Claims for Patent: RE44048

Summary for Patent: RE44048

Title:	4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-YL]benzenesulfonami- de for the treatment of inflammation or an inflammation-associated disorder
Abstract:	.[.A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: ##STR00001## or a pharmaceutically-acceptable salt thereof..]. .Iadd.A method of treating inflammation or an inflammation-associated disorder in a subject by administering a therapeutically-effective dose of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof, to the subject..Iaddend.
Inventor(s):	Talley; John J. (St. Louis, MO), Bertenshaw; Stephen R. (Cheshire, CT), Miyashiro; Julie M. (Morton Grove, IL)
Assignee:	G.D. Searle LLC (New York, NY)
Application Number:	12/205,319
Patent Claims:	1. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation-associated disorder, a therapeutically-effective amount of a compound of Formula I ##STR00101## wherein R.sup.1 is phenyl substituted at a substitutable position with one or more radicals selected from halo, C.sub.1-C.sub.10-alkyl, and sulfamyl wherein R.sup.2 is selected from hydrido, C.sub.1-C.sub.6-haloalkyl, cyano, carboxy, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-carboxyalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-alkylthio, aminocarbonyl, aminocarbonyl-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-N-alkylaminocarbonyl, N-arylaminocarbonyl, C.sub.1-C.sub.6-N,N-dialkylaminocarbonyl, C.sub.1-C.sub.6-N-alkyl-N-aryl-aminocarbonyl, and C.sub.1-C.sub.6-hydroxyalkyl; wherein R.sup.3 is selected from hydrido, C.sub.1-C.sub.10-alkyl, halo, cyano, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-hydroxyalkyl, C.sub.1-C.sub.6-alkylthio, and C.sub.1-C.sub.6-alkylsulfonyl; wherein R.sup.4 is selected from aryl-C.sub.2-C.sub.6-alkenyl, aryl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkenyl and five to ten membered heterocyclic; wherein R.sup.4 is optionally substituted at a substitutable position with one or more radicals selected from halo, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.10-alkyl, C.sub.1-C.sub.6-alkylsulfonyl, cyano, carboxyl, C.sub.1-C.sub.6-alkoxycarbonyl, aminocarbonyl, C.sub.1-C.sub.6-haloalkyl, hydroxyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-hydroxyalkyl, C.sub.1-C.sub.6-haloalkoxy, sulfamyl, C.sub.1-C.sub.6-N-alkylaminocrbonyl, amino, C.sub.1-C.sub.6-N-alkylamino, C.sub.1-C.sub.6-N,N-dialkylamino, five or six membered heterocyclic, nitro, and ##STR00102## and wherein R.sup.7 is hydrido; wherein aryl wherever occurring means phenyl, naphthyl, tetrahydronaphthyl, indene, biphenyl, provided R.sup.2 and R.sup.3 are not identical radicals selected from hydrido, carboxyl and ethoxycarbonyl; further provided that R.sup.2 is not carboxyl or methyl when R.sup.3 is hydrido and when R.sup.4 is phenyl; further provided that R.sup.4 is not triazolyl when R.sup.2 is methyl; further provided that R.sup.4 is not aralkenyl when R.sup.2 is carboxyl, aminocarbonyl or ethoxycarbonyl; further provided that R.sup.4 is not phenyl when R.sup.2 is methyl and R.sup.3 is carboxyl; further provided that R.sup.4 is not 4-chlorophenyl when R.sup.2 is methyl and R.sup.3 is bromo; further provided that R.sup.4 is not unsubstituted thienyl when R.sup.2 is trifluoromethyl; and further provided that R.sup.4 is aryl substituted with sulfamyl when R.sup.1 is phenyl not substituted with sulfamyl; and further provided the compound is not 4-[5-(3-fluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1yl]- benzenesulfonamide; or a pharmaceutically-acceptable salt thereof..]. .[.2. The method of claim 1 wherein R.sup.1 is phenyl, substituted at a substitutable position with one or more radicals selected from fluoro, chloro, methyl, and sulfamyl; wherein R.sup.2 is selected from hydrido, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, and hexanoyl, methoxy, ethoxy, methylthio, aminocarbonyl, aminocarbonylmethyl, N-methylaminocarbonyl, N-ethylaminocarbonyl, N-isopropylaminocarbonyl, N-propylaminocarbonyl, N-butylaminocarbonyl, N-isobutylaminocarbonyl, N-tert-butylaminocarbonyl, N-pentylaminocarbonyl, N-phenylaminocarbonyl, N,N-dimethylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-(3-fluorophenyl)aminocarbonyl, N-(4-methylphenyl)aminocarbonyl, N-(3-chlorophenyl)aminocarbonyl, N-methyl-N-(3-chlorophenyl)aminocarbonyl, N-(4-methoxyphenyl)aminocarbonyl, N-methyl-N-phenylaminocarbonyl, hydroxymethyl, and hydroxypropyl; wherein R.sup.3 is selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, hexyl, fluoro, chloro, bromo, cyano, methoxy, methylthio, methylsulfonyl, hydroxypropyl, hydroxymethyl, and hydroxyethyl; and wherein R.sup.4 is selected from phenyl, naphthyl, biphenyl, cyclohexyl, cyclopentyl, cycloheptyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 4-cyclohexenyl, 1-cyclopentenyl, 4-cyclopentenyl, benzofuryl, 2,3-dihydrobenzofuryl, 1,2,3,4-tetrahydronaphthyl, benzothienyl, indenyl, indanyl, indolyl, dihydroindolyl, chromanyl, benzopyran, thiochromanyl, benzothiopyran, benzodioxolyl, benzodioxanyl, pyridyl, thienyl, thiazolyl, oxazolyl, furyl and pyrazinyl; wherein R.sup.4 is optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, propyl, isopropyl, tert-butyl, isobutyl, hexyl, methylsulfonyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, aminocarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, bromodifluoromethyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, sulfamyl, methylaminosulfonyl, hydroxypropyl, hydroxyisopropyl, hydroxymethyl, hydroxyethyl, trifluoromethoxy, amino, N-methylamino, N-ethylamino, N-ethyl-N-methylamino, N,N-dimethylamino, N,N-diethylamino, formylamino, methylcarbonylamino, trifluoroacetamino, piperadinyl, piperazinyl, morpholino, nitro, and ##STR00103## wherein R.sup.7 is hydrido; or a pharmaceutically-acceptable salt thereof..]. .[.3. The method of claim 2 selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of ethyl 1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylate; ethyl 1-[4-(aminosulfonyl)phenyl]-5-(4-methylphenyl)-1H-pyrazole-3-carbox- ylate; isopropyl 1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylate; N-[4-methylphenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyra- zole-3-carboxamide; N-[3-chlorophenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyra- zole-3-carboxamide; N-[3-fluorophenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyra- zole-3-carboxamide; N-[3-fluorophenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyra- zole-3-carboxamide; phenylmethyl N-[[1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazol-3-yl]carbon- yl]glycinate; 4-[5-(4-bromophenyl)-3-cyano-1H-pyrazol-1-yl]benzenesulfonamide; 4-[3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-chlorophenyl)-3-cyano-1H-pyrazol-1-yl]benzenesulfonamide; 4-[3-cyano-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[3-cyano-5-(4-methylphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[3-cyano-5-(4-methylthiophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(5-chloro-4-methoxyphenyl)-3-cyano-1H-pyrazol-1-yl]benzenesulfonamid- e; 4-[5-(5-bromo-4-methoxyphenyl)-3-cyano-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[3-cyano-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-bromo-5-(4-chlorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfo- namide; 4-[4-bromo-5-(4-methylphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(4-methylphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(3-chloro-4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[4-chloro-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-bromo-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-cyano-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[4-ethyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid- e; 4-[4-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona- mide; 4-[5-(4-methoxyphenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]- benzenesulfonamide; 4-[5-(4-chlorophenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(4-chlorophenyl)-4-ethyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[4-ethyl-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[4-ethyl-5-(4-methoxy-3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-- yl]benzenesulfonamide; 4-[4-ethyl-5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[4-ethyl-5-(3-fluoro-4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-y- l]benzenesulfonamide; 4-[5-(4-fluorophenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[4-methyl-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[4-fluoro-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[4-bromo-5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benze- nesulfonamide; 4-[4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazo- l-1-yl]benzenesulfonamide; 4-[4-chloro-3-(difluoromethyl)-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamid- e; 4-[4-bromo-3-(difluoromethyl)-5-phenyl-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[4-chloro-3-difluoromethyl)-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benz- enesulfonamide; 4-[4-chloro-3-cyano-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-3-cyano-1H-pyrazol-1-yl]benzenesulfonamide- ; 4-[4-chloro-3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamid- e; 4-[4-bromo-3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamid- e; 4-[4-bromo-3-cyano-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; ethyl [1-(4-aminosulfonylphenyl)-4-bromo-5-(4-chlorophenyl)-1H-pyrazol-3-yl]car- boxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-phenyl-1H-pyrazol-3-yl]carboxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(4-chlorophenyl)-1H-pyrazol-- 3yl]carboxylate; ethyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(4-chlorophenyl)-1H-pyrazol-3-yl]ca- rboxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(4-fluorophenyl)-1H-pyrazol-3-yl]ca- rboxylate; methyl [1-(4-aminosulfonylphenyl)-4-bromo-5-(4-fluorophenyl)-1H-pyrazol-3-yl]car- boxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(3-chloro-4-methoxyphenyl)-1H-pyraz- ol-3-yl]carboxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(3,5dichloro-4-methoxyphenyl)-1H-py- razol-3-yl]carboxylate; methyl [1-(4-aminosulfonylphenyl)-5-(3-bromo-4-methoxyphenyl)-4-chloro-1H-pyrazo- l-3-yl]carboxylate; 4-[4-chloro-3-hydroxymethyl-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-3-hydroxymethyl-1H-pyrazol-1-yl]benzenesul- fonamide; 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(4-cyanophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfo- namide; 4-[5-(2,4-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benz- enesulfonamide; 4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona- mide; 4-[5-(3,4-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[5-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes- ulfonamide; 4-[5-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulf- onamide; 4-[5-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[5-(2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(4-aminophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfo- namide; 4-[5-(2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes- ulfonamide; 4-[5-(4-fluoro-2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(4-ethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulf- onamide; 4-[5-(3,5-dimethylphenyl-4-methoxy)-3-(trifluoromethyl)-1H-pyrazo- l-1-yl]benzenesulfonamide; 4-[5-(3-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(3-fluoro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]b- enzenesulfonamide; 4-[5-(4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulf- onamide; 4-[5-(4-chloro-3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-y- l]benzenesulfonamide; 4-[5-(4-ethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[5-(2,4-dimethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes- ulfonamide; 4-[5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona- mide; 4-[5-(4-methoxy-3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]- benzenesulfonamide; 4-[5-(3-bromo-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]ben- zenesulfonamide; 4-[5-(3-chloro-4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(3,4-dimethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesul- fonamide; 4-[5-(3-chloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1- -yl]benzenesulfonamide; 4-[5-(3-chloro-4-methoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1- -yl]benzenesulfonamide; 4-[5-(3-ethyl-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(4-fluoro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze- nesulfonamide; 4-[5-(4-methoxy-3-(3-propenyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl- ]benzenesulfonamide; 4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]b- enzenesulfonamide; 4-[5-(3-chloro-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(3-fluoro-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be- nzenesulfonamide; 4-[5-(3-methyl-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be- nzenesulfonamide; 4-[5-(3-chloro-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be- nzenesulfonamide; 4-[5-(4-(N,N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be- nzenesulfonamide; 4-[5-(4-methyl-3-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[5-(4-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(3-amino-4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[5-(4-methylthiophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesu- lfonamide; 4-[5-(4-methylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-phenyl-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfo- namide; 4-[5-(2-fluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl- ]benzenesulfonamide; 4-[5-(3-chloro-4-methylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[5-(3-chloro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(4-chloro-3-methylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[5-(3,4-dimethoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulf- onamide; 4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol- -1-yl]benzenesulfonamide; 4-[5-(3,5-difluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]be- nzenesulfonamide; 4-[5-(2-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(3-bromo-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]ben- zenesulfonamide; 4-[5-(4-methylsulfonylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenes- ulfonamide; 4-[5-(4-chlorophenyl)-3-(heptafluoropropyl)-1H-pyrazol-1-yl]benzenesulfon- amide; 4-[5-(4-chlorophenyl)-3-(chloro-difluoromethyl)-1H-pyrazol-1-yl]ben- zenesulfonamide; 4-[5-(4-chlorophenyl)-3-(pentafluoroethyl)-1H-pyrazol-1-yl]benzenesulfona- mide; 4-[5-(4-fluorophenyl)-3-(3-hydroxypropyl)-1H-pyrazol-1-yl]benzenesul- fonamide; 4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(3-hydroxypropyl)-1H-pyraz- ol-1-yl]benzenesulfonamide; 4-[5-(3-chloro-4-methoxyphenyl)-3-(chloromethyl)-1H-pyrazol-1-yl]benzenes- ulfonamide; 4-[3-(chloro-difluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazol-1-yl- ]benzenesulfonamide; 4-[5-(phenyl)-3-(fluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(5-bromo-2-thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfon- amide; 4-[5-(5-chloro-2-thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[5-(1-cyclohexenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[5-(1-cyclohexyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(6-benzodioxanyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulf- onamide; 4-[3-(difluoromethyl)-5-(4-methylcyclohexyl)-1H-pyrazol-1-yl]benz- enesulfonamide; 4-[5-(2-benzofuranyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[5-(1,3-benzodioxol-5-yl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzene- sulfonamide; 4-[5-(2-benzofuryl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid- e; 4-[5-(5-bromo-2-thienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesul- fonamide; 4-[5-(5-chloro-2-thienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be- nzenesulfonamide; 4-[5-(5-indanyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(5-methyl-2-thienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulf- onamide; 4-[5-(2,3-dihydrobenzofuran-2-yl)-3-(trifluoromethyl)-1H-pyrazol-- 1-yl]benzenesulfonamide, 4-[5-(1-cyclohexenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(1,2,3,4-tetrahydronaphth-5-yl)-3-(trifluoromethyl)-1H-pyrazol-1- -yl]benzenesulfonamide; 4-[5-(2-benzothienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[5-(3,4-dihydro-2H-1-benzothiopyran-7-yl)-3-(trifluoromethyl)-1H-py- razol-1-yl]benzenesulfonamide; 4-[5-(4-methyl-1,3-benzodioxol-6-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]- benzenesulfonamide; and 4-[5-(4-methyl-1,3-benzodioxol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]- benzenesulfonamide..]. .[.4. The method of claim 3 where the compound is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..]. .[.5. The method of claim 3 where the compound is 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de, or a pharmaceutically-acceptable salt thereof..]. .[.6. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation-associated disorder, a therapeutically-effective amount of a compound of Formula I ##STR00104## wherein R.sup.1 is phenyl substituted at a substitutable position with sulfamyl; wherein R.sup.2 is selected from C.sub.1-C.sub.5-haloalkyl, cyano, carboxyl, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.5-carboxyalkyl, aminocarbonyl, C.sub.1-C.sub.6-N-alkylaminocarbonyl, N-arylaminocarbonyl, C.sub.1-C.sub.6-N,N-dialkylaminocarbonyl, C.sub.1-C.sub.6-N-alkyl-N-arylaminocarbonyl, and C.sub.1-C.sub.6-hydroxyalkyl; wherein R.sup.3 and R.sup.4 together form ##STR00105## wherein m is 2; wherein A is phenyl; and wherein R.sup.6 is one or more radicals selected from halo, C.sub.1-C.sub.10-alkyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.5-haloalkyl, C.sub.1-C.sub.6-alkoxy, amino and nitro; wherein aryl wherever occurring means phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl; or a pharmaceutically-acceptable salt thereof..]. .[.7. The method of claim 6 wherein R.sup.2 is selected from fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, cyano, carbonyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, trifluoroacetyl, aminocarbonyl, N-methylaminocarbonyl, N-ethylaminocarbonyl, N-isopropylaminocarbonyl, N-propylaminocarbonyl, N-butylaminocarbonyl, N-isobutylaminocarbonyl, N-tert-butylaminocarbonyl, N-pentylaminocarbonyl, N-phenylaminocarbonyl, N,N-dimethylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-(3-fluorophenyl)aminocarbonyl, N-(4-methylphenyl)aminocarbonyl, N-(3-chlorophenyl)aminocarbonyl, N-(4-methoxyphenyl)aminocarbonyl, N-methyl-N-phenylaminocarbonyl, hydroxypropyl, hydroxymethyl and hydroxyethyl; wherein A is phenyl; and wherein, R.sup.6 is one or more radicals selected from fluoro, chloro, bromo, methylsulfonyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, amino, and nitro; or a pharmaceutically-acceptable salt thereof..]. .[.8. The method of claim 7 selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 4-[3-(difluoromethyl)-4,5-dihydro-7-methoxy-1H-benz[g]indazol-1-yl]benzen- esulfonamide; 4-[3-(difluoromethyl)-4,5-dihydro-7-methyl-1H-benz[g]indazol-1-yl]benzene- sulfonamide; 4-[4,5-dihydro-7-methoxy-3-(trifluoromethyl)-1H-benz[g]indazol-1-yl]benze- nesulfonamide; 4-[4,5-dihydro-3-(trifluoromethyl)-1H-benz[g]indazol-1yl]benzenesulfonami- de; 4-[4,5-dihydro-7-methyl-3-(trifluoromethyl)-1H-benz[g]indazol-1-yl]ben- zenesulfonamide; methyl[1-(4-aminosulfonylphenyl)-4,5-dihydro-7-methoxy-1H-benz[g]indazol-- 3-yl]carboxylate; and 4-[4,5-dihydro-3-trifluoromethyl-1H-thieno[3,2,g]indazol-1-yl]benzenesulf- onamide..]. .[.9. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation-associated disorder, a therapeutically-effective amount of a compound of Formula I ##STR00106## wherein R.sup.1 is phenyl, wherein R.sup.1 is substituted at a substitutable position with one or more radicals selected from halo, C.sub.1-C.sub.10-alkyl, C.sub.1-C.sub.6-alkoxy, hydroxyl and C.sub.1-C.sub.6-haloalkyl; wherein R.sup.2 is selected from C.sub.1-C.sub.6-haloalkyl; wherein R.sup.3 is hydrido; and wherein R.sup.4 is aryl substituted at a substitutable position with sulfamyl; or a pharmaceutically-acceptable salt thereof; wherein aryl wherever occurring means phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl; or a pharmaceutically-acceptable salt thereof..]. .[.10. The method of claim 9 selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 4-[1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]benzenesulfonam- ide; and 4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]benzen- esulfonamide..]. .[.11. A method of treating inflammation or an inflammation-associated disorder in a subject, said method comprising administering to the subject having or susceptible to such inflammation or inflammation-associated disorder, a therapeutically-effective amount of a compound of Formula II ##STR00107## wherein R.sup.2 is selected from hydrido, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxycarbonyl, cyano, aminocarbonyl, arylaminocarbonyl, C.sub.1-C.sub.6-carboxyalkyl, and C.sub.1-C.sub.6-hydroxyalkyl; wherein R.sup.3 is selected from hydrido, and halo; and wherein R.sup.4 is selected from aryl, C.sub.3-C.sub.10-cycloalkyl, C.sub.3-C.sub.10-cycloalkenyl and heterocyclic; wherein R.sup.4 is optionally substituted at a substitutable position with one or more radicals selected from halo, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-alkylsulfonyl, cyano, nitro, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.10-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, sulfamyl, five or six membered heterocyclic and amino; wherein aryl wherever occurring means phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl; provided R.sup.2 and R.sup.3 are not both hydrido; and further provided that R.sup.4 is not unsubstituted thienyl when R.sup.2 is trifluoromethyl; and further provided the compound is not 4-[5-(3-fluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; or a pharmaceutically-acceptable salt thereof..]. .[.12. The method of claim 11 wherein the compounds are selected from compounds, and their pharmaceutically acceptable salts, of the group consisting of 4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona- mide; 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesul- fonamide; 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfo- namide; 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesu- lfonamide; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze- nesulfonamide; 4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[3-(difluoromethyl)-5-(4-methylphenyl)-1H-pyrazol-1-yl]benzenesulfonami- de; 4-[3-(difluoromethyl)-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[3-(difluoromethyl)-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonam- ide; 4-[3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(3-fluoro-4-methoxyphenyl)-3-trifluoromethyl)-1H-pyrazol-1-yl]benzen- esulfonamide; 4-[4-chloro-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-chlorophenyl)-3-(hydroxymethyl)-1H-pyrazol-1-yl]benzenesulfonamid- e; and 4-[5-(4-(N,N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1- -yl]benzenesulfonamide..]. .[.13. The method of claim 1 for use in treatment of inflammation..]. .[.14. The method of claim 1 for use in treatment of an inflammation-associated disorder..]. .[.15. The method of claim 14 wherein the inflammation-associated disorder is arthritis..]. .[.16. The method of claim 14 wherein the inflammation-associated disorder is pain..]. .[.17. The method of claim 14 wherein the inflammation-associated disorder is fever..]. .[.18. The method of claim 1 for use in the prevention of colorectal cancer..]. .Iadd.19. A method of treating arthritis in a subject, said method comprising administering to the subject having or susceptible to arthritis, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend. .Iadd.20. A method of treating pain in a subject, said method comprising administering to the subject having or susceptible to pain, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend. .Iadd.21. A method of treating osteoarthritis in a subject, said method comprising administering to the subject having or susceptible to osteoarthritis, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend. .Iadd.22. A method of treating rheumatoid arthritis in a subject, said method comprising administering to the subject having or susceptible to rheumatoid arthritis, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend. .Iadd.23. A method of treating juvenile arthritis in a subject, said method comprising administering to the subject having or susceptible to juvenile arthritis, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend. .Iadd.24. A method of treating spondyloarthropathy in a subject, said method comprising administering to the subject having or susceptible to spondyloarthropathies, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend. .Iadd.25. A method of treating menstrual cramps in a subject, said method comprising administering to the subject having or susceptible to menstrual cramps, a therapeutically-effective amount of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam- ide, or a pharmaceutically-acceptable salt thereof..Iaddend.