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US 5,510,388 AGranted
Sulfonylalkanoylamino hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
AssigneeG. D. Searle & Co.
InventorsMichael L. Vazquez, Richard A. Mueller, John J. Talley, Daniel Getman, Gary A. DeCrescenzo, John N. Freskos
Life of this patent
Estimating the term…
Abstract
Sulfonamide-containing hydroxyethylamine compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Claims16
Method of inhibiting a retroviral protease comprising administering a protease inhibiting amount of a compound represented by Formula I ##STR96## or a pharmaceutically acceptable salt thereof, wherein R represents alkyl, alkenyl, alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- R.sup.1 represents hydrogen, --C(CH.sub.3).sub.2 (SCH.sub.3), --C(CH.sub.3).sub.2 (S O!CH.sub.3), --C(CH.sub.3).sub.2 (S O!.sub.2 CH.sub.3), alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl radicals, or the side chain of the amino acid S-methyl cysteine or the sulfoxide (SO) or sulfone (SO.sub.2) derivative thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, norleucine, threonine, glycine, allo-threonine, serine, O-alkyl serine, beta-cyano alanine or valine;
- R.sup.2 represents alkyl, aryl, cycloalkyl, cycloalkylalky or aralkyl radicals, which radicals are optionally substituted with a halogen, alkyl, --NO.sub.2, --CN, --CF.sub.3, --OR.sup.9 or --SR.sup.9 radicals, wherein R.sup.9 represents hydrogen or alkyl radicals;
- R.sup.3 represents hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- R.sup.4 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- t represents 0 or 1;
- and
- Y represents O or S;
- and
- wherein alkyl, alone or in combination, means a straight-chain or branched-chain alkyl radical containing from 1 to 8 carbon atoms;
- alkenyl, alone or in combination, means a straight-chain or branched-chain hydrocarbon radial having one or more double bonds and containing from 2 to 8 carbon atoms;
- alkynyl, alone or in combination, means a straight-chain hydrocarbon radical having one or more triple bonds and containing from 2 to 10 carbon atoms;
- cycloalkyl, alone or in combination, means a saturated or partially saturated monocyclic, bicyclic or tricyclic alkyl radical wherein each cyclic moiety contains from 3 to 8 carbon atoms;
- and aryl, alone or in combination, means a phenyl or naphthyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalky or acetamido radicals.
10 more elements
Method of treating an HIV infection comprising administering an effective amount of a compound represented by Formula I ##STR97## or a pharmaceutically acceptable salt thereof, wherein R represents alkyl, alkenyl, alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- R.sup.1 represents hydrogen, --C(CH.sub.3).sub.2)(SCH.sub.3), --C(CH.sub.3).sub.2 (S O!CH.sub.3), --C(CH.sub.3).sub.2 (S O!.sub.2 CH.sub.3), alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl radicals, or the side chain of the amino acid S-methyl cysteine or the sulfoxide (SO) or sulfone (SO.sub.2) derivative thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, norleucine, threonine, glycine, allo-threonine, serine, O-alkyl serine, beta-cyano alanine or valine;
- R.sup.2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radicals, which radicals are optionally substituted with a halogen, alkyl, --NO.sub.2, --CN, --CF.sub.3, --OR.sup.9 or --SR.sup.9 radicals, wherein R.sup.9 represents hydrogen or alkyl radicals;
- R.sup.3 represents hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- R.sup.4 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- t represents 0 or 1;
- and
- Y represents O or S;
- and
- wherein alkyl, alone or in combination, means a straight-chain or branched-chain alkyl radical containing from 1 to 8 carbon atoms;
- alkenyl, alone or in combination, means a straight-chain or branched-chain hydrocarbon radial having one or more double bonds and containing from 2 to 8 carbon atoms;
- alkynyl, alone or in combination, means a straight-chain hydrocarbon radical having one or more triple bonds and containing from 2 to 10 carbon atoms;
- cycloalkyl, alone or in combination, means a saturated or partially saturated monocyclic, bicyclic or tricyclic alkyl radical wherein each cyclic moiety contains from 3 to 8 carbon atoms;
- and aryl, alone or in combination, means a phenyl or naphthyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl or acetamido radicals.
10 more elements
Method of treating AIDS comprising administering an effective amount of a compound represented by Formula I ##STR98## or a pharmaceutically acceptable salt thereof, wherein R represents alkyl, alkenyl, alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- R.sup.1 represents hydrogen, --C(CH.sub.3).sub.2 (SCH.sub.3), --C(CH.sub.3).sub.2 (S O!CH.sub.3), --C(CH.sub.3).sub.2 (S O!.sub.2 CH.sub.3), alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl radicals, or the side chain of the amino acid S-methyl cysteine or the sulfoxide (SO) or sulfone (SO.sub.2) derivative thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, norleucine, threonine, glycine, allo-threonine, serine, O-alkyl serine, beta-cyano alanine or valine;
- R.sup.2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radicals, which radicals are optionally substituted with a halogen, alkyl, --NO.sub.2, --CN, --CF.sub.3, --OR.sup.9 or --SR.sup.9 radicals, wherein R.sup.9 represents hydrogen or alkyl radicals;
- R.sup.3 represents hydrogen, alkyl, haloalkyl, alkenyl, alknynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl or a aralkyl radicals;
- R.sup.4 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals;
- t represents 0 or 1;
- and
- Y represents O or S;
- and
- wherein alkyl, alone or in combination, means a straight-chain or branched-chain alkyl radical containing from 1 to 8 carbon atoms;
- alkenyl, alone or in combination, means a straight-chain or branched-chain hydrocarbon radial having one or more double bonds and containing from 2 to 8 carbon atoms;
- alkynyl, alone or in combination, means a straight-chain hydrocarbon radical having one or more triple bonds and containing from 2 to 10 carbon atoms;
- cycloalkyl, alone or in combination, means a saturated or partially saturated monocyclic, bicyclic or tricyclic alkyl radical wherein each cyclic moiety contains from 3 to 8 carbon atoms;
- and aryl, alone or in combination, means a phenyl or naphthyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl or acetamido radicals.
10 more elements
Dependencies are inferred from the claim text.