Claims for Patent: 5,760,068

Summary for Patent: 5,760,068

Title:	Substituted pyrazolyl benzenesulfonamides for the treatment of inflammation
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: ##STR1## or a pharmaceutically-acceptable salt thereof.
Inventor(s):	Talley; John J. (St. Louis, MO), Penning; Thomas D. (Elmhurst, IL), Collins; Paul W. (Deerfield, IL), Rogier, Jr.; Donald J. (St. Louis, MO), Malecha; James W. (Libertyville, IL), Miyashiro; Julie M. (Chicago, IL), Bertenshaw; Stephen R. (Brentwood, MO), Khanna; Ish K. (Vernon Hills, IL), Graneto; Matthew J. (St. Louis, MO), Rogers; Roland S. (Richmond Heights, MO), Carter; Jeffery S. (Chesterfield, MO), Docter; Stephen H. (Mt. Prospect, IL), Yu; Stella S. (Morton Grove, IL)
Assignee:	G.D. Searle & Co. (Skokie, IL)
Application Number:	08/648,113
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 ##STR101## 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 ##STR102## and wherein R.sup.7 is hydrido; wherein aryl wherever occurring means phenyl, naphthyl, tetrahydronaphthyl, indane, 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]benzenes ulfonamide; 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 ##STR103## 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-carboxylate; isopropyl 1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylate; N-[4-methylphenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyrazo le-3-carboxamide; N-[3-chlorophenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyrazo le-3-carboxamide; N-[3-fluorophenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyrazo le-3-carboxamide; N-[3-fluorophenyl]-1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazo le-3-carboxamide; phenylmethyl N-[[1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazol-3-yl]carbony l]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]benzenesulfonamide; 4-[5-(5-bromo-4-methoxyphenyl)-3-cyano-1H-pyrazol-1-yl]benzenesulfonamide; 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]benzenesulfona mide; 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]benzenesulfonamide 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]benzenes ulfonamide; 4-[4-ethyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(4-methoxyphenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide; 4-[5-(4-chlorophenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(4-chlorophenyl)-4-ethyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 4-[4-ethyl-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 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]benzenes ulfonamide; 4-[4-ethyl-5-(3-fluoro-4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide; 4-[5-(4-fluorophenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[4-methyl-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[4-fluoro-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[4-bromo-5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesul fonamide; 4-[4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol- 1-yl]benzenesulfonamide; 4-[4-chloro-3-(difluoromethyl)-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-bromo-3-(difluoromethyl)-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[4-chloro-3-difluoromethyl)-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 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]benzenesulfonamide; 4-[4-bromo-3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 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]carb oxylate; 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]carb oxylate; ethyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(4-chlorophenyl)-1H-pyrazol-3-yl]car boxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(4-fluorophenyl)-1H-pyrazol-3-yl]car boxylate; methyl [1-(4-aminosulfonylphenyl)-4-bromo-5-(4-fluorophenyl)-1H-pyrazol-3-yl]carb oxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(3-chloro-4-methoxyphenyl)-1H-pyrazo l-3-yl]carboxylate; methyl [1-(4-aminosulfonylphenyl)-4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-1H-py razol-3-yl]carboxylate; methyl [1-(4-aminosulfonylphenyl)-5-(3-bromo-4-methoxyphenyl)-4-chloro-1H-pyrazol -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]benzenesulfo namide; 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-cyanophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(2,4-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de; 4-[5-(3,4-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzensulfonamide ; 4-[5-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-aminophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-fluoro-2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-ethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(3,5-dimethylphenyl-4-methoxy)-3-(trifluoromethyl)-1H-pyrazol-1-yl]ben zenesulfonamide; 4-[5-(3-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(3-fluoro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide; 4-[5-(4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(4-chloro-3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(4-ethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(2,4-dimethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de; 4-[5-(4-methoxy-3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide; 4-[5-(3-bromo-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide; 4-[5-(3-chloro-4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(3,4-dimethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfo namide; 4-[5-(3-chloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide; 4-[5-(3-chloro-4-methoxy-5-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-y l]benzenesulfonamide; 4-[5-(3-ethyl-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(4-fluoro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide; 4-[5-(4-methoxy-3-(3-propenyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]b enzenesulfonamide; 4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]ben zenesulfonamide; 4-[5-(3-chloro-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(3-fluoro-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide; 4-[5-(3-methyl-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide; 4-[5-(3-chloro-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide; 4-[5-(4-(N,N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide; 4-[5-(4-methyl-3-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 4-[5-(4-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(3-amino-4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(4-methylthiophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfona mide; 4-[5-(4-methylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-phenyl-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(2-fluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(3-chloro-4-methylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 4-[5-(3-chloro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[5-(4-chloro-3-methylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 4-[5-(3,4-dimethoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide; 4-[5-(3,5-difluoro-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide; 4-[5-(2-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(3-bromo-4-methoxyphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesu lfonamide; 4-[5-(4-methylsulfonylphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesul fonamide; 4-[5-(4-chlorophenyl)-3-(heptafluoropropyl)-1H-pyrazol-1-yl]benzenesulfonam ide; 4-[5-(4-chlorophenyl)-3-(chloro-difluoromethyl)-1H-pyrazol-1-yl]benzenesulf onamide; 4-[5-(4-chlorophenyl)-3-(pentafluoroethyl)-1H-pyrazol-1-yl]benzenesulfonami de; 4-[5-(4-fluorophenyl)-3-(3-hydroxypropyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(3-hydroxypropyl)-1H-pyrazol-1-yl]ben zenesulfonamide; 4-[5-(3-chloro-4-methoxyphenyl)-3-(chloromethyl)-1H-pyrazol-1-yl]benzenesul fonamide; 4-[3-(chloro-difluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazol-1-yl]b enzenesulfonamide; 4-[5-(phenyl)-3-(fluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(5-bromo-2-thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonam ide; 4-[5-(5-chloro-2-thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfona mide; 4-[5-(1-cyclohexenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(1-cyclohexyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(6-benzodioxanyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[3-(difluoromethyl)-5-(4-methylcyclohexyl)-1H-pyrazol-1-yl]benzenesulfona mide; 4-[5-(2-benzofuranyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(1,3-benzodioxol-5-yl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfo namide; 4-[5-(2-benzofuryl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(5-bromo-2-thienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona mide; 4-[5-(5-chloro-2-thienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(5-indanyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(5-methyl-2-thienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide; 4-[5-(2,3-dihydrobenzofuran-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide, 4-[5-(1-cyclohexenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(1,2,3,4-tetrahydronaphth-5-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be nzenesulfonamide; 4-[5-(2-benzothienyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(3,4-dihydro-2H-1-benzothiopyran-7-yl)-3-(trifluoromethyl)-1H-pyrazol- 1-yl]benzenesulfonamide; 4-[5-(4-methyl-1,3-benzodioxol-6-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be nzenesulfonamide; and 4-[5-(4-methyl-1,3-benzodioxol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]be nzenesulfonamide. 4. The method of claim 3 where the compound is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de, 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]benzenesulfonamid e, 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 ##STR104## 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 ##STR105## 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]benzenes ulfonamide; 4-[3-(difluoromethyl)-4,5-dihydro-7-methyl-1H-benz[g]indazol-1-yl]benzenesu lfonamide; 4-[4,5-dihydro-7-methoxy-3-(trifluoromethyl)-1H-benz[g]indazol-1-yl]benzene sulfonamide; 4-[4,5-dihydro-3-(trifluoromethyl)-1H-benz[g]indazol-1-yl]benzenesulfonamid e; 4-[4,5-dihydro-7-methyl-3-(trifluoromethyl)-1H-benz[g]indazol-1-yl]benzenes ulfonamide; 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]benzenesulfon amide. 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 ##STR106## 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]benzenesulfonamid e; and 4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]benzenesulfonami de. 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 ##STR107## 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]benzene sulfonamide; 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]benzenesulfonami de; 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenes ulfonamide; 4-[3-(difluoromethyl)-5-(4-methylphenyl)-1H-pyrazol-1-yl]benzenesulfonamide ; 4-[3-(difluoromethyl)-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[3-(difluoromethyl)-5-(4-methoxyphenyl)-1H-pyrazol-1-yl]benzenesulfonamid e; 4-[3-cyano-5-(4-fluorophenyl)-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(3-fluoro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide; 4-[4-chloro-5-phenyl-1H-pyrazol-1-yl]benzenesulfonamide; 4-[5-(4-chlorophenyl)-3-(hydroxymethyl)-1H-pyrazol-1-yl]benzenesulfonamide; and 4-[5-(4-(N,N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benz enesulfonamide. 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.