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US 5,744,481 AGranted
.beta.-amino acid 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
.alpha.- and .beta.-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Claims47
Compound represented by the formula:
- ##STR360## wherein:
- R represents hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxy-carbonyl, heteroaroyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, and mono- and disubstituted aminocarbonyl and mono- and disubstituted aminoalkanoyl radicals wherein the substituents are selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, heterocycloalkyalkyl radicals, or where said aminoalkanoyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical;
- R' represents hydrogen and radicals as defined for R.sup.3 or R and R' together with the nitrogen to which they are attached represent heterocycloalkyl and heteroaryl radical;
- R.sup.1 represents hydrogen, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CO.sub.2 CH.sub.3, --CO.sub.2 CH.sub.3, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --C(CH.sub.3).sub.2 (SH), --C(CH.sub.3).sub.2 (SCH.sub.3), --C(CH.sub.3).sub.2 (SO!CH.sub.3), --C(CH.sub.3).sub.2 (SO!.sub.2 CH.sub.3), alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicals, and amino acid side chains selected from asparagine, S-methyl cysteine and the sulfoxide (SO) and sulfone (SO.sub.2) derivatives thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, histidine, norleucine, glutamine, threonine, glycine, allothreonine, serine, aspartic acid, beta-cyano alanine and valine side chains;
- R.sup.1 ' and R.sup.1 " independently represent hydrogen and radicals as defined for R.sup.1, or one of R.sup.1 ' and R.sup.1 ", together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1 ' and R.sup.1 " are attached, represent a cycloalkyl radical;
- R.sup.2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicals, which radicals are optionally substituted with a group selected from alkyl and halogen radials, --NO.sub.2, --C.tbd.N, CF.sub.3, --OR.sup.9, --SR.sup.9, wherein R.sup.9 represents hydrogen and alkyl radicals;
- R.sup.3 represents alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl and mono- and disubstituted aminoalkyl radicals, wherein said substituents are selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicals, or in the case of a disubstituted aminoalkyl radical, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical;
- and
- R.sup.4 represents radicals as defined by R.sup.3.
6 more elements
Dependencies are inferred from the claim text.