C 6 H 1 ] : C, 58.07; H, 4.44; N, 3.52; Cl, 17.84; S, 8.07. Found: C, 58.15; H, 4.41; N, 3.43; Cl, 17.59; S, 8.88. Example 30 4- [6- (4-Chlorophenyl) spiro [2.4]hept-5-en-5 yl] enzenesulfonamide Following a procedure similar to the one described in Example 7, 7.5 g (20.9 mmol) of 5- (4- chlorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept- 5-ene (the title compound of Example 28) was converted to crude sulfonamide. Purification by silica gel chromatography gave 2.82 g (37%) of 4- [6- (4- chlorophenyl)εpiro[2.4]hept-5-en-5-yl]benzenesulfonamide as a white solid: mp 152.5-153.5 °C; --H NMR (CDCI 3 ) δ 0.68 (s, 4H) , 2.91 (s, 4H) , 4.85-5.05 (br s, 2H) , 7.07 (d, J. = 8.4 Hz, 2H) , 7.20 (d, ϋ = 8.4 Hz, 2H) , 7.27 (d, ∑ * = 8.1 Hz, 2H) , 7.75 (d, J = 8.4 Hz, 2H) . HRMS (El) Calc'd for Ci 9 Hι 8 ClN0 2 S: 359.0747. Found: 359.0747. Anal. Calc'd for Ci 9 Hι 8 ClN0 2 S: C, 63.41; H, 5.04; Cl, 9.85; N, 3.89; S, 8.91. Found: C, 63.47; H, 5.12; Cl, 10.21; N, 3.78; S, 8.98. Example 31 5- (3-Chloro-4-methylphenyl) -6- [4- ( methyl sul fonyl ) phenyl ]spiro[2.4] hept -5 -ene Following a procedure similar to the one described in Example 6, with the subεtitution of 3'- chloro-4' -methylacetophenone [prepared by the addition of methyllithium to 3-chloro-4-methylbenzonitrile (Aldrich) , εee Example 6, Step 1] for 3 ' -chloro-4 ' - methoxyacetophenone (Example 6, Step 7), 5- (3-chloro-4- ethylphenyl ) -6- [4- (methylεulfonyl) henyl] spiro [2.4]hept- 5-ene was prepared as a white solid: mp 142-144 °C; 1 H NMR (CDCI 3 ) δ 0.68 (s, 4H) , 2.33 (s, 3H) 2.90 (d, J = 2.1 Hz, 4H) , 3.04 (s, 3H) , 6.88 (dd, £ = 1.5, 7.5 Hz, 1H) , 7.06 (d, J = 7.5 Hz, 1H) , 7.14 (d, J = 1.5 Hz, 1H) , 7.34 (d, J = 8.7 Hz, 2H) , 7.78 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 2 ιH 2 ιCl0 2 S: 372.0951. Found: 372.0922. Anal. Calc'd for C 2 ιH 2 ιC10 2 S: C, 67.58; H, 5.63; S, 8.58. Found: C, 67.47; H, 5.86; S, 8.52. Example 32 5- ( 3 , 4-Dimethylphenyl ) -6- [4- ( methyl sul fonyl ) phenyl ] spiro [2. ] hept -5 -ene Following a procedure similar to the one described in Example 6, with the substitution of 3 ',4'- dimethylacetophenone (Aldrich) for 3 ' -chloro-4' - methoxyacetophenone (Example 6, Step 7), 5- (3,4- dimethylphenyl ) -6- [4- (methylεulfonyl) henyl] piro [2.4]hept-5-ene was prepared as a white solid: mp 95-96.5 °C; λ R NMR (CDCI 3 ) δ 0.67 (s, 4H) , 2.17 (ε, 3H), 2.23 (ε, 3H) , 2.91 (ε, 4H) , 3.03 (ε, 3H) , 6.82-6.87 (m, 1H) , 6.91-7.01 (m, 2H) , 7.35 (d, J = 8.7 Hz, 2H) , 7.74 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 22 H 24 O 2 S: 352.1497. Found: 352.1496. Anal. Calc'd for C 22 H 24 O 2 S: C, 74.89; H, 6.81; S, 9.08. Found: C, 74.45; H, 6.96; S, 8.93. Example 33 5- (4-Methylphenyl) -6- [4- ( methyl sulf onyl) phenyl] spiro [2.4 ] hept -5 -ene Following a procedure similar to the one described in Example 6, with the substitution of 2-bromo- 4 ' -methylacetophenone (Aldrich) for 2-bromo- (3 ' -chloro-4 ' - methoxy) acetophenone (Example 6, Step 8), 5- (4- - methy Iphenyl) -6- [4- (methylsulfonyl) phenyl] spiro [2.4]hept- 5-ene was prepared as a white solid: mp 146-148 °C; 1 H NMR (CDCI3) δ 0.67 (s, 4H) , 2.32 (s, 3H) , 2.91 (s, 4H) , 3.03 (s, 3H) , 7.04 (ε, 4H) , 7.34 (d, £ = 8.7 Hz, 2H) , 7.74 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 21 H 22 O 2 S: 338.1341. Found: 338.1323. Anal. Calc'd for C 21 H 22 O 2 S: C, 74.45; H, 6.50; S, 9.45. Found: C, 73.90; H, 6.64; S, 9.31. Example 34 5- ( 3 -Methyl -4 -trif luoromethoxyphenyl ) -6- [4- ( me thy lsul fonyl ) phenyl] spiro [2.4] hept -5 -ene Step 1: Preparation of 4- (trif luoromethoxy) acetophenone Under nitrogen, to a stirred εolution of 66 g (353 mmol) of 4- (trifluoromethoxy)benzonitrile (Aldrich) in 600 mL of anhydrouε THF at -78 °C waε added 303 mL (424 mmol) of methyllithium (1.4 M in diethyl ether, Aldrich) . After εtirred for three hours, the solution was warmed to room temperature. A 300 mL of 3 N HCl waε added, and stirring was continued overnight. The THF was removed in vacuo, and the reεulting solution was extracted twice with ethyl acetate. The ethyl acetate extracts were combined, washed with water, brine, and dried over MgSθ 4 . Concentration of solvent in vacuo gave 63.9 g (89%) of the 4-(trifluoromethoxy)acetophenone as a dark brown oil: 1 H NMR (CDCI 3 ) δ 2.61 (ε, 3H) , 7.29 (d, J Z = 9 Hz, 2H) , 8.01 (d, J = 9 Hz, 2H) . Step 2: Preparation of ketal Under nitrogen, to a εtirred solution of 63.9 g (313 mmol) of 4-(trifluoromethoxy)acetophenone (prepared in Step 1) in 200 mL of toluene in a 500 mL round bottom flaεk fitted with a Dean-Stark trap waε added 65.2 g (626 mmol) of neopentyl glycol (Aldrich) and 1.3 g of p- tolueneεulfonic acid monohydrate (Aldrich) . After εtirring overnight at reflux, the εolution waε cooled to room temperature and concentrated in vacuo. The residue was diεεolved in diethyl ether, waεhed with 2 M NaHC0 3 , and dried over MgSθ 4 . Purification by εilica gel plug with triethylamine/hexane (1:99) as the eluent gave 79.7 g (88%) of the ketal as a brown oil: ^-H NMR (CDCI 3 ) δ 0.59 (s, 3H) , 1.25 (s, 3H) , 1.51 (ε, 3H) , 3.38 (ε, 4H) , 7.22 (d, J = 9 Hz, 2H) , 7.45 (d, ∑ * = 9 Hz, 2H) . Step 3 : Metallation of the ketal Under nitrogen, to a εtirred εolution of 79.7 g (275 mmol) of the ketal (prepared in Step 2) in 511 mL of dry hexane waε added 114 mL (545 mmol) of TMEDA (N, N, N' , N' -tetramethylethylenediamine) . After cooling to -78 °C, the εolution was treated with 582 mL (757 mmol) of sec- butyllithium (1.3 M in cyclohexane, Aldrich), and εtirred vigorouεly for five hourε at -78 °C. To thiε solution was added 51.4 mL (826 mmol) of iodomethane and stirred for one hour. After warming to room temperature, the reaction was quenched with 2 N HCl, and extracted with diethyl ether. The diethyl ether extracts were combined, waεhed with 2 N HCl, and dried over MgSθ 4 . Concentration of the εolvent in vacuo gave 74 g of the ketal of 3 ' -methyl-4' - (trifluoromethoxy)acetophenone aε a brown oil, and waε uεed for next εtep without further purification. Step 4: Preparation of 3-methyl-4- (trifluoromethoxy)acetophenone Under nitrogen, to a stirred solution of 74 g of the crude oil (prepared in Step 3) in 200 mL of acetone and 10 mL of water was added 130 g (683 mmol) of p- toluenesulfonic acid monohydrate (Aldrich) . After stirring overnight, the solution was concentrated in vacuo. and the residue was dissolved in ethyl acetate. The ethyl acetate layer was washed with 2 N NaHC0 3 , and dried over MgS0 4 . Purification by silica gel plug with ethyl acetate/ hexane (10:90) as the eluent gave 31.9 g (53% for both Steps 3 and 4) of 3-methyl-4- (trifluoromethoxy)acetophenone as a yellow oil: 1 H NMR (CDC1 3 ) δ 2.37 (s, 3H) , 2.59 (s, 3H) , 7.27 (d, £. = 8 Hz, 1H) , 7.81 (d, i = 8 Hz, 1H) , 7.86 (s, 1H) . Step 5: Preparation of 5- (3-methyl-4- trifluoromethoxyphenyl) -6- T4- (methylsulfonyl)phenyl1 spiro " 2.41hept-5-ene Following a procedure similar to the one described in Example 6 with the substitution of 3'-methyl- 4' - (trifluoromethoxy)acetophenone (prepared in Step 4) for 3'-chloro-4'-methoxyacetophenone (Example 6, Step 7), 5- (3-methyl-4-trifluoromethoxyphenyl)-6-[4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene was prepared as a white solid: mp 79.1-80.3 °C. MS (FAB): m/z 429 (M+Li). λ R NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.22 (ε, 3H) , 2.92 (ε, 4H) , 3.04 (ε, 3H) , 6.91-6.97 (m, 1H) , 7.03-7.08 (m, 2H) , 7.34 (d, J Z = 8 Hz, 2H) , 7.77 (d, *∑ = 8 Hz, 2H) . Anal. Calc'd for C22H21F3O 3 S: C, 62.55; H, 5.01; F, 13.49. Found: C, 62.29; H, 4.93; F, 13.49. Example 35 5-(3-Chloro- -trif luoromethoxyphenyl ) -6 - [ 4 - (methylsulfonyl ) phenyl ] spiro [2.4 ] hept -5 -ene Step 1: Preparation of 3-chloro-4- (trif luoromethoxy) benzoic acid A dried, 750-mL Parr reactor (steel) equipped with a sealed mechanical stirrer and an internal thermocouple was charged with 54.2 g (0.314 mol) of 3- chloro-4-hydroxybenzoic acid, 125.5 mL (1.3 mol) of carbon tetrachloride, 172 g (0.965 mol) of anhydrous antimony trifluoride, and 7.55 g (0.025 mol) of antimony pentachloride. The reactor was sealed and heated at 150 °C with stirring for 4 hours. After cooling, the reactor was opened and the contents were neutralized with saturated NaHCθ 3 and 50% NaOH, then adjuεted down to pH 1 with concentrated HCl. The mixture waε filtered, and the aqueouε filtrate waε εeparated and extracted with 500 mL of ethyl acetate. The combined extractε were extracted with dilute NaOH solution (pH = 11) . To the aqueous extract waε added 200 mL of brine, and the mixture was extracted with ethyl acetate. The extract was concentrated in vacuo, and the residue was treated with 250 mL of methanol and 290 mL (720 mmol) of 2.5 N NaOH and stirred at ambient temperature for 22 hourε. The reaction mixture waε treated with cone. HCl to pH 1, extracted with ethyl acetate, dried (MgS0 4 ) , and concentrated in vacuo to give 35.5 g (47%) of 3-chloro-4- (trifluoromethoxy)benzoic acid as a white solid: 1 H NMR (CDC1 3 ) δ 7.69 (d, J = 8.7 Hz, 1H) , 8.03 (dd, J = 1.8, 8.7 Hz, 1H) , 8.13 (d, J Z = 1.5 Hz, 1H) . Step 2: Preparation of 5- (3-chloro-4- trifluoromethoxyphenyl) -6- T4- (methylsulfonyl) henyl1 spiro \2 .41hept-5-ene Following a procedure similar to the one described in Example 6, with the subεtitution of 3-chloro- 4- (trifluoromethoxy)benzoic acid (prepared in Step 1) for 3-chloro-4-methoxybenzoic acid (Example 6, Step 5), 5- (3- chloro-4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene was prepared as a white solid: mp 104-105.5 °C; *H NMR (CDCI 3 ) δ 0.69 (s, 4H) , 2.92 (br d, £ = 2.7 Hz, 4H) , 3.05 (s, 3H) , 7.00 (dd, J = 2.1, 8.4 Hz, 1H) , 7.16 (dd, -Z = 1.2, 8.7 Hz, 1H) , 7.25 (s, 1H) , 7.33 (d, J = 8.4 Hz, 2H) , 7.81 (d, £ = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 21 H 18 CIF 3 O 3 S: 442.0617. Found: 442.0617. Anal. Calc'd for C 21 H 18 CIF 3 O 3 S: C, 56.95; H, 4.10; Cl, 8.01; F, 12.87; S, 7.24. Found: C, 57.10; H, 4.15; Cl, 7.74; F, 12.55; S, 7.48. Example 36 4- [6- (3 , 5-Dichloro-4-methoxyphenyl) spiro [2.4]hept- 5-en-5-yl]benzenesulfonamide Following a procedure similar to the one described in Example 7, with the subεtitution of butyllithium instead of propylmagnesium chloride, 423 mg (1 mmol) of 5- (3 , 5-dichloro-4-methoxy-phenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene (the title compound of Example 20) was converted to crude sulfonamide. Purification by silica gel chromatography gave 87 mg (15%) of 4- [6- (3 , 5-dichloro-4- methoxyphenyl ) spiro [2.4]hept-5-en-5-yl]benzenesulfonamide as a white solid: mp 94.5-97.0 °C (decomp); R NMR (CDC1 3 ) δ 0.68 (s, 4H) , 2.83-2.95 (m, 4H) , 3.89 (ε, 3H) , 4.81 (br ε, 2H) , 7.05 (s, 2H) , 7.29 (d, £ = 8.5 Hz, 2H) , 7.80 (d, ± Z = 8.6 Hz, 2H) . HRMS (El) Calc'd for C 20 H 19 CI 2 NO 3 S : 423.0463. Found: 423.0455. Example 37 4- [6- (3-Methyl-4- trifluoromethoxyphenyl) spiro [2.4]hept-5-en-5- yl] enzenesulfonamide Following a procedure similar to the one described in Example 7, 470 mg (1.16 mmol) of 5- (3-methy1- 4-trifluoromethoxyphenyl) -6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene (the title compound of Example 34) waε converted to crude εulfonamide. Purification by εilica gel chromatography (MPLC) gave 70 mg (14%) of 4- [6- (3-methyl-4- trifluoromethoxyphenyl) spiro [2.4]hept-5-en-5- yl]benzeneεulfonamide as a white solid: mp 136-137 °C. MS (FAB) : m/z 430 (M+Li). H NMR (CDCl 3 ) δ 0.68 (s, 4H) , 2.22 (s, 3H) , 2.91 (s, 4H) , 4.71 (s, 2H) , 6.92-6.97 ( , 1H) , 7.02-7.07 (m, 2H) , 7.29 (d, J = 8 Hz, 2H) , 7.75 (d, J. = 8 Hz, 2H) . Anal. Calc'd for C 21 H 20 F 3 NO 3 S: C, 59.57; H, 4.76; N, 3.31. Found: C, 59.75; H, 4.88; N, 3.17. Example 38 4- [6-(3-Chloro-4- trif luoromethoxyphenyl ) spiro [2.4] hept -5 -en- 5- yl ] benzenesulfonamide Following a procedure similar to the one described in Example 7, 0.50 g (1.13 mmol) of 5-(3-chloro- 4-trif luoromethoxyphenyl) -6- [4- (methylεul fonyl) phenyl] εpiro [2.4]hept-5-ene (the title compound of Example 35) waε converted to crude εulf onamide. Purification by εilica gel chromatography gave 0.39 g (78%) of 4-[6- (3-chloro-4- trifluoromethoxyphenyl)εpiro[2.4]hept-5-en-5- yl]benzeneεulfonamide aε a white εolid: mp 125.0-128.0 °C; λ NMR (CDCI 3 ) δ 0.62 (s, 4H) , 2.84 (s, 4H) , 4.71 (br s, 2H) , 6.94 (dd, £ = 2.1, 8.4 Hz, 1H) , 7.08 (dd, J = 1.2, 8.7 Hz, 1H) , 7.14-7.26 (m, 3H) , 7.72 (d, J = 8.7 Hz, 2H) . HRMS (El) Calc'd for C 20 H 17 CIF 3 NO 3 S: 443.0570. Found: 443.0603. BIOLOGICAL EVALUATION Rat Carrageenan Foot Pad Edema Test The carrageenan foot edema test was performed with materials, reagents and procedures essentially as described by Winter, et al., (Proc. Soc. Exp. Biol. Med. , 111, 544 (1962)) . Male Sprague-Dawley rats were selected in each group so that the average body weight was as close as poεsible. Ratε were faεted with free access to water for over sixteen hours prior to the test. The rats were dosed orally (1 mL) with compounds suεpended in vehicle containing 0.5% methylcellulose and .025% surfactant, or with vehicle alone. One hour later a subplantar injection of 0.1 mL of 1% εolution of carrageenan/sterile 0.9% saline was administered and the volume of the injected foot was measured with a displacement plethysmometer connected to a presεure tranεducer with a digital indicator. Three hours after the injection of the carrageenan, the volume of the foot was again measured. The average foot swelling in a group of drug-treated animalε waε compared with that of a group of placebo-treated animalε and the percentage inhibition of edema waε determined (Otterneεs and Bliven, Laboratory Models for Teεtinσ NSAIDs, in Non-steroidal Anti- Inflammatory Druσε, (J. Lombardino, ed. 1985) ) . Results are shown in Table I. Rat Carrageenan-induced Analgeεia Test The rat carrageenan analgeεia teεt waε performed with materials, reagents and procedures essentially as deεcribed by Hargreaveε, et al., (Pain, 32, 77 (1988)). Male Sprague-Dawley ratε were treated as previously described for the Carrageenan Foot Pad Edema test. Three hours after the injection of the carrageenan, the rats were placed in a special plexiglass container with a transparent floor having a high intensity lamp as a radiant heat source, positionable under the floor. After an initial twenty minute period, thermal stimulation was begun on either the injected foot or on the contralateral uninjected foot. A photoelectric cell turned off the lamp and timer when light was interrupted by paw withdrawal. The time until the rat withdraws its foot was then measured. The withdrawal latency in seconds was determined for the control and drug-treated groups, and percent inhibition of the hyperalgesic foot withdrawal determined. Results are shown in Table I. TABLE I, RAT PAW EDEMA ANALGESIA % Inhibition % Inhibition @ IQmσ/kσ body weiσht @ lO σ/kσ body weiσht Examples 1 32 15 2 57 34 3 24 4 17 6 21 7 7 20 18 8 15 8 9 15 17 14 18 16 6 19 11 9 20 24 28 22 21 10 25 34 22 27 15 29 24 29 Evaluation of COX-1 and COX-2 activity in vitro a. Preparation of recombinant COX baculoviruseε Recombinant COX-1 and COX-2 were prepared as described by Gierse et al, ΓJ. Biochem. , 305, 479-84 (1995)] . A 2.0 kb fragment containing the coding region of either human or murine COX-1 or human or murine COX-2 was cloned into a BamHl site of the baculovirus transfer vector pVLl393 to generate the baculovirus transfer vector. Recombinant baculoviruseε were iεolated by tranεfecting 4 μg of baculoviruε transfer vector DNA into SF9 cells (2xl0 8 ) along with 200 ng of linearized bacium phosphate method. Recombinant viruses were purified by three rounds of plaque purification and high titer (10 7 - 10 8 pfu/ml) stocks of virus were prepared. For large scale production, SF9 insect cells were infected in 10 liter fermentors (0.5 x 10 6 /ml) with the recombinant baculovirus stock such that the multiplicity of infection was 0.1. After 72 hours the cells were centrifuged and the cell pellet homogenized in Triε/Sucroεe (50 mM: 25%, pH 8.0) containing 1% CHAPS. The homogenate was centrifuged at 10,000xG for 30 minutes, and the reεultant supernatant was stored at -80°C before being asεayed for COX activity. b. Aεεay for COX I and COX II activity: COX activity was assayed as PGE 2 formed/μg protein/time using an ELISA to detect the prostaglandin released. CHAPS-solubilized inεect cell membraneε containing the appropriate COX enzyme were incubated in a potaεεium phoεphate buffer (50 mM, pH 8.0) containing epinephrine, phenol, and heme with the addition of arachidonic acid (10 μM) . Compoundε were pre-incubated with the enzyme for 10-20 minuteε prior to the addition of arachidonic acid. Any reaction between the arachidonic acid and the enzyme waε stopped after ten minutes at 37°C/room temperature by transferring 40 μl of reaction mix into 160 μl ELISA buffer and 25 μM indomethacin. The PGE 2 formed was measured by standard ELISA technology (Cayman Chemical) . Resultε are εhown in Table II. Alεo embraced within this invention is a class of pharmaceutical compositionε compriεing one or more compoundε of Formula I in aεsociation with one or more non-toxic, pharmaceutically-acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as "carrier" materials) and, if desired, other active ingredients. The compoundε of the present invention may be administered by any εuitable route, preferably in the form of a pharmaceutical compoεition adapted to εuch a route, and in a doεe effective for the treatment intended. The compounds and composition may, for example, be administered intravascularly, intraperitoneally, εubcutaneouεly, intramuεcularly or topically. For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, capsule, suspension or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. Examples of such dosage units are tablets or capsules. The active ingredient may also be administered by injection as a composition wherein, for example, saline, dextrose or water may be used as a suitable carrier. The amount of therapeutically active compound that is administered and the doεage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factors, including the age, weight, sex and medical condition of the subject, the severity of the disease, the route and frequency of administration, and the particular compound employed, and thuε may vary widely. The pharmaceutical compoεitionε may contain active ingredient in the range of about 0.1 to 2000 mg, preferably in the range of about 0.5 to 500 mg and moεt preferably between about 1 and 100 mg. A daily doεe of about 0.01 to 100 mg/kg body weight, preferably between about 0.1 and about 50 mg/kg body weight and most preferably between about 1 to 20 mg/kg body weight, may be appropriate. The daily dose can be administered in one to four doses per day. For therapeutic purposeε, the compoundε of this invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds may be admixed with lactose, sucroεe, εtarch powder, celluloεe eεterε of alkanoic acidε, celluloεe alkyl eεters, talc, stearic acid, magneεium εtearate, magneεium oxide, εodium and calcium εalts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration. Such capsuleε or tabletε may contain a controlled-release formulation aε may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic εterile injection εolutionε or εuspensionε. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulationε for oral adminiεtration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, εeεame oil, benzyl alcohol, εodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art. Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations.

Claims: What is claimed is: 1. A compound of Formula I wherein A is selected from wherein each of R! through R^O, if present, is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, alkylamino, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl; and wherein n is a number selected from 0, 1, 2 and 3; or a pharmaceutically-acceptable salt thereof. 2. Compound of Claim 1 wherein, if present, each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; and wherein R 3 is selected from lower alkylsulfonyl, lower haloalkylsulfonyl and aminosulfonyl, and R 8 , if present, is εelected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; or wherein further R 8 and R 9 , if present, together form methylenedioxy; or wherein further, R 3 is εelected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto, and R 8 iε selected from lower alkylsulfonyl, lower haloalkylsulfonyl and aminosulfonyl; or wherein further R 3 and R 4 , if present, together form methylenedioxy; or a pharmaceutically- acceptable salt thereof. 3. Compound of Claim 2 wherein, if present, each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is selected from methylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl and aminosulfonyl, and R 8 , if present, is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n- propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, methylamino, N,N-dimethylamino, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl. dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; or wherein further R 8 and R 9 , if present, together form methylenedioxy; or wherein further R 3 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, methylamino, N,N-dimethylamino, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl, and R 8 is selected from methylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl and aminosulfonyl; or wherein further R 3 and R 4 , if present, together form methylenedioxy; or a pharmaceutically- acceptable salt thereof. 4. A compound of Formula II wherein each of R 1 through R 10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, alkylamino, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl; and wherein n is a number selected from 0, 1, 2 and 3; or a pharmaceutically-acceptable salt thereof. 5. Compound of Claim 4 wherein n is a number selected from 0, 1 and 2; wherein each of R 1 , R 2 and R 4 through R 10 is independently εelected from hydrido, halo, lower alkyl, lower alkylthio, lower alkylamino, cyano, lower haloalkyl, lower haloalkoxy, lower alkoxy, hydroxyl, mercapto, lower hydroxyalkyl and lower alkoxyalkyl; and wherein R 3 iε selected from lower alkylsulfonyl, lower haloalkylsulfonyl and aminosulfonyl; or wherein R 8 and R 9 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. 6. Compound of Claim 5 wherein each of R 1 , R 2 and R 4 through R 10 is independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n- propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, methylamino, N,N-dimethylamino, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is selected from methylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl and aminoεulfonyl; or wherein R 8 and R 9 together form methylenedioxy; or a pharmaceutically-acceptable εalt thereof. 7. Compound of Claim 6 selected from compounds, and their pharmaceutically-acceptable salts, of the group consisting of 5- [6- [4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-en-5-yl] - 1,3-benzodioxole; 2, 6-dichloro-4- [6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-en-5- yl]phenol; 5- (4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-bromo-4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] εpiro [2.4]hept-5-ene; 4- [6- (3-bromo-4-methoxyphenyl) εpiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (3 ,5-dichloro-4-methoxy-phenyl) -6-[4- (methylsulfonyl)phenyl]spiro[2.4]hept-5-ene; 4- [6- (4-trifluoromethoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 5- (2,4-difluorophenyl) -6- [4- (methylεulfonyl)phenyl]εpiro[2.4]hept-5-ene; 5- (2, 4-dichlorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene; 5- (3-chloro-4-methyIphenyl) -6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3 , 4-dimethylphenyl) -6- [4- ( methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3-methyl-4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-chloro-4-trifluoromethoxyphenyl) -6-[4- (methylεulfonyl)phenyl]spiro[2.4]hept-5-ene; 4- [6- (3,5-dichloro-4-methoxyphenyl) εpiro[2.4]hept-5-en-5- yl]benzeneεulfonamide; 4- [6- (3-methyl-4-trifluoromethoxyphenyl)spiro[2.4]hept-5- en-5-yl]benzeneεulfonamide; 4- [6- (3-chloro-4-trifluoromethoxyphenyl) spiro[2.4]hept-5- en-5-yl] enzenesulfonamide; 5-phenyl-6- [4- (methylsulfonyl)phenyl] piro[2.4]hept-5- ene; 5- (4-fluorophenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-chlorophenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-methyIphenyl) -6- [4- (methylsulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (4-methoxyphenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-methylthiophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-cyanophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (4-trifluoromethylphenyl) -6- [4- (methylsulfonyl) phenyl]spiro[2.4]hep -5-ene; 4- (6-phenylεpiro[2.4]hept-5-en-5-yl) benzenes lfonamide; 4- [6- (4-fluorophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-chlorophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-methyIphenyl) spiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4- [6- (4-methoxyphenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-methylthiophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4-[6- (4-cyanophenyl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (4-trifluoromethylphenyl)spiro[2.4]hept-5-en-5- yl)benzenesulfonamide; 6-phenyl-7- [4- (methylεulfonyl)phenyl]εpiro[3.4]oct-6- ene; 6- (4-fluorophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-chlorophenyl) -7- [4- (methylsulfonyl)phenyl] εpiro[3.4]oct-6-ene; 6- (4-methyIphenyl) -7- [4- (methylεulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-methoxyphenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-methylthiophenyl) -7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct-6-ene; 6- (4-cyanophenyl) -7- [4- (methylsulfonyl)phenyl] εpiro[3.4]oct-6-ene; 6- (4-trifluoromethylphenyl) -7- [4- (methylsulfonyl) phenyl] spiro[3.4]oc -6-ene; 4- (7-phenylspiro [3.4]oct-6-en-6-yl)benzeneεulfonamide; 4- [7- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4-[7- (4-chlorophenyl) spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4-[7- (4-methyIphenyl)spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4- [7- (4-methoxyphenyl) spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4- [7- (4-methylthiophenyl) εpiro[3.4] oct-6-en-6-yl] benzeneεulfonamide; 4- [7- (4-cyanophenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (4-trifluoromethylphenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 2-phenyl-3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2- ene; 2- (4-fluorophenyl) -3-[4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-chlorophenyl) -3-[4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-methyIphenyl) -3- [4- (methylsulfonyl)phenyl] εpiro[4.4]non-2-ene; 2- (4-methoxyphenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-methylthiophenyl) -3- [4- (methylsulfonyl) phenyl] spiro[4.4]non-2-ene; 2- (4-cyanophenyl) -3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-ene; 2- (4-trifluoromethyIphenyl) -3- [4- (methylsulfonyl) phenyl] spiro[4.4]non-2-ene; 4- (3-phenyIspiro[4.4]non-2-en-2-yl)benzenesulfonamide; 4-[3- (4-fluorophenyl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (4-chlorophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (4-methyIphenyl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (4-methoxyphenyl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (4-methylthiophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (4-cyanophenyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (4-trifluoromethylphenyl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 5- (3-methyl-4-fluorophenyl) - 6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-fluorophenyl) - 6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-chlorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-chlorophenyl) - 6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-methyl-4-methoxyphenyl) - 6- [4- (methylsulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3-trifluoromethyl-4-methoxyphenyl) - 6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- (3-fluoro-4-methoxyphenyl) - 6-[4- (methylsulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3-chloro-4-methoxyphenyl) - 6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (4-methoxy-2,3,5, 6-tetrafluorophenyl) - 6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-ene; 5- (3 ,4-dimethoxyphenyl) - 6- [4- (methylεulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- 3-chloro-4-fluorophenyl) - 6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 5- 4-chloro-3-fluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 3 ,4-difluorophenyl) - 6- [4- (methylsulfonyl)phenyl] spiro[2.4]hep -5-ene; 3 , 4-dichlorophenyl) - 6-[4- (methylsulfonyl)phenyl] εpiro[2.4]hept-5-ene; 6- (3-trifluoromethy1-4-fluorophenyl) εpiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 4- 6- (3-trifluoromethyl-4-chlorophenyl)spiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 4- 6- (3-methyl-4-fluorophenyl) εpiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 6- (3-methyl-4-chlorophenyl) spiro [2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- 6- (4-methoxy-2,3 , 5, 6-tetrafluorophenyl)spiro[2.4]hept- 5-en-5-y1]benzenesulfonamide; 4- 6- (3-fluoro-4-methoxyphenyl) εpiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 4- 6- (3-trifluoromethyl-4-methoxyphenyl) εpiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 4- 6- (3-methyl-4-methoxyphenyl)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 6- (3-chloro-4-methoxyphenyl) spiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 4- 6- (4-methoxy-2,3 ,5, 6-tetrafluorophenyl) εpiro [2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- 6- (3,4-dimethoxypheny1)spiro[2.4]hept- 5-en-5-yl]benzenesulfonamide; 4- 6- (3-chloro-4-fluorophenyl) spiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; 6- (4-chloro-3-fluorophenyl) εpiro [2.4]hept- 5-en-5-yl]benzeneεulfonamide; 4- 6- (3,4-difluorophenyl) εpiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide; and 4- 6- (3 , 4-dichlorophenyl) spiro[2.4]hept- 5-en-5-yl]benzeneεulfonamide. 8. Compound of Claim 7 which iε 5- (3,5- dichloro-4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-ene, or a pharmaceutically-acceptable salt thereof. 9. Compound of Claim 7 which is 4- [6- (3- chloro-4-methoxyphenyl) spiro[2.4]hept-5-en-5- yl]benzeneεulfonamide, or a pharmaceutically-acceptable salt thereof. 10. A compound of Formula III wherein n is a number selected from 0, 1 and 2; wherein R 6 is εelected from hydrido and halo; wherein R 7 iε εelected from hydrido and halo; wherein R 8 iε selected from hydrido, halo, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, and hydroxyl; wherein R 9 is selected from hydrido, halo, and lower alkyl; or wherein R 8 and R 9 together form methylenedioxy; and wherein R 11 is εelected from lower alkyl and amino; or a pharmaceutically-acceptable salt thereof. 11. The compound of Claim 10 wherein R 6 is εelected from hydrido, fluoro, chloro, bromo, and iodo; wherein R 7 iε selected from hydrido, fluoro, chloro, bromo, and iodo; wherein R 8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, and trifluoromethoxy; wherein R 9 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, and isobutyl; or where R 8 and R 9 together form methylenedioxy; and wherein R 11 iε methyl or amino; and or a pharmaceutically-acceptable εalt thereof. 12. Compound of Claim 11 εelected from compoundε, and their pharmaceutically-acceptable εaltε, of the group conεiεting of 5- (3-chloro-4-methoxyphenyl)-6-[4- (methylεulfonyl)phenyl]εpiro[2,4]hept-5-ene; 4-[6- (3-chloro-4-methoxyphenyl)spiro[2,4]hept-5-en-5- yl]benzenesulfonamide; 5- (3-fluoro-4-methoxyphenyl)-6-[4- (methylεulfonyl)phenyl]εpiro[2,4]hept-5-ene; 4-[6-(3-fluoro-4-methoxyphenyl)εpiro[2,4]hept-5-en-5- yl]benzeneεulfonamide; 5- (3,4-difluorophenyl)-6-[4- (methylεulfonyl)phenyl]spiro[2,4]hept-5-ene; 5-[6-[4- (methylsulfonyl)phenyl]spiro[2,4]hept-5-en-5- yl] -1,3-benzodioxole; 4-[6-(3,4-difluorophenyl)εpiro[2,4]hept-5-en-5- yl]benzenesulfonamide; 2 , 6-dichloro-4- [ 6- [ 4- (methylεulfonyl)phenyl] εpiro[2, 4]hept-5-en-5- yl]phenol 5- (4-trifluoromethoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2, 4]hept-5-ene; 5- (4-methoxyphenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2, 4]hept-5-ene; 5- (3-bromo-4-methoxyphenyl) -6- [4- (methylεulfonyl)phenyl] εpiro [2, 4]hept-5-ene; 4- [6- (4-methoxyphenyl) spiro[2,4]hept-5-en-5- yl]benzeneεulfonamide; 4- [6- (3-bromo-4-methoxyphenyl) εpiro[2,4]hept-5-en-5- yl]benzeneεulfonamide; 5- (4-trifluoromethylphenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2, 4]hept-5-ene; 5- (3 , 5-dichloro-4-methoxy-phenyl) -6- [4- (methylεulfonyl)phenyl]εpiro[2,4]hept-5-ene; 4- [6- (4-trifluoromethoxyphenyl) εpiro[2,4]hept-5-en-5- yl]benzeneεulfonamide; 5- (3-chloro-4-fluorophenyl) -6- [4- (methylεulfonyl)phenyl] εpiro [2, 4]hept-5-ene; 5- (2, 4-difluorophenyl) -6- [4- (methylεulfonyl)phenyl] εpiro[2,4]hept-5-ene; 5- (2, 4-dichlorophenyl) -6- [4- (methylsulfonyl)phenyl]spiro [2, 4]hept-5-ene; 4- [6- (4-trifluoromethyIphenyl) spiro [2, 4]hept-5-en-5- yl]benzeneεulfonamide; 4- [6- (3-chloro-4-fluorophenyl) spiro [2,4]hept-5-en-5- yl]benzeneεulfonamide; 5- (3 ,4-dichlorophenyl) -6-[4- (methylεulfonyl)phenyl] εpiro [2, 4]hept-5-ene; 5- (4-chlorophenyl) -6- [4- (methylεulfonyl)phenyl] εpiro[2,4]hept-5-ene; 4- [6- (3,4-dichlorophenyl) spiro[2,4]hept-5-en-5- yl]benzenesulfonamide; 4- [6- (4-chlorophenyl) spiro[2, 4]hept-5-en-5- yl]benzeneεulfonamide; 5- (3-chloro-4-methyIphenyl) -6- [4- (methylεulfonyl)phenyl] spiro [2, 4]hept-5-ene; 5- (3 , -dimethylphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2, 4] ept-5-ene; 5- (4-methyIphenyl) -6- [4- (methylsulfonyl)phenyl] spiro [2, 4]hept-5-ene; 5- (3-methyl-4-trifluoromethoxyphenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2, 4]hept-5-ene; 5- (3-chloro-4-trifluoromethoxyphenyl) -6- [4- (methylεulfonyl)phenyl] spiro[2, 4]hept-5-ene; 4- [6- (3, 5-dichloro-4-methoxyphenyl) spiro[2, 4]hept-5- en-5-yl]benzenesulfonamide; 4- [6- (3-methyl-4- trifluoromethoxyphenyl) spiro[2, 4]hept-5-en-5- yl]benzenesulfonamide; 4-[6-(3-chloro-4- trifluoromethoxyphenyl) spiro [2, 4]hept-5-en-5- yl]benzeneεulfonamide; 5- (4-fluorophenyl) -6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-ene; 4- [6- (4-fluorophenyl) spiro[2.4]hept-5-en-5- yl]benzenesulfonamide; 6- (4-fluorophenyl) -7- [4- (methylsulfonyl)phenyl] εpiro[3.4]oct-5-ene; 4- [7- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; and 2- (4-fluorophenyl) -3- [4- (methylsulfonyl)phenyl] εpiro[4.4]non-5-ene. 13. A compound of Formula IV wherein n is a number εelected from 0, 1, 2 and 3; and wherein each of R 1 through R 5 and R 7 through R 10 iε independently εelected from hydrido, halo, alkyl, alkoxy, alkylthio, alkylamino, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylεulfonyl, haloalkylεulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof. 14. Compound of Claim 13 wherein n iε a number εelected from 0, 1 and 2; wherein each of R 1 , R 2 , R 4 , R 5 , R 7 , R 9 and R 10 iε independently εelected from hydrido, halo, lower alkyl, lower alkoxy, lower allylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; and wherein R 3 iε εelected from lower alkylsulfonyl and aminosulfonyl and R 8 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower haloalkoxy, lower hydroxyalkyl, mercapto, hydroxyl, lower alkoxyalkyl, cyano and lower haloalkyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower haloalkoxy, lower hydroxyalkyl, hydroxyl, mercapto, lower alkoxyalkyl, cyano and lower haloalkyl, and R 8 is εelected from lower alkylεulfonyl and aminosulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. 15. Compound of Claim 14 wherein each of R 1 , R 2 , R 4 , R 5 , R 7 , R 9 and R 10 is hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, iεopropyl, butyl, tert-butyl, iεobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methylamino, N,N-dimethylamino, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 iε methylsulfonyl or aminosulfonyl, and R 8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, and R 8 is methylsulfonyl or aminosulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. 16. Compound of Claim 15 selected from compounds, and their pharmaceutically-acceptable saltε, of the group consiεting of 2- [6- [4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-en-5- yl] yridine; 5-fluoro-2- [6- [4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5-y1] yridine; 5-chloro-2- [6- [4- (methylsulfonyl)phenyl]spiro [2.4]hept-5-en-5-yl]pyridine; 5-methyl-2- [6-[4- (methylsulfonyl)phenyl] spiro [2.4]hept-5-en-5-yl]pyridine; 4- [6- (pyridin-2-yl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (5-fluoropyridin-2-yl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (5-chloropyridin-2-yl)spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (5-methylpyridin-2-yl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 2- [7- [4- (methylsulfonyl)phenyl] spiro[3.4] oct-6-en-6- yl]pyridine; 5-fluoro-2- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct- 6-en-6-y1]pyridine; 5-chloro-2- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct- 6-en-6-yl]pyridine; 5-methyl-2- [7- [4- (methylsulfonyl)phenyl] spiro[3.4]oct- 6-en-6-y1]pyridine; 4- [7- (pyridin-2-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (5-fluoropyridin-2-yl) spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4- [7- (5-chloropyridin-2-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (5-methylpyridin-2-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2- yl]pyridine; 5-fluoro-2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non- 2-en-2-yl]pyridine; 5-chloro-2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non- 2-en-2-yl]pyridine; 5-methyl-2- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non- 2-en-2-yl]pyridine; 4- [3- (pyridin-2-yl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 4- [3- (5-fluoropyridin-2-yl) εpiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (5-chloropyridin-2-yl)εpiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (5-methylpyridin-2-yl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 2- (6-phenylspiro[2.4]hept-5-en-yl) -5- (methylsulfonyl) pyridine; 2- [6- (4-fluorophenyl) εpiro[2.4]hept-5-en-yl] -5- (methylεulfonyl)pyridine; 2- [6- (4-chlorophenyl) εpiro[2.4]hept-5-en-yl] -5- (methylεulfonyl)pyridine; 2- [6- (4-methyIphenyl)εpiro[2.4]hept-5-en-yl] -5- (methylsulfonyl)pyridine; 2- (6-phenylspiro[2.4]hept-5-en-5-yl) -5- pyridineεulfonamide; 2- [6- (4-fluorophenyl) εpiro[2.4]hept-5-en-5-yl) -5- pyridineεulfonamide; 2- [6- (4-chlorophenyl) piro[2.4]hept-5-en-5-yl) -5- pyridinesulfonamide; 2- [6- (4-methyIphenyl) spiro[2.4]hept-5-en-5-y1) -5- pyridinesulfonamide; 2- (7-phenyIspiro [3.4]oct-6-en-6-yl] -5- (methylsulfonyl) pyridine; 2- [7- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-chlorophenyl) spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- [7- (4-methylphenyl)spiro[3.4]oct-6-en-6-yl] -5- (methylsulfonyl)pyridine; 2- (7-phenylεpiro[3.4]oct-6-en-6-yl) -5- pyridineεulfonamide; 2- [7- (4-fluorophenyl)εpiro[3.4]oct-6-en-6-yl] -5- pyridinesulfonamide; 2- [7- (4-chlorophenyl) εpiro[3.4]oct-6-en-6-yl] -5- pyridineεulfonamide; 2- [7- (4-me hyIphenyl) spiro[3. ]oct-6-en-6-yl] -5- pyridinesulfonamide; 2- (3-phenyIspiro [4.4]non-2-en-2-yl) -5- (methylsulfonyl) pyridine; 2- [3- (4-fluorophenyl)spiro[4.4]non-2-en-2-yl] -5- (methylsulfonyl)pyridine; 2- [3- (4-chlorophenyl) spiro[4.4]non-2-en-2-yl] -5- (methylsulfonyl)pyridine; 2- [3- (4-methyIphenyl) spiro[4.4]non-2-en-2-yl] -5- (methylsulfonyl)pyridine; 2- (3-phenylspiro[4.4]non-2-en-2-yl) -5- pyridinesulfonamide; 2- [3- (4-fluorophenyl) spiro[4.4]non-2-en-2-yl] -5- pyridineεulfonamide; 2- [3- (4-chlorophenyl)spiro[4.4]non-2-en-2-yl] -5- pyridineεulfonamide; and 2- [3- (4-methyIphenyl) spiro[4.4]non-2-en-2-yl] -5- pyridinesulfonamide. 17. A compound of Formula V wherein n iε a number εelected from 0, 1, 2 and 3; and wherein each of R 1 through R 6 and R 8 through R 10 iε independently εelected from hydrido, halo, alkyl, alkoxy, alkylthio, alkylamino, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylεulfonyl and aminoεulfonyl; or a pharmaceutically-acceptable salt thereof. 18. Compound of Claim 17 wherein n is a number selected from 0, 1 and 2; wherein each of R 1 , R 2 , R 4 , R 5 , R 6 , R 9 and R 10 is independently selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, cyano, lower haloalkyl, lower haloalkoxy, lower hydroxyalkyl, lower alkoxyalkyl, hydroxyl and mercapto; and wherein R 3 is selected from lower alkylεulfonyl and aminosulfonyl and R 8 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower haloalkoxy, lower hydroxyalkyl, mercapto, hydroxyl, lower alkoxyalkyl, cyano and lower haloalkyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 iε selected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower haloalkoxy, lower hydroxyalkyl, hydroxyl, lower alkoxyalkyl, cyano and lower haloalkyl, and R 8 is εelected from lower alkylεulfonyl and aminoεulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable salt thereof. 19. Compound of Claim 18 wherein each of R 1 , R 2 , R 4 , R 5 , R β , R 9 and R 10 is hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, iεopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is methylsulfonyl or aminosulfonyl, and R 8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, hydroxyl, methylthio, ethylthio, methylamino, N,N-dimethylamino, cyano, mercapto, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl; or wherein further R 8 and R 9 together form methylenedioxy; or wherein further, R 3 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, hydroxyl, methylthio, ethylthio, cyano, mercapto, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, and R 8 is methylsulfonyl or aminosulfonyl; or wherein further R 3 and R 4 together form methylenedioxy; or a pharmaceutically-acceptable εalt thereof. 20. Compound of Claim 19 εelected from compounds, and their pharmaceutically-acceptable saltε, of the group conεiεting of 5-[6-[4- (methylεulfonyl)phenyl] εpiro[2.4]hept-5-en-5- yl]pyridine; 2-fluoro-5- [6- [4- (methylεulfonyl)phenyl] spiro [2.4]hept-5-en-5-yl]pyridine; 2-chloro-5- [6- [4- (methylsulfonyl)phenyl]spiro [2.4]hept-5-en-5-yl]pyridine; 2-methyl-5-[6-[4- (methylsulfonyl)phenyl] spiro[2.4]hept-5-en-5-yl]pyridine; 4- [6- (pyridin-5-yl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (2-fluoropyridin-5-yl) εpiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4-[6- (2-chloropyridin-5-yl) εpiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 4- [6- (2-methylpyridin-5-yl) spiro[2.4]hept-5-en-5-yl] benzenesulfonamide; 5- [7- [4- (methylsulfonyl)phenyl] εpiro[3.4]oct-6-en-6- yl]pyridine; 2-fluoro-5-[7-[4- (methylεulfonyl)phenyl] piro[3.4]oct- 6-en-6-yl]pyridine; 2-chloro-5- [7- [4- (methylεulfonyl)phenyl]spiro[3.4]oct- 6-en-6-y1]pyridine; 2-methyl-5- [7- [4- (methylsulfonyl)phenyl]spiro[3.4]oct- 6-en-6-yl]pyridine; 4- [7- (pyridin-5-yl) spiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-fluoropyridin-5-yl) spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 4- [7- (2-chloropyridin-5-yl)εpiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [7- (2-methylpyridin-5-yl)spiro[3.4]oct-6-en-6-yl] benzeneεulfonamide; 5- [3- [4- (methylεulfonyl)phenyl] εpiro[4.4]non-2-en-2- yl]pyridine; 2-fluoro-5- [3- [4- (methylsulfonyl) henyl] spiro[4.4]non- 2-en-2-yl]pyridine; 2-chloro-5- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non- 2-en-2-yl]pyridine; 2-methyl-5- [3-[4- (methylsulfonyl)phenyl] spiro[4.4]non- 2-en-2-yl]pyridine; 4- [3- (pyridin-5-yl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4-[3- (2-fluoropyridin-5-yl)εpiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (2-chloropyridin-5-yl)spiro[4.4]non-2-en-2-yl] benzenesulfonamide; 4- [3- (2-methylpyridin-5-yl) spiro[4.4]non-2-en-2-yl] benzeneεulfonamide; 5- (6-phenylspiro[2.4]hept-5-en-5-yl) -2- (methylsulfonyl) pyridine; 5- [6- (4-fluorophenyl) spiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-chlorophenyl) εpiro[2.4]hept-5-en-5-yl] -2- (methylεulfonyl)pyridine; 5- [6- (4-methyIphenyl)εpiro[2.4]hept-5-en-5-yl] -2- (methylsulfonyl)pyridine; 5- (6-phenylspiro[2.4]hept-5-en-5-yl) -2- pyridinesulfonamide; 5- [6- (4-fluorophenyl)εpiro[2.4]hept-5-en-5-yl] -2- pyridineεulfonamide; 5- [6- (4-chlorophenyl) εpiro[2.4]hept-5-en-5-yl] -2- pyridineεulfonamide; 5- [6- (4-methyIphenyl) εpiro[2.4]hept-5-en-5-yl] -2- pyridineεulfonamide; 5- (7-phenylεpiro[3.4]oct-6-en-6-yl) -2- (methylsulfonyl) pyridine; 5- [7- (4-fluorophenyl) spiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5-[7- (4-chlorophenyl) εpiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5- [7- (4-methyIphenyl)εpiro[3.4]oct-6-en-6-yl] -2- (methylεulfonyl)pyridine; 5- (7-phenyIspiro[3.4]oct-6-en-6-yl) -2- pyridineεulfonamide; 5- [7- (4-fluorophenyl)spiro[3.4]oct-6-en-6-yl] -2- pyridineεulfonamide; 5- [7- (4-chlorophenyl)εpiro[3.4]oct-6-en-6-yl] -2- pyridineεulfonamide; 5- [7- (4-methyIphenyl)εpiro[3.4]oct-6-en-6-yl] -2- pyridineεulfonamide; 5- (3-phenylspiro[4.4]non-2-en-2-yl) -2- (methylsulfonyl) pyridine; 5- [3- (4-fluorophenyl) εpiro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5- [3- (4-chlorophenyl) spiro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5- [3- (4-methyIphenyl) spiro[4.4]non-2-en-2-yl] -2- (methylsulfonyl)pyridine; 5- (3-phenylspiro[4.4]non-2-en-2-yl) -2- pyridineεulfonamide; 5- [3- (4-fluorophenyl) spiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide; 5- [3- (4-chlorophenyl) spiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide; and 5-[3- (4-methyIphenyl) spiro[4.4]non-2-en-2-yl] -2- pyridinesulfonamide. 21. A compound of Formula VI wherein n iε a number selected from 0, 1, 2 and 3; and wherein each of R 1 through R 7 , R 9 and R 10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, hydroxyalkyl, alkoxyalkyl, hydroxyl, mercapto, alkylsulfonyl and aminosulfonyl; or a pharmaceutically- acceptable salt thereof. 22. Compound of Claim 21 wherein n is a number selected from 0, 1 and 2; wherein each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently εelected from hydrido, halo, lower alkyl, lower alkoxy, lower alkylthio, lower haloalkoxy, lower hydroxyalkyl, hydroxyl, lower alkoxyalkyl, mercapto, cyano and lower haloalkyl; and wherein R 3 is selected from lower alkylεulfonyl and aminoεulfonyl; or a pharmaceutically- acceptable εalt thereof. 23. Compound of Claim 22 wherein each of R 1 , R 2 , R 4 through R 7 , R 9 and R 10 is independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, methylthio, ethylthio, cyano, hydroxyl, mercapto, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxymethyl, methoxymethyl and ethoxymethyl; and wherein R 3 is methylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable εalt thereof. 24. Compound of Claim 23 εelected from compounds, and their pharmaceutically-acceptable saltε, of the group conεisting of 4- [6-[4- (methylsulfonyl)phenyl]εpiro[2.4]hept-5-en-5- yl]pyridine; 4- [6- (4-pyridinyl) εpiro[2.4]hept-5-en-5-yl] benzeneεulfonamide; 4- [7- [4- (methylεulfonyl)phenyl] εpiro[3.4]oct-6-en-6- yl]pyridine; 4- [7- (4-pyridinyl)εpiro[3.4]oct-6-en-6-yl] benzenesulfonamide; 4- [3- [4- (methylsulfonyl)phenyl] spiro[4.4]non-2-en-2-yl] pyridine; and 4- [3- (4-pyridinyl) spiro[4.4]non-2-en-2-yl] benzenesulfonamide. 25. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of Claim 1; or a pharmaceutically-acceptable salt thereof. 26. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of Claim 4; or a pharmaceutically-acceptable salt thereof. 27. A pharmaceutical composition compriεing a therapeutically-effective amount of a compound, εaid compound εelected from a family of compoundε of Claim 5; or a pharmaceutically-acceptable εalt thereof. 28. A pharmaceutical compoεition compriεing a therapeutically-effective amount of a compound, εaid compound εelected from a family of compoundε of Claim 6; or a pharmaceutically-acceptable εalt thereof. 29. A pharmaceutical compoεition compriεing a therapeutically-effective amount of a compound, εaid compound εelected from a family of compoundε of Claim 7; or a pharmaceutically-acceptable salt thereof. 30. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a compound of Claim 8; or a pharmaceutically-acceptable salt thereof. 31. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a compound of Claim 9; or a pharmaceutically-acceptable salt thereof. 32. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of Claim 10; or a pharmaceutically-acceptable salt thereof. 33. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of Claim 13; or a pharmaceutically-acceptable salt thereof. 34. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from a family of compounds of Claim 17; or a pharmaceutically-acceptable salt thereof. 35. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, εaid compound εelected from a family of compoundε of Claim 21; or a pharmaceutically-acceptable salt thereof. 36. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or suεceptible to εuch inflammation or inflammation- aεεociated diεorder, a therapeutically-effective amount of a compound of Claim 1; or a pharmaceutically- acceptable εalt thereof. 37. A method of treating inflammation or an inflammation-associated disorder in a subject, said method compriεing adminiεtering to the subject having or susceptible to such inflammation or inflammation- associated disorder, a therapeutically-effective amount of a compound of Claim 4; or a pharmaceutically- acceptable salt thereof. 38. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising adminiεtering to the εubject having or εuεceptible to εuch inflammation or inflammation- associated disorder, a therapeutically-effective amount of a compound of Claim 5; or a pharmaceutically- acceptable salt thereof. 39. A method of treating inflammation or an inflammation-asεociated disorder in a subject, said method comprising administering to the subject having or suεceptible to εuch inflammation or inflammation- aεεociated diεorder, a therapeutically-effective amount of a compound of Claim 6; or a pharmaceutically- acceptable εalt thereof. 40. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation- associated disorder, a therapeutically-effective amount of a compound of Claim 7; or a pharmaceutically- acceptable salt thereof. 41. A method of treating inflammation or an inflammation-associated disorder in a subject, εaid method compriεing adminiεtering to the εubject having or εuεceptible to εuch inflammation or inflammation- associated disorder, a therapeutically-effective amount of a compound of Claim 8; or a pharmaceutically- acceptable salt thereof. 42. A method of treating inflammation or an inflammation-asεociated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation- associated disorder, a therapeutically-effective amount of a compound of Claim 9; or a pharmaceutically- acceptable salt thereof. 43. A method of treating inflammation or an inflammation-asεociated diεorder in a εubject, εaid method compriεing administering to the subject having or susceptible to such inflammation or inflammation- asεociated diεorder, a therapeutically-effective amount of a compound of Claim 10; or a pharmaceutically- acceptable salt thereof. 44. A method of treating inflammation or an inflammation-asεociated disorder in a subject, εaid method comprising administering to the subject having or suεceptible to such inflammation or inflammation- associated disorder, a therapeutically-effective amount of a compound of Claim 13; or a pharmaceutically- acceptable εalt thereof. 45. A method of treating inflammation or an inflammation-aεεociated diεorder in a εubject, said method comprising administering to the subject having or εuεceptible to εuch inflammation or inflammation- aεεociated diεorder, a therapeutically-effective amount of a compound of Claim 17; or a pharmaceutically- acceptable εalt thereof. 46. A method of treating inflammation or an inflammation-aεεociated diεorder in a εubject, εaid method compriεing adminiεtering to the subject having or susceptible to such inflammation or inflammation- asεociated disorder, a therapeutically-effective amount of a compound of Claim 21; or a pharmaceutically- acceptable salt thereof. 47. The method of Claim 36 for use in treatment of inflammation. 48. The method of Claim 36 for use in treatment of an inflammation-associated disorder. 49. The method of Claim 48 wherein the inflammation-associated disorder is arthritis. 50. The method of Claim 48 wherein the inflammation-associated disorder is pain. 51. The method of Claim 48 wherein the inflammation-asεociated diεorder is fever.

Inventors: HUANG HORNG-CHI, LI JINGLIN, MANNING ROBERT E, REITZ DAVID B, HUANG, HORNG-CHI, LI, JINGLIN, MANNING, ROBERT, E., REITZ, DAVID, B.
Applicants: HUANG HORNG CHI, LI JINGLIN, MANNING ROBERT E, REITZ DAVID B, SEARLE & CO, G.D. SEARLE & CO., HUANG, HORNG-CHI, LI, JINGLIN, MANNING, ROBERT, E., REITZ, DAVID, B.
Application year: 1995
Main classification: C07C317
IPC codes: A61K31, A61P29, A61P43, C07C13, C07C25, C07C35, C07C43, C07C311, C07C317, C07C323, C07D213, C07D317