Substituted pyrazolyl benzenesulfonamides for the treatment of inflammation
AssigneeG.D. Searle & Co.
InventorsJohn J. Talley, Thomas D. Penning, Paul W. Collins, Donald J. Rogier, Jr., James W. Malecha, Julie M. Miyashiro, Stephen R. Bertenshaw, Ish K. Khanna, Matthew J. Graneto, Roland S. Rogers, Jeffery S. Carter, Stephen H. Docter, Stella S. Yu
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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.
Claims18
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.
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.
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.
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.
Dependencies are inferred from the claim text.