1,2-aryl and heteroaryl substituted imidazolyl compounds for the treatment of inflammation
AssigneeG.D. Searle & Co.
InventorsIsh K. Khanna, Richard M. Weier, Paul W. Collins, Yi Yu, Xiangdong Xu, Richard A. Partis, Francis J. Koszyk
Life of this patent
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Abstract
A class of imidazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: ##STR1## wherein R.sup.1 -R.sup.6 are as described in the specification; or a pharmaceutically-acceptable salt thereof.
Claims86
A compound of Formula I ##STR70## wherein R.sup.1 and R.sup.2 are independently selected from aryl and heteroaryl, wherein R.sup.1 and R.sup.2 are unsubstituted or substituted with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, haloalkylsulfonyl, halo, alkylthio, alkylsulfinyl, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro;
- wherein R.sup.3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, formyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, cycloalkyloxy, cycloalkyloxyalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, heterocyclocarbonyl, aralkylcarbonyl, heterocycloalkylcarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, N-alkoxy-N-alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl;
- wherein R.sup.4 is a radical selected from hydrido, alkyl and halo;
- wherein R.sup.5 is selected from hydroxyl and alkoxy;
- and
- wherein R.sup.6 is hydrido;
- or wherein R.sup.5 and R.sup.6 together form a double bond;
- provided at least one of R.sup.1 and R.sup.2 is substituted with alkylsulfonyl or aminosulfonyl;
- or a pharmaceutically-acceptable salt thereof.
A compound of Formula VI ##STR71## wherein R.sup.3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, formyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl;
- wherein R.sup.4 is a radical selected from hydrido, alkyl and halo;
- and wherein R.sup.13 and R.sup.14 are independently selected from aryl and heteroaryl, wherein R.sup.13 and R.sup.14 are unsubstituted or substituted with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkylsulfinyl, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro;
- provided at least one of R.sup.13 and R.sup.14 is substituted with alkylsulfonyl or aminosulfonyl;
- or a pharmaceutically-acceptable salt thereof.
A compound of Formula II ##STR72## wherein R.sup.3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocyclicalkyl, heteroaralkyl, formyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, haloaryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, aryl and heteroaryl, wherein the aryl and heteroaryl radicals are unsubstituted or substituted with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy;
- wherein R.sup.7 is a radical selected from alkyl, haloalkyl and amino;
- and
- wherein R.sup.8 is one or more radicals selected from hydrido, halo, alkyl, haloalkyl, alkoxy, amino, haloalkoxy, alkylsulfinyl, cyano, carboxyl, hydroxyl, hydroxyalkyl, alkoxyalkyl, alkylamino, nitro and alkylthio;
- or a pharmaceutically-acceptable salt thereof.
A compound of Formula III ##STR73## wherein R.sup.3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocyclicalkyl, heteroaralkyl, formyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, haloaryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, aryl and heteroaryl, wherein the aryl and heteroaryl radicals are unsubstituted or substituted with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy;
- wherein R.sup.4 is a radical selected from hydrido, alkyl and halo;
- wherein R.sup.9 is one or more radicals selected from hydrido, halo, alkyl, haloalkyl, alkoxy, amino, haloalkoxy, alkylsulfinyl, cyano, carboxyl, hydroxyl, hydroxyalkyl, alkoxyalkyl, alkylamino, nitro and alkylthio;
- and
- wherein R.sup.10 is a radical selected from alkyl, haloalkyl and amino;
- or a pharmaceutically-acceptable salt thereof.
A compound of Formula IV ##STR74## wherein R.sup.3 is selected from alkyl, haloalkyl, alkoxycarbonyl, aralkoxyalkyl, aryloxyalkyl, haloaryloxyalkyl, arylthioalkyl, N-aryl-N-alkylaminoalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylalkylthioalkyl, heteroarylthioalkyl and aryl unsubstituted or substituted with halo, alkoxy and haloalkoxy;
- and
- wherein R.sup.11 and R.sup.12 are independently selected from hydrido, halo, alkyl, haloalkyl, alkoxy, alkylsulfonyl and sulfamyl;
- provided one of R.sup.11 and R.sup.12 is alkylsulfonyl or sulfamyl;
- or a pharmaceutically-acceptable salt thereof.
A compound of Formula V ##STR75## wherein R.sup.3 is selected from alkyl, haloalkyl, alkoxycarbonyl, aralkoxyalkyl, aryloxyalkyl, haloaryloxycarbonyl, arylthioalkyl, N-aryl-N-alkylaminoalkyl, heterocyclicalkoxyalkyl and aryl unsubstituted or substituted with halo, alkoxy and haloalkoxy;
- and
- wherein R.sup.11 and R.sup.12 are independently selected from hydrido, halo, alkyl, haloalkyl, alkoxy, alkylsulfonyl, haloalkylsulfonyl and sulfamyl;
- or a pharmaceutically-acceptable salt thereof.
Dependencies are inferred from the claim text.