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US 5,510,349 AGranted
Retroviral protease inhibitors
AssigneeG.D. Searle & Co.
InventorsJohn J. Talley, Daniel P. Getman, Gary A. DeCrescenzo, Ko-Chung Lin, Michael L. Vazquez, Richard A. Mueller, Kathryn L. Reed, Robert M. Heintz, Michael Clare, John N. Freskos, Eric T. Sun
Life of this patent
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Abstract
Urea-containing hydroxyethylamine compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Claims46
Compound represented by the formula:
- ##STR175## wherein R' represents alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, aralkyl, aralkoxycarbonylalkyl, heteroaralkyl, aminoalkyl and aminocarbonylalkyl radicals, wherein the amino group of said aminoalkyl and aminocarbonylalkyl radicals may be mono-or di-substituted with substitutents selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl and heteroaralkyl radicals;
- R.sup.1 represents hydrogen, --CH.sub.2 SO.sub.2 NH.sub.2, --CO.sub.2 CH.sub.3, --CONHCH.sub.3, --CON(CH.sub.3).sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONH.sub.2, --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!CH.sub.3), alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicals and amino acid side chains selected from asparagine, S-methyl cysteine and the corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, alloisoleucine, tert-leucine, phenylalanine, ornithine, alanine, histidine, norleucine, glutamine, valine, threonine, serine, aspartic acid, beta-cyano alanine, and allothreonine side chains;
- R.sup.2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicals optionally substituted with a group selected from --OR.sup.9, --SR.sup.9, and halogen radicals, wherein R.sup.9 represents hydrogen and alkyl radicals;
- R.sup.3 represents alkyl, 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;
- R.sup.4 and R.sup.5, independently represent hydrogen and radicals as defined by R.sup.3, or R.sup.4 and R.sup.5 together with the nitrogen atom to which they are bonded represent heterocycloalkyl and heteroaryl radicals;
- and
- R.sup.20 and R.sup.21 represent radicals as defined for R.sup.1 ;
- and Y and Y' independently represent O and S.
5 more elements
Dependencies are inferred from the claim text.