US 5,514,778 AGranted

Anti-picornaviral agents

AssigneeEli Lilly and Company

InventorsMarlys Hammond, Stephen W. Kaldor

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Abstract

The present invention provides a group of novel compounds that inhibit the proteolytic activity of 3C proteases which are found in picornaviruses, particularly rhinoviruses. In picornaviruses the RNA genome is translated into a single large viral polyprotein precursor. The precursor demonstrates auto-proteolytic activity, cleaving itself into mature viral gene products. Therefore, compounds of the current invention are particularly useful in treating picornaviral infections by interrupting the processing of the viral gene products into mature and infectious viral particles. The current invention also provides a novel process the preparation of compounds of the current invention. The process entails the selective reduction of an imide intermediate representing a marked improvement over processes known in the art for making peptidyl-aldehydes.

Claims9

Dependent claims

A process for preparing a compound of Formula I ##STR9## wherein X is (CR.sup.1 CR.sup.2)n;

Y is an amino acid sequence of 3 or less amino acid residues, an amino-protecting group, or -C(O)R.sup.3 ;
n is 2;
R.sup.1 is hydrogen and R.sup.2 is hydrogen or alkyl;
R.sup.3 is hydrogen, alkyl, arylalkyl, heteroarylalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, alkoxy, cycloalkoxy, arylalkoxy, heteroarylalkoxy, aryloxy, heteroaryloxy, cycloalkyl, heterocyclic, heterocycloxy, alkylamino, cycloalkyamino, arylamino, heterocycloamino, cycloalkylmethoxy, arylmethoxy, heterocyclomethoxy, alkylmethylamino, arylmethylamino or hetercyclomethylamino,
which comprises regioselectively reducing an imide of Formula III in the presence of NaBH.sub.4 and an acidified hydroxylic solvent ##STR10## such that reduction at the 2-position of said imide occurs to a greater extent than reduction at the 6-position, and wherein X and Y have the meanings given for Formula I.

2 more elements

Dependencies are inferred from the claim text.