SUBSTITUTED SULFONYLPHENYLHETEROCYCLES AS CYCLOOXYGENASE-2 AND 5-LIPOXYGENASE INHIBITORS

Abstract: This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation.

Description: SUBSTITUTED SULFONYLPHENYLHETEROCYCLES AS CYCLOOXYGENASE-2 AND 5-LIPOXYGENASE INHIBITORS * ^ 5 FIELD OF THE INVENTION This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating 10 disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation and allergic conditions such as asthma. BACKGROUND OF THE INVENTION 15 Prostaglandins play a major role in the inflammation proceεs, and the inhibition of prostaglandin production, especially production of PGG 2 , PGH 2 and PGE 2 , has been a common target of 20 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 25 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, 30 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 * 35 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. In another portion of the arachidonic acid pathway, physiologically active leukotrienes, such as leukotriene B 4 (LTB 4 ) , leukotriene C 4 (LTC 4 ) and leukotriene D 4 (LTD 4 ) and other metabolites, are produced by the 5-lipoxygenase-mediated (5-LO) oxidation of arachidonic acid. These leukotrienes have been implicated in various inflammation-related disorders and allergic diseases, and thus compounds which inhibit 5-lipoxygenase are useful in the treatment of disease states in which leukotrienes play an important role. It is believed that selective dual inhibitors of both cyclooxygenase-2 and 5-lipoxygenase, which affect the two enzymes at low concentrations, will more completely and permanently affect the damage caused by the various diseases and disorders mediated by cyclooxygenase-2 and 5-lipoxygenase but without the gastrointestinal side effects associated with traditional NSAIDs. The references below that disclose antiinflammatory activity, show continuing efforts to find a safe and effective antiinflammatory agent. The novel compounds disclosed herein are such safe and also effective antiinflammatory agents furthering such efforts. The invention's compounds are found to show usefulness in vivo as antiinflammatory agents with minimal side effects. The compounds disclosed herein preferably selectively inhibit cyclooxygenase-2 over cyclooxygenase-1. Compounds which selectively inhibit cyclooxygenase-2 have been described in U.S. patents 5,380,738, 5,344,991, 5,393,790 and WO documents W094/15932, WO94/27980, WO95/00501, W094/13635, WO94/20480, and W094/26731. Compounds which inhibit 5-lipoxygenase have been described in U.S. patents 5,364,877, 5,302,603, 5,234,950, 5,098,932 and 5,354,865, among others. Compounds which inhibit cyclooxygenase and 5- lipoxygenase have been described in U.S. Patent Nos. 5,298,521, 5,242,940, 5,234,939, and 5,356,898, among others. However, these previous mixed inhibitors do not selectively inhibit cyclooxygenase-2 and therefore still cause the gastrointestinal side effects which substantially reduce their usage and effectiveness. The invention's compounds are found to show usefulness in vivo as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase with minimal side effects. DESCRIPTION OF THE INVENTION A class of compounds useful in treating cyclooxygenase-2 and 5-lipoxygenase-mediated disorders is defined by Formula I: wherein A is a 5- or 6-member ring substituent selected from partially unsaturated or unsaturated heterocyclo and carbocyclic rings, wherein A is optionally substituted with a radical selected from acyl, halo, alkyl, haloalkyl, cyano, nitro, carboxy1, alkoxy, oxo, aminocarbonyl, alkoxycarbonyl, carboxyalkyl, cyanoalkyl, and hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, alkyl, alkenyl, alkynyl, alkyloxy, alkylthio, alkylcarbonyl, cycloalkyl, aryl, haloalkyl, hydroxyalkyl, hydroxyalkyloxy, hydroxyalkyloxyalkyl, hydroxyalkylthio, hydroxyalkylthioalkyl, oximinoalkoxy, oximinoalkoxyalky1, (alkyl) oximinoalkoxy, (alkyl)oximinoalkoxyalkyl, oximinoalkylthio, oximinoalkylthioalkyl, (alkyl)oximinoalkylthio, (alkyl)oximinoalkylthioalkyl, carbonylalkyloxy, carbonylalkyloxyalky1, carbonylalkylthio, carbonylalkylthioalkyl, heterocyclo, cycloalkenyl, aralkyl, heterocycloalkyl, acyl, alkylthioalkyl, alkyloxyalkyl, alkenylthio, alkynylthio, alkenyloxy, alkynyloxy, alkenylthioalkyl, alkynylthioalkyl, alkenyloxyalky , alkynyloxyalkyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, alkylarylalkynyloxy, alkylarylalkenyloxy, alkylarylalkynylthio, alkylarylalkenylthio, haloalkylcarbonyl, alkoxyalkyl, alkylaminocarbonylalkyl, heteroaralkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, heteroaralkoxy, heteroaralkylthio, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, haloaryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, alkoxycarbonylalky1, alkoxycarbonylcyanoalkenyl, aminocarbonylalkyl, N-alkylaminocarbonyl, N- arylaminocarbonyl, N,N-dialkylaminocarbonyl, N-alkyl-N- aryla inocarbony1, cycloalkylaminocarbonyl, heterocycloaminocarbonyl, carboxyalkylaminocarbonyl, alkylcarbonylalkyl, aralkoxycarbonylalkylaminocarbony1, haloaralkyl, carboxyhaloalkyl, alkoxycarbonylhaloalkyl, aminocarbonylhaloalkyl, alkylaminocarbonylhaloalkyl, N- alkylamino, N,N-dialkylamino, N-arylamino, N- aralkylamino, N-alkyl-N-aralkylamino, N-alkyl-N- arylamino, aminoalkyl, N-alkylaminoalkyl, N,N- dialkylaminoalkyl, N-arylaminoalkyl, N- aralkylaminoalkyl, N-alkyl-N-aralkylaminoalkyl, N-alkyl- N-arylaminoalkyl, aminoalkoxy, aminoalkoxyalkyl, aminoalkylthio, aminoalkylthioalkyl, cycloalkyloxy, cycloalkylalkyloxy, cycloalkylthio, cycloalkylalkylthio, aryloxy, aralkoxy, arylthio, aralkylthio, alkylsulfinyl, alkylsulfonyl, aminoεulfonyl, N-alkylaminosulfonyl, N- arylaminosulfonyl, arylsulfonyl, N,N- dialkylaminosulfonyl, N-alkyl-N-arylaminosulfonyl, wherein Ar is selected from aryl and heteroaryl, wherein Ar is optionally substituted with one or two 10 substituents selected from halo, hydroxyl, mercapto, amino, nitro, cyano, carbamoyl, alkyl, alkenyloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, haloalkyl, alkoxycarbonyl, N- alkylcarbamoyl, N,N-dialkylcarbamoyl, alkanoylamino, 15 cyanoalkoxy, carbamoylalkoxy, alkoxycarbonylalkoxy and . wherein R! is one or more substituents selected from heterocyclo, cycloalkyl, cycloalkenyl and aryl, wherein R- is optionally substituted at a substitutable 20 position with one or more radicals selected from alkyl, haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, halo, alkoxy and alkylthio; 25 wherein R 2 is selected from alkyl and amino; wherein R 3 and R 4 together form a group of the * formula -B-X-B 1 which together with the carbon atom to which B and B 1 are attached, defines a ring having 6 ring atoms, wherein B and B 1 , which may be the same or 30 different, each is alkylene and X is oxy, and which ring may bear one, two or three substituents, which may be the same or different, selected from hydroxyl, alkyl, alkoxy, alkenyloxy and alkynyloxy; wherein R 5 is selected from hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, a inocarbonyl, alkylaminocarbonyl, alkoxycarbonyl, acyl, and cyano; wherein R 6 is selected from hydrido, alkyl, aryl and aralkyl; wherein R 7 is selected from alkyl, alkoxy, alkenyl and alkynyl; wherein R 8 is oximino optionally substituted with alkyl; and wherein n is 0 or 1; R 5 provided Ar is substituted with R when A is oxazolyl; 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 the invention 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 the invention would be useful in the treatment of asthma, bronchitis, menstrual cramps, tendinitis, bursitis, skin-related conditions such as psoriasis, eczema, burns and dermatitis, and from post¬ operative inflammation including from ophthalmic surgery such as cataract surgery and refractive surgery. Compounds of the invention 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 or treatment of cancer, such as colorectal cancer. Compounds of the invention 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, neuromuscular junction disease including myasthenia gravis, white matter disease including multiple sclerosis, sarcoidosis, nephrotic syndrome, Behcet's syndrome, polymyositis, gingivitis, nephritis, hypersensitivity, swelling occurring after injury, myocardial ischemia, and the like. The compounds would also be useful in the treatment of ophthalmic diseases, such as retinitis, retinopathies, uveitis, ocular photophobia, and of acute injury to the eye tissue. The compounds would also be useful in the treatment of pulmonary inflammation, such as that associated with viral infections and cystic fibrosis. The compounds would also be useful for the treatment of certain central nervous system disorders such as cortical dementias including Alzheimer's disease. The compounds of the invention are useful as anti-inflammatory agents, such as for the treatment of arthritis, with the additional benefit of having significantly less harmful side effects. These compounds would also be useful in the treatment of allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, atherosclerosis and central nervous system damage resulting from stroke, ischemia and trauma. The compounds would also be useful in the treatment of pain, but not limited to postoperative pain, dental pain, muscular pain, and pain resulting from cancer. Besides being useful for human treatment, these compounds are also useful for treatment of mammals, including horses, dogs, cats, rats, mice, sheep, pigs, etc. The present compounds may also be used in co- therapies, partially or completely, in place of other conventional antiinfla matories, such as together with steroids, NSAIDs, LTB 4 antagonists and LTA 4 hydrolase inhibitors. Suitable LTB 4 inhibitors include, among others, ebselen, Bayer Bay-x-1005, Ciba Geigy compound CGS- 25019C, Leo Denmark compound ETH-615, Lilly compound LY- 293111, Ono compound ONO-4057, Terumo compound TMK-688, Lilly compounds LY-213024, 264086 and 292728, Ono compound 0N0-LB457, Searle compound SC-53228, calcitrol, Lilly compounds LY-210073, LY223982, LY233469, and LY255283, ONO compound ONO-LB-448, Searle compounds SC- 41930, SC-50605 and SC-51146, and SK&F compound SKF- 104493. Preferably, the LTB 4 inhibitors are selected from ebselen, Bayer Bay-x-1005, Ciba Geigy compound CGS- 25019C, Leo Denmark compound ETH-615, Lilly compound LY- 293111, Ono compound ONO-4057, and Terumo compound TMK- 688. Suitable 5-LO inhibitors include, among others, masoprocol, tenidap, zileuton, pranlukast, tepoxalin, rilopirox, flezelastine hydrochloride, enazadrem phosphatej and bunaprolast. The present invention preferably includes compounds which selectively inhibit cyclooxygenase-2 over cyclooxygenase-1 as well as inhibit the 5- lipoxygenase enzyme. Preferably, the compounds have a cyclooxygenase-2 IC 50 of less than about 0.5 μM, and also have a selectivity ratio of cyclooxygenase-2 inhibition over cyclooxygenase-1 inhibition of at least 50, and more preferably of at least 100, and inhibit 5- lipoxygenase at less than about 10 μM. Even more preferably, the compounds have a cyclooxygenase-1 IC 50 of greater than about 1 μM, and more preferably of greater than 20 μM and have a 5-lipoxygenase IC 50 of less than about 1 μM. Such preferred selectivity may indicate an ability to reduce the incidence of common NSAID-induced side effects. A preferred class of compounds consists of those compounds of Formula I wherein A is a radical selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, halo, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkyloxy, lower hydroxyalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl)oximinoalkoxyalkyl, lower carbonylalkyloxy, lower carbonylalkyloxyalkyl, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkylthio, lower oximinoalkylthioalkyl, lower (alkyl) oximinoalkylthio, lower (alkyl) oximinoalkylthioalkyl, lower carbonylalkylthio, lower carbonylalkylthioalky1, lower alkylthio, lower alkylcarbonyl, lower cycloalkyl, phenyl, lower haloalkyl, 5- or 6-membered heterocyclo, lower cycloalkenyl, lower aralkyl, lower heterocycloalkyl, acyl, lower alkylthioalkyl, lower alkyloxyalkyl, lower alkenylthio, lower alkynylthio, lower alkenyloxy, lower alkynyloxy, lower alkenylthioalkyl, lower alkynylthioalkyl, lower alkenyloxyalkyl, lower alkynyloxyalkyl, phenylcarbonyl, lower aralkylcarbonyl, lower aralkenyl, lower alkylarylalkynyloxy, lower alkylarylalkenyloxy, lower alkylarylalkyny thio, lower alkylarylalkenylthio, lower haloalkylcarbonyl, lower alkylaminocarbonylalky1, lower heteroaralkoxyalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaralkylthioalkyl, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower aralkylthioalkyl, lower aralkoxyalkyl, lower alkoxyaralkoxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonylcyanoalkenyl, lower aminocarbonylalkyl, lower N-alkylaminocarbonyl, N-phenylaminocarbonyl, lower N,N-dialkylaminocarbonyl, lower N-alkyl-N- arylaminocarbonyl, lower cycloalkylaminocarbonyl, lower heterocycloaminocarbonyl, lower carboxyalkylaminocarbonyl, lower alkylcarbonylalkyl, lower aralkoxycarbonylalkylaminocarbonyl, lower haloaralkyl, lower carboxyhaloalkyl, lower alkoxycarbonylhaloalkyl, lower aminocarbonylhaloalkyl, lower alkylaminocarbonylhaloalkyl, lower N-alkylamino, lower N,N-dialkylamino, N-phenylamino, lower N- aralkylamino, lower N-alkyl-N-aralkylamino, lower N- alkyl-N-arylamino, lower aminoalkyl, lower N- alkylaminoalkyl, lower N,N-dialkylaminoalkyl, lower N- arylaminoalkyl, lower N-aralkylaminoalkyl, lower N- alkyl-N-aralkylaminoalkyl, lower N-alkyl-N- arylaminoalkyl, lower aminoalkoxy, lower aminoalkoxyalkyl, lower aminoalkylthio, lower aminoalkylthioalkyl, lower cycloalkyloxy, lower cycloalkylalkyloxy, lower cycloalkylthio, lower cycloalkylalkylthio, phenyloxy, lower aralkoxy, phenylthio, lower aralkylthio, lower alkylsulfinyl, lower alkylsulfonyl, aminosuIfonyl, lower N- alkylaminosulfonyl, lower N-arylaminosulfonyl, lower arylsulfonyl, lower N,N-dialkylaminosulfonyl, lower N- alkyl-N-arylaminosulfonyl, ? 6 H ? 6 H R b - ^ -N R o s R Y 0 R 0 N R R wherein Ar is selected from aryl selected from phenyl, biphenyl and naphthyl, and 5- and 6-membered heteroaryl, wherein Ar is optionally substituted with one or two substituents selected from halo, hydroxyl, mercapto, amino, nitro, cyano, carbamoyl, lower alkyl, lower alkenyloxy, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkylamino, lower dialkylamino, lower haloalkyl, lower alkoxycarbonyl, lower N-alkylcarbamoyl, lower N,N- dialkylcarbamoyl, lower alkanoylamino, lower cyanoalkoxy, lower carbamoylalkoxy, lower R 5 ^(R 8 )-^ R4 alkoxycarbonylalkoxy and κ ; wherein R- 1 is at least one substituent selected from 5- and 6-membered heterocyclo, lower cycloalkyl, lower cycloalkenyl and aryl selected from phenyl, biphenyl and naphthyl, where R 1 is optionally substituted at a substitutable position with one or more radicals selected from lower alkyl, lower haloalkyl, cyano, carboxy1, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino, nitro, lower alkoxyalkyl, lower alkylsulfinyl, halo, lower alkoxy and lower alkylthio; wherein R 2 is selected from lower alkyl and amino; wherein R 3 and R 4 together form a group of the formula -B-X-B 1 which together with the carbon atom to which B and B 1 are attached, defines a ring having 6 ring atoms, wherein B and B 1 , which may be the same or different, each is alkylene and X is oxy, and which ring may bear one, two or three substituents, which may be the same or different, selected from hydroxyl, lower alkyl, lower axkoxy, lower alkenyloxy and lower alkynyloxy; wherein R 5 is selected from hydroxyl, lower alkoxy, lower alkylcarbonyloxy, phenylcarbonyloxy, carboxyl, aminocarbonyl, lower alkylaminocarbonyl, lower alkoxycarbonyl, lower acyl, and cyano; wherein R 6 is selected from hydrido, lower alkyl, phenyl and lower aralkyl; wherein R 7 is selected from lower alkyl, lower alkoxy, lower alkenyl and lower alkynyl; wherein R 8 is oximino optionally substituted with alkyl; and wherein n is 0 or 1; or a pharmaceutically-acceptable salt thereof. A more preferred class of compounds consists of those compounds of Formula I wherein A is a radical selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, halo, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkyloxy, lower hydroxyalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl) oximinoalkoxyalkyl, lower carbonylalkyloxy, lower carbonylalkyloxyalkyl, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkalkylthio, lower oximinoalkylthioalkyl, lower (alkyl)oximinoalkylthio, lower (alkyl)oximinoalkylthioalkyl, lower carbonylalkylthio, lower carbonylalkyIthioalky1, lower alkylthio, lower alkylcarbonyl, lower cycloalkyl, phenyl, lower haloalkyl, 5- or 6-membered heterocyclo, lower cycloalkenyl, lower aralkyl, lower heterocycloalkyl, acyl, lower alkylthioalkyl, lower alkyloxyalkyl, lower alkenylthio, lower alkynylthio, lower alkenyloxy, lower alkynyloxy, lower alkenylthioalkyl, lower alkynylthioalkyl, lower alkenyloxyalkyl, lower alkynyloxyalkyl, phenylcarbonyl, lower aralkylcarbonyl, lower aralkenyl, lower alkylarylalkynyloxy, lower alkylarylalkynylthio, lower haloalkylcarbonyl, lower alkylaminocarbonylalkyl, lower arylthioalkyl, lower aryloxyalkyl, lower aralkylthioalkyl, lower aralkoxyalkyl, lower alkoxycarbonylalkyl, lower aminocarbonylalkyl, lower N- alkylaminocarbonyl, N-phenylaminocarbonyl, lower alkylcarbonylalkyl, lower N-alkylamino, N-phenylamino, lower N-aralkylamino, lower aminoalkyl, lower N- alkylaminoalkyl, lower N-arylaminoalkyl, lower N- aralkylaminoalkyl, lower aminoalkoxy, lower aminoalkoxyalkyl, lower aminoalkylthio, lower aminoalkylthioalkyl, lower cycloalkyloxy, lower cycloalkylalkyloxy, lower cycloalkylthio, lower cycloalkylalkylthio, phenyloxy, lower aralkoxy, phenylthio, lower aralkylthio, lower alkylsulfinyl, lower alkylsulfonyl, aminosulfonyl, lower N- alkylaminosulfonyl, N-phenylaminosulfonyl, phenylsulfonyl, oximino, wherein Ar is selected from aryl selected from phenyl, biphenyl, naphthyl, and 5- and 6-membered heteroaryl, wherein Ar is optionally substituted with one or two substituents selected from halo, hydroxyl, mercapto, amino, nitro, cyano, lower alkyl, lower alkoxy, and R- ■ Y R J ; wherein R^ is at least one substituent selected from 5- and 6-membered heteroaryl, and aryl selected from phenyl, biphenyl and naphthyl, where Y is optionally substituted at a substitutable position with one or more radicals selected from lower alkyl, lower haloalkyl, cyano, carboxyl, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, nitro, lower alkoxyalkyl, lower alkylsulfinyl, halo, lower alkoxy and lower alkylthio; wherein R 2 is selected from lower alkyl and amino; wherein R 3 and R 4 together form a tetrahydropyran ring and which ring may bear one, two or three substituents, which may be the same or different, selected from hydroxyl, lower alkyl, and lower alkoxy; wherein R 5 is selected from hydroxyl and lower alkoxy; wherein R 6 is selected from hydrido, lower alkyl, phenyl and lower aralkyl; and wherein R 7 is selected from lower alkyl, lower alkoxy, lower alkenyl and lower alkynyl; or a pharmaceutically-acceptable salt thereof. An even more preferred class of compounds consists of those compounds of Formula I wherein A is a radical selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, triazolyl, imidazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, halo, lower alkyl, lower haloalkyl, oxo, cyano, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkynyl, lower alkenyl, aryl, lower cycloalkyl, 5- or 6- membered heterocyclo, aralkyl, lower alkyloxy, aryloxy, arylthio, 5- or 6-membered heterocyclooxy, lower aralkylthio, lower aralkyloxy, lower alkylthio, lower alkynyloxy, lower alkynylthio, lower alkynyloxyalkyl, lower alkenyloxy, lower alkenylthio, lower alkenyloxyalkyl, lower alkyloxyalkyl, lower alkylthioalkyl, lower hydroxyalkyloxy, lower alkylarylalkynyloxy, lower alkoxycarbonylalkyl, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl) oximinoalkoxy, lower (alkyl)oximinoalkoxyalkyl, lower carbonylalkyloxy, lower carbonylalkyloxyalkyl, ; wherein Ar is selected from phenyl, thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, and pyridyl, wherein Ar is optionally substituted with one or two substituents selected from halo, hydroxyl, mercapto, lower alkyl, R 5 4 lower alkoxy, and R ; wherein Y is at least one substituent selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, pyridyl, and phenyl, where Y is optionally substituted at a substitutable position with one or more radicals selected from lower alkyl, lower haloalkyl, hydroxyl, lower hydroxyal yl, lower haloalkoxy, nitro, lower alkoxyalkyl, halo, lower alkoxy and lower alkylthio; wherein R 2 is selected from lower alkyl and amino; wherein R 3 and R 4 together form a tetrahydropyran ring, and which ring may bear one, two or three substituents, which may be the same or different, selected from hydroxyl, lower alkyl, and lower alkoxy; wherein R 5 is selected from hydroxyl and lower alkoxy; wherein R 6 is selected from hydrido, and lower alkyl; and wherein R 7 is selected from lower alkyl and lower alkoxy; or a pharmaceutically-acceptable salt thereof. A class of compounds of particular interest consists of those compounds of Formula I wherein A is a radical selected from thienyl, oxazolyl, furyl, pyrrolyl, triazolyl, thiazolyl, imidazolyl, isoxazolyl, pyrazolyl, eye 1 opentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, fluoro, chloro, bromo, methyl, trifluoromethyl, oxo, cyano, carboxyl, methoxy, aminocarbonyl, methoxycarbonyl, ethoxycarbonyl, acetyl, carboxypropyl, and hydroxymethyl; wherein Y is a radical selected from oxy, ethyl, propyl, isopropyl, butyl, 1-propynyl, 2- propynyl, methyloxy, ethyloxy, propyloxy, methylthio, (Z) -1-propenyloxy, (E) -2-propenyloxy, (Z) -2-propenyloxy, (E) -1-propenyloxy, (Z) -1-propenyloxymethyl, (E) -2- propenyloxymethyl, (Z) -2-propenyloxymethyl, (E) -1- propenyloxymethyl, 1-propynyloxy, 2-propynyloxy, 1- propynylthio, 2-propynylthio, hydroxymethyloxy, 1- hydroxyethyloxy, 2-hydroxypropyloxy, hydroxymethyloxymethyl, 1-hydroxyethyloxymethyl, 2- hydroxypropyloxymethyl, me hyloxymethyl, ethyloxymethyl, propyloxymethyl, 1-propynyloxymethyl, oximinomethyloxy, oximinomethyloxymethyl, (methyl)oximinomethyloxy, (methyl)oximinomethyloxymethyl, triazolylmethyloxy, triazolyImethyloxymethyl, 1- (methoxycarbonyl) ethyl, methylthiomethy1, ethylthiomethyl, methylphenylpropynyloxy, N-ethyl-N- methylaminocarbonylmethyloxy, N-ethyl-N- methylaminoethyloxy, carbonylmethyloxy, carbonylbutyloxy, and carbonyImethyloxymethyl; wherein Ar is selected from thienyl, pyridyl, thiazolyl, and phenyl, where Ar is optionally substituted with one or two substituents selected from fluoro, chloro, bromo, hydroxyl, mercapto, methyl, methoxy, and ; wherein R^ is selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isoxazolyl, pyrazolyl, pyridyl, and phenyl, where R^ is optionally substituted at a substitutable position with one or more radicals selected from methyl, trifluoromethyl, hydroxyl, hydroxymethyl, trifluoromethoxy, nitro, methoxymethyl, fluoro, chloro, bromo, methoxy and methylthio; wherein R 2 iε methyl or amino; wherein R 3 and R 4 together form a tetrahydropyran ring, and which ring may bear one, two or three substituents, which may be the same or different, selected from hydroxyl, methyl, and methoxy; and wherein R 5 is selected from hydroxyl and methoxy; or a pharmaceutically-acceptable salt thereof. Within Formula I there is a subclass of compounds of high interest represented by Formula II: wherein A is a ring substituent selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl; wherein A is optionally substituted with a radical selected from acyl, halo, hydroxyl, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, ana lower hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkynyl, lower alkenyl, lower hydroxyalkyl, aryl, lower cycloalkyl, 5- or 6-membered heterocyclo, aralkyl, lower alkyloxy, aryloxy, arylthio, lower cycloalkyloxy, 5- or 6-membered heterocyclooxy, lower aralkylthio, lower aralkyloxy, lower alkylthio, lower alkynyloxy, lower alkynylthio, lower alkynyloxyalkyl, lower alkenyloxy, lower alkenylthio, lower alkenyloxyalkyl, lower alkyloxyalkyl, lower alkylthioalkyl, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkylthio, lower oximinoalkylthioalkyl, lower (alkyl) oximinoalkylthio, lower (alkyl)oximinoalkylthioalkyl, lower alkylarylalkynyloxy, lower dialkylammoalkyloxy, lower dialkylaminocarbonylalkyloxy, lower alkoxycarbonylalkyl, lower carbonylalkylthio, lower carbonylalkylthioalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl) oximinoalkoxyalkyl, lower carbonylalkyloxy, and lower carbonylalkyloxyalkyl; wherein R^ is a substituent selected from 5- and 6- membered heterocyclo, lower cycloalkyl, lower cycloalkenyl and aryl selected from phenyl, biphenyl and naphthyl, wherein R 1 is optionally substituted at a substitutable position with one or more radicals selected from lower alkyl, lower haloalkyl, cyano, carboxyl, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino, lower alkoxyalkyl, lower alkylsulfinyl, halo, lower alkoxy and lower alkylthio; wherein R 2 is selected from lower alkyl and amino; wherein R 9 is one or two substituents selected from halo, hydroxyl, amino, nitro, cyano, carbamoyl, alkyl, alkenyloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, haloalkyl, alkoxycarbonyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, alkanoylamino, cyanoalkoxy, carbamoylalkoxy, and alkoxycarbonylalkoxy; and wherein R 10 is selected from hydrido, alkyl, alkenyl, alkynyl, cyanoalkyl, alkanoyl, and benzoyl optionally substituted with a substituent selected from halo, alkyl and alkoxy; or a pharmaceutically-acceptable salt thereof. A preferred class of compounds consists of those compounds of Formula II wherein A is a ring substituent selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl; wherein A is optionally subεtituted with a radical εelected from acyl, halo, hydroxyl, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y iε a radical selected from oxy, lower alkyl, lower alkynyl, 5- or 6-membered heterocyclo, lower heterocyloalkyloxyalkyl, lower hydroxyalkyl, lower alkyloxy, lowei- alkylthio, lower alkyloxyalkyl, lower alkenyloxy, lower alkenyloxyalkyl, lower alkynyloxy, lower alkynylthio, lower alkynyloxyalkyl, lower alkyIthioalky1, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkylthio, lower oximinoalkylthioalkyl, lower (alkyl) oximinoalkylthio, lower (alkyl) oximinoalkylthioalkyl, lower carbonylalkylthio, lower carbonylalkylthioalkyl, lower alkylarylalkynyloxy, lower dialkylammoalkyloxy, lower dialkylaminocarbonylalkyloxy, lower alkoxycarbonylalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl) oximinoalkoxy, lower (alkyl) oximinoalkoxyalkyl, lower carbonylalkyloxy, and lower carbonylalkyloxyalkyl; wherein R 1 is phenyl optionally subεtituted at a εubεtitutable position with one or more radicals selected from lower alkyl, lower haloalkyl, hydroxyl, lower hydroxyalkyl, halo, and lower alkoxy; wherein R 2 is selected from lower alkyl and amino; wherein R 9 is one or two subεtituentε εelected from halo, hydroxyl, amino, lower alkyl, lower alkoxy; and wherein R 10 iε εelected ' from hydrido, and lower alkyl; or a pharmaceutically-acceptable εalt thereof. A claεε of compounds of particular interest consiεtε of thoεe compoundε of Formula II wherein A is a radical selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl; wherein A is optionally substituted with a radical selected from formyl, fluoro, chloro, bromo, hydroxyl, methyl, ethyl, iεopropyl, butyl, tert-butyl, iεobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, fluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, oxo, cyano, nitro, carboxyl, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, hexyloxy, methylenedioxy, aminocarbonyl, methoxycarbonyl, carboxypropyl, carboxymethyl, carboxyethyl, cyanomethyl, and hydroxymethyl; wherein Y is a radical selected from oxy, ethyl, propyl, isopropyl, butyl, 1-propynyl, 2- propynyl, methyloxy, ethyloxy, propyloxy, methylthio, (Z) -1-propenyloxy, (E) -2-propenyloxy, (Z) -2-propenyloxy, (E) -1-propenyloxy, (Z) -1-propenyloxymethyl, (E) -2- propenyloxymetbyl, (Z) -2-propenyloxymethyl, (E) -1- propenyloxymethyl, 1-propynyloxy, 2-propynyloxy, 1- propynylthio, 2-propynylthio, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxymethyloxy, 1- hydroxyethyloxy, 2-hydroxypropyloxy, hydroxymethyloxymethyl, 1-hydroxyethyloxymethyl, 2- hydroxypropyloxymethyl, methyloxymethyl, ethyloxymethyl, propyloxymethyl, 1-propynyloxymethyl, hydroxymethylthio, 1-hydroxyethylthio, 2-hydroxypropylthio, hydroxymethylthiomethyl, 1-hydroxyethylthiomethyl, 2- hydroxypropylthiomethy1, oximinomethylthio, oximinomethylthiomethyl, (methyl)oximinomethylthio, (methyl)oximinomethylthiomethyl, triazolylmethyloxy, triazolyImethyloxymethyl, carbonylmethylthio, carbonylbutylthio, carbonylmethylthiomethyl, oximinomethyloxy, oximinomethyloxymethyl, (methyl)oximinomethyloxy, methylthiomethyl, (methyl) oximinomethyloxymethyl, ethylthiomethyl, 1- (methoxycarbonyl)ethyl, methylphenylpropynyloxy, N- ethyl-N-methylaminocarbonylmethyloxy, N-ethyl-N- methy1aminoethyloxy, triazolyl, carbonylmethyloxy, carbonylbutyloxy, and carbonyImethyloxymethyl; wherein Y is phenyl optionally εubεtituted at a εubstitutable position with one or more radicals selected from methyl, ethyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, fluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, fluoro, dichloropropyl, hydroxyl, hydroxymethyl, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, and hexyloxy; wherein R 2 is selected from methyl and amino; wherein R 9 is one or two substituents selected from fluoro, chloro, bromo, hydroxyl, amino, methyl, ethyl, isopropyl, butyl, tert-butyl, iεobutyl, pentyl, hexyl, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, and hexyloxy; and wherein R 10 iε εelected from hydrido, and methyl; or a pharmaceutically-acceptable εalt thereof. A class of compounds of particular interest consists of those compounds of Formula I 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -4- (3-fluoro-4-methoxyphenyl) oxazol- 5-y1]benzeneεulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -4- (3 , 4-dichlorophenyl) oxazol-5- y1]benzeneεulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -4- (3-fluorophenyl)oxazol-5- yl]benzenesulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -4- (4-methylphenyl)oxazol-5- y1]beήzenesulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxy-2- methylpyran-4-yl)phenoxy]methyl] -4-phenyloxazol-5- yl]benzenesulfonamide; 4- [2- [ [3-fluoro-5- (3,4, 5, 6-tetrahydro-2, 6-dimethyl-4- methoxypyran-4-yDphenoxy]methyl] -4-phenyloxazol-5- yl]benzenesulfonamide; [5- [4- (methylsulfonyl)phenyl] -2- [ [3- (3,4, 5, 6-tetrahydro- 4-me hoxy-2H-pyran-4-yDphenoxy]methyl] -4- phenyloxazole; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yl)phenoxy]methyl] -5- (3-fluoro-4-methoxyphenyl) oxazol- 4-y1]benzeneεulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -5- (3, 4-dichlorophenyl)oxazol-4- yl]benzenesulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -5- (3-fluorophenyl)oxazol-4- yl]benzenesulfonamide; 4- [2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy] ethyl] -5- (4-methylphenyl)oxazol-4- yl]benzeneεulfonamide; 4- [2- [ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2- methylpyran-4-yl)phenoxy]methyl] -5-phenyloxazol-4- yl]benzenesulfonamide; 4- [2- [ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-2, 6-dimethyl-4- methoxypyran-4-yDphenoxy]methyl] -5-phenyloxazol-4- yl]benzeneεulfonamide; [4- [4- (methylsulfonyl)phenyl] -2-[ [3- (3 , 4, 5, 6-tetrahydro- 4-methoxy-2H-pyran-4-yDphenoxy]methyl] -5- phenyloxazole; 4- [2- [ [4- (3 , , 5, 6-tetrahydro-4-methoxy-2-methylpyran-4- yl) hien-2-yl]thiomethyl] -5-phenyloxazol-4- yl]benzenesulfonamide; 4- [2- [ [4- (3 , 4, b, 6-tetrahydro-4-methoxy-2-methylpyran-4- yl)thien-2-yl]thio] -5-phenyloxazol-4- yl]benzenesulfonamide; 4- [2- [ [4- (3 , 4, 5, 6-tetrahydro-2, 6-dimethyl-4-methoxypyran- 4-yl)thien-2-yl] thiomethyl] -5-phenyloxazol-4- yl]benzeneεulfonamide; 4-[2-[[4-(3,4,5, 6-tetrahydro-2, 6-dimethyl-4-methoxypyran- 4-yl) hien-2-yl]thio] -5-phenyloxazol-4- yl]benzeneεulfonamide; 4- [ 2 - [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; methyl 5- [4- (aminosulfonyl) henyl] -α-[ [3- (tetrahydro-4- methoxypyran 4-yl)phenyl]methyl] -4-phenyloxazole-2- acetate; N- [2- [5- [4- (aminoεulfonyl)phenyl] -4-phenyloxazol-2- yl] ethyl] -2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yl)phenoxy-N-methylacetamide; N- [2- [4- [4- (aminosulfonyl)phenyl] -5-phenyloxazol-2- yl]ethyl] -2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yl)phenoxy-N-methylacetamide; 4- [2- [ [2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy] ethyl] -N-methylaminoethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; 4- [2- [ [2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy] ethyl] -N-methylaminoethyl] -5-phenyloxazol-4- yl]benzeneεulfonamide; 4- [2- [ [4- [3- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy] -i-propynyl]phenyl]methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; 4- [2- [ [4- [3- [3-fluoro-5- (tetrahydro-4-hydroxypyran-4- yDphenoxy] -1-propynyl] -phenyl]methyl] -4-phenyloxazol- 5-y1]benzeneεulfonamide; 4- [2- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -4- (4-fluorophenyl)oxazol-5- yl]benzeneεulfonamide; 4- [2- [4- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy]methyl]phenylmethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; 4- [5- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy]methyl] -3-phenyliεoxazol-4- yl]benzeneεulfonamide; 4- [2- [ [ [3- ( etrahydro-4-methoxypyran-4- yl)phenylmethyl] oxy]methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; • 4- [2- [ [ [3- (tetrahydro-4-methoxypyran-4- yl)phenylmethyl] thio]methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; 4- [2- [ [ [3- (tetrahydro-4-methoxypyran-4- yl)phenylmethyl]thio] ethyl] -4-phenyloxazol-5- yl]benzenesulfonamide; 4- [2- [3- (tetrahydro-4-methoxypyran-4-yl)phenyl]methoxy] -4- phenyloxazol-5-yl]benzenesulfonamide; 4- [2- [3- (tetrahydro-4-methoxypyran-4- yl) henyl]methylthio] -4-phenyloxazol-5- yl]benzenesu1fonamide; N- [2- [5- [4- (aminosulfonyl)phenyl] -4-phenyloxazol-2- yl]ethylamino] -2- [3-fluoro-5- (tetrahydro-4- methoxypyran-4-yl)phenoxy]acetamide; 4- [5- (4-chlorophenyl) -3- (3-methoxyphenyl) oxymethyl-lH pyrazol-1-yl]benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (3-methoxyphenyl) thiomethyl-IH pyrazol-1-yl]benzenesulfonamide; 4-[5-phenyl-3-[ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy]acetyl] -lH-pyrazol-1- yl]benzenesulfonamide; l-[4- (methylsulfonyl)phenyl] -2-[ [3- (3 , 4, 5, 6-tetrahydro- 4-methoxy-2H-pyran-4-yl)phenoxy]acetyl] -5- phenylpyrazole; 4-[5-phenyl-3-[ r 3-fluoro-5- (3, 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]acetyl] -lH-pyrazol-1- yl]benzenesulfonamide; 4- [5-phenyl-3- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] acetyl] -lH-pyrazol-1- y1]benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- [ [3-fluoro-5- (3 , 4,5,6- tetrahydro-4-methoxy-2H-pyran-4-yDphenoxy]methyl] -1H- pyrazol-1-yl]benzeneεulfonamide; 4- [1-pheny1-3- [ [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy]acetyl] -lH-pyrazol-5- yl]benzenesulfonamide; 4- [l-phenyl-3- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yDphenoxy]acetyl] -lH-pyrazol-5- yl]benzenesulfonamide; 4- [l-phenyl-3- [ [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy]acetyl] -lH-pyrazol-5- yl]benzeneεulfonamide; 4- [4-phenyl-2- [ [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran- -yDphenoxy]acetyl] -5- thiazolyl]benzenesulfonamide; 5-phenyl-4- [4- (methylsulfonyl)phenyl] -2- [ [3- (3 , 4, 5, 6- tetrahydro-4-methoxy-2H-pyran-4- yDphenoxy]acetyl] thiazole; 4-[5-phenyl-2-[ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]acetyl] -4- thiazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)L..ϊnzyloxy]acetyl] -5- thiazolyl]benzenesulfonamide; 4- [3-phenyl-5- [ [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy]acetyl] -4- isoxazolyl]benzenesulfonamide; 3-phenyl-4- [4- (methylsulfonyl)phenyl] -5- [ [3- (3 , 4, 5, 6- tetrahydro-4-methoxy-2H-pyran-4- yDphenoxy]acetyl] isoxazole; 4- [3-pheny1-5- [ [3-fluoro-5- (3, 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yDphenoxy]acetyl] -4- iεoxazolyl]benzeneεulfonamide; 4- [3-phenyl-5- [ [3- (3, 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy]acetyl] -4- isoxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [3- (3, 4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy]acetyl] -1- imidazolyl]benzeneεulfonamide; 5-phenyl-4- [4- (methylsulfony1)phenyl] -2-[[3-(3,4,5,6- tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy]acetyl] imidazole; 4- [5-phenyl-2- [ [3-fluoro-5- (3,4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]acetyl] -4- imidazolyl]benzenesulfonamide; 4- [2-phenyl-4- [ [3- (3,4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] acetyl] -1- imidazolyl]benzeneεulfonamide; 4- [3-pheny1-4- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)phenoxy]acetyl] -2- pyridyl]benzeneεulfonamide; 3-phenyl-2- [4- (methylsulfonyl)phenyl] -4- [ [3- (3, 4, 5, 6- tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy]acetyl]pyridine; 4- [2-phenyl-4- [ [3-fluoro-5- (3, 4, 5, 6-tetrahydro-4- me hoxy-2H-pyran-4-yl)phenoxy]acetyl] -3- pyridyl]benzenesulfonamide; 4- [2-phenyl-4- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy]acetyl] -3- pyridyl]benzenesulfonamide; 4- [2- [3- (4-methoxy-3 ,4,5, 6-tetrahydro-2H-pyran-4 yDphenoxy] -4-pheny1-5-oxazolyl]benzenesulfonamide; 4- [2- [3-fluoro-5- (4-methoxy-3 ,4,5, 6-tetrahydro-2H-pyran- 4-yl)phenoxy] -4-phenyl-5-oxazolyl]benzenesulfonamide; 4- (4-fluorophenyl) -2- [ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy)methyl] -5- (4- (methylεulfonyl)phenyl)oxazole; 4- (4-fluorophenyl) -5- (4- (methylεulfonyl)phenyl) -2- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy)methyl]oxazole; 4- [4-phenyl-2- [ [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy]acetyl] -5- oxazolyl]benzeneεulfonamide; 4-phenyl-5- [4- (methylεulfonyl)phenyl] -2- [ [3- (3 , 4, 5, 6- tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy]acetyl]oxazole; 4- [4-phenyl-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl- [ [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H-pyran- 4-yl)benzylc y]acetyl] -5-oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) 2-thienyloxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[ [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) -3-pyridinyloxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[ [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) -3-pyridylmethoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-2- [ [6- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)pyridin-2-ylmethoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-2- [ [3- (2, 6-dimethyl-3 ,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]acetyl] -5- oxazolyl]benzeneεulfonamide; 4-phenyl-2- [ [2- (3, 4, 5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl) thiazol-4-ylmethoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-2-[ [3-fluoro-5- (IS, 5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octany1)phenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-2- [ [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yDphenoxy]acetyl] -5-oxazolyl]benzeneεulfonamide; 4-phenyl-5- [4- .'methylεulfonyl)phenyl] -2- [ [3- (3 , 4, 5, 6- tetrahydro-4-hydroxy-2H-pyran-4- yl)phenoxy]acetyl] oxazole; 4-phenyl-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-hydroxy- 2H-pyran-4-yDphenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-2- [ [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yl)benzyloxy]acetyl] -5-oxazolyl]benzeneεulfonamide; 4-phenyl-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-hydroxy- 2H-pyran-4-yl)benzyloxy]acetyl] -5- oxazolyl]benzenesulfonamide; -phenyl-2 - [ [ 3 - ( 3 , 4 , 5 , 6-tetrahydro-4-hydroxy-2H-pyran-4- yl) hienyloxy]acetyl] -5-oxazolyl]benzenesulfonamide; - [4-pheny1-2- [ [5- (3,4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-ylmethoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [6- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-2-ylmethoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3- (2, 6-dimethyl-3, 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[ [2- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)thiazol-4-ylmethoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3-fluoro-5- (1S,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octany1)phenoxy] acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [3- (3, 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy] (E-oximinomethyl) ethyl] -5- oxazoiyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy] (Z-oximinomethyl) ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy] (E-oximino)ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylεulfonyl)phenyl] -2- [2- [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yDphenoxy] (E-oximinomethyl)ethyl]oxazole; 4-phenyl-5-[4-[4-(methylsulfonyl)phenyl]-2-[2-[3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy] (Z-oximinomethyl) ethyl]oxazole; 4- [4-pheny1-2- [2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy] (E-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] (E-oximino) ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2- 2-[3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] (Z-oximino) ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] (E-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran- ' 4-yl) thienyloxy] (E-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[2-[3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)thienyloxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy] (E-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[2-[5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-ylmethoxy] (E-oximino) ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [2- [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-ylmethoxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [6- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy] (E-oximino)ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2-[6-(3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [3- (2 , 6-dimethyl-3 ,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] (E-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [2- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] (Z-oximino)ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-ylmethoxy] (E-oximino) ethyl] -5- oxazolyl]ben .enesulfonamide; 4- [4-phenyl-2- [2- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)thiazol-4-ylmethoxy] (Z-oximino) ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[2-[3-fluoro-5-(lS,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octany1)phenoxy] (Z-oximino) ethyl] - 5-oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[2-[3-fluoro-5- (1S,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octany1)phenoxy] (E-oximino)ethyl] - 5-oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)phenoxy]propyn-1-yl] -5- oxazolyl]benzeneεul onamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [3- [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy] ropyn-1-yl] oxazole; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]propyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3-[3-(3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)benzyloxy]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]propyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)thienyloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy]propyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)pyridin-3-ylmethoxy]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [6- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy]propyn-l-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[3- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [2- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran^4-yl)thiazol-4-ylmethoxy]propyn-l-yl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[3- [3-fluoro-5- (1S,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octany1)phenoxy]propyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yDphenoxy] ropyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5-[4-[4-(methylεulfonyl)phenyl]-2-[3-[3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yl)phenoxy]propyn-1-yl]oxazole; 4-[4-phenyl-2-[3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenoxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)benzyloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [3-fluoro-5- (3 , 4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thienyloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-ylmethoxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [6- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1)pyridin-2-ylmethoxy]propyn-1-y1] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2-[3-[2-(3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiazol-4-ylmethoxy]propyn-l-yl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[3-[3-fluoro-5-(lS,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octany1)phenoxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)phenoxy]propyl] -5- oxazolyl]ber. ienesulfonamide; 4-phenyl-5-[4-[4-(methylεulfonyl)phenyl]-2-[3-[3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy]propyl] oxazole; 4- [4-pheny1-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (3 , , 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- L 3- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) -2-thienyloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)pyridin-3-yloxy]propy1] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-ylmethoxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3-[6-(3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)pyridin-2-ylmethoxy]propy1] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[3-[3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-ylmethoxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[3- [3-fluoro-5- (1S,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3-[3-(3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1)phenoxy]propyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylεulfonyl)phenyl] -2- [3- [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yl)phenoxy]propyl] oxazole; 4- [4-pheny1-2- [3- [3-fluoro-5- (3 , 4, 5 , 6-tetrahydro-4- hydroxy-2H-pyran-4-y phenoxy]propyl] -5- oxazolyl]ber^enesulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)benzyloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) -2-thienyloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [ -pheny1-2- [3- [5- (3 , 4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1) vridin-3-ylmethoxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3-[6- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1)pyridin-2-ylmethoxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [3- (2, 6-dimethyl-3 ,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [2- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) hiazol-4-ylmethoxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[3-[3-fluoro-5-(lS,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octanyl) henoxy]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ 2 - [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4-phenyl-5- [4- [4- (methylεulfonyl)phenyl] -2- [2- [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy] ethyl]oxazole; 4-[4-phenyl-2-[2-[3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[2-[3-fluoro-5-(3,4,5,6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- T2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) -5-thienyloxy] ethyl] -5- oxazoly1]benzenesulfonamide; 4- [4-phenyl-2- [2- [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [5- (3 ,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-ylmethoxy]ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [6- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy]ethyl] -5- oxazoly1]benzenesulfonamide; 4- [4-phenyl-2- [2- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- T2- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)thiazol-4-ylmethoxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[2-[3-fluoro-5-(lS,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy] ethyl] -5- oxazolyl]benzeneεulfonamide, • 4-[4-phenyl-2-[2-[3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yDphenoxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [2- [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yl)phenoxy]ethyl]oxazole; 4- [4-pheny1-2- [2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenoxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- • .] - [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [2- [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) -5-thienyloxy]ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[2- [5- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2-[5-(3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-ylmethoxy]ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- ' ;;- [6- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-2-ylmethoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [2- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [2- [2- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiazol-4-ylmethoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[2-[3-fluoro-5-(lS,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[3- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4-phenyl-5- [4- '_ • * - (methylεulfonyl)phenyl] -2- [1-hydroxy-2- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy] ethyl]oxazole; 4-[4-phenyl-2-[l-hydroxy-2-[3-fluoro-5- (3,4,5,6- tetrahydro-4-methoxy-2H-pyran-4-yl)phenoxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[3-(3,4,5,6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazoly1]benzeneεulfonamide, • 4-[4-phenyl-2-[l-hydroxy-2-[3-fluoro-5-(3,4,5,6- tetrahydro-4-methoxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ -hydroxy-2- [3- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl) thiophenyl] ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)pyridin-3-yloxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[5-(3,4,5,6-tetrahydro-4- methoxy-2H-pyran-4-yl)pyridin-3-ylmethoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[6- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)pyridin-2-ylmethoxy]ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [3- (2, 6-dimethyl-3 ,4,5,6- tetrahydro-4-methoxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2- .-hydroxy-2-[2-(3,4,5,6-tetrahydro-4- methoxy-2H-pyran-4-yl) thiazol-4-ylmethoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[3-fluoro-5- (1S,5R 3α- methoxy-6, 8-dioxabicyclo[3.2.1]octany1)phenoxy] ethyl] - 5-oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[3- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenoxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [l-hydroxy-2- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yDphenoxy] ethyl] oxazole; 4- [4-phenyl-2- [l-hydroxy-2- [3-fluoro-5- (3,4,5,6- tetrahydro-4-hydroxy-2H-pyran-4-yDphenoxy]ethyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [3- (3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [3-fluoro-5- (3,4,5,6- tetrahydro-4-hydroxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazoly1]benzenesulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [3- (3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl) thiophenyl] ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[5-(3,4,5,6-tetrahydro-4- hydroxy-2H-pyran-4-yl)pyridin-3-yloxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- ri-hydroxy-2- [5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)pyridin-3-ylmethoxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[6-(3,4,5,6-tetrahydro-4- hydroxy-2H-pyran-4-yl)pyridin-2-ylmethoxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [3- (2, 6-dimethyl-3,4,5,6- tetrahydro-4-hydroxy-2H-pyran-4-yl)benzyloxy] ethyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [l-hydroxy-2- [2- (3 , 4, 5, 6-tetrahydro-4- hydroxy 2H-pyran-4-yl) thiazol-4-ylmethoxy]ethyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[l-hydroxy-2-[3-fluoro-5-(lS,5R 3α- hydroxy-6, 8-dioxabicyclo[3.2.1]octanyl)phenoxy] ethyl] - 5-oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[ r3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)phenoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [ [3- (3 , 4, 5 , 6- tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy]methyl]oxazole; 4- [4-phenyl-2- [ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy] ethyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy]methyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]methyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiophenyl]methyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy]methyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [5- (3, 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)pyridin-3-ylmethoxy]methy1] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [6- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy]methyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2-[ [3- (2, 6-dimethyl-3, 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy]methyl] -5- oxazolyl]ber..eneεulfonamide; 4- [4-phenyl-2- [ [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-ylmethoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [3-fluoro-5- (IS, 5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yDphenoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl]-2-[[3-(3,4,5,6- tetrahydro-4-hydroxy-2H-pyran-4- yl)phenoxy]methyl] oxazole; 4- [4-pheny1-2- [ [3-fluoro-5- (3, 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenoxy]methyl] -5- oxazolyl]ber.zeneεulfonamide; 4-[4-phenyl-2-[ [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)benzyloxy]methyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [3-fluoro-5- (3, 4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]methyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiophenyl]methyl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [5- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy]methyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1)pyridin-3-ylmethoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [6- (3, 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1)pyridin-2-ylmethoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3- (2, 6-dimethyl-3, 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy]methyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [2- (3, 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiazol-4-ylmethoxy]methyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3-fluoro-5- (1S,5R 3α-hydroxy-6, 8- dioxabicyclo [3.2.1]octany1)phenoxy]methyl] -5- oxazolyl]benzeneεul onamide; 4- [4-phenyl-2- H- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy] (E-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide, • 4-phenyl-5-[4-[4-(methylεulfonyl)phenyl]-2-[3-[3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4-yDphenoxy] (E & Z-propen) -1-yl]oxazole; 4- [4-pheny1-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenoxy] (Z-propen) -1-yl] -5- oxazolyl] enzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] (Z-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- . :'- [3- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiophenyl] (E-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [5- (3 ,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-ylmethoxy] (E-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [6- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy] (Z-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3- (2 , 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] (Z-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- '.?- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-ylmethoxy] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[3- [3-fluoro-5- (1S,5R 3α-methoxy-6 , 8- dioxabicyclo[3.2.1] octany1)phenoxy] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yDphenoxy] (E-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4-phenyl-5-[4-[4- (methylεulfonyDphenyl] -2- [3- [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yl)phenoxy] (E-propen) -1-yl] oxazole; 4- [4-pheny1-2- [3- [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yDphenoxy] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-y1)benzyloxy] (E-propen) -1-y1] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy] (Z-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3- [3- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiophenyl] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy] (Z-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-ylmethoxy] (Z-propen) -1-yl] -5- oxazolyl]beri eneεulfonamide; 4- [4-phenyl-2- [3-[6-(3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-2-ylmethoxy] (E-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (2, 6-dimethyl-3 ,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy] (E-propen) -1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [2- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiazol-4-ylmethoxy] (Z-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[3-[3-fluoro-5-(lS,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy] (E-propen) -1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [3- (3, 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yDphenoxy] -1,2, 3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4-yl)phenoxy] - 1,2, 3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [3-fluoro-5- (3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yDphenoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)benzyloxy] -1,2,3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] -1,2,3-triazol-4- ylmethyl-5-] 5-oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [3- (3, 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiophenyl] -1,2, 3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yloxy] -1,2,3-triazol-4-ylmethyl- 5-] -5-oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [5- (3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-ylmethoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzenesulfonamide; 4-[4-phenyl-2- [ [6- (3, 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-2-ylmethoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzenesulfonamide; 4- [4-phenyl-2-[ [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)benzyloxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2- [ [2- (3,4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-ylmethoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [3-fluoro-5- (1S,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yDphenoxy] -1,2,3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzeneεulfonamide; 4-phenyl-5-[4-[4- (methylεulfonyDphenyl] -2- [ [3- (3,4,5,6- tetrahydro-4-hydroxy-2H-pyran-4-yl)phenoxy] -1,2,3- triazol-4-ylmethyl-5-]oxazole; 4- [4-pheny1-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yDphenoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)benzyloxy] -1,2,3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [ [3- (3, 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)thiophenyl] -1,2,3-triazol-4-ylmethyl-5-] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[ [5- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-yloxy] -1,2,3-triazol-4-ylmethyl- 5-] -5-oxazoi 1]benzeneεulfonamide; 4- [4-phenyl-2- [ [5- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-3-ylmethoxy] -1,2,3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [ [6- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)pyridin-2-ylmethoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [ [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)benzyloxy] -1,2,3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [ [2- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiazol-4-ylmethoxy] -1,2, 3-triazol-4- ylmethyl-5-] -5-oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[[3-fluoro-5-(lS,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octanyl)phenoxy] -1,2, 3-triazol-4- ylmethyl-5-j -5-oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [ [3- (3, 4, 5, 6-tetrahydro-2H-pyran-4-yl) ]E- oximinomethyl]phenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[ [ [3- (3, 4, 5, 6-tetrahydro-2H-pyran-4-yl) ]Z- oximinomethyl]phenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [ [E-O-methyl- [3- (3,4, 5, 6-tetrahydro-2H- pyran-4-y1) ]oximinomethy1]phenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [ [Z-O-methyl- [3- (3, 4, 5, 6-tetrahydro-2H- pyran-4-yl) ]oxi inomethyl]phenoxy]acetyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- Y - [ [3- (3,4, 5, 6-tetrahydro-2H-pyran-4- yl) ] Z-oximinomethyl]phenoxy]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [ [3- (3, 4, 5, 6-tetrahydro-2H-pyran-4- yl) ] E-oximinomethyl]phenoxy]propyn-l-yl] -5- oxazoly1]benzenesulfonamide; 4- [4-phenyl-2- [3- [E-O-methyl- [3- (3, 4, 5, 6-tetrahydro-2H- pyran-4-y1) ]oximinomethyl]phenoxy]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [Z-O-methyl- [3- (3 , 4, 5, 6-tetrahydro-2H- pyran-4-y1) ]oximinomethyl]phenoxy]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3-[3-(3,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)phenyl]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- ι ±- (methylsulfonyDphenyl] -2- [3- [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenyl]propyn-1-yl]oxazole; 4- [4-phenyl-2- [3- [3-fluoro-5- (3, 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenyl]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)pyridin-3-yl]propyn-l-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenyl]propyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-yl]propyn-l-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3- [3-fluoro-5- (1S,5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1] octany1)phenyl]propyn-1-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3-[3-(3,4,5,6-tetrahydro-4-hydroxy-2H- pyran-4-y1)phenyl]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [3- [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- y1)phenyl]propyn-1-yl]oxazole; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenyl]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4-[4-phenyl-2-[3-[5- (3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)p ridin-3-yl]propyn-l-yl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3- (2, 6-dimethyl-3 ,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-y1)phenyl]propyn-1-y1] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3-[2-(3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl) thiazol-4-yl]propyn-l-yl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[3-[3-fluoro-5-(lS,5R 3α-hydroxy-6, 8- dioxabicyclo[3.2.1]octany1)phenyl]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [3- (3 ,4,5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl)phenyl]propyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [3-[3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenyl]propyl]oxazole; 4- [4-phenyl-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenyl]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [5- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-y1)pyridin-3-yl]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-pheny1-2- [3- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- methoxy-2H-pyran-4-yl)phenyl]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-phenyl-2- [3- [2- (3 , 4, 5, 6-tetrahydro-4-methoxy-2H- pyran-4-yl) thiazol-4-yl]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [3-fluoro-5- (IS, 5R 3α-methoxy-6, 8- dioxabicyclo[3.2.1]octany1)phenyl]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3-[3-(3,4,5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)phenyl]propyl] -5- oxazolyl]benzenesulfonamide; 4-phenyl-5- [4- [4- (methylsulfonyl)phenyl] -2- [3- [3- (3,4,5, 6-tetrahydro-4-hydroxy-2H-pyran-4- yl)phenyl]propyl]oxazole; 4- [4-pheny1-2- [3- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenyl]propyl] -5- oxazolyl]benzenesulfonamide; 4-[4-phenyl-2-[3-[5-(3,4,5,6-tetrahydro-4-hydroxy-2H- pyran-4-y1)pyridin-3-y1]propyl] -5- oxazolyl]benzeneεulfonamide; 4- [4-pheny1-2- [3- [3- (2, 6-dimethyl-3 , 4, 5, 6-tetrahydro-4- hydroxy-2H-pyran-4-yl)phenyl]propyl] -5- oxazolyl]benzenesulfonamide; 4- [4-phenyl-2- [3- [2- (3 , 4, 5, 6-tetrahydro-4-hydroxy-2H- pyran-4-yl)thiazol-4-yl]propyl] -5- oxazolyl]benzeneεulfonamide; and 4-[4-phenyl-2-[3-[3-fluoro-5- (1S,5R 3α-hydroxy-6 , 8- dioxabicyclo[3.2.1]octany1)phenyl]propyn-1-yl] -5- oxazolyl]benzeneεulfonamide. The term "hydrido" denoteε a εingle hydrogen atom (H) . This hydrido radical may be attached, for example, to an oxygen atom to form a hydroxyl radical or two hydrido radicals may be attached to a carbon atom to form a methylene (-CH2-) radical. Where used, either alone ci within other terms such as "haloalkyl", "alkylsulfonyl" , "alkoxyalkyl" and "hydroxyalkyl", the term "alkyl" 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 radicalε include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert- butyl, pentyl, iso-amyl, hexyl and the like. The term "alkenyl" embraces linear or branched radicals having at leaεt one carbon-carbon double bond of two to about twenty carbon atomε or, preferably, two to about twelve carbon atomε. riore preferred alkyl radicals are "lower alkenyl" radicals having two to about εix carbon atomε. Exampleε of alkenyl radicals include ethenyl, propenyl, allyl, propenyl, butenyl and 4-methylbutenyl. The term "alkynyl" denotes linear or branched radicals having two to about twenty carbon atoms or, preferably, two to about twelve carbon atoms. More preferred alkynyl radicalε are "lower alkynyl" radicals having two to about ten carbon atoms. Most preferred are lower alkynyl radicals having two to about six carbon atoms. Exampleε of such radicals include propargyl, butynyl, and the like. The terms "alkenyl", "lower alkenyl", embrace radicals having "cis" and "trans" orientationε, or alternatively, "E" and "Z" orientationε. The term "cycloalkyl" embraces saturated carbocyclic radicals having three to twelve carbon atoms. More preferred cycloalkyl radicals are "lower cycloalkyl" radicals having three to about eight carbon atoms. Examples of εuch radicalε include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "cycloalkenyl" embraces partially unsaturated carbocyclic radicalε having three to twelve carbon atoms. More preferred cycloalkenyl radicals are "lower cycloalkenyl" radicals having four to about eight carbon atoms. Examples of such radicals include cyclobutenyl, cyclopentenyl and cyclohexenyl. 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. "Lower haloalkyl" embraces radicalε having 1-6 carbon atomε. Exampleε of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. The term "hydroxyalkyl" embraces linear or branched alkyl radicals havinrr one to about ten carbon atoms any one of which may be subεtituted with one or more hydroxyl radicals. More preferred hydroxyalkyl radicals are "lower hydroxyalkyl" radicals having one to six carbon atoms and one or more hydroxyl radicals. Examples of such radicals include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl. The term "cyanoalkyl" embraces linear or branched alkyl radicals having one to about ten carbon atoms any one of which may be subεtituted with one or more cyano radicalε. More preferred cyanoalkyl radicalε are "lower cyanoalkyl" radicalε having one to εix carbon atomε and one or more cyano radicalε. Exampleε of εuch radicals include cyanomethyl, cyanoethyl, cyanopropyl, cyanobutyl and cyanohexyl. The terms "alkoxy" and "alkyloxy" embrace linear or branched oxy-containing radicalε each having alkyl portionε of one to about ten carbon atomε. More preferred alkoxy radicalε 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" embraces alkyl radicals having one or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicalε. The "alkoxy" radicalε may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkoxy radicals, or with hydroxyl radicals to from "hydroxyalkyloxy" radicals. More preferred haloalkoxy radicals are "lower haloalkoxy" radicals having one to six carbon atoms and one or more halo radicalε. Examples of such radicalε include fluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy and fluoropropoxy. More preferred hydroxyalkyloxy radicalε are "lower hydroxyalkyloxy" radicalε having alkyl poriotnε of 1 to 6 carbonε. The term "alkenyloxy" embraceε radicals having alkenyl portions of two to about ten carbon atoms attached to an oxygen atom. More preferred alkenyloxy radicals are "lower alkenyloxy" radicalε having two to εix carbon atoms. The term "alkynyloxy" embraces radicals having alkynyl portionε of two to about ten carbon atoms attached to an oxygen atom. More preferred alkynyloxy radicalε are "lower alkynyloxy" radicalε having two to six carbon atoms. Examples of such lower alkynyloxy radicals include propynyloxy, and butynyloxy. The term "aryl", alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such ringε may be attached together in a pendent manner or may be fused. The term "aryl" embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl. Aryl moieties may also be εubstituted at a subεtitutable poεition with one or more εubεtituents selected independently from alkyl, alkoxyalkyl, alkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkoxy, aralkoxy, hydroxyl, amino, halo, nitro, alkylamino, acyl, cyano, o-rboxy, aminocarbonyl, alkoxycarbonyl and aralkoxycarbonyl . The term "heterocyclyl" embraces saturated, partially unsaturated and unsaturated heteroatom-containing ring-shaped radicals, where the heteroatoms may be selected from nitrogen, sulfur and oxygen. Examples of saturated heterocyclyl radicals include saturated 3 to 6-membered heteromonocylic group containing 1 to 4 nitrogen atoms (e.g. pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.); saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms (e.g. morpholinyl, etc.); saturated 3 to 6- membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms (e.g., thiazolidinyl, etc.) . Exampleε of partially unsaturated he ' .πrocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. The term "heteroaryl" embraceε unsaturated heterocyclyl radicals. Examples of unεaturated heterocyclyl radicals, alεo termed "heteroaryl" radicals include unsaturated 3 to 6 membered heteromonocyclic group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1, 2, 4-triazolyl, 1H- 1, 2, 3-triazolyl, 2H-1, 2, 3-triazolyl, etc.) tetrazolyl (e.g. lH-tetrazolyl, 2H-tetrazolyl, etc.), etc.; unsaturated condensed heterocyclyl group containing 1 to 5 nitrogen atomε, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benvotriazolyl, tetrazolopyridazinyl (e.g., tetrazolo[1, 5-b]pyridazinyl, etc.), etc.; unεaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, furyl, etc.; unεaturated 3 to 6-membered heteromonocyclic group containing a εulfur atom, for example, thienyl, etc.; unεaturated 3- to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1, 2, 4-oxadiazolyl, 1, 3, 4-oxadiazolyl, 1,2,5- oxadiazolyl, etc.) etc.; unsaturated condensed heterocyclyl group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms (e.g. benzoxazolyl, benzoxadiazolyl, etc.); unsaturated 3 to 6-membered heteromonocycl ; group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl (e.g., 1,2,4- thiadiazolyl, 1,3,4- thiadiazolyl, 1, 2, 5-thiadiazolyl, etc.) etc.; unsaturated condensed heterocyclyl group containing 1 to 2 εulfur atoms and 1 to 3 nitrogen atoms (e.g., benzothiazolyl, benzothiadiazolyl, etc.) and the like. The term also embraces radicals where heterocyclyl radicals are fused with aryl radicals. Examples of such fused bicyclic radicalε include benzofuran, benzothiophene, and the like. Said "heterocyclyl group" may have 1 to 3 εubεtituentε such aε alkyl, hydroxyl, halo, alkoxy, oxo, amino and alkylamino. The term "alkylthio" embraceε radicalε containing a linear or branched alkyl radical, of one to about ten carbon atomε attached to a divalent εulfur atom. More preferred alkylthio radicalε are "lower alkylthio" radicals having alkyl radicals of one to εix carbon atoms. Examples of such lower alkylthio radicals are methylthio, ethylthio, propylthio, butylthio and hexylthio. The term "alkylthioalkyl" embraces radicalε containing an alkylthio radical attached through the divalent εulfur atom to an alkyl radical of one to about ten carbon atomε. More preferred alkylthioalkyl radicalε are "lower alkylthioalkyl" radicalε having alkyl radicalε of one to six carbon atoms. Examples of εuch lower alkylthioalkyl radicalε include methy1thiomethy1. The term "oximinoalkoxy" embraceε alkyloxy radicals having one to about ten carbon atoms any one of which may be subεtituted with one or more oximino radicals (-C=NOH) . More preferred oximinoalkoxy radicals are "lower oximinoalkoxy" radicals having alkoxy radicals containing one to six carbon atoms. Examples of such radicals include oximinomethoxy, oximinopropoxy, and oximinobutoxy. The term "oximinoalkoxyalkyl" embraces alkyloxyalkyl radicals with alkyl and portions having one to about ten carbon atoms any one of which may be εubstituted with an oximino radical (-C=NOH) . More preferred oximinoalkoxyalkyl radicalε are "lower oximinoalkoxyalkyl" radicals having alkyl radicals containing one to six carbon atoms. The terms " (alkyl)oximinoalkoxyalkyl" and " (alkyl)oximinoalkoxy" embrace oximinoalkoxyalkyl and oximinoalkoxy radicals, as defined above, where the oximino portion is substituted on the oxygen atom with alkyl radicals having one to c- out ten carbon atoms. More preferred oximinoalkoxyalkyl radicalε are "lower " (alkyl) oximinoalkoxyalkyl" and "lower (alkyl)oximinoalkoxy" radicalε having alkyl radicals containing one to six carbon atomε. The term "alkenylthio" embraces radicals containing a linear or branched ' alkenyl radical, of two to about ten carbon atoms attached to a divalent εulfur atom. More preferred alkenylthio radicalε are "lower alkenylthio" radicalε having alkenyl radicalε of two to εix carbon atomε. The term "alkynylthio" embraceε radicalε containing a linear or branched alkynyl radical, of two to about ten carbon atomε attached to a divalent εulfur atom. More preferred alkynylthio radicalε are "lower alkynylthio" radicals having alkynyl radicals of two to six carbon atoms. The term "alkylεulfinyl" embraceε radicalε containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent -S(=0)- radical. More preferred alkylsulfinyl radicalε are "lower alkylsulfinyl" radicalε having alkyl radicalε of one to six carbon atoms. Examples of such lower alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, butylsulfinyl and hexylsulfinyl. The term "sulfonyl", whether used alone or linked to other terms such as alkylsulfonyl, denotes reεpectively divalent radicalε -S0 2 -. "Alkylsulfonyl" embraceε alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. More preferred alkylsulfonyl radicals are "lower alkylsulfonyl" radicals having one to six carbon atoms. Examples of such lower alkylεulfonyl radicalε include methylsulfonyl, ethylεulfonyl and propylεulfonyl. The "alkylsulfonyl" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkylsulfonyl radicals. The terms "sulfamyl", "aminosulfonyl" and "sulfonamidyl" denote NH 2 O 2 S-. The term "acyl" denoteε a radical provided by the residue after removal of hydroxyl from an organic acid. Examples of such acyl radicals include alkanoyl and aroyl radicals. Examples of such lower alkanoyl radicals include formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, trifluoroacetyl. The term "carbonyl", whether used alone or with other terms, such as "alkoxycarbonyl", denotes -(C=0)-. The term "aroyl" embraces aryl radicalε with a carbonyl radical aε defined above. Exampleε of aroyl include benzoyl, naphthoyl, and the like and the aryl in εaid aroyl may be additionally εubεtituted. The termε "carboxy" or "carboxyl", whether uεed alone or with other terms, such as "carboxyalkyl", denotes -CO 2 H. The term "carboxyalkyl" embraces alkyl radicalε εubstituted with a carboxy radical. More preferred are "lower carboxyalkyl" which embrace lower alkyl radicals as defined above, and may be additionally substituted on the alkyl radical with halo. Examples of such lower carboxyalkyl radicals include carboxymethyl, carboxyethyl and carboxypropyl. The term "alkoxycarbonyl" means a radical containing an alkoxy radical, aε defined above, attached via an oxygen atom to a carbonyl radical. More preferred are "lower alkoxycarbonyl" radicals with alkyl porions having 1 to 6 carbons. Examples of such lower alkoxycarbonyl (ester) radicals include substituted or unsubstituted methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl. The terms "alkylcarbonyl" , "arylcarbonyl" and "aralkylcarbonyl" include radicals having alkyl, aryl and aralkyl radicals, as defined above, to a carbonyl radical. Examples of such radicalε include εubεtituted or unsubstituted methylcarbonyl, ethylcarbonyl, phenylcarbonyl and benzylcarbonyl. The term "aralkyl" embraces aryl-substituted alkyl radicals such as benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, and diphenylet ' i. l. The aryl in εaid aralkyl may be additionally εubεtituted with halo, alkyl, alkoxy, halkoalkyl and haloalkoxy. The termε benzyl and phenylmethyl are interchangeable. The term "heteroaralkyl" embraceε heteroaryl-εubεtituted alkyl radicalε, such as pyridylmethyl, quinolylmethyl, thienylmethyl, furylethyl, and quinolylethyl. The heteroaryl in said heteroaralkyl may be additionally subεtituted with halo, alkyl, alkoxy, halkoalkyl and haloalkoxy. The term "aralkoxy" embraceε aralkyl radicalε attached through an oxygen atom to other radicalε. The term "aralkoxyalkyl" embraceε aralkoxy radicalε attached through an oxygen atom to an alkyl radical. The term "aralkylthio" embraceε aralkyl radicalε attached to a εulfur atom. The term "aralkylthioal 'l" embraceε aralkylthio radicalε attached through a εulfur atom to an alkyl radical. The term "heteroaralkoxy" embraceε heteroaralkyl radicals attached through an oxygen atom to other radicals. The term "heteroaralkylthio" embraces heteroaralkyl radicalε attached through a sulfur atom to other radicals. The term "aminoalkyl" embraces alkyl radicals substituted with amino radicals. More preferred are "lower aminoalkyl" radicalε. Exampleε of such radicals include aminomethyl, aminoethyl, and the like. The term "alkylamino" denotes amino groups which have been subεtituted with one or two alkyl radicals. Preferred are "lower N-alkylamino" radicals having alkyl porions having 1 to 6 carbon atoms. Suitable lower alkylamino may be mono or dialkylamino such as N- methylamino, N-ethylamino, N,N-dimethylamino, N,N- diethylamino or the like. The term "cycloalkylamino" denotes amino groups which have been subεtituted with one or two cycloalkyl radicals, as defined above. The term "arylamino" denotes amino groups which have been substituted with one or two aryl radicals, such as N- phenylamino. The "arylamino" radicals may be further subεtituted on the aryl ring portion of the radical. The term "aralkylamino" embraceε aralkyl radicalε attached through an nitrogen atom to other radicalε. The termε "N-arylaminoalkyl" and "N-aryl-N-alkyl- aminoalkyl" denote amino groups which have been subεtituted with one aryl radical or one aryl and one alkyl radical, reεpectively, and having the amino group attached to an alkyl radical. Exampleε of εuch radicalε include N-phenylaminomethyl and N-phenyl-N- methylaminomethyl. The term "aminocarbonyl" denoteε an amide group of the formula -C(=0)NH2- The term "alkylaminocarbonyl" denoteε an aminocarbonyl group which has been subεtituted with one or two alkyl radicals on the amino nitrogen atom. Preferred are "N- alkylaminocarbonyl" "N,N-dialkylaminocarbonyl" radicals. More preferred are "lower N- alkylaminocarbonyl" "lower N,N-dialkylaminocarbonyl" radicals with lower alkyl portions aε defined above. The term "alkylaminocarbonylhaloalkyl" denoteε an aminocarbonyl group which haε been substituted with one or two alkyl radicals on the amino nitrogen atom, attached to an haloalkyl radical. Preferred are "N- alkylaminocarbonylhaloalkyl" "N,N- alkylaminocarbonylhaloalkyl" radicals. More preferred are "lower N-alkylaminocarbonylhaloalkyl" "lower N,N- alkylammocarbonylhaloalkyl" radicals with lower alkyl and lower haloalkyl portions as defined above. The term "alkylammoalkyl" embraces radicals having one or more alkyl radicals attached to an aminoalkyl radical. The term "aryloxyalkyl" embraces radicalε having an aryl radicalε attached to an alkyl radical through a divalent oxygen atom. The term "arylthioalkyl" embraceε radicalε having an aryl radicals attached to an alkyl radical through a divalent sulfur atom. When the above radicals are included as linker moiety "Y" in Formulas I-II, such radicals are divalent radicalε. In addition, the orientation of the radicalε between "A" and "Ar" are reverεible. For example, the term "alkylthio" repreεentε both -CH 2 S- and -SCH 2 -, and "carbonylmethy oxy" repreεentε both -C(0)CH 2 θ- and -OCH 2 C(0)-. For termε such as aralkyl, and heteroarylalkyl, the moiety may be linked to "A" and "Ar" through a divalent alkyl radical, or through the alkyl radical at one end and the aryl or heteroaryl portion at the other. The use of heterocyclyl and aryl moieties includes divalent attachment at subεtitutable εites. The use of a substituted amine group, does not include attachment through a divalent nitrogen atom (i.e., -N(CH3)-) but instead (-N(H)CH2~) . The present invention compriεeε a pharmaceutical compoεition compriεing a therapeutically-effective amount of a compound of Formulas I-II in asεociation with at leaεt one pharmaceutically-acceptable carrier, adjuvant or diluent. The preεej : invention also compriseε a method of treating inflammation or inflammation-associated disorderε in a subject, the method comprising treating the subject having or susceptible to such inflammation or disorder, with a therapeutically-effective amount of a compound of Formulas I-II. The method includes prophylactic or chronic treatment, especially in the case of arthritis and other inflammatory conditions which can lead to deterioration in the joints. Also included in the family of compounds of Formula I are the stereoisomers and tautomers thereof. Compounds of the present invention can possess one or more asymmetric carbon atoms and are thus capable of existing in the form of optical isomers as well as in the form of racemic or nonracemic mixtures thereof. Accordingly, some of the compounds of this invention may be present racemic mixtures which are also included in this invention. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processeε, for example by formation of diastereoisomeric εalts by treatment with an optically active acid or base. Examples of appropriate acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric and camphorsulfonic acid and then separation of the mixture of diastereoiεomerε by crystallization followed by liberation of the optically active bases from these salts. A different process for εeparation of optical isomers involves the uεe of a chiral chromatography column optimally choεen to maximize the εeparation of the enantiomers. Still another available method involves synthesis of covalent diastereoisomeric molecules by reacting an amine functionality of precursorε to compounds of Formula I with an optically pure acid in an activated form or an optically pure isocyanate. Alternatively, diaεtereomeric derivatives can be prepared by reacting a carboxyl functionality of precursorε to compoundε of Formula I with an optically pure amine baεe. The εyntheεized diastereoisomers can be εeparated by conventional means such as chromatography, distillation, crystallization or εublimation, and then hydrolyzed to deliver the enantiomerically pure compound. The optically active compoundε of Formula I can likewiεe be obtained by utilizing optically active εtarting materials. These isomers may be in the form of a free acid, a free base, an eεter or a jalt. Also included in the family of compounds of Formula I are the pharmaceutically-acceptable salts thereof. The term "pharmaceutically-acceptable salts" embraceε εaltε commonly used to form alkali metal salts and to form addition salts of free acids or free baseε. The nature of the εalt is not critical, provided that it is pharmaceutically-acceptable. Suitable pharmaceutically-acceptable acid addition saltε 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, εulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclyl, carboxylic and sulfonic classes of organic acids, example of which are formic, acetic, propionic, εuccinic, glycolic, gluconic, lactic, malic, tartaric, citric, aεcorbic, glucuronic, maleic, fumaric, pyruvic, aεpartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic) , methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, stearic, cyclohexylaminoεulfonic, algenic, β -hydroxybutyric, salicylic, galactaric and galacturonic acid. Suitable pharmaceutically- acceptable base addition saltε of compounds of Formula I include metallic saltε made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,N' -dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these saltε may be prepared by conventional means from the correεponding compound of Formula I by reacting, for example, the appropriate acid or base with the compound of Formula I. GENERAL SYNTHETIC PROCEDURES The compounds of the invention can be synthesized according to the following procedures of Schemeε I- XXIII, wherein the R!-R9 εubεtituents are as defined for Formula I-II, above, except where further noted. Scheme I Synthetic Scheme I shows the preparation of sulfonylphenyl derivatives 3, where one of Z or W is a leaving group. A substituted aromatic or heteroaryl 2, such a tetrahydropyran subεtituted aryl, and a base such as anhydrous potassium carbonate are dissolved in anhydrous solvent such as DMF. A solution of sulfonylphenyl derivative 1 in anhydrous DMF is added and stirred at room temperature to provide the sulfonylphenyl derivatives 3. Scheme II Y 0 Base II RY—CCH 3 R 1 C0 2 CH 3 0 Synthetic Scheme II shows the preparation of pyrazole compounds embraced by Formula I where R is Ar or Z (as defined in Scheme I) , and R a is a radical defined above for the substituentε optionally εubεtituted on A. In step 1, ketone 4 is treated with a base, preferably NaOMe or NaH, and an ester, or ester equivalent, to form the intermediate diketone 5 (in the enol form) which iε uεed without further purification. In εtep 2, diketone 5 in an anhydrouε protic εolvent, εuch aε absolute ethanol or acetic acid, is treated with the hydrochloride salt or the free base of a substituted hydrazine at reflux to afford a mixture of pyrazoles 6 and 7. Recrystallization from diethyl ether/hexane or chromatography affords 6 usually as a solid. Similar pyrazoles can be prepared by methods described m U.S. Pat. Nos. 4,146,721, 5,051,518, 5,134,142 and 4,914,121 which are incorporated by reference. Scheme III Oxidize Scheme III shows the four εtep procedure for forming pyrazoleε 11 of the present invention (where R^ iε alkyl) from ketoneε 8. In εtep 1, ketone 8 iε reacted with a base, such as lithium bis (trimethylεilyl)amide or lithium diisopropylamide (LDA) to form the anion. In step 2, the anion is reacted with an acetylating reagent to provide diketone 9. In εtep 3, the reaction of diketone 9 with hydrazine or a εubεtituted hydrazine, gives pyrazole 10. In step 4, the pyrazole 10 iε oxidized with an oxidizing reagent, εuch aε Oxone® (potaεεium peroxymonosulfate) , 3-chloroperbenzoic acid (MCPBA) or hydrogen peroxide, to give a mixture of the desired 3- (alkylsulfonyDphenyl-pyrazole 11 and the 5- (alkylsulfonyl)phenyl-pyrazole isomer. The desired pyrazole 11, uεually a white or pale yellow εolid, iε obtained in pure form either by chromatography or recrystallization. Alternatively, diketone 9 can be formed from ketone 8 by treatment with a base, such as sodium hydride, in a solvent, such as dimethylformamide, and further reacting with a nitrile to form an aminoketone. Treatment of the aminoketone with acid forms the diketone 9. Similar pyrazoleε can be prepared by methodε deεcribed in U.S. Pat. No. 3.984,431 which iε incorporated by reference. Scheme IV 17 Diaryl/heteroaryl thiophenes (where T is S, and Rb is alkyl) can be prepared by the methods described in U.S. Patent Nos. 4,427,693, 4,302,461, 4,381,311, 4,590,205, and 4,820,827, and PCT documents WO 95/00501 and W094/15932, which are incorporated by reference. Similar pyrroleε (where T iε N) , furanones and furans (where T iε 0) can be prepared by methods described in PCT documentε WO 95/00501 and W094/15932. Scheme V MCPBA RYCOC1 Base Diaryl/heteroaryl oxazoles can be prepared by the methods described in U.S. Patent Noε. 3,743,656, 3,644,499 and 3,647,858, and PCT documentε WO 95/00501 and W094/15932, which are incorporated by reference. Scheme VI 25 26 1) C1S0 3 H 2) NH 4 OH Diaryl/heteroaryl isoxazoles can be prepared by the methods described in PCT documents WO92/05162, and WO92/19604, and European Publication EP 26928 which are incorporated by reference. Sulfonamides 27 can be formed from the hydrated isoxazole 26 in a two εtep procedure. Firεt, hydrated isoxazole 26 is treated at about 0 °C with two or three equivalentε of chloroεulfonic acid to form the correεponding εulfonyl chloride. In εtep two, the εulfonyl chloride thus formed is treated with concentrated ammonia to provide the sulfonamide derivative 27. Scheme VII lation; 31 32 Scheme VII shows the three step preparation of the substituted imidazoles 32 of the present invention. In step 1, the reaction of substituted nitriles (R^-CN) 28 with primary phenylamineε 29 in the preεence of alkylaluminum reagentε such as trimethylalummum, triethylalummum, dimethylalummum chloride, diethylaluminum chloride in the presence of inert solventε εuch as toluene, benzene, and xylene, gives amidines 30. In step 2, the reaction of amidine 30 with 2-haloketones (where X is Br or Cl) in the presence of baseε, εuch aε εodium bicarbonate, potaεsium carbonate, sodium carbonate, potassium bicarbonate or hindered tertiary amines such as N, N' - diisopropylethylamme, gives the 4, 5-dihydroimidazoles 31 (where R^ iε alkyl, R c iε hydroxyl and R^ is hydrido) . Some of the suitable solvents for this reaction are isopropanol, acetone and dimethylformamide. The reaction may be carried out at temperatures of about 20°C to about 90°C. In εtep 3, the 4, 5-dihydroimidazoleε 31 may be dehydrated in the preεence of an acid catalyεt εuch aε 4-toluenesulfonic acid or mineral acids to form the 1, 2-disubεtituted imidazoles 32 of the invention. Suitable solvents for this dehydration step are e.g., toluene, xylene and benzene. Trifluoroacetic acid can be used as solvent and catalyst for this dehydration step. In some cases (e.g., where YR = methyl or phenyl) the intermediate 31 may not be readily isolable. The reaction, under the conditions described above, proceeds to give the targeted imidazoles directly. Similarly, imidazoles can be prepared having the sulfonylphenyl moiety attached at position 2 and Y attached at the nitrogen atom at position 1. Diaryl/heteroaryl imidazoles can be prepared by the methods described in U.S. Patent Nos. 4,822,805, and PCT document WO 93/14082, which are incorporated by reference. Scheme VIII OTMS R H TMSCN catalyst ,Y CN 37 Oxidation 38 39 The subject imidazole compounds 39 of this invention may be synthesized according to the sequence outlined in Scheme VIII. Aldehyde 33 may be converted to the protected cyanohydrin 34 by reaction with a trialkylεilyl cyanide, εuch as trimethylsilyl cyanide (TMSCN) in the presence of a catalyst: such as zinc iodide (Znl 2 ) or potaεεium cyanide (KCN) . Reaction of cyanohydrin 34 with a εtrong base followed by treatment with benzaldehyde 35 (where R 2 is alkyl) and uεing both acid and baεe treatments, in that order, on workup gives benzoin 36. Exampleε of strong baseε εuitable for this reaction are lithium diisopropylamide (LDA) and lithium hexamethyldisilazane. Benzoin 36 may be converted to benzil 37 by reaction with a suitable oxidizing agent, such as bismuth oxide or manganese dioxide, or by a Swern oxidation using dimethyl sulfoxide (DMSO) and trifluoroacetic anhydride. Benzil 37 may be obtained directly by reaction of the anion of cyanohydrin 34 with a substituted benzoic acid halide. Any of compounds 36 and 37 may be used as intermediates for conversion to imidazoles 38 (where R 2 is alkyl) according to chemical procedureε known by thoεe εkilled in the art and deεcribed by M. R. Grimmett, "Advances in Imidazole Chemistry" in Advances in Heterocyclic Chemistry, 12, 104 (1970) . The converεion of 37 to imidazoles 38 is carried out by reaction with ammonium acetate and an appropriate aldehyde (RYCHO) in acetic acid. Benzoin 36 may be converted to imidazoles 38 by reaction with formamide. In addition, benzoin 36 may be converted to imidazoles by first acylating with an appropriate acyl group (RYCO-) and then treating with ammonium hydroxide. Those skilled in the art will recognize that the oxidation of the sulfide (where R 2 is methyl) to the sulfone may be carried out at any point along the way beginning with compounds 35, and including oxidation of imidazoles 38, using, for examples, reagents such as hydrogen peroxide in acetic acid, m- chloroperoxybenzoic acid (MCPBA) and potasεium peroxymonoεulfate (OXONE®) . Diaryl/heteroaryl imidazoleε can be prepared by the methods described in U.S. Patent Nos. 3,707,475, 4,686,231, 4,503,065, 4,472,422, 4,372,964, 4,576,958, 3,901,908, European publication EP 372,445, and PCT document WO 95/00501, which are incorporated by reference. Scheme IX 40 41 Diaryl/heteroaryl cyclopentenes can be prepared by the methods described in U.S. Patent No. 5,344,991, and PCT document WO 95/00501, which are incorporated by reference. Scheme X Similarly, Synthetic Scheme X shows the procedure for the preparation of 1, 2-diaryIbenzene antiinflammatory agents 47 from 2-bromo-biphenyl intermediateε 46 (prepared similar to that described in Synthetic Scheme IX) and the appropriate substituted phenylboronic acids. Using a coupling procedure similar to the one developed by Suzuki et al. [ Synth . Commun . , 11, 513 (1981)], intermediates 46 are reacted with the boronic acids in toluene/ethanol at reflux in the presence of a Pd° catalyst, e.g., tetrakis (triphenylphoεphine)palladium(0) , and 2M εodium carbonate to give the correεponding 1,2- diaryIbenzene antiinflammatory agentε 47 of this invention. Scheme XI 48 49 50 Diaryl/heteroaryl thiazoleε can be prepared by the methodε deεcribed in U.S. Patent No. 4,051,250, 4,632,930, European Application EP 592,664, and PCT document WO 95/00501, which are incorporated by reference. Isothiazoles can be prepared as described in PCT document WO 95/00501. Scheme XI I Diaryl/heteroaryl pyridines can be prepared by the methods described in U.S. Patent Nos. 5,169,857, 4,011,328, and 4,533,666, which are incorporated by reference. For example, Synthetic Scheme XII shows the procedure used to prepare 3-alkylcarbonylaminoalkyl pyridine antiinflammatory agents 53, 3-haloalkyl pyridine antiinflammatory agentε 55, 3-hydroxyalkyl pyridine antiinflammatory agentε 56, heteroatom substituted 3-alkyl pyridine antiinflammatory agents 58 and 3-aryloxyalkyl pyridine antiinflammatory agentε 59 from the corresponding carbonitriles 51. The 3- alkylcarbonylaminoalkyl pyridine antiinflammatory agentε 53 (where R' is alkyl) are prepared in a two step procedure from the carbonitriles 51. In step one, the carbonitrile 51 is reduced using reducing agents, such as diisobutyl aluminum hydride (DIBAL) in a solvent such aε toluene or boraneε in a εolvent εuch as tetrahydrofuran, at room temperature or reflux to form the aminoalkyl pyridine 52. Additional reducing reagent may be added to the solution. In step two, an acid chloride is added to the aminoalkyl pyridine 52 in a solvent such as ethyl ether or tetrahydrofuran and stirred to form the alkylcarbonylaminoalkyl pyridines 53. The 3-haloalkyl pyridine antiinflammatory agents 55 are prepared in a two step procedure from the carbonitriles 51. In step one, the carbonitriles 51 are reduced using agents, such as diisobutyl aluminum hydride (DIBAL) in a solvent such as toluene, at room temperature to form the aldehydes 54. The 3- hydroxyalkyl pyridines 56 also can be isolated from this reaction. In step two, a halogenating agent, such as diethylamino sulfur trifluoride (DAST) is added to the aldehyde 54 to form the haloalkyl pyridineε 55. Reduction of aldehydeε 54 with agents such as diisobutyl aluminum hydride (DIBAL) followed by methanol and water in methanol to yield the 3-hydroxyalkyl pyridines 56. Compound 56 is convertible to alkoxyalkyl and aralkoxyalkyl compoundε 59 by sequential treatment first with a base and then with an alkyl or aralkyl halide. An example of a suitable base is sodium hydride. Examples of alkyl and aralkyl halides are methyl iodide and benzyl chloride. Alternatively, compound 56 may be converted to the haloalkyl compound 57 using a suitable halogenating agent, such as thionyl chloride. Under such circumεtanceε, the hydrochloride εalt may be iεolated. Thiε in turn may be converted to compoundε 58 by reaction with the appropriate alcohol, thiol, or amine. It may be advantageous to carry out this reaction in the presence of a base. Examples of suitable alcohols are methanol, ethanol, benzyl alcohol and phenol. Examples of suitable thiols are n-butyl mercaptan, benzylthiol and thiophenol. Examples of suitable amines are dimethylamine, benzylamine, N- methylbenzylamine, aniline, N-methylaniline and diphenylamine. Examples of εuitable baεeε are sodium hydride and potassium carbonate. Alternatively, amines are accessible by reaction of aldehyde 54 with a primary or secondary amine in the presence of a reducing agent. Examples of suitable primary amines are methyl amine and ethylamine. An example of a suitable secondary amine is dimethylamine. Suitable reducing agentε include sodium cyanoborohydride and sodium borohydride. Scheme XIII Oxidation 60 61 Scheme XIII shows a method to form the alkylsulfonylphenyl subεtituted heterocycleε 61 of the current invention by oxidation of alkylthio or alkylsulfinyl derivatives 60. Aqueous hydrogen peroxide (30%) is added to a suspension of a (methylthio)phenyl subεtituted heterocycle 60 in acetic acid. The mixture is stirred while heating to about 100°C for about 2 hours. Alternatively, m- chloroperoxybenzoic acid (MCPBA) , and other oxidizing agents [potassium peroxymonosulfate (OXONE®) ] can be used to form the sulfonyl radicals 61. Scheme XIV 62 NaOAc , H 2 0 63 C 64 Synthetic Scheme XIV shows the three step procedure used to prepare sulfonamide antiinflammatory agents 63 and the two step procedure used to prepare fluoromethyl sulfone antiinflammatory agentε 64 from their corresponding methyl sulfoneε 62. In step one, THF solutions of the methyl sulfoneε 62 at -78°C are treated with an alkyllithium reagent, e.g., methyllithium, n-butyllithium, etc. In εtep two, the anionε generated in εtep one are treated with an organoborane, e.g., triethylborane, tributylborane, etc., at -78°C then allowed to warm to ambient temperature prior to εtirring at reflux. In step three, an aqueous εolution of εodium acetate and hydroxylamine-O-εulfonic acid iε added to provide the corresponding sulfonamide antiinflammatory agentε 63 of this invention. As an alternative to the borane chemistry found in step two above, the base treated sulfone is reacted with an alkylsilane, such as (iodomethyl) trimethylεilane or (chloromethyl) trimethylεilane, at room temperature to give a silylalkylsulfone. The εilylalkylεulfone is converted to a sulfinic acid εalt by heating to about 90°C with tetrabutylammonium fluoride. Treatment proceedε aε in εtep three above to produce the εulfonamide. Alternatively, the anion solutions generated in step one may be warmed to 0°C and treated with N- fluorodibenzeneεulfonamide to provide the correεponding fluoromethyl sulfone antiinflammatory agents 64 of this invention. Scheme XV Synthetic Scheme XV shows the four step procedure used to prepare anti-inflammatory compound of Formula II. In step one, a dichloromethane solution of 1- (substitutedphenyl) -2-hydroxy-2-[4- (methylsulfonyl)phenyl]ethanone 65 (described in U. S. Patent 5,380,738) is treated with benzyloxyacetyl chloride in the presence of pyridine base to provide 2- benxyloxymethyl-4- (substitutedphenyl) -5-[4- (methylsulfonyl phenyl]oxazole 66 in good yield. In step two, the benzyloxy group is removed by hydrogenolysis in the presence of a catalytic amount of 10% palladium on charcoal to provide the hydroxymethyl compound 67. In step three, the hydroxymethyl compound 67 is treated with a solution of methanesulfonyl chloride in the presence of triethylamine base to produce the unstable mesylate 68 that iε used directly in the next step. In step four, a mixture of the mesylate and a 3,4,5,6-tetrahydro-2H pyran in dimethylformamide (DMF) is treated with potassium carbonate to effect ether formation and provide the anti-inflammatory agents 69 (where R^ is halo, alkoxy, or alkyl) ' of the present invention. Scheme XVI 74 Synthetic Scheme XVI εhowε the four εtep procedure that iε uεed to prepare anti-inflammatory compound of Formula II. In εtep one, benzoin 70 iε mixed with ethyl carbamate (urethane) and heated to reflux to provide oxazolone 71 in high yield. In εtep two, oxazolone 71 iε treated with a mixture of phoεphorus oxychloride and triethylamine base to produce 2-chloro- 5-phenyloxazolt 72. In εtep three, 2-chloro-5- phenyloxazole 72 iε treated firεt with chloroεulfonic acid to effect regioεelective chloroεulfonation, followed by treatment with aqueous ammonia provides 2- chloro-5- (4-sulfonamido)phenyloxazole 73 in high yield. In step four, 2-chloro-5- (4-sulfonamido)phenyloxazole 73 and a tetrahydro-2H-pyran-substituted phenol is treated with potassium carbonate to effect ether formation and provide the anti-inflammatory agents of the present invention 74. Scheme XVII COo 2C<-H"3 Base R 1 - CCH 3 ( C0 2 CH 3 ) 2 ^ O R 2 79 Synthetic Scheme XVII showε a four step method of making the pyrazole phenylethers 79 of the present invention. In step 1, the dione 76 is formed from ketone 75 through the addition of a base, such as lithium bi (trimethylsilyl)amide or lithium diisopropylamide (LDA) , followed by reacting with an appropriate acetylating reagent, such as (Cθ2CH3)2- Treatment of the dione 76 with a phenylhydrazine yields the pyrazole ester 77. The pyrazole ester 77 is first treated with base to hydrolyze the ester and is then reduced to the alcohol 78 by treatment with borane in THF. In εtep four, the alcohol 78 iε treated with methaneεulfonyl chloride in the preεence of triethylamine baεe to produce the unεtable meεylate that iε directly reacted with a 3, 4, 5, 6-tetrahydro-2H pyran in dimethylformamide and K2CO3 to effect ether formation and provide the anti-inflammatory agentε 79 of the preεent invention. Scheme XVIII Scheme XVIII shows a procedure for forming an alkynyl oxazole 84 (where R 2 is amino) , εimilar to that εhown in Scheme V above. The ketone εulfonamide 81 is formed from ketone 80 through chloroεulfonation and ammonolyεis with ammonium hydroxide in a solvent εuch aε acetone. The ketone sulfonamide 81 is halogenated, εuch aε with HBr in acetic acid and bromine, to form the haloketone εulfonamide 82. Subεtitution with butynoic acid in the presence of K2CO3 , a crown ether, such as 18-crown-6, and dimethylacetamide (DMA) yields the alkynyl ketoeεter 83 . Converεion of the alkynyl ester 83 to the alkynyl oxazole 84 proceeds as previously deεcribed in Scheme V. Scheme XIX -CH 2 Br 88 Synthetic Scheme XIX εhows the procedures for forming heterocycloalkynyletherε 87 , heterocyclotriazole etherε 88 and heterocycloalkyletherε 89, from the corresponding alkyneε 85. The alkyneε 85 are halogenated εuch aε with N-bromoεuccinimide (NBS) and 2 , 2 ' -azobiε (2- methylpropionitrile) (AIBN) to form the haloalkynes 86. Substitution with the appropriate aryl or aralkyl alcohols in the presence of potassium carbonate yields the alkynyl ethers 87 of the present invention. The alkynyletherε 87 can be converted to heterocyclo- containing spacers 88 by treatment with azidotrimethylsilane, followed by acid. Alternatively, the alkynylethers 87 can be reduced, such as with hydrogen in the presence of catalyst, such aε palladium, to yield the heterocycloalkyletherε 89. Scheme XX 0s04 , H 2 0 2 95 Scheme XX εhowε another method of forming the alkynylethers 92, alkylethers 93, alkenylethers 94 and the diols 95 of the present invention from the appropriate alkynes 90. In Step one, the alkyneε 90 (where P is a protecting group such as tetrahydropyranyl, trialkylεilyl, tert- butyldimethylsilyl or diphenylalkylεilyl) are acid treated to form the alkynyl alcoholε 91. Subεtitution of the alcohol 91 with aralkyl halides or heteroaryl halides in the preεence of 1,8- diazabicyclo[5.4.0]undecane (DBU) yields the propynylethers 92 of the present invention. Reduction of the alkynylethers 92 with hydrogen in the preεence of metal catalyst yields the alkylethers 93. Alternatively, treatment with diimide reduces the alkynylethers 92 to the alkenylethers 94. Oxidation of the alkenylether 94, such as with osmium tetraoxide and hydrogen peroxide, yields the diols 95 of the present invention. Scheme XXI Additional antiinflammatory agents containing various substituted alkylether spacer radicals including carbonylalkylethers 98, aminoalkylethers 100, hydroxyalkylethers 101, oxyiminoalkyletherε 99, and amidoalkyletherε 102, can be prepared from ketoneε 96, by the procedureε shown in Scheme XXI. The ketones 96 are halogenated to form halomethylketone 97 εuch aε by treatment with NBS in the presence of AIBN. Substitution of appropriate alcohols with the halides 97 in the presence of base, such as potassium carbonate, generates the ketoalkylethers 98. The ketoalkylethers 98 can be converted to the oxyimino- containing spacers 99 (where R9 is alkyl) by treatment with εubεtituted oxyamineε, εuch aε hydroxylamine. Hydroxyalkyl spacers 101 can be prepared by reducing the carbonyl in the ketoalkylethers 99 such as with sodium borohydride. Amination of the ketoalkylethers 99 by reaction with ammonium acetate and sodium cyanoborohydride in the presence of acetic acid generates the aminoalkylethers 100. Acetylation of the aminoethers 100 by acid chlorides or anhydrides in the presence of base, such as trialkylamines, produces the amidoalkylethers 102. Scheme XXI I 107 Scheme XXII εhowε the preparation of etherε 105 and amideε 107 antiinflammatory agentε of the preεent invention. Eεters 103 where Y is alkyl, can be converted to the alcoholε 104 by treatment with a reducing agent, such as DIBAL-H. The ethers 105 are formed by reacting with an aralkyl halide in the presence of base. Alternatively, the esterε 103 can be hydrolyzed to the acidε 106 with base such as LiOH. Amides 107 are formed from the acid 106 by treatment with thionyl chloride to form the acid chlorideε, followed by substitution with aralkylamines. Scheme XXIII 110 Scheme XXIII εhowε the preparation of the antiinflammatory eεters 109 and amides 110 of the present invention. Base treatment of ester 108, such as with sodium hydride, followed by addition of an aralkyl halide or heteroaralkyl halide forms the ester 109. Formation of the amide 110 from the eεterε 109 occurε in a three step procedure. Treatment with base, such aε lithium hydroxide, and thionyl chloride yields the acid chloride. Addition of an amine yields the amide 110. Scheme XXIV z = o,s 112 116 Scheme XXIV shows the preparation of the antiinf lammatory ethers and thioethers 116 of the present invention. Ethyl bromoacetate is added to a mixture of hydroxy or mercaptan-substituted- (tetrahydro-2H-pyran-4- yl ) benzene 111 and base to give the acetate 112. The acid 113 is formed from acetate 112 such as by treatment with ethanolic LiOH. Addition of bromoethanone 114 to the acid 115 in a solvent such as dimethylformamide gives the benzoin ester 115. The benzoin ester 115 is heated with acetic acid and ammonium acetate to give the oxazole 116. Scheme XXV Scheme XXV showε the preparation of the antiinflammatory amides 123 and amines 124 of the present invention. Protected amino acid 118 and bromoethanone 117 is treated with base and 18-crown-6 to afford the benzoin ester 119. This benzoin ester 119 is treated with acetic acid and ammonium acetate and heated to provide the protected 2- (aminoalkyl)oxazole 120. The protected 2- (aminoalkyl)oxazole 120 is deprotected, such as by hydrogenation with 10% Pd on carbon, to give the 2- (aminoalkyl)oxazole 121. ( etrahydro-2H-pyran-4- yDphenoxyacetic acid derivative 122 is coupled with 2- (aminoalkyl)oxazole 121 such as with HOBt and EDC to afford amide 123. Reduction of amide 123 such as with LiAlH 4 provides the amine 124. Scheme XXVI 125 126 LiOH, H 2 0 EtOH NH 4 OAc, HOAc, reflux 130 Scheme XXVI εhowε the preparation of the antiinflammatory ether derivatives 130 of the present invention. A solution of the appropriate hetero- substituted ester and base iε added to a [tetrahydropyran-4-yl] -α-bromotoluene 125 to give the [tetrahydropyran-4-yl]phenylmethyl ester 126. The acid 127 is formed from ester 126 such as bv treatment with ethanolic LiOH. Baεe iε added to acid 127 and 2- bromoethanone 128 iε added to form the benzoin ester 129. Acetic acid and ammonium acetate are added to benzoin ester 129 and heated to give the oxazole 130. Scheme XXVII 134 Scheme XXVII shows a method for preparing oxazoles 135. A εolution of aldehyde 131 and zinc iodide in an organic solvent such as dichloromethane is treated with trimethylsilylcyanide to give the trimethylεilyl cyanohydrin. The trimethylεilyl cyanohydrin iε added to a solution of R^-magnesium bromide in diethyl ether while maintaining the temperature between 25-35 °C to give the benzoin 132. The benzoin 132, pyridine, and acid chloride are reacted at room temperature to yield the benzoin ester 133. Addition of ammonium acetate to the benzoin ester 133 and heating yields the oxazole 135. Alternatively, the hydroxy-oxazoline 134 is isolated. Dehydration of the hydroxy-oxazoline 134 yields the oxazoles 135. By reversing the positions of Y and the phenyl group in benzoin 132, oxazoleε can be prepared where Y is at position 4. Scheme XXVIII 136 NH 4 0H Scheme XXVIII shows a method of preparing oxazolylbenzenesulfonamides 138 of the present invention. The oxazole 136 iε stirred with chloroεulfonic acid at about 5 °C to give the sulfonyl chlorides 137. The sulfonyl chloride 137 is reacted at about 5 °C with ammonium hydroxide to give the sulfonamides 138 of the current invention. The following examples contain detailed descriptions of the methodε of preparation of compounds of Formulas I-II. 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. All compounds showed NMR spectra consistent with their assigned structureε. Example 1 4- [5- (4-Chlorophenyl) -3- [ [3-fluoro-5- (3,4,5,6- t etrahydro -4 -methoxy- 2H -pyran- 4 - yl ) phenoxy] ethyl] -lH-pyrazol-1 - yl ] benzenes lfonamide Step 1. Preparation of methyl-4- ( 4-chloroΩhenyl) -2 , - dioxobutanoate . Dimethyl oxalate (15.27 g, 0.129 moi) and 4'- chloroacetophenone (20.0 g, 0.129 moi) were diluted with methanol (300 mL) and εodium methoxide (25 wt% in methanol, 70 mL) was added in one portion. The reaction was stirred at room temperature for 16 hours (the reaction became an insoluble mass during this time) . The solid was mechanically broken up, hydrochloric acid (cone. 70 mL) was added, and the white suspension was stirred vigorously at room temperature for 1 hour. The suεpenεion waε cooled to 0 °C and held for 0.5 hour. The εolid was filtered, and the filter cake was waεhed with cold water (100 mL) . Upon drying, methyl-4- [4- (chloro)phenyl] -2, 4- dioxobutanoate waε obtained (16.94 g, 54.4%) aε the enol: mp 108.5-110.5 °C. ^-H NMR (CDCl 3 /300 MHz) δ 7.94 (d, J=8.66 Hz, 2H) , 7.48 (d, J=8.66 Hz, 2H) , 7.04 (ε, IH) , 3.95 (ε, 3H) , 3.48 (ε, IH) . Step 2. Preparation of methyl l-(4- aminoεulfonylphenvD -5- (4-chlorophenyl) -lH-pyrazole-3- carboxylate Methyl-4- [4- (chloro)phenyl] -2,4- dioxobutanoate (5.0 g, 20.78 mmol) waε added to 4- εulfonamidylphenyl hydrazine hydrochloride (5.11 g, 22.86 mmol) and methanol (50 mL) . The reaction veεsel was heated to reflux and held for 16 hours. A precipitate formed overnight. The suspension waε cooled to 0 °C, held for 0.5 hour, filtered and waεhed with cold water to provide, after air drying, 7.91 g, 91% of crude pyrazole. Recrystallized 3.50 g from boiling ethanol to yield 3.14 g (90%) of pure methyl 1- (4-aminosulfonylphenyl) -5- (4-chlorophenyl) -1H- pyrazole-3-carboxylate: mp 227 °C; l -H NMR (CDCl 3 /300 MHz) δ 7.91 (d, J=8.86 Hz, 2H) , 7.44 (d, J=8.86 Hz, 2H) , 7.33 (d, J=8.66 Hz, 2H) , 7.14 (d, J=8.66 Hz, 2H) , 7.03 (s, IH) , 3.96 (ε, 3H) . Maεε Spectrum, MH+ = 392. Anal. Calc'd for Ci 7 H 1 3 θ ClS: C, 52.11; H, 3.60; N, 10.72; Cl, 9.05; S, 8.18. Found: C, 52.07; H, 3.57; N, 10.76; Cl, 9.11; S, 8.27. Step 3. Preparation of 1- (4-aminoεulfonylphenyl) -5- (4-chlorophenyl) -lH-pyrazole-3-carboxylic acid Methyl 1- (4-aminoεulfonylphenyl) -5- (4- chlorophenyl) -lH-pyrazole-3-carboxylate (1.0 g, 2.66 mmol) waε added to tetrahydrofuran (20 mL) . Aqueouε sodium hydroxide (2.5 N, 2.7 mL) and water (2.5 mL) were added, and the suεpenεion waε heated to reflux and held for 16 hourε. The εolids all dissolved during this time. The reaction was cooled to room temperature, and hydrochloric acid solution (I N, 11 mL) was added. The aqueous εuεpenεion waε extracted with methylene chloride (2x20 mL) . The combined organic solution was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to an oil. Trituration with 30 mL of dichloromethane yielded, upon filtration and drying, 0.90 g (94%) of 1- (4-aminosulfonylphenyl) -5- (4-chlorophenyl) -1H- pyrazole-3-carboxylic acid as a white εolid: mp 126- 128 °C. Step 4. Preparation of 4- [5- (4-chlorophenyl) -3- hvdroxymethyl-lH-pyrazol-1-yllbenzenesulfonamide. 4- [4- (Aminosulfonyl)phenyl-5- (4-chlorophenyl) - lH-pyrazole-3-carboxylic acid (3.8 g, 10 mmol) and tetrahydrofuran (100 mL) was stirred at room temperature during the dropwise addition of 1.0 M borane-tetrahydrofuran complex (30 mL, 30 mmol) . The mixture was allowed to reflux for 16 hours. The solution was cooled and methanol was added dropwiεe until gas evolution ceased. Ethyl acetate (100 mL) was added and the solution washed with IN hydrochloric acid, brine, εat. aq. sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated. The resultant material waε recryεtallized from ethanol:water to yield 4- [5- (4- chlorophenyl) -3-hydroxymethyl-lH-pyrazol-1- yl]benzeneεulfonamide (2.6 g, 71%) as a white solid: mp 192-194 °C; ^-H NMR (DMSO-d 6 /300 MHz) δ 7.81 (d, J=8.7 Hz, 2H) , 7.46 (d, J=8.4 Hz, 2H) , 7.42 (brs, 2H) , 7.40 (d, J=8.7 Hz, 2H) , 7.26 (d, J=8.4 Hz, 2H) , 6.63 (s, IH) , 5.35 (t, J=8.0 Hz, IH) , 4.50 (d, J=8.0 Hz, 2H) . Anal. Calc'd for C 16 H 14 N 3 SO 2 CI: C, 52.82; H, 3.88; N, 11.55. Found: C, 52.91; H, 3.88; N, 11.50. Step 5. Preparation of 4- [5- (4-chlorophenyl) -3- f T3- fluoro-5- (3,4,5, 6-tetrahvdro-4-methoxy-2H-pyran-4- vDphenoxy1methv11 -lH-pyrazol-1-yllbenzenesulfonamide. A solution of (569 mg, 1.56 mmol) of 4- [5- (4- chlorophenyl) -3-hydroxymethyl-lH-pyrazol-l- yl]benzeneεulfonamide in 50 mL of dichloromethane waε stirred at 25 °C as triethylamine (315 mg, 3.12 mmol) was added dropwise, followed by the addition of methanesulfonyl chloride (215 mg, 1.88 mmol) . The reaction was stirred for 5 minutes, after which the organic solution was washed with IN HCl, dried over sodium sulfate and concentrated in vacuo to give a yellow oil (500 mg) , which waε characterized as the expected mesylate by its NMR spectrum. This material was used without further purification. 4- (5-Fluoro-3- hydroxyphenyl) -4-methoxytetrahydropyran (373 mg, 1.649 mmol) and anhydrous potassium carbonate (228 mg, 1.649 mmol) were dissolved in 25 mL of anhydrous DMF. The solution was stirred at room temperature under a blanket of dry nitrogen for 20 minutes, then a solution of meεylate (500 mg, 1.374 mmol) in anhydrouε DMF (15 mL) was added in one portion. The resulting solution was εtirred at room temperature for 72 hourε, then IN HCl (30 mL) waε added. After εtirring an additional 0.5 hour, the εyεtem waε extracted with ethyl acetate (2x40 mL) . The combined organic εolution was sequentially washed with 1 N HCl (40 mL) , saturated aqueous NaHC0 3 (2x40 mL) , 50% saturated NaCl (2x40 mL) , and brine (40 mL) , dried over MgSθ 4 and filtered. The solvents were evaporated under reduced presεure to yield an oil. The oil waε purified by flaεh chromatography on εilica gel eluting with 40% ethyl acetate in hexane to yield, upon concentration of the appropriate fractionε (200 mg, 25%) of 4- [5- (4- chlorophenyl) -3- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxy-2H-pyran-4-yDphenoxy]methyl] -lH-pyrazol-1- yl]benzenesulfonamide as a foam: Mass Spectrum: 572 (M+) . High resolution mass spectrum Calc'd for C 28 H 27 N 3 O 4 CIFS: 572.1422. Found: 572.1361. Anal. Calc'd. for C 28 H 27 N 3 θ ClFS- 1.4 H 2 0: C, 57.86; H, 5.17; N, 7.23; Cl, 6.10; S, 5.52. Found: C, 57.87; H, 4.92; N, 6.97; Cl, 6.10; S, 5.71. Example 2 4- ( 4 -Fluorophenyl ) -5- ( 4- ( me thy lsulf onyDphenyl) -2-[[3-(3,4,5,6- tetrahydro-4-methoxy-2H-pyran-4 - yl ) phenoxy ) methyl] oxazole Step 1. Esterif ication of 1- (4-f luorophenyl) -2- hydroxy-2- [4- (methylεulf onylphenyl) ethanone A solution containing (2.07 g, 6.71 mmol) of 1- (4- fluorophenyl ) -2-hydroxy-2- [4- (methylεulfonylphenyl) ethanone (U. S. Patent 5,380,738, Jan. 10, 1995) in 100 mL of dichloromethane waε εtirred at 25 °C aε (2.71 mL, 33.55 mmol) of pyridine waε added, followed by the addition of (1.27 mL, 8.05 mmol) of benzyloxyacetyl chloride. The reaction was stirred at 25 °C for 48 hours, after which the resulting yellow solution was washed with IN HCl, dried over Na 2 Sθ 4 and concentrated in vacuo . The oily yellow solid was purified via flash chromatography on a silica gel column using 20% ethyl acetate/hexane as the eluent. This provided 2.22 g (73 %) of a white foam, which was characterized as the benzoin ester on the basis of its NMR spectra: 1 H-NMR (CDC1 3 , 300 MHz) 8 3.03 (s, 3H) , 4.23 (d, IH, J=17.0 Hz), 4.33 (d, IH, j=17.0 Hz), 4.67 (s, 2H) , 6.95 (ε, IH) , 7.13 (t, 2H, J=8.5 Hz), 7.35 (m, 5H) , 7.66 (d, 2H, J=8.1 Hz) and 7.98 (m, 4H) . 19 F-NMR (CDCI 3 , 280 MHz) δ -102.5. Step 2. Preparation of 2-benzyloxymethyl-4- (4- fluorophenyl) -5- f4- (methylsulfonyl)phenv!1oxazole. A solution containing (2.22 g, 4.86 mmol) of the benzoin ester from Step 1 and (3.74 g, 48.6 mmol) of ammonium acetate in 100 mL of acetic acid was heated to 80 °C for 2 hours. The reaction was cooled to 25 °C and poured into water. The product was extracted into ethyl acetate and the combined organic extracts were washed with an aqueous solution of εodium bicarbonate. The solution was dried over sodium εulfate and concentrated in vacuo to give a yellow oil. Thiε crude material waε purified by flaεh chromatography on a silica gel column using 25% ethyl acetate/hexane as the eluent to give 2- benxyloxymethyl-4- (4-fluorophenyl) -5- [4- (methylsulfonyl)phenyl]oxazole (1.92 g, 90%) as a clear oil: X H-NMR (CDCI 3 , 300 MHz) δ 3.07 (s, 3H) , 4.70 (ε, 2H) , 4.72 (s, 2H) , 7.11 (t, 2H, J=8.8 Hz) , 7.22-7.40 ( , 5H) , 7.58 (m, 2H) , 7.76 (d, 2H, J=8.8 Hz) and 7.91 (d, 2H, J=8.8 Hz) . 19 F-NMR (CDCI 3 , 280 MHz) δ -111.88. Step 3. Preparation of 4- (4-fluorophenyl) -2- hydroxymethyl-5- [4- (methylsulfonyl)phenyl]oxazole. To a solution containing 2-benxyloxymethyl-4- (4- fluorophenyl) -5- [4- (methylsulfonyl)phenyl]oxazole from Step 2 (5.0 g, 11.4 mmol) in 20 mL of 50% THF/methanol was added 100 mg of 10% Pd on charcoal in a Fisher- Porter bottle. The reaction veεεel was evacuated and charged with hydrogen at 50 psi for 24 hours. The Pd on carbon was removed by filtration through diatomaceous earth and the filtrate was concentrated in vacuo to give 4- (4-fluorophenyl) -2-hydroxymethyl-5- [4- (methylεulfonyl)phenyl]oxazole (3.8 g, 97 %) as a white crystalline solid (recrystallized from 50% ethyl acetate-isooctane) : mp 156-157 °C; ^-H-NMR (CDC1 3 , 300 MHz) δ 3.07 (s, 3H) , 3.21 (bs, IH) , 4.81 (s, 2H) , 7.10 (t, 2H, J=8.5 Hz), 7.56 (m, 2H) , 7.72 (d, 2H, J=8.8 Hz) and 7.90 (d, 2H, J=8.8 Hz); 19 F-NMR (CDCI 3 , 280 MHz) δ -111.5. LRMS m/z 348 (M+H) . HRMS Calc'd. for C 17 H 14 NO 4 FS: 348.0706. Found: 348.0681. Anal. Calc'd. for C 17 H 1 4NO 4 FS: C, 58.78; H, 4.06; N, 4.03. Found: C, 58.67; H, 4.02; N, 4.01. Step 4. ' Preparation of 4- (4-fluorophenyl) -5- (4- (methylεulfonvDphenyl) -2- [ [ 3 - (3.4, 5.6-tetrahγdro-4- methoxy-2H-pyran-4-yl)phenoxy)methy11oxazole. A εolution containing 4- (4-fluorophenyl) -2- hydroxymethyl-5- [4- (methylεulfonyl)phenyl]oxazole from Step 3 (169 mg, 0.487 mmol) in 20 mL of dichloromethane waε εtirred at 25 °C aε triethylamine (136 μL, 0.974 mmol) was added dropwise, followed by the addition of methanesulfonyl chloride (56 μL, 0.730 mmol) . The reaction was stirred for 5 minutes, after which the organic solution was washed with IN HCl, dried over sodium sulfate and concentrated in vacuo to give a yellow oil which was characterized aε the expected meεylate by its NMR spectrum: 1 H-NMR (CDCI 3 , 400 MHz) δ 3.08 (s, 3H) , 3.17 (s, 3H) , 5.37 (s, 2H) , 7.12 (t, 2H, J=8.8 Hz), 7.58 (m, 2H) , 7.78 (d, 2H, J=8.8 Hz) and 7.94 (d, 2H, J=8.8 Hz) . This material was used without further purification. The mesylate was dissolved m 20 mL of DMF and potasεium carbonate (81 mg, 0.584 mmol) was added, followed by the addition of 4- (3-hydroxyphenyl) -4-methoxy-3 , 4, 5, 6- tetrahydro-2H-pyran (122 mg, 0.584 mmol). The reaction was stirred at 25 °C for 3 days and poured into 100 mL of water. The aqueous solution was extracted with ethyl acetate and the combined extracts were dried over sodium sulfate and concentrated in vacuo to give a beige solid. This material was purified by flash chromatography on a silica gel column using 50% ethyl acetate/hexane as the eluent to give 4- (4-fluorophenyl) -5- (4- (methylεulfonyl)phenyl) - 2- [ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy)methyl]oxazole (185 mg, 71%) as a white crystalline solid: l -H-NMR (CDC1 3 , 300 MHz) δ 1.90- 2.05 (m, 4H) , 2.97 (s, 3H) , 3.08 (ε, 3H) , 3.81 (m, 4H) , 5.25 (ε, 2H) , 6.98-7.17 (m, 5H) , 7.33 (t, IH, J=7.7 Hz), 7.60 (m, 2H) , 7.78 (d, 2H, J=8.5 Hz) and 7.93 (d, 2H, J=8.5 Hz) . 19 F-NMR (CDCI 3 , 280 MHz) δ -111.6. -LRMS m/z 544 (M+Li) . HRMS Calc'd. for C 29 H 28 N0 6 FS: 544.1781 (M+Li) . Found: 544.1831 (M+Li) . Example 3 4- (4 -Fluorophenyl) -2- [ [3-f luoro-5- (3,4,5,6- tetrahydro-4 -methoxy- 2H -pyran- 4 - yl ) phenoxy ) methyl] -5- ( 4- ( methyl sulfonyl ) phenyl ) oxazole 4- ( 4 -Fluorophenyl) -2- [ [3-f luoro-5- (3 , 4, 5 , 6- t etr ahydro - 4 -methoxy- 2 H-pyran- 4 -y 1 ) phenoxy ) methyl ] - 5 - (4- (methylεulf onyl) henyl) oxazole waε prepared in a similar faεhion from the reaction of the mesylate (Example 2, Step 4) and 4- (3-f luoro-5-hydroxyphenyl) - 4-methoxy-3,4,5,6-tetrahydro-2H-pyran: ^-H-NMR (CDCI 3 , 300 MHz) δ 1.84-2.02 (m, 4H) , 2.98 (s, 3H) , 3.08 (s, 3H) , 3.81 (m, 4H) , 5.23 (ε, 2H) , 6.76 (m, 2H) , 6.92 (s, IH) , 7.13 (m, 2H) , 7.60 (m, 2H) , 7.79 (d, 2H, J=8.5 Hz) and 7.93 (d, 2H, J=8.5 Hz) . 19 F-NMR (CDCI 3 , 280 MHz) δ -110.8 and -111.7. Anal. Calc'd. for C 29 H 27 Nθ 6 F 2 : C, 62.69; H, 4.90; N, 2.52. Found: C, 62.53; H, 4.96; N, 2.51. Example 4 4-[2-[3-Fluoro-5-( 4-methoxy-3, 4,5, 6-tetrahydro- 2H-pyran-4-yl )phenoxy] -4-phenyl-5- oxazolyl] benzenesulfonamide Step 1. Preparation of 4.5-diphenγloxazolone. Benzoin (31.8 g, 0.15 moi) and urethane (42.79 g, 0.45 moi) were heated to reflux for 3.0 hours. The hot mixture was poured into water (150 mL) . Acetone (150 mL) was added and heat was applied until the mixture dissolved. The solution was cooled and filtered, producing a white solid which was used in the next step without further purification. Step 2. Preparation of 2-chloro-4, 5-diphenyloxazole. 4, 5-Diphenyloxazolone from Step 1 (30 g, 0.126 moi) , triethylamine (12.8 g, 0.126 moi), and phosphorous oxychloride (96.6 g, 0.63 moi) were stirred at reflux for 4.0 hours. The mixture waε concentrated in vacuo , diεεolved in ether (250 mL) , washed with IN HCl, brine, and water, dried over MgS04 and concentrated to a light yellow oil which was used in the next step without further purification or characterization. Step 3. Preparation of 4- r2-chloro-4-phenyl-5- oxazolyl1benzenesulfonamide. Chlorosulfonic acid (20 mL) was cooled to 0 °C with stirring. 2-Chloro-4, 5-diphenyloxazole from Step 2 (1.53 g, 6 mmol) was added, and the stirred solution was warmed to room temperature over 1.0 hour. The mixture was added dropwise to ice and dichloromethane (50 mL) with stirring. The resultant organic layer was washed once with water and added to a 0 °C stirred solution of ammonium hydroxide (10 mL) . The mixture waε εtirred foi 1.0 hour and extracted with dichloromethane (3x50 mL) . The combined organic layerε were washed with 1 N HCl followed by brine and water, dried over MgS04 and concentrated. Recrystallization from ethyl acetate/hexanes gave a white εolid (1.5 g, 75%) : mp 158-159 °C. Anal. Calc'd. for C15H11N2O3SCI: C, 53.82; H, 3.31; N, 8.37. Found: C, 53.92; H, 3.32; N, 8.33. Step 4. Preparation of 4- \ 2- \ 3 -tluoro-5- (4-methoxy- 3,4,5, 6-tetrahvdro-2H-pyran-4-vDphenoxy1 -4-phenyl-5- oxazolyl1benzeneεulfonamide 4-[2-Chloro-4-phenyl-5- oxazolyl]benzeneεulfonamide from Step 3 (0.74 g, 2.2 mmol), N,N'-dimethylformamide (DMF) (20 mL) , potaεεium carbonate (0.61 g, 4.4 mmol) , and 4- (3-fluoro-5- hydroxyphenyl) -4-methoxy-3 ,4,5, 6-tetrahydro-2H-pyran [prepared aε deεcribed by G. C. Crawley, et al, J. Med . Chem . , 35, 2600-2609 (1992)] (0.75 g, 7.5 mmol) were εtirred at room temperature for 16.0 hourε . The εolution was diluted with ethyl acetate (100 mL) , washed with IN HCl, brine and water, dried over MgS04 and concentrated. The residue was diεsolved in ethyl acetate/hexanes (1:1) and filtered through silica. The eluant was concentrated and the residue was recrystallized from ethyl acetate/hexanes to afford 4- [2- [3-fluoro-5- (4-methoxy-3 ,4,5, 6-tetrahydro-2H-pyran- 4-yDphenoxy] -4-phenyl-5-oxazolyl]benzenesulfonamide as a white solid (0.4 g, 35%) : mp 159-161 °C. λ H NMR (CDCI3) 300 MHz δ 7.9 (d, J=8.7 Hz, 2H) 7.72 (d, J=8.7 Hz, 2H) 7.6 (m, 2H) 7.4 (m, 3H) 7.24-7.30 (m, 2H) 7.0- 7.1 (dt, J=9.5 Hz and J=1.8 Hz, IH) 4.85 (bε, 2H) 3.85 (dd, J=9.9 Hz and J=1.8 Hz, 4H) 3.05 (ε, 3H) 2.0 (m, 4H) . Anal. Calc'd. for C27H25N2O6SF: C, 61.82; H, 4.80; N, 5.34. Found: C, 61.77; H, 4.82; N, 4.31. Example 5 4- [2- [3- (4-Methoxy-3 ,4,5, 6-tetrahydro-2H-pyran- 4-yl)phenoxy] -4-phenyl-5- oxazolyl]benzenesulfonamide 4-[2-Chloro-4-phenyl-5- oxazolyl]benzeneεulfonamide from Example 4, Step 3, (0.6 g, 1.8 mmol), DMF (20 mL) , potassium carbonate (0.5 g, 3.6 mmol), and 4 (3-hydroxyphenyl) -4-methoxy- 3, 4, 5, 6-tetrahydro-2H-pyran (0.37 g, 1.8 mmol) [prepared as described by G. C. Crawley, et al, J " . Med. Chem. , 35, 2600-2609 (1992)] were stirred at room temperature for 16.0 hours. The εolution waε diluted with ethyl acetate (100 mL) , washed with IN HCl, brine and water, dried over MgS04 and concentrated. The residue was disεolved in ethyl acetate/hexanes (1:1) and filtered through silica. The eluant was concentrated and the residue recrystallized from ethyl acetate/hexanes to give 4- [2- [3- (4-methoxy-3,4,5, 6-tetrahydro-2H-pyran-4- yl)phenoxy] -4-phenyl-5-oxazolyl]benzenesulfonamide as a white solid (0.4 g, 44 %) : mp 145-147 °C. !H NMR (CDCI3) 300 MHz δ 7.88 (d, J=8.9 Hz, 2H) 7.70 (d, J=8.9 Hz, 2H) 7.6 (m, 2H) 7.36-7.5 (m, 6H) 7.0-7.1 (dt, J=6.4 Hz and J=2.2 Hz, IH) 4.85 (bs, 2H) 3.7 (m, 4H) 3.05 (s, 3H) 2.0 (m, 4H) . Anal. Calc'd. for C27H26N206S: C 64.02; H, 5.17; N, 5.53. Found: C, 63.94; H, 5.17; N, 5.55. EXAMPLE 6 4- [5- (4-Chlorophenyl) -3- (3- methoxyphenyl) thiomethyl-lH pyrazol-1- yl]benzenesulfonamide Step 1. Preparation of methyl 4- (4-chlorophenyl) -2 , 4- dioxobutanoate. Dimethyl oxalate (15.27 g, 0.129 moi), and 4'- chloroacetophenone (20.0 g, 0.129 moi) were added to methanol (300 mL) . Sodium methoxide (25 wt% in methanol, 70 mL) was added dropwise over about 0.5 hour. The reaction was stirred at room temperature for 16 hours, whereupon the sodium εalt of the butanoate precipitated from εolution. The mixture waε treated with 70 mL of cone. HCl and the white εuεpenεion was stirred vigorously at room temperature for 1 hour. The suspenεion waε cooled to 0 °C and held for 0.5 hour. The εolid waε filtered, and the filter cake waε waεhed with cold water (100 mL) . After drying ij' vacuo, methyl 4- [4- (chloro)phenyl] -3- ketobutyrate waε obtained (16.94 g, 54.4%) aε the enol: 1 H NMR (CDCI3/3OOMHZ) δ 7.94 (d, J=8.66 Hz, 2H) , 7.48 (d, J=8.66 Hz, 2H) , 7.04 (s, IH) , 3.95 (ε, 3H) , 3.48 (ε, IH) . Step 2. Preparation of 4- [4- (aminosulfonvDphenyl-5- (4 chlorophenyl) -lH-pyrazole-3-carboxylic acid. 4-Sulfonamidophenylhydrazine hydrochloride (1.45 g, 6.5 mmol) and methyl-4- (4-chlorophenyl) -2,4- dioxobutanoate from Step 1 (1.2 g, 5.0 mmol) were diεsolved in 50 mL of methanol and heated to reflux for 20 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo and the reεidue diεsolved in ethyl acetate, washed with water and brine, dried over anhydrous MgS04, filtered and re-concentrated to give a light brown solid. The crude solid was crystallized from methanol and water to provide 1.6 g, 85% of pure compound. This material was dissolved in 150 mL of methanol and treated with 75 mL of 3N NaOH. The solution was heated to reflux for 3 hours, and concentrated in vacuo . The reεidue waε acidified with cone. HCl and waε extracted into ethyl acetate. After removal of the ethyl acetate, the acid waε isolated and dried to afford 1.4 g, (75%, mp 135 °C) that was used directly in the next step. Step 3. Preparation of 4- [5- (4-chlorophenyl) -3- hvdroxymethyl-lH pyrazol-1-yllbenzeneεulfonamide. 4- [4- (Aminυεulfonyl)phenyl-5- (4 chlorophenyl) - lH-pyrazole-3-carboxylic acid from Step 2 (3.8 g, 10 mmol) and tetrahydrofuran (100 mL) were εtirred at room temperature during dropwiεe addition of 1.0 M borane-tetrahydrofuran complex (30 mL, 30 mmol) . The mixture waε held at reflux for 16 hourε. The mixture waε cooled and methanol waε added dropwiεe until gas evolution ceased. Ethyl acetate (100 mL) was added and the mixture waε waεhed with IN hydrochloric acid, brine, εat. aq. sodium bicarbonate solution, and water, dried over magnesium sulfate, filtered and concentrated. The resultant alcohol was recrystallized from ethanol:water to yield a white solid (2.6 g, 71%) : mp 192-194 °C. 1H NMR (DMSO-d6/300 MHz) δ 7.81 (d, J=8, 7 Hz, 2H) , 7.46 (d, J=8.4 Hz, 2H) , 7.42 (brs, 2H) , 7.40 (d, J=8.7 Hz, 2H) , 7.26 (d, J=8.4 Hz, 2H) , 6.63 (s, IH) , 5.35 (t, J=8.0 Hz, IH) , 4.50 (d, J=8.0 Hz, 2H) . Anal. Calc'd for C16H14N3SO2CI: C, 52.82; C, 52.91; H, 3.88; H, 3.88; N, 11.55; N, 11.50. Step 4. Preparation of 4- [ 5 - (4-chlorophenyl) -3- (3- methoxyphenyl)thiomethyl-lH-pyrazol-1- yllbenzeneεulfonamide. 4- [5- (4-Chlorophenyl) -3-hydroxymethyl) -1H- pyrazol-1-yl]benzenesulfonamide from Step 3 (500 mg, 1.374 mmol) was dissolved in anhydrous THF (30 mL) . Triethylamine (0.385 mL, 2.749 mmol) and methanesulfonyl chloride (0.16 mL, 2.062 mmol) were added εequentially, and the cloudy εuspension was stirred at room temperature for 0.5 hour. The reaction was diluted with ethyl acetate (35 mL) and washed with aqueous HCl (IN, 50 mL) . The organic solution was dried over anhydrouε MgSθ4 and filtered, then the εolvent was evaporated under reduced presεure to yield a crude oil. The oil was disεolved in anhydrouε THF (10 mL) . 3-Methoxythiophenol (0.205 mL, 1.649 mmol) waε dissolved in anhydrous THF. Sodium hydride (95%, 42 mg, 1.649 mmol) was added, and the reεulting frothy suspension was stirred at room temperature for 20 minutes, forming a clear, colorless solution. The solution of the meεylate prepared above waε added, then the reaction waε warmed to 40 °C and held for 16 hours. The reaction was cooled to room temperature then IN HCl (30 mL) was added. After stirring an additional 0.5 hour, the εystem was extracted with ethyl acetate (2x40 mL) . The combined organic solution was sequentially washed with 1 N HCl (40 mL) , saturated aqueous NaHCθ3 (2x40 mL) , 50% saturated NaCl (2x40 mL) , and brine (40 mL), then dried over anhydrous MgS04 and filtered. The solventε were evaporated under reduced pressure to yield an oil. The oil was purified by flash chromatography over silica gel eluting with 40% ethyl acetate in hexane to yield 4-[5- (4-chlorophenyl)-3- (3- methoxyphenyl)thiomethyl-lH-pyrazol-1- yl]benzenesulfonamide (273 mg, 41%) as a foam: Mass Spectrum: 486 (MH+) . High resolution mass spectrum Calc'd. for C23H20N3O3CIS2: 486.0713. Found: 486.0757. Ana: . Calc'd. for C23H20N3O3CIS2: C, 56.84; H, 4.15; N, 8.65; Cl, 7.29; S, 13.19. Found: C, 56.56; H, 4.22; N, 8.61; Cl, 7.41; S, 13.00. EXAMPLE 7 4- [5- ( 4 -Chlorophenyl ) -3- ( 3 -methoxyphenyl ) oxymethyl-lH- pyrazol -1-yl ] benzenesulfonamide 4- [5- (4 -Chlorophenyl) -3- (3- me thoxypheny 1 ) oxyme thy 1 - lH-pyrazo 1 - 1 - yl] benzeneεulfonamide waε prepared from 4- [5- (4- chlorophenyl ) -3-hydroxymethyl-lH-pyrazol-l- yl] benzeneεulfonamide (prepared in Example 6, step 3) in 39% yield by the method outlined in Example 1, Step 4: Masε Spectrum: 470 (MH+) . High reεolution maεε εpectrum Calc'd. for C23H20N3O4CIS: 470.0979. Found: 470.0983. Anal. Calc'd. for C23H20N3O4CIS: C, 58.78; H, 4.29; N, 8.94; Cl, 7.54; S, 6.82. Found: C, 58.85; H, 4.29; N, 8.90; Cl, 7.63; S, 6.93. Example 8 4- [2- [ [3-Fluoro-5- (3,4,5, 6-tetrahydro-4- methoxypyran-4-yl )phenoxy]methyl] -4-phenyloxazol- 5-yl] benzenesulfonamide Step 1. Preparation of 2-bromo-2- [ (4- aminosulfonyl)phenyl1 -1-phenyl-ethanone. Chlorosulphonic acid (100 mL) was cooled to 0 °C. Deoxybenzoin (10 g, 51 mmol) waε added, and the reaction waε warmed from 0 °C to room temperature over 4 h. The εolution waε carefully poured into ice water, filtered, and the aqueous layer was extracted with three 250 mL portions of CH 2 C1 . The combined organic extracts were washed once with brine (75 mL) and stirred over ice cold NH OH (125 mL) for 16 h. The CH 2 Cl 2 layer was separated and washed consecutively with IN HCl (2 x 75 mL) , saturated aqueous NaHC0 3 (75 mL) and brine (75 mL) , dried over Na 2 S0 4 , filtered, and concentrated. The crude material (4.23 g) waε εuεpended in acetic acid (75 mL) and a εolution of HBr in acetic acid (33 V% HBr in HOAc, 25 mL) , and bromine (0.79 mL, 15.4 mmol) was added. After 0.25 h at room temperature, the reaction was complete by TLi and the reaction was concentrated to remove the acetic acid. The residue was disεolved in ethyl acetate (250 mL) and NaHS0 3 (10%, 250 mL) . The organicε were washed with saturated aqueous bicarbonate (75 mL) and brine (75 mL) , dried over a 2 Sθ 4 , filtered, and concentrated yielding 2-bromo-2- [ (4- aminosulfonyDphenyl] -1-phenyl-ethanone which was used below without further purification. Step 2. Preparation of 4- [2-hydroxymethyl-4- phenyloxazol-5-yllbenzeneεulfonamide. Glycolic acid monosodium salt (1.55 g, 15.8 mmol) and 2-bromo-2- [ (4-aminosulfonyl)phenyl] -1-phenylethanone (Step 1) were suspended in DMF (350 mL) and stirred at room temperature for 16 h. The reaction was concentrated. The resulting residue was combined with ammonium acetate (2.31 g, 30 mmol) and acetic acid (25 mL) , and the mixture was heated to reflux for 3 h. The reaction was concentrated to dryness, and the residue was disεolved in ethyl acetate (250 mL) , washed with water, saturated aqueous bicarbonate and brine, dried, filtered, and concentrated. The crude material was purified by flash column chromatography on silica gel, eluting with a gradient from 50% to 75% ethyl acetate in hexane, to yield 1.89 g (37%) of 4- [2-hydroxymethyl-4-phenyloxazol- 5-yl]benzenesulfonamide: 1 H NMR (acetone-dg/300 MHz) δ 4.76 (m, 2H) , 6.68 (s, 2H) , 7.45 (m, 3H) , 7.65 (m, 2H) , 7.77 (d, 2H, J = 6.8 Hz), 7.94 (d, 2H, J = 8.7 Hz) . Step 3. Preparation of 4- [2-chloromethγl-4-phenyloxazol- 5-yllbenzenesulfonamide. A solution of 4- [2-hydroxymethyl-4-phenyloxazol-5- yl]benzenesulfonamide (Step 2) (1.0 g, 3 mmol) and triethylamine (0.61 g, 6 mmol) was stirred in tetrahydrofuran (100 mL) at 0 °C. Lithium chloride (0.25 g, 6 mmol) was added, followed by the dropwise addition of methanesulfonyl chloride (0.38 g, 3.3 mmol) . After stirring for 3 h from 0 °C to 25 °C, ethyl acetate (100 mL) was added, and the mixture was washed with IN hydrochloric acid, brine and water, dried over magnesium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography on silica gel eluting with a 1:1 mixture of ethyl acetate: hexanes. The appropriate fractions were concentrated to a clear oil which εolid fied upon standing to give 4- [2- chloromethyl-4-phenyloxazol-5-yl]benzenesulfonamide as a white solid which was used in the next step without further purification or characterization. Step 3. Preparation of 4- [2- ι [3-fluoro-5- (3.4, 5, 6- tetrahvdro-4-methoxypyran-4-yl)phenoxylmethyl1 -4- phenyloxazol-5-yllbenzenesulfonamide. A mixture of 4- [2-chloromethyl-4-phenyloxazol-5- yl]benzeneεulfonamide (Step 3) (0.5 g, 1.4 mmol), potaεεium carbonate (0.4 g, 2.8 mmol), dimethylformamide (20 mL) , and 3-fluoro-5- (4-methoxy-3 , 4, 5, 6-tetrahydro-2H- pyran-4-yl)phenol [prepared aε described in J. Med Chem. , 35, 2600-2609 (1992)] (0.3 g, 1.4 mmol) was stirred at room temperate for 16 h. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (4 x 30 mL) . The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated. The resulting crude product was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexanes to give 0.3 g (40%) of 4- [2- [ [3-fluoro-5- (3, 4, 5, 6- tetrahydro-4-methoxy-pyran-4-y1)phenoxy]methyl] -4-pheny1- oxazol-5-yl]benzeneεulfonamide aε a εticky white solid: .p. 70-80 °C. λ Η. NMR (CDCl 3 /300 MHz) δ 7.92 (d, 2H, J = 8.9 Hz), 7.77 (d, 2H, J = 8.9 Hz), 7.62 (m, 2H) , 7.43 (m, 3H) , 6.94 (s, IH) , 6.78 (m, 2H) 5.24 (s, 2H) , 4.82 (bs, 2H) , 3.82 (m, 4H) , 3.00 (s, 3H) , 1.95 (m, 4H) . Anal, calcd for C 28 H 27 FN 2 0 6 S: C, 62.44; H, 5.05; N, 5.20. Found : C , 62 . 50 ; H , 5 . 11 ; N , 5 . 24 . Example 9 Methyl 5- [4- (aminosulfonyl)phenyl] -α-[[3-(3,4,5,6- tetrahydro-4-methoxypyran-4-yl )phenyl]methyl] -4- phenyloxazole-2-acetate Step 1. Preparation of 2- [ (4-chlorosulfonvDphenyll -1- phenylethanone. Deoxybenzoin (10 g, 0.051 moi) was added in portions to neat chlorosulfonic acid (50 mL) at -78 °C. The reaction mixture was stirred at -78 °C for 2 h, then warmed to room temperature and for 1.5 h. The reaction mixture was cooled to -78 °C carefully poured onto crushed ice. The resulting solid was collected by filtration, waεhed with water, and dried to give 10.3 g (68%) of the desired sulfonyl chloride as a yellow solid. This crude material was used for the next reaction without further purification: HRMS: calcd for C 14 H 11 O 3 SCI 295.0196, found 295.0205. Step 2. Preparation of 2- T (4-aminosulfonvDphenyll -1- phenylethanone. A solution of the sulfonyl chloride from Step 1 (9 g, 0.03 moi) in tetrahydrofuran (100 mL) was slowly added to ammonium hydroxide (100 mL) at 5 °C. The reaction mixture was stirred for 1.5 h at 5 °C and for 30 minutes at room temperature. The resulting solid was collected by filtration, washed with excesε water and hexane, then vacuum dried to give 3.47 g (41%) of the deεired sulfonamide as a white solid: m.p. 259-261.5 °C. 1 H NMR (DMSO-d 6 /300 MHz) δ 4.52 (ε, 2H) , 7.30 (ε, 2H) , 7.43 (bd, 2H, J = 8.26 Hz) , 7.54 (dd, 2H, J = 7.56 Hz), 7.65 (dd, IH, J = 7.35 Hz) , 7.75 (d, 2H, J = 8.26 Hz), 8.04 (d, 2H, J = 7.45 Hz) . HRMS: calcd for C 14 H 13 NO 3 S 276.0694, found 276.0709. Step 3. Preparation of 2-bromo-2- \ (4- aminosulfonyl)phenyll -1-phenyl-ethanone. The sulfonamide from Step 2 (5.0 g, 0.018 moi) was suspended in dichloroethane (50 mL) , then a solution of 30% HBr in acetic acid (20 mL) , acetic acid (70 mL) and bromine (1 mL) was added at room temperature. The reaction mixture waε stirred for 40 minutes at room temperature and was concentrated in vacuo . Water (200 mL) was added to the resulting concentrated residue, and the mixture was extracted with ethyl acetate (2 x 250 mL) . The combined ethyl acetate extracts were washed with 5% sodium bicarbonate (2 x 250 mL) , and brine (2 x 250 mL) , dried over magnesium sulfate, filtered and concentrated under reduced presεure. Methylene chloride (50 mL) was added to the concentrated residue and a solid precipitated. I'his solid was collected by filtration, washed with cold methylene chloride and air-dried to give 3.5 g (55%) of 2-bromo-2- [ (4-aminosulfonyl)phenyl] -1- phenylethanone as a yellow solid: m.p. 153.6-155 °C. 1 H NMR (DMSO-d 6 /300 MHz) δ 7.25 (s, IH) , 7.38 (s, 2H) , 7.54 (dd, 2H, J = 7.55 Hz), 7.62-7.74 (m, 3H) , 7.82 (d, 2H, J = 8.46 Hz) , 8.07 (d, 2H, J = 8.66 Hz) . HRMS: calcd for Cι 4 H 12 N0 3 SBr 353.9800, found 353.9824. Step 4. Preparation of benzyl methyl 2-[3-[(4- methoxy) tetrahydropyran-4-yl1phenylmethyl1malonate. A solution of benzyl methyl malonate (0.88 g, 4.22 mmol) in 3 mL of anhydrous DMA was added to a suspenεion of sodium hydride (0.11 g, 4.45 mmol) in 2 mL of anhydrous DMA at 5 °C, and the reaction mixture waε εtirred for 40 min at 5 °C. Then 3-[(4- methoxy) tetrahydropyran-4-yl] -α-bromotoluene [prepared aε described in US Patent 5,424,320] (1.21 g, 4.24 mmol) waε disεolved in 6 mL of anhydrouε DMA and added to this solution. The reaction mixture was εtirred for 2 h at 5 °C, and for 18 h at room temperature. The reaction mixture waε quenched with water (100 mL) . The aqueouε εolution waε extracted with ethyl acetate (3 x 70 mL) . The combined organic extractε were waεhed with brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on silica gel, eluting with 20% ethyl acetate in hexane, to give 0.93 g (53%) of benzyl methyl 2- [3- [ (4-methoxy)tetrahydropyran-4- yl]phenylmethyl]malonate as a clear oil: HRMS: calcd for C 24 H 28 0 6 413.1964, found 413.1952. Step 5. Preparation of monomethyl 2- T3- f (4- methoxy) tetrahydropyran-4-yl1phenylmethyl1malonate A solution of benzyl methyl 2-[3-[(4- methoxy)tetrahydropyran-4-yl]phenyl-methyl]malonate (0.3 g, 7.27 mmol) in 15 mL of ethyl acetate was combined with 10% palladium on activated carbon (0.17 g) . The reaction mixture was stirred under 40 psi of hydrogen gas for 18 h at room temperature. The reaction mixture waε filtered ® through Celite and washed with exceεs ethyl acetate. The filtrate was concentrated and dried under vacuum to give 0.2 g (85%) of monomethyl 2- [3- [(4- methoxy)tetrah dropyran-4-yl]phenyl-methyl]malonate as a clear oil: HRMS: calcd for Cι 7 H 22 θ 6 323.1495, found 323.1473. Step 6. Preparation of methyl 5- [4- (aminosulfonvDphenyll -α-T T3- (3 , 4, 5, 6-tetrahvdro-4- methoxypyran-4-vDphenyllmethyl1 -4-phenyloxazole-2- acetate. Solid NaOH (87 mg, 2.17 mmol) was added to a solution of the monomethyl 2-[3-[(4- methoxy) tetrahydropyran-4-yl]phenyl-methyl]malonate (Step 5) (0.7 g, 2.17 mmol) in ethanol (10 mL) and water (2 mL) , and the mixture waε stirred for 15 min at room temperature. The εolventε were removed at reduced preεεure. Several mL of abεolute ethanol were added to the resulting residue, which was concentrated again at reduced pressure. This procedure was repeated three times until a white solid formed, which was dried under vacuum. The resulting carboxylic acid sodium salt waε suspended in 2 mL of anhydrous DMF. A solution of 2- bromo-2- [ (4-amino-sulfonyDphenyl] -1-phenylethanone (Step 3) (0.77 g, 2.17 mmol) in anhydrous DMF (3 mL) was added at room temperature to the DMF solution of the sodium carboxylate. The reaction mixture was stirred for 18 h at room temperature, and the DMF was removed at reduced pressure. Ethyl acetate (150 mL) was added to the concentrated residue, and the mixture was filtered. The filtrate was concentrated and dried to give the desired crude α-acyloxy ketone. Acetic acid (5 mL) and ammonium acetate (1.5 g. 19.2 mmol) were added to this concentrated residue, and the mixture was heated at 100 °C for 3 h. The reaction mixture was cooled to room temperature, and the excess acetic acid was removed under vacuum. The reεulting residue was partitioned between water (100 mL) and ethyl acetate (200 mL) . The organic layer was separated, washed with saturated aqueouε sodium bicarbonate (2 x 100 mL) , saturated brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on silica gel, eluting with 2:1 ethyl acetate in hexane, to give 0.24 g of a white solid which was recryεtallized from methanol and water to give 0.13 g (19%) of methyl 5- [4- (aminosulfonyDphenyl] -α- [ [3- (3,4,5, 6-tetrahydro-4-methoxypyran-4-yl)phenyl] -methyl] - 4-phenyloxazol<---2-acetate as a white solid: m.p. 88.7- 94.9 °C. l H NMR (CDCl 3 /300 MHz) δ 1.78-1.88 (m, 4H) , 2.84 (s, 3H) , 3.47-3.53 (m, 4H) , 3.65-3.77 (m, 5H) , 4.28 (dd, IH, J = 7.05 Hz), 5.00 (ε, 2H) , 7.16-7.32 (m, 4H) , 7.36- 7.40 (m, 3H) , 7.54-7.58 (m, 2H) , 7.68 (d, 2H, J = 8.70 Hz), 7.88 ( d, 2H, J = 8.70 Hz) . HRMS: calcd for C 3 iH 32 N 2 0 7 S 577.2008. Found 577.1961. Example 10 N- [2- [5- [4- (Aminosulfonyl)phenyl] -4-phenyloxazol 2-yl] ethyl] -2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4- methoxypyran-4-yl)phenoxy-N-methylacetamide N- [2- [4- [4- (Aminosulf onyDphenyl] -5 -pheny loxazol 2-yl] ethyl] -2- [3-f luoro-5- (3,4,5, 6 -tetrahydro- 4 - methoxypyran-4 -yl ) phenoxy-N-methylacetamide Step 1. Preparation of ethyl 3-f luoro-5- (4-methoxy- 3,4,5, 6-tetrahvdro-2H-pyran-4-vDphenoxyacetate . A mixture of ethyl bromoacetate (0.5 g, 3 mmol) , 3- f luoro-5- (4-methoxy-3 ,4,5, 6-tetrahydro-2H-pyran-4- yl) phenol (Example 8, Step 4) (0.3 g, 1.3 mmol) and K 2 Cθ 3 (0.11 g, 0.8 mmol) in dimethylformamide (5.0 mL) was stirred at room temperature for 16 h under an argon atmosphere. The reaction mixture was partitioned between 5% citric acid '25 mL) and EtOAc (25 mL) . The organic phase waε waεhed with water, dried (Na 2 S0 4 ), filtered and concentrated. The reεulting εyrup waε purified by flaεh column chromatography on εilica gel, eluting with 25% EtOAc in hexane, to give 0.3 g (73%) of ethyl 3-fluoro-5- (4-methoxy-3 ,4,5, 6-tetrahydro-2H-pyran-4- yDphenoxyacetate as a colorless viscous liquid: 1 H NMR (CDCl 3 /300 MHz) δ 6.77 (d, 2H, J = 10.5 Hz), 6.52 (d, IH, J = 10.5 Hz), 4.61 (ε, 2H) , 4.28 (q, 2H, J = 6.9 Hz), 3.82 (m, 4H) , 2.99 (ε, 3H) , 1.92 (m, 4H) , 1.31 (t, 3H, J = 6.9 Hz) . FABMS m/z = 313 (M+H) . HRMS calcd for Cι 6 H 22 0 5 313.1451, found 313.1399. Step 2. Preparation of 3-fluoro-5- (4-methoxy-3 , 4 , 5, 6- tetrahvdro-2H-pyran-4-yl)phenoxyacetic acid. A solution of ethyl 3-fluoro-5- (4-methoxy-3, 4, 5, 6- tetrahydro-2H-pyran-4-yl)phenoxyacetate (Step 1) (0.3 g, 1 mmol) in ethanolic LiOH (1M, 1.5 mL) was stirred at room temperature for 2 h. The reaction mixture waε diluted with 5% citric acid (10 mL) and extracted with ether (2 x 15 mL) . The ether extractε were combined and waεhed with water (2 x 20 mL) , dried (Na 2 S0 4 ) , filtered, and concentrated under reduced pressure to give 0.26 g (95%) of 3-fluoro-5- (4-methoxy-3 , 4, 5, 6-tetrahydro-2H- pyran-4-yl)phenoxyacetic acid aε a colorless viscous liquid: 3 -H NMR (CDCl 3 /300 MHz) δ 6.78 (d, 2H, J = 10.5 Hz) , 6.50 (d, IH, J = 10.5 Hz), 4.68 (ε, 2H) , 3.82 (m, 4H) , 2.99 (s, 3H) , 1.92 (m, 4H) ; FABMS m/z = 284 (M+H) . HRMS calcd for C 14 H 17 FO 5 283.0982, found 283.0993. Step 3. Preparation of 4- f2- [2- (N-methyl-N- phenylmethoxycarbonylamino) -ethyll -4-phenyl-oxazol-5- yllbenzeneεulfonamide and 4- [2- \ 2 - (N-methyl-N- phenylmethoxycarbonylamino) ethyll -5-phenyloxazol-4- ylIbenzene- εulfonamide. A mixture of N-phenylmethoxycarbony1-N-methyl-β- alanine (1.7 g, 7.2 mmol) and 2-bromo-2- [ (4- aminoεulfonyl)phenyl] -1-phenylethanone (Example 8, Step 1) (2.0 g, 5.65 mmol) in dimethylacetamide (5.00 mL) was treated with K 2 CO 3 (0.54 g, 3.9 mmol) and 18-crown-6 (0.05 g) and stirred at room temperature for 16 h. After the removal of the solvent in vacuo , the residue was partitioned between cold water (25 mL) and EtOAc (50 mL) . The organic phase was washed with water (2 x 25 mL) , dried (Na 2 S0 4 ) , filtered, and concentrated under reduced pressure. The resulting subεtance waε purified by flash column chromatography on silica gel, eluting with 30% EtOAc in hexane, to afford the desired α-acyloxyketone (2.2 g) as an amorphous substance. This benzoin eεter (2.1 g) waε dissolved in glacial acetic acid (20 mL) , ammonium acetate (1.8 g, 23.4 mmol) was added, and the reεulting mixture waε heated at 90 °C under a nitrogen atmoεphere for 2.5 h. After cooling and the removal of the εolvent in vacuo, the reεidue was partitioned between water (50 mL) and EtOAc (75 mL) . The organic phase was washed with water (2 x 25 mL) dried (Na 2 S0 4 ) , filtered, and concentrated under reduced presεure. The reεulting material waε purified by flaεh column chromatography on εilica gel, eluting with 40% EtOAc in hexane, to provide 1.15 g (57%) of 4- [2- [2- (N-methyl-N- phenylmethoxycarbonyl-amino) ethyl] -4-phenyl-oxazol-5- yl]benzeneεulfonamide and 4- [2- [2- (N-methyl-N- phenylmethoxycarbonylamino)ethyl] -5-phenyloxazol-4- yl]benzenesulfonamide as a white amorphous material containing the two isomeric oxazole productε: 1 H NMR (CDCl 3 /300 MHz) δ 7.85 (d, 2H, J = 8.7 Hz), 7.67 (m, 2H) , 7.54 (m, 2H) , 7.42 (m, 3H) , 7.28 (m, 5H) , 5.08 (d, 2H, J = 9.0 Hz), 4.9 (br, 2H) , 3.8 (t, 2H, J = 6.9 Hz), 3.17 (m, 2H) , 2.99 & 2.94 (s, 3H) . FABMS m/z = 492 (M+H) . HRMS calcd for C 26 H 25 3 O 5 S 492.1593, found 492.1581. Step 4. Preparation of 4- \ 2- \ 2 - (N-methylamino) ethyll -4- phenyloxazol-5-yllbenzeneεulfonamide and 4-[2-[2-(N- methylamino) ethyll -5-phenyloxazol-4- yllbenzenesulfonamide. A solution of 4- [2- [2- (N-methyl-N- phenylmethoxycarbonylamino) ethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide and 4- [2- [2- (N-methyl-N-phenyl- methoxycarbonylamino) ethyl] -5-phenyloxazol-4- yl]benzenesulfonamide (0.7 g, 1.4 mmol) from Step 3, in MeOH (15 mL) containing acetic acid (0.1 mL) was treated with 10% Pd on carbon (0.4 g) and stirred under an atmosphere of hydrogen at 50 psi at room temperature for 3 h. The catalyεt was removed by filtration, the filtrate was concentrated under reduced presεure, and the reεulting εubstance was purified by reverse-phaεe HPLC uεing a gradient of 5-70% CH 3 CN in water to give 0.42 g of 4- [2- [2- (N-methylamino) ethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide and 4- [2- [2- (N-methylamino) ethyl] - 5-phenyloxazol-4-yl]benzeneεulfonamide trifluoroacetate εaltε aε a white powder: !H NMR (CD 3 OD/300 MHz) δ 7.88 (d, 2H, J = 8.7 Hz), 7.74 (d, 2H, J = 8.7 Hz), 7.6 (m, 2H) , 7.43 (m, 3H) , 3.55 (t, 2H, J = 6.6 Hz), 3.36 (t, 2H, J = 6.6 Hz), 2.82 (s, 3H) ; FABMS m/z = 358 (M+H) . Step 5. Preparation of N- \ 2 - T5- [4- (aminosulfonvDϋhenyll - 4-phenyloxazol-2-yl1ethyll -2- [3-fluoro-5- (3.4,5,6- tetrahvdro-4-methoxypyran-4-yl)phenoxy-N-methylacetamide and N- [2- [4- [4- (aminosulfonvDphenyll -5-phenyloxazol-2- yllethyll -2- f3-fluoro-5- (3,4,5, 6-tetrahvdro-4- methoxypyran-4-vDphenoxy-N-methylacetamide. To a solution of 3-fluoro-5- (4-methoxy-3 , 4, 5, 6- tetrahydro-2H-pyran-4-yl)phenoxyacetic acid (0.27 g, 0.95 mmol) from Step 2 in dimethylacetamide (2.00 mL) and dichloromethane (3.00 mL) , was added HOBt (0.22 g, 1.45 mmol) and EDC (0.19 g, 1 mmol), and the resulting mixture waε stirred at 0 °C for 1 h. This reaction mixture was treated with a solution of the free amines generated by the addition of N-methylmorpholine (0.1 mL) to a solution of the 4- [2- [2- (N-methylamino) ethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide and 4- [2- [2- (N-methylamino)ethyl] - 5-phenyloxazol-4-yl]benzeneεulfonamide trifluoroacetateε (0.36 g, 0.8 mmol) from Step 4 in dimethylacetamide (1.0 mL) at 0 °C. The reεulting mixture was warmed to room temperature in 16 h. The reaction mixture was diluted with dichloromethane (20 mL) , and washed sequentially with 5% citric acid, (2 x 10 mL) , saturated NaHCθ 3 (2 xlO mL) , water, dried (Na 2 S0 4 ) , and filtered. After the removal of the solvent under reduced pressure, the residue was purified by flash column chromatography on silica gel, eluting with 1% MeOH in EtOAc, to afford the desired product as a white amorphouε (0.25 g, 52%) εubεtance. This material was further purified by reverse- phase HPLC using a gradient of 5-90% CH 3 CN. The appropriate fractions were combined and freeze-dried to afford an isomeric mixture of N-[2-[5-[4- (aminoεulfonyDphenyl] -4-phenyloxazol-2-yl] ethyl] -2- [3- fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4-yl)phenoxy- N-methylacetamide and N- [2- [4- [4- (amino-εulfonyl)phenyl] - 5-phenyloxazol-2-yl] ethyl] -2- [3-fluoro-5- (3,4,5,6- tetrahydro-4-methoxypyran-4-yl)phenoxy-N-methylacetamide aε a white powder: 1 H NMR (CD 3 OD/3OO MHz) δ 7.85 (m, 2H) , 7.71 & 7.64 (d, 2H, J = 8.7 Hz), 7.54 (m, IH) , 7.4-7.3 (m, 4H) , 6.82- 6.48 ( , 3H) , 4.82 & 4.76 (ε, 2H) , 3.78 (m, 2H) , 3.75 (m, 4H) , 3.17 (m, 2H) , 3.16 & 3.07 (ε, 3H) , 2.96 & 2.89 (ε, 3H) , 1.92-1.83 (m, 4H) . FABMS m/z = 624 (M+H) . HRMS calcd for C 32 H 35 N 3 O 7 FS 624.2180, found 624.2177. Example 11 4- [2- [ [2- [3-Fluoro-5-(3,4,5, 6-tetrahydro-4 methoxypyran-4-yl )phenoxy] ethyl] -N- methylaminoethyl] -4-phenyloxazol-5- yl] benzenesulfonami e 4- [2- [ [2- [3 -Fluoro- 5- (3,4,5, 6-t etrahydro-4 - methoxypyran-4-yl )phenoxy] ethyl] -N- methylaminoethyl] -5 -phenyloxazol-4- yl] benzenesulfonamide A solution of N- [2- [5- [4- (aminoεulf onyDphenyl] -4- phenyloxazol-2-yl] ethyl] -2- [3-fluoro-5- (3,4,5,6- tetrahydro -4 -methoxypyran- 4 -yl) phenoxy-N-methylacetamide and N- [2- [4- [4- (aminoεulf onyDphenyl] -5-phenyloxazol-2- yl] ethyl] -2- [3-f luoro-5- (3,4 , 5, 6-tetrahydro-4- methoxypyran-4-yl) phenoxy-N-methylacetamide (Example 10) (0.1 g, 0.16 mmol) in dry THF (4.00 mL) was combined with LiAlH 4 (0.016 g, 0.4 mmol) and stirred at room temperature for 16 h under argon. The reaction mixture was cooled, and cold EtOAc (15 mL) was added. After stirring for 15 min, 0.5 N NaOH (15 mL) was added and the reaction mixture was filtered through Celite . The organic phase was washed with cold 0.5 N NaOH (10 mL) , water, dried (Na 2 S0 4 ) , filtered, and concentrated under reduced preεεure. The resulting material was purified by reverεe-phase HPLC using a gradient of 5-90% CH 3 CN in water. The appropriate fractions were combined and freeze- dried to provide an isomeric mixture of 4- [2- [[2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxy-pyran-4- yDphenoxy] ethyl] -N-methylaminoethyl] -4-phenyloxazol-5- yl] -benzeneεulfonamide and 4- [2- [ [2- [3-fluoro-5- (3 , 4, 5, 6- tetrahydro-4-methoxy-pyran-4-yl)phenoxy] ethyl] -N- methylaminoethyl] -5-phenyloxazol-4-yl]benzeneεulfonamide as trifluoroacetate εalts: 1 H NMR (CD 3 OD/300 MHz) δ 7.88 (d, 2H, J = 8.7 Hz), 7.71 (dd, 2H, J = 8.7, 2.4 Hz), 7.57 (m, 2H) , 7.42 (m, 3H) , 6.83 (m, 2H) , 6.65 (m, IH) , 4.46 & 4.38 (t, 2H J = 6.0 Hz), 3.79 - 3.62 (m, 8H) , 3.51 & 3.41 (t, 2H, J = 6.6 Hz), 3.12, 2.96 & 2.93 (s, 6H) , 1.88 (m, 4H) . FABMS m/z = 610 (M+H) . HRMS calcd for C 32 H 37 N 3 0 6 FS 610.2387, found 610.2373. Example 12 4-[2- [[4-[3- [3-Fluoro-5- (3,4,5, 6-tetrahydro-4- methoxypyran-4-yl) phenoxy] -1- propynyl]phenyl]methyl] -4-phenyloxazol-5- yl] benzenesulfonamide Step 1. Preparation of 4- [ [2- (4-iodophenvDmethyl1 -4- phenyloxazol-5- yllbenzenesulfonamide. A mixture of 2-bromo-2- [ (4-aminosulfonyl)phenyl] -1- phenylethanone (Example 8, Step 1) (2.0 g, 5.65 mmol) and 4-iodophenylacetic acid (1.8 g, 6.9 mmol) in dimethylacetamide (6.0 mL) was treated with potasεium carbonate (0.57 g, 4.13 mmol) and 18-crown-6 (0.06 g) and εtirred at room temperature for 4 h. The reaction mixture waε diluted with cold water (50 mL) and extracted with ethyl acetate (3 x 30 mL) . The combined organic phaεeε were waεhed with water (2 x 25 mL) , dried (Na 2 S0 4 ), filtered, and concentrated under reduced preεεure. The resulting material was purified by flaεh chromatography on εilica gel, eluting with 40% EtOAc in hexane, to give the desired α-acyloxy ketone as an amorphous substance, which was used in the next reaction without furthei purification: λ E NMR (CDCI 3 /3OO MHz) δ 7.86 (m, 4H) , 7.63 (d, 2H, J = 8.4 Hz) , 7.59 (m, 3H) , 7.41 (t, 2H, J = 7.8 Hz), 7.03 (d, 2H, J = 8.4 Hz), 6.89 (s, IH) , 4.82 (s, 2H) , 3.73 (q, 2H, J = 5.1 Hz) . FABMS m/z = 536 (M+H + ) . HRMS: calcd for C 22 H 19 NO 5 SI 536.0029, found 536.0023. A mixture of this α-acyloxy ketone (2.2 g, 4.1 mmol), and ammonium acetate (1.3 g, 16.9 mmol) in acetic acid (15.0 mL) was heated at 100 °C under a nitrogen atmosphere for 2.5 h. The reaction mixture waε concentrated in vacuo, and the residue was partitioned between water (50 mL) and EtOAc (50 mL) . The organic phaεe was washed with water (2 x 30 mL) , dried (Na 2 S0 4 ) , filtered, and concentrated under reduced presεure. The reεulting εolid waε triturated with methanol, cooled and filtered to give 1.1 g (52%) of 4- [[2- (4- iodophenyl)methyl] -4-phenyloxazol-5-yl]benzeneεulfonamide as a pale yellow powder: m.p. 198-201 °C. 1 H NMR (CDCI 3 /3OO MHz) δ 7.86 (d, 2H, J = 8.7 Hz), 7.7 (dd, 4H) , 7.59 (m, 2H) , 7.41 (m, 3H) , 7.15 (d, 2H, J = 8.1 Hz), 4.81 (s, 2H) , 4.16 (s, 2H) ; FABMS m/z = 517 (M+H + ); HRMS calcd for C 22 H 18 N 2 O 3 S 1 I 1 517.0083, found 517.0063. Step 2. Preparation of 3-fluoro-5- (4-methoxy-3 , 4 , 5 , 6- tetrahvdro-2H-pyran-4-yl)phenylpropynyl ether. A mixture of propargyl bromide (0.9 g, 7.6 mmol, 80% in toluene) and 3-fluoro-5- (4-methoxy-3, 4, 5, 6-tetrahydro- 2H-pyran-4-yl)phenol (Example 8, Step 4) (0.5 g, 2.2 mmol) in dimethylacetamide (5 mL) waε εtirred in the presence of K 2 C0 3 (0.17 g, 1.2 mmol) and 18-crown-6 (0.02 g) for 16 h at room temperature. After the removal of the solvent in vacuo, the residue waε partitioned between EtOAc (30 mL) and water (30 mL) . The organic phaεe waε waεhed with water, dried (Na 2 S0 4 ) , filtered, and concentrated. The reεidue waε purified by flaεh column chromatography on εilica gel, eluting with 25% EtOAc in hexane, to give 0.35 g (64%) of 3-fluoro-5- (4-methoxy- 3 , 4, 5, 6-tetrahydro-2H-pyran-4-yl)phenylpropynyl ether aε a pale yellow viscous liquid, which solidified upon drying: m.p. 75-77 °C. !H NMR (CDCl 3 /300 MHz) δ 6.81 (d, IH, J = 1.5 Hz), 6.75 (m, IH) , 6.62 (m IH) , 4.69 (d, 2H, J = 2.4 Hz), 3.82 ( , 4H) , 3.0 (s, 3H) , 2.55 (t, IH, J = 4.5 Hz), 2.1-1.8 (m, 4H) . FABMS m/z = 271 (M+Li) . HRMS calcd for Cι 5 Hι 8 F0 3 Li 271.1322, found 271.1317. Step 3. Preparation of 4- [2- [ [4- [3- [3-fluoro-5- (3 , 4 , 5 , 6- tetrahydro-4-methoxypyran-4-yl)phenoxy1 -1- propynyllphenyllmethyl1 -4-phenyloxazol-5-yllbenzene¬ εulfonamide. A solution of 4- [ [2- (4-iodophenyl)methyl] -4- phenyloxazol-5-yl]benzene-sulfonamide (Step 1) (0.5 g, 0.97 mmol) and 3-fluoro-5- (4-methoxy-3 , 4, 5, 6-tetrahydro- 2H-pyran-4-yl)phenylpropynyl ether (Step 2) (0.28 g, 1.1 mmol) in dimethylformamide (2.00 mL) containing triethyl amine (0.16 mL, 1.14 mmol), was treated with PdCl 2 (PPh 3 ) 2 (0.1 g) , and Cul (0.02 g) and stirred at room temperature for 4 h, under an argon atmosphere. The reaction mixture was partitioned between 5% citric acid (20 mL) and EtOAc (50 mL) . The organic phase was waεhed with 5% citric acid (2 x 15 mL) , water (2 x 15 mL) , dried (Na 2 S0 4 ) , filtered, and concentrated under reduced pressure. The resulting substance was purified by flash column chromatography on silica gel, eluting with 40% EtOAc in hexane, to afford 0.38 g (60%) of 4- [2- [ [4- [3- [3-fluoro- 5- (3 , 4, 5, 6-tetrahydro-4-methoxypyran-4-yl)phenoxy] -1- propynyl]phenyl] -methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide as a pale yellow amorphous material: m.p. 86-100 °C. ^-B. NMR (CDCl 3 /300 MHz) δ 7.85 (d, 2H, J = 8.7 Hz), 7.65 (d, 2H, J = 8.7 Hz), 7.55 (m, IH) , 7.42-7.2 (m, 8H) , 6.82 (br s, IH) , 6.75-6.6 (m, 2H) , 4.91 (ε, 2H) , 4.86 (ε, 2H) , 4.21 (ε, 2H) , 3.79 (m, 4H) , 2.98 (ε, 3H) , 2.1-1.85 (m, 4H) . FABMS m/z = 653 (M+H) . HRMS calcd for C 35 H 34 N 2 O 6 FS 653.2122, found 653.2133. Example 13 4-[2-[[4-[3- [3 -Fluoro-5- (3,4,5, 6-tetrahydro-4- hydroxypyran-4-yl )phenoxy] -1-propynyl] - phenyl]methyl] -4-phenyloxazol-5- yl] benzenesulfonamide Step 1. Preparation of 3-fluoro-5- (4-hvdroxy-3 , 4, 5, 6- tetrahvdro-2H-pyran-4-yl)phenylpropynyl ether. To a solution of 3-fluoro-5- (4-hydroxy-3, 4, 5, 6- tetrahydro-2H-pyran-4-yl) -phenol [prepared as described in J. Med Chem. , 35, 2600-2609 (1992)] (0.8 g, 3.8 mmol) in dimethylacetamide (2.00 mL) , was added propargyl bromide (2.5 mL, 80% solution in toluene) , K 2 CO 3 (0.3 g, 2.2 mmol), and 18-crown-6 (0.03 g) , and the resulting mixture waε heated at 80 °C for 24 h under a nitrogen atmoεphere. The reaction mixture waε diluted with cold water (50 mL) and extracted with EtOAc (2 x 25 mL) . The organic extractε were combined, waεhed with water (2 x 20 mL) , dried (Na 2 Sθ 4 ) , filtered, and concentrated under reduced preεεure. The residual brown liquid was purified by flash column chromatography on silica gel, eluting with 60% EtOAc in hexane, to afford 0.5 g (53%) of 3- fluoro-5- (4-hydroxy-3,4,5, 6-tetrahydro-2H-pyran-4- yDphenylpropynyl ether, which cryεtallized from CH 2 Cl 2 /hexane aε a light brown powder: m.p. 120-122 °C. !H NMR (CDC1 3 /300 MHz) δ 6.9 (d, H, J = 1.5 Hz), 6.64 (d, IH, J = 9.9 Hz), 6.84 (d, IH, J = 9.9 Hz) , 4.69 (d, 2H, J = 2.4 Hz) , 3.88 (m, 4H) , 2.55 (t, IH, J = 2.4 Hz) , 2.14 (m, 2H) , 1.66 (m, 2H) . FABMS m/z = 251 (M+H) . HRMS calcd for C 14 H 16 FO 3 251.1083, found 251.1053. Step 2. Preparation of 4- \ 2- \ [ A- \ 3 - f3-fluoro-5- ( , 4 , 5 , 6- tetrahydro-4-hvdroxypyran-4-yl)phenoxy1 -1- propynyl1 henyl1methyl1 -4-phenyloxazol-5-yl1benzene¬ εulfonamide. To a solution of 4- [ [2- (4-iodophenyl)methyl] -4- phenyloxazol-5-yl]benzeneεulfonamide (Example 12, Step 1) (0.35 g, 0.68 mmol) and 3-fluoro-5- (4-hydroxy-3 , 4, 5, 6- tetra-hydro-2H-pyran-4-yl)phenylpropynyl ether (Step 1) (0.185 g, 0.78 mmol) in dimethylformamide (2.0 mL) containing triethylamine (0.15 mL, 1.1 mmol), PdCl 2 (PPh 3 ) 2 (0.1 g) and Cul (0.02 g) were added, and the resulting mixture was stirred at room temperature for 3 h, under an argon atmosphere. The reaction mixture was partitioned between 5% citric acid (20 mL) and EtOAc (50 mL) . The organic phase was washed with 5% citric acid (2 x 15 mL) , water (2 x 15 mL) , dried (Na 2 Sθ 4 ) , filtered, and concentrated under reduced pressure. The resulting subεtance waε purified by flaεh column chromatography on silica gel, eluting with 60% EtOAc in hexane, to afford 0.25 g (47%) of 4- [2- [ [4- [3- [3-fluoro-5- (3, 4, 5, 6- tetrahydro-4-hydroxypyran-4-yl) -phenoxy] -1- propynyl]phenyl]methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide as a pale yellow amorphous material: 1H NMR (CDCl 3 /300 MHz) δ 7.85 (d, 2H, J = 8.4 Hz), 7.66 (d, 2H, J = 8.4 Hz), 7.58 (m, 2H) , 7.44 - 7.33 (m, 7H) , 6.95 (br, IH) , 6.82 (d, IH, J = 10 Hz) , 6.64 (d, IH, J = 10 Hz) , 4.91 (s, 2H) , 4.83 (s, 2H) , 4.21 (s, 2H) , 3.88 (m, 4H) , 2.15 (m, 2H) , 1.6 (m, 2H) . FABMS m/z = 639 (M+H) . HRMS calcd for C 36 H 32 N 2 F0 6 S 639.1965, found 639.1954. Example 14 4- [2- [ [3-Fluoro-5- (3,4,5, 6-tetrahydro-4- methoxypyran-4-yl ) henoxy]methyl] -4- ( 4- fluorophenyl )oxazol-5-yl] benzenesulfonamide Step 1. Preparation of 2- [ (4-AminoεulfonvDphenvD -1- (p- fluorophenyl) -ethanone. Neat 2- (phenyl) -1- (p-fluorophenyl) ethanone (6.10 g, 28.54 mmol) waε cooled to -78 °C in a dry ice methanol bath. Chloroεulfonic acid (15.0 mL) waε added, and the εolution waε warmed to room temperature over 1 h. The εolution was stirred for 2 h and poured directly into ice (500 mL in 1000 mL Erlenmeyer flask) . The resulting heterogeneous aqueous εolution waε extracted with ethyl acetate (2 x 300 mL) . The ethyl acetate layers were combined, extracted with water (1 x 100 mL) and mixed with ammonium hydroxide solution (50 mL) for 1 h. The ethyl acetate was collected, extracted with IN HCl (2 x 200 mL) , brine (1 x 200 mL) , and dried over sodium εulfate. The εolvent waε removed to a volume of 50 mL and cryεtalε formed. The cryεtalε were kept at room temperature for 4 h and collected by vacuum filtration to give 3.1 g (37%) of 2- [ (4-aminosulfonyl)phenyl] -1- (p- fluoro-phenyl) ethanone: m.p. 198-204 °C. 1 H NMR (CD 3 OD/300 MHz) δ 4.46 (s, 2H) , 7.23 (t, 2H, J = 8.8 Hz) , 7.43 (d, 2H, J = 8.5 Hz), 7.85 (d, 2H, J = 8.5 Hz), 8.10- 8.20 (m, 2H) . FABMS m/z = 294 (M+H + ) . HRMS calcd for Cι H 13 FN0 3 S 294.0600. Found 294.0583. Step 2. Preparation of 2- [ (4-aminoεulfonvDphenyD -2- bromo-1- (p-fluoro-phenyl)ethanone. To a εolution of 2- [ (4-aminosulfonyl)phenyl] -1- (p- fluorophenyl) ethanone (Step 1) (2.93 g, 10.00 mmol) in acetic acid (25 mL) at room temperature was added 33% HBr in acetic acid (5.0 mL) , followed by bromine (1.59 g, 10.00 mmol), and the εolution was stirred at room temperature for 1 h. The acetic acid was removed at reduced preεsure, and the resulting yellow liquid was poured into ethyl acetate (100 mL) . This solution was washed with saturated sodium bicarbonate (2 x 100 mL) , followed by brine (100 mL) . The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed at reduced presεure to give 3.21 g (86%) of 2-[ (4-aminosulfonyl)phenyl]-2-bromo-l- (p- fluorophenyl) ethanone as a gummy foam: 1 H NMR (CDCI 3 /3OO MHz) δ 5.05 (bε, 2H) , 6.30 (s, IH) , 7.16 (t, 2H, J = 8.6 Hz), 7.67 (d, 2H, J = 8.5 Hz), 7.92 (d, 2H, J = 8.5 Hz), 8.02-8.07 (m, 2H) . FABMS m/z = 389 (M+NH 3 + ) . HRMS calcd for Ci 4 Hι 2 BrFN0 3 S 371.9705. Found 371.9721. Step 3. Preparation of 4- \ 2- \ [3-fluoro-5- (3 , 4, 5.6- tetrahvdro-4-methoxypyran-4-yDphenoxy1methyl1 -4- (4- fluorophenyl)oxazol-5-yllbenzenesulfonamide. A mixture of 2- [ (4-aminosulfonyDphenyl] -2-bromo-l- (p-fluorophenyl) -ethanone (Step 2) (513 mg, 1.37 mmol) and the sodium salt of 3-fluoro-5- (4-methoxy-3 , 4, 5, 6- tetrahydro-2H-pyran-4-yl)phenoxyacetic acid (Example 10, Step 2) (419 mg, 1.37 mmol) were combined in dimethylformamide (3.0 mL) and stirred at room temperature for 1 h. The solvent was removed at reduced presεure, and the residue taken up in ethyl acetate (20 mL) . This solution was washed with saturated aqueous sodium chloride (2 x 10 mL) , saturated sodium bicarbonate (2 x 20 mL) , and aqueous sodium chloride (2 x 10 mL) . The ethyl acetate solution was dried over sodium εulfate, and the εolvent waε removed at reduced preεεure. The resulting residue was purified by flash column chromatography on silica gel to give 419 mg (62%) of the desired α-acyloxyketone as a white foam: m.p. 78-81.°C. X H NMR (CDCl 3 /300 MHz) δ 1.91-1.98 (m, 4H) , 2.96 ( s, 3H) , 3.80-3.83 (m, 4H) , 4.83 (ab, 2H, J ab = 16.7 Hz, ΔV = 18.4 Hz), 4.93 (bs, 2H) , 6.59 (dt, IH, J = 10.0 Hz, J = 2.2 Hz), 6.98 (s, IH) , 7.13 (m, 2H) , 7.59 (d, 2H, J = 8.5 Hz), 7.89-8.00 (m, 4H) . FABMS m/z = 582 (M+Li + ) . HRMS calcd for C 28 H 28 F 2 N0 8 S 576.1504. Found 576.1507. This benzoin ester , ' 180 mg, 0.31 mmol) and ammonium acetate (180 mg, 2.5 mmol) waε heated at reflux in acetic acid (5 mL) for 30 min, and the solvent was removed at reduced pressure. The resulting residue was purified by flash column chromatography on silica gel to give 65 mg (37%) of 4- [2- [ [3-fluoro-5- (3 , 4,5, 6-tetrahydro-4-methoxypyran- 4-yDphenoxy]methyl] -4- (4-fluoro-phenyl)oxazol-5- yl]benzeneεulfonamide aε a white foam: m.p. 70-72 °C. 1 H NMR (CDCI 3 /3OO MHz) δ 1.85-2.01 (m, 4H) , 2.98 (s, 3H) , 3.80-3.83 (m, 4H) , 4.82 (bs, 2H) , 5.22 (ε, 2H) , 6.70-6.80 (m, 2H) , 6.92 (m, IH) , 7.04-7.18 (m, 2H) , 7.58-7.64 (m, 2H) , 7.74 (d, 2H, J = 8.7 Hz), 9.92 (d, 2H, J = 8.7 Hz) . FABMS: m/z = 563 (M+Li) . HRMS calcd for C 28 H 27 F 2 N 2 0 6 S 557.1558. ' Found 557.1538. Examp 1 e 15 4- [2- [4- [ [3-Fluoro-5- (3,4,5, 6-tetrahydro-4- methoxypyran-4-yl )phenoxy]methyl] phenylmethyl] -4- phenyloxazol-5-yl]benzenesulfonamide Step 1. Preparation of methyl 4- [3-fluoro-5- (4-methoxy- 3,4,5, 6-tetrahydro-2H-pyran-4-yl)phenoxymethyl1benzoate. A mixture of 3-fluoro-5- (4-methoxy-3 , 4, 5, 6- tetrahydro-2H-pyran-4-yl)phenol (Example 8, Step 4) (1.5 g, 6.6 mmol), methyl 4- (bromomethyDbenzoate (1.7 g, 7.4 mmol), K 2 CO 3 (0.6 g, 4.3 mmol), 18-crown-6 (0.05 g) and KI (0.05 g) in dimethylacetamide (5.00 mL) was stirred at room temperature for 16 h, and at 80 °C for 2 h. The reaction mixture was poured into cold water (100 mL) and extracted with EtOAc (2 x 25 mL) . The combined organic extracts were washed with water (2 x 25 mL) , dried (Na 2 Sθ 4 ) , filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 20% EtOAc in hexane, to furnish 2.2 g (88%) of methyl 4- [3- fluoro-5- (4-methoxy-3,4,5, 6-tetrahydro-2H-pyran-4- yl)phenoxymethyl]benzoate as a white solid: m.p. 88-89 °C. X H NMR (CDCI 3 / 300 MHz) δ 8.07 (d, 2H, J = 7.8 Hz), 7.5 (d, 2H, J . 7.8 Hz), 6.81 (s, IH) , 6.72 (d, IH, J = 9.9 Hz) , 6.6 (d, IH, J = 9.9 Hz), 5.12 (ε, 2H) , 3.93 (ε, 3H) , 3.82 (m, 4H) , 2.97 (ε, 3H) , 1.92 (m, 4H) . FABMS m/z 375 (M+H) . Step 2. Preparation of 4- r3-£luoro-5- (4-methoxy-3 , 4 , 5 , 6- tetrahydro-2H-pyran-4-yl)phenoxymethyl1benzoic acid. A solution of methyl 4- [3-fluoro-5- (4-methoxy- 3,4,5, 6-tetrahydro-2H-pyran-4-yl)phenoxymethyl]benzoate (Step 1) (1.9 g, 5.1 mmol) in THF (5.0 mL) was treated with methanolic 1M LiOH (8.0 mL) and stirred at room temperature for 2 h. The reaction mixture was acidified with 5% citric acid and extracted with EtOAc (2 x 25 mL) . The organic extracts were combined and washed with water (2 x 25 mL) , dried (Na 2 Sθ 4 ) , filtered, and concentrated to give the corresponding acid (1.7 g, 93%) as a white powder. Crystallization from EtOAc/hexane provided an analytically pure sample of 4- [3-fluoro-5- (4-methoxy- 3,4,5, 6-tetrahydro-2H-pyran-4-yl)phenoxymethyl]benzoic acid: m.p. 184-186 °C. λ E NMR (CDCI 3 /3OO MHz) δ 8.14 (d, 2H, J = 8.4 Hz), 7.54 (d, 2H, J = 8.4 Hz), 6.82 (ε, IH) , 6.75 (m, IH) , 6.62 (m, IH) , 5.14 (ε, 2H) , 3.83 (m, 4H) , 2.98 (ε, 3H) , 1.93 (m 4H) . FABMS m/z = 360 (M + ) . HRMS calcd for C 20 H 21 FO 5 360.1373, found 360.1372. Step 3. Preparation of 4- r2- \ 4- \ [3-fluoro-5- (3 , 4 , 5, 6- tetrahydro-4-methoxypyran-4- yl)phenoxy1methyl1phenylmethyl1 -4-phenyloxazol-5- yl1benzeneεulfonamide. A εolution of 4- [3-fluoro-5- (4-methoxy-3 , 4, 5, 6- tetrahydro-2H-ρyran-4-yl)phenoxymethyl]benzoic acid (Step 2) (0.6 g, 1.67 mmol) and 2-bromo-2- [ (4- aminosulfonyDphenyl] -1-phenyl-ethanone (0.5 g, 1.4 mmol) in dimethylacetamide (3.00 mL) was treated with K 2 CO 3 (0.17 g, 1.23 mmol) and 18-crown-6 (0.02 g) , and the resulting mixture waε εtirred at room temperature for 2.5 h. The reaction mixture waε poured into cold water (50 mL) and extracted with EtOAc (3 x 25 mL) . The organic extractε were combined and waεhed with water (2 x 25 mL) , dried (Na 2 Sθ 4 ) , filtered and concentrated under reduced preεεure to afford 0.9 g of the desired benzoin ester as an amorphous subεtance which was uεed in the next step without further purification: FABMS m/z = 634 (M+H) . HRMS calcd for C 34 H 3. .FNSO 8 634.1911, found 634.1939. This benzoin ester (0.8 g, 1.3 mmol) was dissolved in glacial acetic acid (8.0 mL) , ammonium acetate (0.5 g, 6.5 mmol) was added, and the resulting mixture was heated at 100 °C under a nitrogen atmosphere for 3 h. After the removal of the solvent in vacuo, the residue was partitioned between water (50 mL) and EtOAc (30 mL) . The organic phase waε waεhed with water (2 x 25 mL) , dried (Na 2 S0 4 ) , filtered, and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel, eluting with 40% EtOAc in hexane, to provide 0.45 g (58%) of 4- [2- [4- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yDphenoxy]methyl]phenylmethyl] -4-phenyloxazol-5- yl]benzenesulfonamide as a white amorphouε material: m.p. 93-99 °C. H NM " J. (CDCl 3 /300 MHz) δ 8.19 (d, 2H, J = 8.4 Hz), 7.92 (d, 2H, J = 8.1 Hz), 7.82 (d, 2H, J = 8.7 Hz), 7.68 (m, 2H) , 7.57 (d, 2H, J = 8.1 Hz), 7.45 (m, 3H) , 6.84 (ε, IH) , 6.73 (d, IH, J = 9.9 Hz), 6.64 (d, lh, J = 9.9 Hz), 5.14 (ε, 2H) , 4.84 (s, 2H) , 3.83 (m, 4H) , 2.99 (s, 3H) , 1.97 (m, 4H) ; FABMS m/z = 615 (M+H) . HRMS calcd for C 34 H 32 FN 2 SO 6 615.1965, found 615.1937. Example 16 4- [5- [ [3-Fluoro-5- (3,4,5, 6-tetrahydro-4 methoxypyran-4-yl)phenoxy]methyl] -3- phenylisoxazol-4-yl]benzenesulfonamide A εolution of 4- [5-methyl-3-phenylisoxazol-4- yl]benzeneεulfonamide (1.0 g, 3.2 mmol) and N, N, N' , N'- tetramethylethylenediamine (1.12 g, 9.6 mmol) in tetrahydrofuran (100 mL) waε cooled to -78 °C. Butyllithium (6 mL, 1.6 M, 9.6 mmol) waε then added to thiε solution. After 30 min, hexachloroethane (2.27 g, 9.6 mmol) was added to the reaction mixture, the reaction mixture was warmed to -30 °C, and then quenched with dilute hydrochloric acid. The reaction mixture was extracted with ethyl acetate (100 mL) , washed with brine, dried and concentrated to afford a 1:1 mixture of the desired 5-chloromethyl isoxazole product and the starting material as an inseparable mixture, which was carried to the next stage without further purification. The crude 5-chloromethyl isoxazole (0.25 g, 0.718 mmol) was added to a solution of 3-fluoro-5- (4-methoxy-3 , 4, 5, 6- tetrahydro-2H-pyran-4-yl)phenol (Example 8, Step 4) (0.324 g) in dioxane (5 mL) and aqueous sodium hydroxide (IN, 2.86 mL) , and the reaction mixture was stirred for 3 days at room temperature. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (2 x 20 mL) . The organic layers were combined and washed wi ^ water and brine, dried, filtered, and concentrated. The resulting residue was purified by flaεh column chromatography on εilica gel, eluting with 1:2 ethyl acetate in hexane, to give 0.130 g (67%) of 4-[5- [ [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran-4-yl) - phenoxy] -methyl] -3-phenylisoxazol-4-yl]benzenesulfonamide aε a cryεtalline solid: Η. NMR (CDCI 3 /3OO MHz) δ 7.93 (d, 2H, J = 8.5 Hz), 7.42-7.36 (m, 7H) , 6.78-6.54 (m, 3H) , 5.15 (s, 2H) , 3.79-3.82 (m, 4H) , 2.99 (s, 3H) , 1.88-1.86 (m, 4H) . FABMS m/z = 545 (M+Li) . HRMS calcd for C 28 H 27 N2F0 6 S 538.1652. Found 539.1652 (M+H) . Example 17 4-[2-[ [[3-(3,4,5,6-Tetrahydro-4-methoxypyran-4 yl) henylmethyl] oxy] methyl] -4-phenyloxazol-5- yl] benzenesulfonamide Step 1. Preparation of methyl 3-1 " (4- methoxy) tetrahydropyran-4-yllphenyl-methoxyacetate. A solution of methyl glycolate (0.35 g, 3.9 mmol) in 5 mL of anhydrous DMF was added to a suspension of εodium hydride (0.11 y, 4.6 mmol) in 5 mL of anhydrouε DMF at 5 °C, and the reaction mixture was stirred for 40 minutes at 5 °C. A εolution of 3- [ (4-methoxy) tetrahydropyran-4- yl] -α-bromotoluene (1 g, 3.9 mmol) in 10 mL of anhydrous DMF was added to the cold methyl glycolate solution while maintaining the temperature at 5 °C. The mixture was stirred for 2 h at 5 °C, then for 18 h at room temperature. The mixture was quenched with water (100 mL) and the aqueous solution was extracted with ethyl acetate (2 x 100 mL) . The combined organic extracts were washed with saturated brine (1 x 100 mL) , dried over magneεium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on silica gel, eluting with 25% ethyl acetate in hexane, to give 0.57 g (50%) of methyl 3- [ (4-methoxy) - tetrahydropyran-4-yl]phenylmethoxyacetate as a clear oil: HRMS calcd for Cι 6 H 22 θ 5 295.1545. Found 295.1502. Step 2. Preparation of 3- [ (4-methoxy) -tetrahydropyran-4- yllphenylmethoxy-acetic acid. A solution of methyl 3- [ (4-methoxy) -tetrahydropyran- 4-yl]phenylmethoxy-acetate (Step 1) (0.5 g, 1.7 mmol) and LiOH (0.18 g, 4.25 mmol) in 10% water and methanol (5 mL) was stirred for 6 h at room temperature. The solventε were removed at reduced preεεure, and the concentrated reεidue waε partitioned between ethyl acetate (100 mL) and 1 N HCl (30 mL) . The organic layer waε εeparated and waεhed with εaturated brine (1 x 100 mL) , dried over magneεium εulfate, filtered and concentrated. The concentrated residue was vacuum dried to give 0.46 g (97%) of 3- [ (4-methoxy) -tetrahydropyran-4-yl]phenyl- methoxyacetic acid as a yellow εolid: HRMS calcd for C 15 H 20 O 5 280.1311. Found 280.1304. Step 3. Preparation of 4- [2- [ [ \ 3 - (3 , 4, 5 , 6-tetrahydro-4- methoxypyran-4-yl)phenylmethylloxylmethyll -4- phenyloxazol-5-yllbenzeneεulfonamide. An aqueous solution of 2.5 N NaOH (1.2 mL, 2.7 mmol) was added to 3- [ (4-methoxy) tetrahydropyran-4- yl]phenyImethoxyacetic acid (0.76 g, 2.7 mmol) in ethanol (10 mL) , and the mixture was stirred for 15 min at room temperature. The solvents were removed at reduced preεεure. Several mL of absolute ethanol were added to this concentrated residue, and the mixture waε again concentrated at reduced preεεure. Thiε procedure waε repeated three timeε until a white solid formed, which was dried under high vacuum. The resulting carboxylic acid sodium salt was εuεpended in 4 mL of anhydrouε DMF. A εolution of 2-bromo-2- [ (4-amino-εulfonyl)phenyl] -1- phenyl-ethanone (1.1 g, 2.7 mmol) in 4 mL of DMF waε added at room temperature. The reaction mixture waε stirred for 18 h at room temperature, and the DMF was removed at reduced pressure. Ethyl acetate (100 mL) was added to this concentrated residue, and this mixture was filtered. The filtrate was concentrated and dried to give the desired crude α-acyloxy ketone. Acetic acid (5 mL) and ammonium acetate (0.8 g, 10 mmol) were added to thiε concentrated residue, and this mixture waε heated at 100 °C for 3 h. The reaction mixture was cooled to room temperature, and the excess acetic acid was removed under vacuum. The resulting residue was partitioned between water (100 mL) and ethyl acetate (100 mL) . The organic layer was εeparated, washed with saturated aqueous sodium bicarbonate (2 x 100 mL) , saturated brine (1 x 100 mL) , dried over magnesium εulfate, filtered and concentrated. The concentrated reεidue was purified by flash column chromatography on silica gel, eluting with 20% to 45% ethyl acetate in hexane, to give 0.19 g (13%) of 4- [2- [[[3-(3,4,5, 6-tetrahydro-4-methoxypyran-4- yl)phenylmethyl] oxy]methyl] -4-phenyloxazol-5- yl]benzenesulfonamide as a white solid: m.p. 62.1-71.2 °C. !H NMR (CDCl 3 /300 MHz) δ 1.91-1.95 (m, 4H) , 2.94 (s, 3H) , 3.75-3.88 m, 4H) , 4.73 (ε, 2H) , 4.74 (ε, 2H) , 4.92 (ε, 2H) , 7.30-7.44 (m, 7H) , 7.60-7.63 (m, 2H) , 7.73-7.76 (m, 2H) , 7.89-7.92 ( m, 2H) . HRMS calcd for C 29 H 30 N 2 O 6 S 535 . 1903 . Found 535 . 1865 . Example 18 4-[2-[ [[3-( ,4,5,6-Tetrahydro-4-methoxypyran-4- yl )phenylmethyl] thio] methyl] -4-phenylox zol-5- yl] benzenesulfonami e Step 1. Preparation of Methyl 3- [ (4-methoxy) - tetrahydropyran-4-yll henyl-methylthioacetate. A εolution of 3- [ (4-methoxy) tetrahydropyran-4-yl] -α- bromotoluene (1.0 g, 3.87 mmol) in 10 mL of anhydrouε THF waε cooled to 5 °C. A εolution of methyl thioglycolate (0.41 g, 3.87 mmol) and DBU (0.59 g, 3.87 mmol) in 10 mL of THF waε added while maintaining the temperature at 5 °C . The reaction mixture waε stirred for 2 h at room temperature. The reaction mixture was diluted with 250 mL of ethyl acetate, and the organic layer was washed with 1 N HCl (2 x 100 mL) , saturated sodium bicarbonate (1 x 100 mL) , brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on εilica gel, eluting with 40% ethyl acetate in hexane, to give 0.87 g (72%) of methyl 3- [ (4-methoxy) - tetrahydropyran-4-yl]phenyl-methylthioacetate aε a clear oil: ! H NMR (CDCl 3 /300 MHz) δ 1.94-2.09 (m, 4H) , 2.97 (ε, 3H) , 3.08 (s, 2H) , 3.73 (ε, 3H) , 3.77-3.92 (m, 6H) , 7.26-7.36 (m, 4H) . HRMS calcd for Cι 6 H 22 θ 4 S 311.1317. Found 311.1271. Step 2. Preparation of 3- [ (4-methoxy) -tetrahvdropyran-4- yll henylmethyl-thioacetic acid. A εolution of methyl 3- [ (4-methoxy) -tetrahydropyran- 4-yl]phenyImethyl-thioacetate (Step 1) (0.8 g, 2.58 mmol) and LiOH (0.27 g, 6.44 mmol) in 10% water and methanol (10 mL) waε εtirred for 18 h at room temperature. The solvents were removed at reduced preεεure, and the concentrated reεidue was partitioned between ethyl acetate (200 mL) and 1 N HCl (100 mL) . The organic layer was separated and washed with saturated brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue was vacuum dried to give 0.75 g (98%) of 3- [ (4-methoxy) -tetrahydropyran-4- yl]phenyl-methylthioacetic acid as a clear oil: 1 H NMR (CDCl 3 /300 MHz) δ 1.94-2.10 (m, 4H) , 2.11 (s, IH) , 2.98 (s, 3H) , 3.10 (s, 2H) , 3.81-3.91 (m, 6H) , 7.28-7.38 (m, 4H) . HRMS calcd for C 15 H 20 O 4 S 297.1161. Found 297.1140. Step 3. Preparation of 4- [2- [ f [3- (3 , 4, 5, 6-tetrahydro-4- methoxypyran-4-yl)phenylmethyl1 thiolmethyl1 -4- phenyloxazol-5-yllbenzeneεulfonamide. An aqueouε solution of 2.5 N NaOH (0.97 mL, 2.43 mmol) was added to a solution of 3- [ (4-methoxy) - tetrahydropyran-4-yl]phenyImethylthioacetic acid (Step 2) (0.72 g, 2.43 mmol) in ethanol (10 mL) , and the mixture was stirred for 15 min at room temperature. The solventε were removed at reduced pressure. Several mL of absolute ethanol were added to this concentrated residue, and the mixture was again concentrated at reduced presεure. This procedure was repeated three timeε until a white solid formed, which was dried under high vacuum. The reεulting carboxylic acid sodium salt was suspended in 10 mL of anhydrouε DMF. A solution of 2-bromo-2- [ (4- aminoεulfonyl)phenyl] -1-phenylethanone (Example 8, Step 1) (0.86 g, 2.43 mmol) in 8 mL of DMF waε added at room temperature. The reaction mixture waε εtirred for 1 h at room temperature, and the DMF was removed at reduced presεure. Ethyl acetate (100 mL) was added to this concentrated reεidue, and this mixture was filtered. The filtrate waε concentrated and dried to give the desired crude α-acyloxy ketone. Acetic acid (5 mL) and ammonium acetate (0.8 g, 10 mmol) were added to this concentrated reεidue, and the mixture waε heated at 100 °C for 2 h. The mixture waε cooled to room temperature, and the excess acetic acid was removed under vacuum. The resulting residue was partitioned between water (100 mL) and ethyl acetate (250 mL) . The organic layer was separated, washed with saturated aqueous sodium bicarbonate (2 x 100 mL) , εaturated brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue waε purified by flaεh column chromatography on silica gel, eluting with 40% ethyl acetate in hexane, to give 0.28 g (21%) of 4- [2- [[[3- (3,4,5, 6-tetrahydro-4-methoxypyran-4- yl)phenylmethyl] hio]methyl] -4-phenyl-oxazol-5- yl]benzenesulfonamide as a white εolid: m.p. 77.2-81.7 °C. l H NMR (CDCl 3 /300 MHz) δ 1.80-1.94 (m, 4H) , 2.93 (ε, 3H) , 3.76-3.86 (m, 6H) , 3.90 (ε, 2H) , 4.96 (ε, 2H) , 7.24- 7.32 (m, 3H) , 7.41-7.44 (m, 4H) , 7.61-7.64 (m, 2H) , 7.71 (bd, 2H, J = 8.40 Hz), 7.91 (bd, 2H, J = 8.40 Hz) . HRMS calcd for C 29 H ? oN 2 0 5 S 2 551.1674. Found 551.1668. Example 19 4-[2-[ [[3-(3,4,5,6 -Tetrahydro- 4 -methoxypyran- 4 • yl ) phenylmethyl] thio] ethyl] -4 -phenyloxazol-5- yl] benzenesulfonamide Step 1. Preparation of ethyl 3- [[(4- methoxy) tetrahvdropyran-4-yllphenyl- methylthiolpropionate . A εolution of 3- [ (4-methoxy) tetrahydropyran- 4-yl] -α- bromotoluene (1.0 g, 3.87 mmol) in 10 mL of anhydrous THF was cooled to 5 °C . A solution of methyl 3- mercaptopropionate (0.46 g, 3.87 mmol) and DBU (0.59 g, 3.87 mmol) in 10 mL of THF was added while maintaining the temperature at 5 °C . The reaction mixture was stirred for 1 h at 5 °C and for 18 h at room temperature. The reaction mixture was diluted with 200 mL of ethyl acetate, and this solution was washed with 1 N HCl (1 x 100 mL) , saturated sodium bicarbonate (1 x 100 mL) , brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. "he concentrated residue was purified by flash column chromatography on silica gel, eluting with 20% ethyl acetate in hexane, to give 0.94 g (75%) of methyl 3- [ [ (4-methoxy) -tetrahydro-pyran-4- yl]phenylmethylthio]propionate as a pink oil: 1 H NMR (CDCl 3 /300 MHz) δ 1.93-2.09 (m, 4H) , 2.54 (t, 2H, J = 7.4 Hz), 2.68 (t, 2H, J = 7.5 Hz), 2.97 (ε, 3H) , 3.68 (ε, 3H) , 3.75 (ε, 2H) , 3.80-3.92 (m, 4H) , 7.23-7.36 (m, 4H) . HRMS calcd for C 17 H2 4 O 4 S 325.1474. Found 325.1494. Step 2. Preparation of 3- \ \ (4-methoxy)tetrahydropyran-4- yllphenylmethyl-thiolpropionic acid. A solution of methyl 3- [ [ (4-methoxy) tetrahydropyran- 4-yl]phenyl-methyl-thio]propionate (Step 1) (0.91 g, 2.8 mmol) and LiOH (0.29 g, 7.01 mmol) in 10% water and methanol (10 ml ' . was stirred for 18 h at room temperature. The solvents were removed at reduced presεure, and the concentrated reεidue waε partitioned between ethyl acetate (200 mL) and 1 N HCl (100 mL) . The organic layer was separated and washed -with saturated brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated reεidue was vacuum dried to give 0.9 g of 3-[[(4- methoxy) tetrahydropyran-4-y1]phenylmethy1-thio]propionic acid as a clear, colorless oil: HRMS calcd for C 16 H 22 O 4 S 310.1239, found 310.1241. Step 3. Preparation of 4- [2- \ 2- \ [5- (3 , 4, 5 , 6-tetrahvdro-4- methoxypyran-4-yl)phenyl-methyl1thiolethyll -4- phenyloxazol-5-yllbenzenesulfonamide. An aqueous solution of 2.5 N NaOH (1.03 mL, 2.6 mmol) waε added to a εolution of 3-[[(4- methoxy) tetrahydropyran-4-y1]phenylmethylthio]propionic acid (0.8 g, 2.6 mmol) in ethanol (10 mL) , and the mixture was stirred for 15 min at room temperature. The solvents were removed at reduced pressure. Several mL of absolute ethanol were added to the concentrated reεidue, and the mixture waε again concentrated at reduced pressure. This procedure was repeated three times until a white solid formed, which was dried under high vacuum. The resulting carboxylic acid sodium salt was suspended in 10 mL of anhydrous DMF and combined with a solution of 2-bromo-2-[ (4-aminoεulfonyl)phenyl] -1-phenylethanone (Example 8, St p 1) (0.91 g, 2.6 mmol) in 10 mL of DMF. The resulting mixture was stirred for 18 h at room temperature, and the DMF was removed at reduced presεure. Ethyl acetate (100 mL) was added to this concentrated reεidue, and thiε mixture waε filtered. The filtrate was concentrated and dried to give the desired crude α- acyloxy ketone. Acetic acid (5 mL) and ammonium acetate (0.8 g, 10 mmol) were added to thiε concentrated reεidue, and thiε mixture waε heated at 100 °C for 2 h. The reaction mixture waε cooled to room temperature, and the excess acetic acid waε removed under vacuum. The reεulting reεidue waε partitioned between water (100 mL) and ethyl acetate (250 mL) . The organic layer waε separated, washed with saturated aqueous εodium bicarbonate (2 x 100 mL) , saturated brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on silica gel, eluting with 40% to 45% ethyl acetate in hexane, to give 0.06 g (4%) of 4-[2-[2- [ [5- (3 , 4, 5 , 6-tetrahydro-4-methoxypyran-4-yl)phenyl¬ methyl] thio] ethyl] -4-phenyloxazol-5-yl]benzenesulfonamide as a white solid: m.p. 60.9-66.4 °C. 1 H NMR (CDCl 3 /300 MHz) δ 1.93-2.01 (m, 4H) , 2.91-2.95 (m, 5H) , 3.12 (t, 2H, J = 7.20 Hz), 3.76-3.87 (m, 6H) , 4.50 (ε, 2H) ,7.29-7.43 (m, 7H) , 7.58-7.61 (m, 2H) , 7.69-7.72 (m, 2H) , 7.88-7.91 (m, 2H) . HRMS calcd for C 30 H 32 2 θ 5 S 2 565.1831. Found 565.1852. Example 20 4-[2-[3-(3,4,5, 6-Tetrahydro-4-methoxypyr n-4 yl) phenyl] methoxy] -4-phenyloxazol-5- yl] benzenesulfonamide A solution of 3- [tetrahydro- (4-methoxy)pyran-4- yl]benzyl alcohol (prepared aε deεcribed in US Patent 5,424,320) { 0 . 0 n g, 0.3 mmol) in 2 mL of anhydrouε DMA waε added to a εuεpension of sodium hydride (7.2 mg, 0.3 mmol) in 2 mL of anhydrous DMA at 5 °C, and the reaction mixture waε εtirred for 20 minuteε at 5 °C. A εolution of 4- [ (2-chloro) -4-phenyloxazol-5-yl]benzeneεulfonamide in 2 mL of anhydrous DMA was then added. The reaction mixture waε εtirred for 2 h at 5 °C and for 5 h at room temperature. The reaction mixture waε quenched with water (50 mL) . The aqueouε solution was extracted with ethyl acetate (2 x 50 mL) . The combined organic layerε were waεhed with saturated brine (1 x 100 mL) , dried over magnesium sulfate, filtered and concentrated. The concentrated residue waε purified by flash column chromatography on silica gel, eluting with 40% ethyl acetate in hexane, to give 0.1 g (64%) of 4- [2- [3- (3,4,5, 6-tetrahydro-4-methoxypyran-4-yl)phenyl]methoxy] - 4-phenyloxazol-5-yl] -benzeneεulfonamide aε a white εolid: X H NMR (CDCI 3 /3OO MHz) δ 1.95-2.06 (m, 4H) , 2.98 (ε, 3H) , 3.81-3.88 (m, 4H) , 4.81 (s, 2H) , 5.53 (s, 2H) , 7.39-7.46 (m, 6H) , 7.55-7.67 (m, 5H) , 7.84 ( d, 2H, J = 8.70 Hz) . HRMS calcd for C 28 H 28 N 2 0 6 S 521.1746. Found 521.1701. Example 21 4-[2-[3-(3,4,5, 6-Tetrahydro-4-methoxypyran-4- yl ) phenyl]methylthio] -4-phenyloxazol-5- yl] benzenes lfonamide To a solution of 4- [ (2-chloro) -4-phenyloxazol-5- yl]benzenesulfonamide (0.21 g, 0.63 mmol) in 2 mL of anhydrous THF at 5 °C waε added a εolution of 3- [tetrahydro- (4-methoxy)pyran-4-yl]benzyl mercaptan (prepared as described in US Patent 5,424,320) (0.15 g, 0.63 mmol) and DBU (95 mg, 0.63 mmol) in 5 mL of THF while maintaining the temperature at 5 °C. The reaction mixture was εtirred for 1 h at 5 °C for 5 h at room temperature. The reaction mixture was diluted with 100 mL of ethyl acetate and waεhed with 1 N HCl (1 x 100 mL) , saturated aqueous NaHC0 3 (1 x 100 mL) , brine (1 x 100 mL) , dried ove? magnesium sulfate, filtered and concentrated. The concentrated residue waε purified by flaεh column chromatography on εilica gel, eluting with 40% ethyl acetate in hexane, to give 0.19 g (56%) of 4- [2-[3-(3,4,5, 6-tetrahydro-4-methoxypyran-4- yl)phenyl]methylthio] -4-phenyloxazol-5- yl]benzeneεulfonamide aε a white solid: m.p. 74.7-7 .5 °C. 1 H NMR (CDCI 3 /3OO MHz) δ 1.85-1.97 (m, 4H) , 2.92 (s, 3H) , 3.71-3.85 (m, 4H) , 4.48 (s, 2H) , 4.87 (s, 2H) , 7.29- 7.47 (m, 7H) , 7.60-7.69 (m, 4H) , 7.86-7.90 (m, 2H) . HRMS calcd for C 28 H 28 N 2 θ5S 537.1518. Found 537.1516. Example 22 N- [2- [5- [4- (Aminosulfonyl)phenyl] -4-phenyloxazol- 2-yl] ethylamino] -2- [3-fluoro-5- (3,4,5,6- tetrahydro-4-methoxypyran-4-yl )phenoxy] acetamide Step 1. Preparation of 4-[2-[2-(N- phenylmethoxycarbonylamino) ethyll -4-phenyloxazol-5- yllbenzenesulfonamide. A mixture of N-phenylmethoxycarbonyl-β-alanine (1.5 g, 6.7 mmol) and 2-bromo-2- [ (4-aminoεulfonyl)phenyl] -1- phenylethanone (Example 8, Step 1) (2.0 g, 5.65 mmol) in dimethylacetamide (10.00 mL) waε treated with K 2 CO 3 (0.47 g, 3.4 mmol) and 18-crown-6 (0.033 g) and εtirred at room temperature for 16 h. After the removal of the solvent in vacuo, the residue waε partitioned between cold water (25 mL) and EtOAc (50 mL) . The organic phase waε waεhed with water (2 x 25 mL) , dried (Na 2 Sθ 4 ), and concentrated under reduced preεsure. The reεulting εubεtance (2.8 g) waε purified by flaεh column chromatography on εilica gel, eluting with 40% EtOAc in hexane, to afford the deεired benzoin eεter (2.0 g) aε an amorphous substance which was used without further purification. The benzoin ester (1.6 g) was diεsolved in glacial acetic acid (16 mL) , treated with ammonium acetate (1.25 g, 16.2 mmol) and heated at 90 °C under a nitrogen atmosphere for 3 h. After the removal of the solvent in vacuo, the residue waε partitioned between water (50 mL) and EtOAc (50 mL) . The organic phaεe was washed with water (2 x 25 mL) , dried (Na 2 Sθ 4 ), and concentrated under reduced preεεure. The resulting material was purified by flaεh column chromatography on εilica gel, eluting with 50% EtOAc in hexane, to provide 0.85 (55%) of 4-[2-[2-(N- phenylmethoxycarbonyl-amino) ethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide as a white amorphous material: 1 H NMR (CDCl 3 /300 MHz) δ 7.86 (d, 2H, J = 8.4 Hz), 7.69 (d, 2H, J = 8.4 Hz), 7.59 (m, 2H) , 7.40 (m, 3H) , 7.33 (m, 5H) , 5.45 (br, IH) , 5.10 (s, 2H) , 4.91 (s, 2H) , 3.74 (q, 2H, J = 6.0 Hz), 3.09 (t, 2H, J = 6.0 Hz) .; FABMS m/z = 478 (M+H) . HRMS calcd for C 25 H 24 N 3 θ 5 S 478.1437. Found 478.1412. Step 2. Preparation of 4- \ 2 - (2-aminoethyl) -4-phenyl- oxazol-5-vDbenzeneεulfonamide. A solution of 4-[2-[2-(N- phenylmethoxycarbonylamino) ethyl] -4-phenyl-oxazol-5- yl]benzeneεulfonamide (Step 1) (0.75 g, 1.6 mmol) in MeOH (15 mL) containing acetic acid (0.1 mL) waε treated with 10% Pd on carbon (0.35 g) and εtirred under an atmoεphere of hydrogen at 50 pεi at room temperature for 2.5 h. The catalyεt waε removed by filtration, and the filtrate waε concentrated under reduced preεsure to afford a white powder which was purified by reverεe-phaεe HPLC uεing a gradient of 10-90% CH 3 CN in H 2 0 to afford 0.55 g of 4- [2- (2-aminoethyl) -4-phenyloxazol-5-yl]benzeneεulfonamide aε itε trifluoroacetate salt: 1 H NMR (CD 3 OD/300 MHz) δ 7.91 (d, 2H, J = 7.9 Hz), 7.74 (m, 2H, ) , 7.63 (m, 2H) , 7.44 (m, 3H) , 3.49 (t, 2H, J = 6.6 Hz), 3.33 (t, 2H, J = 6.6 Hz) . FABMS m/z = 344 (M+H) . HRMS calcd for Cι 7 Hι 8 N3θ 5 S 344.1069. Found 344.1048. Step 3. Preparation of N- \ 2 - \5- [4- (aminoεulfonvDphenyll - 4-phenyloxazol-2-vπethylaminol -2- r3-£luoro-5- (3,4,5,6- tetrahvdro-4-methoxypyran-4-yl)phenoxy1 -acetamide. To a εolution of 3-fluoro-5- (4-methoxy-3 , 4, 5, 6- tetrahydro-2H-pyran-4-yl) -phenoxyacetic acid (0.24 g, 0.85 mmol) (Example 8, Step 3) in dimethylacetamide (2.00 mL) and dichloromethane (3.00 mL) , HOBt (0.18 g, 1.18 mmol) and EDC ,' 0.17 g, 0.89 mmol) were added, and the resulting mixture was stirred at 0 °C for 1 h. This reaction mixture was treated with a solution of the free amine generated by the addition of N-methylmorpholine (0.1 mL) to a solution of 4- [2- (2-aminoethyl) -4- phenyloxazol-5-yl]benzeneεulfonamide trifluoroacetate (0.3 g, 0.51 mmol) in dimethylacetamide (1.0 mL) at 0 °C. The resulting mixture was warmed to room temperature in 16 h. The reaction mixture was diluted with dichloromethane (20 mL) , and washed sequentially with 5% citric acid, (2 x 10 mL) , saturated NaHC0 3 (2 xlO mL) , water, and dried (Na 2 S0 4 ) . After the removal of the solvent under reduced presεure, the residue was purified by flash column chromatography on silica gel, eluting with 80% EtOAc in hexane, to afford 0.31 g (52%) of N-[2- [5- [4- (aminoεu.' ".OnyDphenyl] -4-phenyloxazol-2-yl] ethyl- amino] -2- [3-fluoro-5- (3,4,5, 6-tetrahydro-4-methoxypyran- 4-yl)phenoxy]acetamide aε a white amorphouε substance: ^-H NMR (CDCl 3 /300 MHz) δ 7.88 (d, 2H, J = 8.7 Hz), 7.72 (d, 2H, J = 8.7 Hz), 7.58 (m, 3H) , 7.43 (m, 3H) , 6.74 (d, IH, J = 9.6 Hz) 6.7 (m, IH) , 6.48 (m, IH) , 4.97 (ε, 2H) , 4.51 (ε, 2H) , 3.9 (q, 2H, J = 6.0 Hz), 3.79 (m, 4H) , 3.13 (t, 2H, J = 6.3 Hz), 2.95 (ε, 3H) , 1.84 (m, 4H) . FABMS m/z = 610 (M+H) . HRMS calcd for C 31 H 33 N 3 O 7 FS 610.2023. Found 610.2016. BIOLOGICAL EVALUATION Rat Carrageenan Foot Pad Edema Test The carrao,'ienan foot edema test was performed with materials, reagents and procedures esεentially as described by Winter, et al. , { Proc. Soc . Exp . Biol . Med . , Ill, 544 (1962)) . Male Sprague-Dawley rats were selected in each group so that the average body weight was as close aε poεεible. 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 suspended in vehicle containing 0.5% methylcellulose and 0.025% surfactant, or with vehicle alone. One hour later a subplantar injection of 0.1 mL of 1% εolution of carrageenan/εterile 0.9% εaline waε adminiεtered and the volume of the injected foot waε measured with a displacement plethysmometer connected to a pressure transducer with a digital indicator. Three hourε after the injection of the carrageenan, the volume of the foot was again measured. The average foot swelling in a group of drug-treated animals was compared with that of a group of placebo-treated animals and the percentage inhibition of edema waε determined (Otterneεε and Bliven, Laboratory Models for Testing NSAIDε, in Non- εteroidal Anti-Inflammatory Drugs, (J. Lombardino, ed. 1985)) . The % inhibition shows the % decrease from control paw volume determined in this procedure and the data for selected compounds in thiε invention are εummarized in Table I. TABLE I. RAT PAW EDEMA % Inhibition @ lOmg/kg body weight Example 3 15 Evaluation of COX-1 and COX-2 activity in vi tro The compoundε of thiε invention exhibited inhibition in vi tro of COX-2. The COX-2 inhibition activity of the compoundε of thiε invention illustrated in the Examples was determined by the following methods. a. Preparation of recombinant COX baculoviruses Recombinaii- COX-1 and COX-2 were prepared as described by Gierse et al, [J " . 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 (Invitrogen) to generate the baculovirus transfer vectors for COX-1 and COX-2 in a manner similar to the method of D.R. O'Reilly et al {Baculovirus Expression Vectors : A Laboratory Manual (1992)). Recombinant baculoviruseε were isolated by transfecting 4 μg of baculovirus transfer vector DNA into SF9 insect cells (2x108) along with 200 ng of linearized baculovirus plasmid DNA by the calcium phosphate method. See M.D. Summers and G.E. Smith, A Manual of Methods for Baculovirus Vectors and Innict Cell Cul ture Procedures, Texas Agric. Exp. Station Bull. 1555 (1987) . Recombinant viruses were purified by three rounds of plaque purification and high titer (10^ - 10^ pfu/ml) stocks of virus were prepared. For large εcale production, SF9 insect cells were infected in 10 liter fermentors (0.5 x 106/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 Tris/Sucrose (50 mM: 25%, pH 8.0) containing 1% 3-[(3- cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). The homogenate was centrifuged at 10,000xG for 30 minutes, and the resultant supernatant was stored at -80°C before being assayed for COX activity. b. Asεav for COX-1 and COX-2 activity COX activity was aεsayed as PGE 2 formed/μg protein/time using an ELISA to detect the prostaglandin released. CHAPS-solubilized insect 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 εtopped after ten minuteε at 37°C/room temperature by tranεferring 40 μl of reaction mix into 160 μl ELISA buffer and 25 μM indomethacin. The PGE 2 formed waε measured by standard ELISA technology (Cayman Chemical) . Resuitε are εhown in Table II. Assay for 5-Lipoxygenase activity The 5-lipoxygenase (5-LO) activity of the compounds were determined by the calcium ionophore- induced Leukotriene B4 (LTB4) production in human whole blood. Venous blood waε collected from healthy human donors using heparin as an anti-coagulant. Human blood sampleε (0.2 ml of a 1:4 dilution in RPMI 1640 medium) were incubated in 96-well culture plateε for 15 minuteε at 37°C with teεt compoundε diεεolved in ethanol (EtOH; final concentration <1%), or vehicle. Typically 7 concentrationε of teεt compounds were examined in duplicate. A-23187 [Sigma] was added to the blood to a final concentration of 20 μg/ml, and the mixtures were incubated for 10 minutes at 37°C. The reaction waε εtopped by placing the εampleε on ice. The samples were then centrifuged at 800 x g at 4°C for 10 minutes to pellet the cells, and the supernatantε were recovered for quantitation of LTB4 by ELISA (Cayman Chemical Co.; sensitivity 3 pg/ml) . IC 5 o' s were estimated from a four parameter logistic model with two parameterε fixed, the minimum (0% inhibition) and maximum (100% inhibition) . The IC 50 value is the concentration that produces 50% inhibition between the fixed values of the minimum and maximum. Data is reported as the mean IC 50 for each compound. Results are shown in Table II. TABLE II. Examp l e COX-2 COX- 1 5 - LO -IC.5 0— μM ) IC5 o_LμM ) IC.50— LμM ) 1 <0.1 38 0.15 2 0.2 >10 0.05 3 <0.1 >100 0.02 4 <0.1 <0.1 14 5 <0.1 <0.1 17 6 <0.1 2.2 0.44 7 <0.1 3.8 0.65 8 <0.1 1.3 0.3 9 10 80 >10 12 <0.1 >100 >10 14 <0.1 5.0 0.2 16 <0.1 >100 >10 17 0.5 >100 9.8 19 <0.1 2.3 >10 21 <0.1 2.6 >10 22 1.1 >100 >10 Also embraced within thiε invention iε a class of pharmaceutical compositions comprising the active compounds of this combination therapy in association with one or more non-toxic, pharmaceutically-acceptable carriers and/c_' diluents and/or adjuvants (collectively referred to herein aε "carrier" materialε) and, if deεired, other active ingredientε. The active compounds of the present invention may be administered by any suitable route, preferably in the form of a pharmaceutical compoεition adapted to εuch a route, and in a dose effective for the treatment intended. The active compounds and compoεition may, for example, be adminiεtered orally, intravascularly (IV) , intraperitoneally, subcutaneously, intramuscularly (IM) or topically. For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, hard or soft capsule, lozenges, diεpensable powders, 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 (IV, IM, subcutaneouε or jet) as a composition wherein, for example, saline, dextrose, or water may be used as a suitable carrier. The pH of the composition may be adjusted, if necessary, with suitable acid, base, or buffer. Suitable bulking, dispersing, wetting or suspending agents, including mannitol and PEG 400, may also be included in the composition. A suitable parenteral compoεition can alεo include a compound formulated aε a εterile εolid εubstance, including lyophilized powder, in injection vials. Aqueous εolution can be added to diεεolve the compound prior to injection. The amount of therapeutically active compoundε that are adminiεtered and the doεage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factorε, including the age, weight, εex and medical condition of the subject, the severity of the inflammation or inflammation related disorder, the route and frequency of administration, and the particular compound employed, and thus may vary widely. The prodrug compositions should include similar dosages as for the parent compounds. The pharmaceutical compositionε may contain active ingredientε in the range of about 0.1 to 1000 mg, preferably in the range of about 0.5 to 250 mg and most preferably between about 1 and 60 mg. A daily dose of about 0.01 to 100 mg/kg body weight, preferably between about 0.05 and about 20 mg/kg body weight and most preferably between about 0.1 to 10 mg/kg body weight, may be appropriate. The daily dose can be adminiεtered in one to four doses per day. In the case of skin conditions, it may be preferable to apply a topical preparation of compoundε of thiε invention to the affected area two to four times a day. For disorders of the eye or other external tisεueε, e.g., mouth and skin, the formulations are preferably applied as a topical gel, spray, ointment or cream, or as a suppository, containing the active ingredients in a total amount of, for example, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably 0.4 to 15% w/w. When formulated in an ointment, the active ingredients may be employed with either paraffinic or a water-miscible ointment baεe. Alternatively, the active ingredientε may be formulated in a cream with an oil-in- water cream baεe. If deεired, the aqueouε phaεe of the cream base may include, for example at least 30% w/w of a polyhydric alcohol such as propylene glycol, butane- 1,3-diol, mannitol, sorbitol, glycerol, polyethylene glycol and mixtureε thereof. The topical formulation may deεirably include a compound which enhances absorption or penetration of the active ingredient through the sk.n or other affected areas. Examples of such dermal penetration enhancers include dimethylsulfoxide and related analog . The compoundε of thiε invention can also be administered by a tranεdermal device. Preferably topical adminiεtration will be accompliεhed uεing a patch either of the reservoir and porous membrane type or of a εolid matrix variety. In either caεe, the active agent iε delivered continuouεly from the reservoir or microcapsuleε through a membrane into the active agent permeable adhesive, which is in contact with the skin or mucoεa of the recipient. If the active agent iε absorbed through the skin, a controlled and predetermined flow of the active agent is administered to the recipient. In the case of microcapsules, t.he encapεulating agent may alεo function as the membrane. The transdermal patch may include the compound in a suitable solvent system with an adhesive system, such as an acrylic emulsion, and a polyester patch. The oily phase of the emulsionε of thiε invention may be conεtituted from known ingredientε in a known manner. While the phase may comprise merely an emulsifier, it may comprise a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts aε a stabilizer. It is alεo preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(ε) make-up the εo-called emulεifying wa;. and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily disperεed phase of the cream formulations. Emulsifiers and emulsion εtabilizers suitable for use in the formulation of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate, among others. The choice of suitable oils or fats for the formulation is baεed on achieving the desired cosmetic properties, since the εolubility of the active compound in moεt oilε likely to be uεed in pharmaceutical emulsion formulations is very low. Thus, the cream should preferably be a non-greasy, non-staining and washable product with suitable conεiεtency to avoid leakage from tiibes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, iεopropyl myriεtate, decyl oleate, iεopropyl palmitate, butyl stearate, 2- ethylhexyl palmitate or a blend of branched chain eεterε may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oilε can be used. Formulations suitable for topical administration to the eye alεo include eye drops wherein the active ingredients are diεsolved or suεpended in suitable carrier, especially an aqueous solvent for the active ingredients. The antiinflammatory active ingredients are preferably present in such formulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10% and particularly about 1.5% w/w. For therapeutic purposes, the active compounds of this combination invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compoundε may be admixed with lactose, sucroεe, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, εtearic acid, magneεium stearate, magnesium oxide, sodium and calcium saltε of phoεphoric and εulfuric acidε, gelatin, acacia gum, εodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapεulated for con- venient administration. Such capsuleε or tabletε may contain a controlled-release formulation as may be provided in a disperεion of active compound in hydroxy- propylmethyl celluloεe. Formulationε for parenteral administration may be in the form of aqueous or non- aqueouε isotonic sterile injection solutions or suεpenεions. These εolutionε and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various bufferε. Other adjuvantε and modes of administration are well and widely known in the pharmaceutical art. Although this invention has been deεcribed with reεpect to specific embodiments, the details of theεe embodimentε are not to be construed as limitations.

Claims: What is claimed is : 1. A compound of Formula I wherein A is a 5- or 6-member ring substituent selected from partially unεaturated or unεaturated heterocyclo and carbocyclic ringε, wherein A iε optionally substituted with a radical selected from acyl, halo, alkyl, haloalkyl, cyano, nitro, carboxyl, alkoxy, oxo, aminocarbonyl, alkoxycarbonyl, carboxyalkyl, cyanoalkyl, and hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, alkyl, alkenyl, alkynyl, alkyloxy, alkylthio, alkylcarbonyl, cycloalkyl, aryl, haloalkyl, hydroxyalkyl, hydroxyalkyloxy, hydroxyalkyloxyalkyl, hydroxyalkylthio, hydroxyalkylthioalkyl, oximinoalkoxy, oximinoalkoxyalkyl, (alkyl) oximinoalkoxy, (alkyl)oximinoalkoxyalkyl, oximinoalkylthio, oximinoalkylthioalkyl, (alkyl)oximinoalkylthio, (alkyl)oximinoalkylthioalkyl, carbonyialkyloxy, carbonylalkyloxyalkyl, carbonylalkylthio, carbonylalkylthioalkyl, heterocyclo, cycloalkenyl, aralkyl, heterocycloalkyl, acyl, alkylthioalkyl, alkyloxyalkyl, alkenylthio, alkynylthio, alkenyloxy, alkynyloxy, alkenylthioalkyl, alkynylthioalkyl, alkenyloxyalkyl, alkynyloxyalkyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, alkylarylalkynyloxy, alkylarylalkenyloxy, alkylarylalkynylthio, alkylarylalkenylthio, haloalkylcarbonyl, alkoxyalkyl, alkylaminocarbonylalkyl, heteroaralkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, heteroaralkylthioalky1, heteroaralkoxy, heteroaralkylthio, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, haloaryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, alkoxycarbonylalkyl, alkoxycarbonylcyanoalkenyl, aminocarbonylalkyl, N-alkylaminocarbonyl, N- arylaminocarbonyl, N,N-dialkylaminocarbonyl, N-alkyl-N- arylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloaminocarbony1, carboxyalkylaminocarbonyl, alkylcarbonylalkyl, aralkoxycarbonylalkylaminocarbonyl, haloaralkyl, carboxyhaloalkyl, alkoxycarbonylhaloalkyl, aminocarbonylhaloalkyl, alkylaminocarbonylhaloalkyl, N- alkylamino, N,N-dialkylamino, N-arylamino, N- aralkylamino, N-alkyl-N-aralkylamino, N-alkyl-N- arylamino, aminoalkyl, N-alkylaminoalkyl, N,N- dialkylaminoalkyl, N-arylaminoalkyl, N- aralkylaminoalkyl, N-alkyl-N-aralkylaminoalkyl, N-alkyl- N-arylaminoalkyl, aminoalkoxy, aminoalkoxyalkyl, aminoalkylthio, aminoalkylthioalkyl, cycloalkyloxy, cycloalkylalkyjoxy, cycloalkylthio, cycloalkylalkylthio, aryloxy, aralkoxy, arylthio, aralkylthio, alkylεulfinyl, alkylsulfonyl, aminosulfonyl, N-alkylaminosulfonyl, N- arylaminoεulfonyl, arylεulfonyl, N,N- dialkylaminoεulfonyl, N-alkyl-N-arylaminoεulfonyl, wherein Ar is selected from aryl and heteroaryl, wherein Ar is optionally substituted with one or two subεtituentε εelected from halo, hydroxyl, mercapto, amino, nitro, cyano, carbamoyl, alkyl, alkenyloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, haloalkyl, alkoxycarbonyl, N- alkylcarbamoyl, N,N-dialkylcarbamoyl, alkanoylamino, , carbamoylalkoxy, alkoxycarbonylalkoxy and . wherein R! is one or more substituents selected from heterocyclo, cycloalkyl, cycloalkenyl and aryl, wherein R! is optionally substituted at a substitutable position with one or more radicals selected from alkyl, haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylεulfinyl, halo, alkoxy and alkylthio; wherein R 2 is selected from alkyl and amino; wherein P 3 and R 4 together form a group of the formula -B-X-B 1 which together with the carbon atom to which B and B 1 are attached, defineε a ring having 6 ring atomε, wherein B and B 1 , which may be the same or different, each iε alkylene and X is oxy, and which ring may bear one, two or three substituentε, which may be the same or different, εelected from hydroxyl, alkyl, alkoxy, 'alkenyloxy and alkynyloxy; wherein R 5 iε selected from hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonyl, acyl, and cyano; wherein R 6 is selected from hydrido, alkyl, aryl and aralkyl; wherein R 7 is selected from alkyl, alkoxy, alkenyl and alkynyl; wherein R 8 is oximino optionally subεtituted with alkyl; and wherein n is 0 or 1; provided Ar is substituted with when A is oxazolyl; or a pharmaceutically-acceptable salt thereof. 2. Compound of Claim 1 wherein A iε a radical εelected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, halo, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkyloxy, lower hydroxyalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl)oximinoalkoxyalkyl, lower carbonylalkyloxy, lower carbonylalkyloxyalkyl, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkylthio, lower oximinoalkylthioalkyl, lower (alkyl)oximinoalkylthio, lower (alkyl)oximinoalkylthioalkyl, lower carbonylalkylthio, lower carbonylalkylthioalkyl, lower alkylthio, lower alkylcarbonyl, lower cycloalkyl, phenyl, lower haloalkyl, 5- or 6-membered heterocyclo, lower cycloalkenyl, lower aralkyl, lower heterocycloalkyl, acyl, lower alkylthioalkyl, lower alkyloxyalkyl, lower alkenylthio, lower alkynylthio, lower alkenyloxy, lower alkynyloxy, lower alkenylthioalkyl, lower alkynyl hioalkyl, lower alkenyloxyalkyl, lower alkynyloxyalkyl, pheny1carbony1, lower aralkylcarbonyl, lower aralkenyl, lower alkylarylalkynyloxy, lower alkylarylalkenyloxy, lower alkylarylalkynylthio, lower alkylarylalkenylthio, lower haloalkylcarbonyl, lower alkylaminocarbonylalkyl, lower heteroaralkoxyalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaralkylthioalkyl, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower aralkylthioalkyl, lower aralkoxyalkyl, lower alkoxyaralkoxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonylcyanoalkenyl, lower aminocarbonylalkyl, lower N-alkylaminocarbonyl, N-phenylaminocarbonyl, lower N,N-dialkylaminocarbonyl, lower N-alkyl-N- arylaminocarbonyl, lower cycloalkylaminocarbonyl, lower heterocycloaminocarbonyl, lower carboxyalkylammocarbonyl, lower alkylcarbonylalkyl, lower aralkoxycarbonylalkylaminocarbonyl, lower haloaralkyl, lower carboxyhaloalkyl, lower alkoxycarbonylhaloalkyl, lower aminocarbonylhaloalkyl, lower alkylaminυcarbonylhaloalkyl, lower N-alkylamino, lower N,N-dialkylamino, N-phenylamino, lower N- aralkylamino, lower N-alkyl-N-aralkylamino, lower N- alkyl-N-arylamino, lower aminoalkyl, lower N- alkylaminoalkyl, lower N,N-dialkylaminoalkyl, lower N- arylaminoalkyl, lower N-aralkylaminoalkyl, lower N- alkyl-N-aralkylaminoalkyl, lower N-alkyl-N- arylaminoalkyl, lower aminoalkoxy, lower aminoalkoxyalkyl, lower aminoalkylthio, lower aminoalkylthioalkyl, lower cycloalkyloxy, lower cycloalkylalkyloxy, lower cycloalkylthio, lower cycloalkylalkylthio, phenyloxy, lower aralkoxy, phenylthio, lower aralkylthio, lower alkylεulfinyl, lower alkylεulfonyl, aminosulfonyl, lower N- alkylaminoεulfonyl, lower N-arylaminoεulfonyl, lower arylεulfonyl, lower N,N-dialkylaminosulfonyl, lower N- alkyl-N-arylaminosulfonyl, wherein Ar is selected from aryl selected from phenyl, biphenyl and naphthyl, and 5- and 6-membered heteroaryl, wherein Ar is optionally subεtituted with one or two εubεtituentε selected from halo, hydroxyl, mercapto, amino, nitro, cyano, carbamoyl, lower alkyl, lower alkenyloxy, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkylamino, lower dialkylamino, lower haloalkyl, lower alkoxycarbonyl, lower N-alkylcarbamoyl, lower N,N- dialkylcarbamoyl, lower alkanoylamino, lower cyanoalkoxy, lower carbamoylalkoxy, lower R 5 alkoxycarbonylalkoxy and " - ( R 8 )-rR " R4 ; wherein Y is at least one substituent selected from 5- and 6-membered heterocyclo, lower cycloalkyl, lower cycloalkenyl and aryl selected from phenyl, biphenyl and naphthyl, where R! is optionally subεtituted at a subεtitutable poεition with one or more radicalε selected from lower alkyl, lower haloalkyl, cyano, carboxyl, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino, nitro, lower alkoxyalkyl, lower alkylsulfinyl, halo, lower alkoxy and lower alkylthio; wherein R 2 iε εelected from lower alkyl and amino; wherein R 3 and R 4 together form a group of the formula -B-X-B 1 which together with the carbon atom to which B and B 1 are attached, defineε a ring having 6 ring atoms, wherein B and B 1 , which may be the same or different, each is alkylene and X iε oxy, and which ring may bear one, two or three εubεtituentε, which may be the εame or different, εelected from hydroxyl, lower alkyl, lower alkoxy, lower alkenyloxy and lower alkynyloxy; wherein R 5 iε selected from hydroxyl, lower alkoxy, lower alkylcarbonyloxy, phenylcarbonyloxy, carboxyl, aminocarbonyl, lower alkylaminocarbonyl, lower alkoxycarbonyl, lower acyl, and cyano; wherein R 6 iε selected from hydrido, lower alkyl, phenyl and lower aralkyl; wherein R 7 is selected from lower alkyl, lower alkoxy, lower alkenyl and lower alkynyl; wherein R 8 iε oximino optionally substituted with alkyl; and wherein n is 0 or 1; or a pharmaceutically-acceptable salt thereof. 3. Compound of Claim 2 wherein A is a radical selected from ι hienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, halo, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y iε a radical εelected from oxy, thio, εulfinyl, εulfonyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkyloxy, lower hydroxyalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl) oximinoalkoxyalkyl, lower carbonylalkyloxy, lower carbonylalkyloxyalkyl, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkalkylthio, lower oximinoalkylthioalkyl, lower (alkyl)oximinoalkylthio, lower (alkyl)oximinoalkylthioalkyl, lower carbonylalkylthio, lower carbonylalkylthioalkyl, lower alkylthio, lower alkylcarbonyl, lower cycloalkyl, phenyl, lower haloalkyl, 5- or 6-membered heterocyclo, lower cycloalkenyl, lower aralkyl, lower heterocycloalkyl, acyl, lower alkylthioalkyl, lower alkyloxyalkyl, lower alkenylthio, lower alkynylthio, lower alkenyloxy, lower alkynyloxy, lower alkenylthioalkyl, lower alkynylthioalkyl, lower alkenyloxyalkyl, lower alkynyloxyalkyl, phenylcarbonyl, lower aralkylcarbonyl, lower aralkenyl, lower alkylarylalkynyloxy, lower alkylarylalkynylthio, lower haloalkylcarbonyl, lower alkylaminocarbonylalkyl, lower arylthioalkyl, lower aryloxyalkyl, lower aralkylthioalkyl, lower aralkoxyalkyl, lower alkoxycarbonylalkyl, lower aminocarbonylalkyl, lower N- alkylaminocarbonyl, N-phenylaminocarbonyl, lower alkylcarbonylalkyl, lower N-alkylamino, N-phenylamino, lower N-aralkylamino, lower aminoalkyl, lower N- alkylaminoalkyl, lower N-arylaminoalkyl, lower N- aralkylaminoalkyl, lower aminoalkoxy, lower aminoalkoxyalkyl, lower aminoalkylthio, lower aminoalkylthioalkyl, lower cycloalkyloxy, lower cycloalkylalkyloxy, lower cycloalkylthio, lower cycloalkylalkylthio, phenyloxy, lower aralkoxy, phenylthio, lower aralkylthio, lower alkylsulfinyl, lower alkylsul f onyl, aminosulfonyl, lower N- alkylaminoεulfonyl, N-phenylaminosulfonyl, phenylεulfonyl, oximino, wherein Ar is selected from aryl selected from phenyl, biphenyl, naphthyl, and 5- and 6-membered heteroaryl, wherein Ar is optionally substituted with one or two substituents selected from halo, hydroxyl, mercapto, amino, nitro, cyano, lower alkyl, lower alkoxy, and Y —(-* R ; wherein R! is at leaεt one εubstituent selected from 5- and 6-membered heteroaryl, and aryl selected from phenyl, biphenyl and naphthyl, where R! is optionally substituted at a εubεtitutable position with one or more radicals selected from lower alkyl, lower haloalkyl, cyano, carboxyl, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, nitro, lower alkoxyalkyl, lower alkylεulfinyl, halo, lower alkoxy and lower alkylthio; wherein R 2 is selected from lower alkyl and amino; wherein R 3 and R 4 together form a tetrahydropyran ring and which ring may bear one, two or three substituents, which may be the same or different, selected from hydroxyl, lower alkyl, and lower alkoxy; wherein R 5 is selected from hydroxyl and lower alkoxy; wherein R 6 is selected from hydrido, lower alkyl, phenyl and lower aralkyl; and wherein R 7 iε selected from lower alkyl, lower alkoxy, lower alkenyl and lower alkynyl; or a pharmaceutically-acceptable salt thereof. 4. Compound of Claim 3 wherein A is a radical εelected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, triazolyl, imidazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A is optionally substituted with a radical selected from acyl, halo, lower alkyl, lower haloalkyl, oxo, cyano, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y is a radical selected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkynyl, lower alkenyl, aryl, lower cycloalkyl, 5- or 6- membered heterocyclo, aralkyl, lower alkyloxy, aryloxy, arylthio, 5- or 6-membered heterocyclooxy, lower aralkylthio, lower aralkyloxy, lower alkylthio, lower alkynyloxy, lower alkynylthio, lower alkynyloxyalkyl, lower alkenyloxy, lower alkenylthio, lower alkenyloxyalkyl, lower alkyloxyalkyl, lower alkylthioalkyl, lower hydroxyalkyloxy, lower alkylarylalkynyloxy, lower alkoxycarbonylalkyl, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl) oximinoalkoxy, lower (alkyl)oximinoalkoxyalkyl, lower carbonylalkyloxy, lower carbonylalkyloxyalkyl, wherein Ar is εelected from phenyl, thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, iεothiazolyl, isoxazolyl, pyrazolyl, and pyridyl, wherein Ar is optionally substituted with one or two substituents selected from halo, hydroxyl, mercapto, lower alkyl, R 5 ■ R 4 * lower alkoxy, and R ; wherein R! is at least one εubstituent selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, pyridyl, and phenyl, where R! iε optionally εubstituted at a εubstitutable pυεition with one or more radicalε selected from lower alkyl, lower haloalkyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, nitro, lower alkoxyalkyl, halo, lower alkoxy and lower alkylthio; wherein R 2 is εelected from lower alkyl and amino; wherein R 3 and R 4 together form a tetrahydropyran ring, and which ring may bear one, two or three εubstituents, which may be the same or different, selected from hydroxyl, lower alkyl, and lower alkoxy; wherein R 5 is selected from hydroxyl and lower alkoxy; wherein R 6 is εelected from hydrido, and lower alkyl; and wherein R 7 is selected from lower alkyl and lower alkoxy; or a pharmaceutically-acceptable salt thereof. 5. Compound of Claim 4 wherein A iε a radical εelected from thienyl, oxazolyl, furyl, pyrrolyl, triazolyl, thiazolyl, imidazolyl, iεoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl, wherein A iε optionally substituted with a radical selected from acyl, fluoro, chloro, bromo, methyl, trifluoromethyl, oxo, cyano, carboxyl, methoxy, aminocarbonyl, methoxycarbonyl, ethoxycarbonyl, acetyl, carboxypropyl, and hydroxymethyl; wherein Y is a radical selected from oxy, ethyl, propyl, isopropyl, butyl, 1-propynyl, 2- propynyl, methyloxy, ethyloxy, propyloxy, methylthio, (Z) -1-propenyloxy, (E) -2-propenyloxy, (Z) -2-propenyloxy, (E) -1-propenyloxy, (Z) -1-propenyloxymethyl, (E) -2- propenyloxymethyl, (Z) -2-propenyloxymethyl, (E) -1- propenyloxymethyl, 1-propynyloxy, 2-propynyloxy, 1- propynylthio, 2-propynylthio, hydroxymethyloxy, 1- hydroxyethyloxy, 2-hydroxypropyloxy, hydroxymethyloxymethyl, 1-hydroxyethyloxymethyl, 2- hydroxypropyloxymethyl, methyloxymethyl, ethyloxymethyl, propyloxymethyl, 1-propynyloxymethyl, oximinomethyloxy, oximinomethyloxymethyl, (methyl) oximinomethyloxy, (methyl)oximinomethyloxymethyl, triazolylmethyloxy, triazolyImethyloxymethyl, 1- (methoxycarbonyl) ethyl, methylthiomethyl, ethylthiomethyl, methylphenylpropynyloxy, N-ethyl-N- methylaminocarbonylmethyloxy, N-ethyl-N- methylaminoethyloxy, carbonylmethyloxy, carbonylbutyloxy, and carbonyImethyloxymethyl; wherein Ar iε selected from thienyl, pyridyl, thiazolyl, and phenyl,, where Ar is optionally εubεtituted with one or two εubεtituents selected from fluoro, chloro, bromo, R= ■ R 4 hydroxyl, mercapto, methyl, methoxy, and ; wherein R! is εelected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, iεoxazolyl, pyrazolyl, pyridyl, and phenyl, where R! is optionally subεtituted at a substitutable position with one or more radicals selected from methyl, trifluoromethyl, hydroxyl, hydroxymethyl, trifluoromethoxy, nitro, methoxymethyl, fluoro, chloro, bromo, methoxy and methylthio; wherein R 2 is methyl or amino; wherein R 3 and R 4 together form a tetrahydropyran ring, and which ring may bear one, two or three εubεtituentε, which may be the εame or different, selected from hydroxyl, methyl, and methoxy; and wherein R 5 is selected from hydroxyl and methoxy; or a pharmaceutically-acceptable salt thereof. 6. Compound of Claim 5 selected from compounds and their pharmaceutically-acceptable salts, of the group consisting of 4- [2- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yl)phenoxy]methyl] -4-phenyloxazol-5- yl]benzenesulfonamide; methyl 5- [4- (aminoεulfonyDphenyl] -α-[ [3- (tetrahydro-4- methoxypyran-4-y1)phenyl]methyl] -4-phenyloxazole-2- acetate; N- [2- [5- [4- (aminoεulfonyl)phenyl] -4-phenyloxazol-2- yl] ethyl] -2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy- -methylacetamide; N- [2- [4- [4- (aminoεulfonyl)phenyl] - -phenyloxazol-2- yl] ethyl] -2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- y1)phenoxy-N-methylacetamide; 4- [2- [ [2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy]ethyl] -N-methylaminoethyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; 4- [2- [ [2- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- y1)phenoxy] ethyl] -N-methylaminoethyl] -5-phenyloxazol-4- yl]benzeneεulfonamide; 4- [2- [ [4- [3- [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy] -1-propynyl]phenyl]methyl] -4-phenyloxazol-5- yl]benzeneεulfonamide; 4-[2-[ [4-[3- [3-fluoro-5- (tetrahydro-4-hydroxypyran-4- yDphenoxy] -1-propynyl] -phenyl]methyl] -4-phenyloxazol- 5-yl]benzenesulfonamide; 4- [2- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yl)phenoxy]methyl] -4- (4-fluorophenyl)oxazol-5- yl]benzenesulfonamide; 4- [2- [4- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yDphenoxy]methyl]phenylmethyl] -4-phenyloxazol-5- yl]benzenesulfonamide; 4- [5- [ [3-fluoro-5- (tetrahydro-4-methoxypyran-4- yl)phenoxy]methyl] -3-phenylisoxazol-4- yl]benzenesulfonamide; 4- [2- [ [ [3- (tetrahydro-4-methoxypyran-4- yl)phenylmethyl] oxy]methyl] -4-phenyloxazol-5- yl]benzenesulfonamide; 4- [2- [ [ [3- (tetrahydro-4-methoxypyran-4- yl)phenylmethyl] thio]methyl] -4-phenyloxazol-5- yl]benzenesulfonamide; 4- [2- [ [ [3- (tetrahydro-4-methoxypyran-4- yl)phenylmethyl] thio] ethyl] -4-phenyloxazol-5- yl]benzenesulfonamide; 4- [2- [3- (tetrahydro-4-methoxypyran-4-yl)phenyl]methoxy] -4- phenyloxazol-5-yl]benzeneεulfonamide; 4- [2- [3- (tetrahydro-4-methoxypyran-4- y1)phenyl]methylthio] -4-phenyloxazol-5- yl]benzenesulfonamide; N- [2- [5- [4- (aminosulfonyl)phenyl] -4-phenyloxazol-2- yl] ethylamino] -2- [3-fluoro-5- (tetrahydro-4- methoxypyran-4-y1) henoxy]acetamide; 4- [5- (4-chlorophenyl) -3- (3-methoxyphenyl) oxymethyl-lH pyrazol-1-yl]benzenesul onamide; 4- [5- (4-chlorophenyl) -3- (3-methoxyphenyl) thiomethyl-IH pyrazol-1-yl]benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- [ [3-fluoro-5- (3,4,5,6- tetrahydro-4-methoxy-2H-pyran-4-y1)phenoxy] -1H- pyrazol-1-yl]benzeneεulfonamide; 4- [5- (4-chlorophenyl) -3- [ [3-fluoro-5-(3,4,5,6- tetrahydro-4-methoxy-2H-pyran-4-yDphenoxy]methyl] - lH-pyrazol-1-yl]benzenesulfonamide; 4- [2- [3- (4-methoxy-3, 4,5, 6-tetrahydro-2H-pyran-4 yDphenoxy] -4-phenyl-5-oxazolyl]benzenesulfonamide; 4- [2- [3-fluoro-5- (4-methoxy-3, 4, 5, 6-tetrahydro-2H- pyran-4-yDphenoxy] -4-pheny1-5- oxazolyl]ber'ienesulfonamide; 4- (4-fluorophenyl) -2- [ [3-fluoro-5- (3,4,5, 6-tetrahydro- 4-methoxy-2H-pyran-4-yl)phenoxy)methyl] -5- (4- (methylsulfonyl)phenyl)oxazole; and 4- (4-fluorophenyl) -5- (4- (methylεulfonyDphenyl) -2-[ [3- (3,4,5, 6-tetrahydro-4-methoxy-2H-pyran-4- yl)phenoxy)methyl]oxazole. 7. A compound of Formula II wherein A iε a ring subεtituent selected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, isothiazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl; wherein A iε optionally substituted with a radical εelected from acyl, halo, hydroxyl, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y iε a radical εelected from oxy, thio, sulfinyl, sulfonyl, lower alkyl, lower alkynyl, lower alkenyl, lower hydroxyalkyl, aryl, lower cycloalkyl, 5- or 6-membered heterocyclo, aralkyl, lower alkyloxy, aryloxy, arylthio, lower cycloalkyloxy, 5- or 6-membered heterocyclooxy, lower aralkylthio, lower aralkyloxy, lower alkylthio, lower alkynyloxy, lower alkynylthio, lower alkynyloxyalkyl, lower alkenyloxy, lower alkenylthio, lower alkenyloxyalkyl, lower alkyloxyalkyl, lower alkylthioalkyl, lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkylthio, lower oximinoalkylthioalkyl, lower (alkyl) oximinoalkylthio, lower (alkyl)oximinoalkylthioalkyl, lower alkylarylalkynyloxy, lower dialkylammoalkyloxy, lower dialkylaminocarbonylalkyloxy, lower alkoxycarbonylalkyl, lower carbonyl .kylthio, lower carbonylalkylthioalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl)oximinoalkoxyalkyl, lower carbonylalkyloxy, and lower carbonylalkyloxyalkyl; wherein R! is a substituent selected from 5- and 6- membered heterocyclo, lower cycloalkyl, lower cycloalkenyl and aryl selected from phenyl, biphenyl and naphthyl, wherein R! iε optionally εubεtituted at a εubstitutable position with one or more radicals εelected from lower alkyl, lower haloalkyl, cyano, carboxyl, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino, lower alkoxyalkyl, lower alkylsulfinyl, halo, lower alkoxy and lower alkylthio; wherein R' iε selected from lower alkyl and amino; wherein R 9 is one or two εubεtituents selected from halo, hydroxyl, amino, nitro, cyano, carbamoyl, alkyl, alkenyloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, haloalkyl, alkoxycarbonyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, alkanoylamino, cyanoalkoxy, carbamoylalkoxy, and alkoxycarbonylalkoxy; and wherein R 10 is selected from hydrido, alkyl, alkenyl, alkynyl, cyanoalkyl, alkanoyl, and benzoyl optionally subεtituted with a substituent selected from halo, alkyl and alkoxy; or a pharmaceutically-acceptable εalt thereof. 8. Compound of Claim 7 wherein A iε a ring εubstituent se. " υcted from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, triazolyl, isoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl; wherein A is optionally subεtituted with a radical εelected from acyl, halo, hydroxyl, lower alkyl, lower haloalkyl, oxo, cyano, nitro, carboxyl, lower alkoxy, aminocarbonyl, lower alkoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, and lower hydroxyalkyl; wherein Y is a radical selected from oxy, lower alkyl, lower alkynyl, 5- or 6-membered heterocyclo, lower heterocyloalkyloxyalkyl, lower hydroxyalkyl, lower alkyloxy, lower alkylthio, lower alkyloxyalkyl, lower alkenyloxy, lower alkenyloxyalkyl, lower alkynyloxy, lower alkynylthio, lower alkynyloxyalkyl, lower alkylthioalkyl lower hydroxyalkylthio, lower hydroxyalkylthioalkyl, lower oximinoalkylthio, lower oximinoalkylthioalkyl, lower (alkyl)oximinoalkylthio, lower (alkyl)oximinoalkylthioalkyl, lower carbonylalkylthio, lower carbonylalkylthioalkyl, lower alkylarylalkynyloxy, lower dialkylaminoalkyloxy, lower dialkylammocarbonylalkyloxy, lower alkoxycarbonylalkyl, lower hydroxyalkyloxy, lower hydroxyalkyloxyalkyl, lower oximinoalkoxy, lower oximinoalkoxyalkyl, lower (alkyl)oximinoalkoxy, lower (alkyl) oximinoalkoxyalkyl, lower carbonylalkyloxy, and lower carbonylalkyloxyalkyl; wherein R! is phenyl optionally substituted at a subεtitutable poεition with one or more radicalε εelected from lower alkyl, lower haloalkyl, hydroxyl, lower hydroxyalkyl, halo, and lower alkoxy; wherein R 2 iε selected from lower alkyl and amino; wherein R 9 is one or two substituentε εelected from halo, hydroxyl, amino, lower alkyl, lower alkoxy; and wherein R 10 iε εelected from hydrido, and lower alkyl; or a pharmaceutically-acceptable εalt thereof. 9. Compound of Claim 8 wherein A iε a radical εelected from thienyl, oxazolyl, furyl, pyrrolyl, thiazolyl, imidazolyl, iεoxazolyl, pyrazolyl, cyclopentenyl, phenyl, and pyridyl; wherein A iε optionally εubεtituted with a radical selected from formyl, fluoro, chloro, bromo, hydroxyl, methyl, ethyl, isopropyl, butyl, tert-butyl, lεobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl , trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, fluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, oxo, cyano, nitro, carboxyl, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, hexyloxy, methylenedioxy, aminocarbonyl, methoxycarbonyl, carboxypropyl, carboxymethyl, carboxyethyl, cyanomethyl, and hydroxymethyl; wherein Y is a radical selected from oxy, ethyl, propyl, isopropyl, butyl, 1-propynyl, 2- propynyl, methyloxy, ethyloxy, propyloxy, methylthio, (Z) -1-propenyloxy, (E) -2-propenyloxy, (Z) -2-propenyloxy, (E) -1-propenyloxy, (Z) -1-propenyloxymethyl, (E) -2- propenyloxymethyl, (Z) -2-propenyloxymethyl, (E) -1- propenyloxymethyl, 1-propynyloxy, 2-propynyloxy, 1- propynylthio, ^-propynylthio, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxymethyloxy, 1- hydroxyethyloxy, 2-hydroxypropyloxy, hydroxymethyloxymethyl, 1-hydroxyethyloxymethyl, 2- hydroxypropyloxymethyl, methyloxymethyl, ethyloxymethyl, propyloxymethyl, 1-propynyloxymethyl, hydroxymethylthio, 1-hydroxyethylthio, 2-hydroxypropylthio, hydroxymethylthiomethyl, 1-hydroxyethylthiomethyl, 2- hydroxypropylthiomethy1, oximinomethylthio, oximinomethylthiomethyl, (methyl)oximinomethylthio, (methyl) oximinomethylthiomethyl, triazolylmethyloxy, triazolyImethyloxymethyl, carbonyImethylthio, carbonylbutylthio, carbonylmethylthiomethyl, oximinomethyloxy, oximinomethyloxymethyl, (methyl) oximinomethyloxy, methylthiomethyl, (methyl)oximinomethyloxymethyl, ethylthiomethyl, 1- (methoxycarbonyl) ethyl, methylphenylpropynyloxy, N- ethyl-N-methylaminocarbonylmethyloxy, N-ethyl-N- methylaminoethyloxy, triazoly1, carbonylmethyloxy, carbonylbutyloxy, and carbonyImethyloxymethyl; wherein R! is phenyl optionally substituted at a subεtitutable position with one or more radicals selected from methyl, ethyl, iεopropyl, butyl, cert-butyl, iεobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, fluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, fluoro, 5 dichloropropyl, hydroxyl, hydroxymethyl, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, and hexyloxy; wherein R 2 is selected from methyl and amino; wherein R 9 is one or two substituents selected from fluoro, chloro, bromo, hydroxyl, amino, methyl, ethyl, 10 iεopropyl, butyl, tert-butyl, iεobutyl, pentyl, hexyl, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, and hexyloxy; and wherein R 10 iε selected from hydrido, and methyl; or a pharmaceutically-acceptable salt thereof. 15 10. A pharmaceutical composition comprising a therapeutically-effective amount of a compound of Claim 1-9, or a pharmaceutically-acceptable salt thereof. 11. A method of treating a condition benefited by 20 the inhibition of 5-lipoxygenase, cyclooxygenase-2 or both 5-lipoxygenaεe and cyclooxygenaεe-2, εaid method compriεing treating the εubject having or susceptible to such inflammation or inflammation-asεociated diεorder, with a therapeutically-effective amount of a compound of 25 Claim 1-9, or a pharmaceutically-acceptable εalt thereof. 12. The method of Claim 11 wherein the condition iε inflammation or an inflammation-aεεociated disorder. 30 13. The method of Claim 12 wherein the condition is inflammation. t 14. The method of Claim 12 wherein the condition 35 iε an inflammation-aεεociated diεorder. 15. The method of Claim 14 wherein the inflammation-associated disorder iε arthritiε. 16. The method of Claim 14 wherein the inflammation-associated disorder is pain. 17. The method of Claim 14 wherein the inflammation-aεεociated disorder is fever.

Inventors: BROWN DAVID L, CARTER JEFFERY S, DEVADAS BALEKUDRU, GRANETO MATTHEW J, LU HWANG-FUN, NAGARAJAN SRINIVASAN, NORMAN BRYAN H, ROGERS ROLAND S DI, SIKORSKI JAMES A, TALLEY JOHN J, BROWN, DAVID, L., CARTER, JEFFERY, S., DEVADAS, BALEKUDRU, GRANETO, MATTHEW, J., LU, HWANG-FUN, NAGARAJAN, SRINIVASAN, NORMAN, BRYAN, H., ROGERS, ROLAND, S. +DI, SIKORSKI, JAMES, A., TALLEY, JOHN, J.
Applicants: BROWN DAVID L, CARTER JEFFERY S, DEVADAS BALEKUDRU, GRANETO MATTHEW J, LU HWANG FUN, NAGARAJAN SRINIVASAN, NORMAN BRYAN H, ROGERS KATHY L & HF, SEARLE & CO, SIKORSKI JAMES A, TALLEY JOHN J, BROWN, DAVID, L., CARTER, JEFFERY, S., DEVADAS, BALEKUDRU, G.D. SEARLE & CO., GRANETO, MATTHEW, J., LU, HWANG-FUN, NAGARAJAN, SRINIVASAN, NORMAN, BRYAN, H., ROGERS, KATHY, L. +HF, SIKORSKI, JAMES, A., TALLEY, JOHN, J.
Application year: 1996
Main classification: C07D405
IPC codes: A61P29, C07D231, C07D405, C07D413