Merck + Co., Inc.

John Hannah

Burton G Christensen

Richard L Tolman

David H Shih

Richard A Dybas

William J Leanza

Edward F Rogers

David B Johnston

Victor M Garsky

Thomas R Beattie

Robert B Stein

Malcolm MacCoss

Ronald W Ratcliffe

Roger M Freidinger

Arthur F Wagner

Louis Barash

Richard Colonno

The pentapeptide Val Val Asn Asp Leu has been found to be the shortest peptide sequence that inhibits the activity of the ribonucleotide reductase enzyme of herpes simplex virus in vitro thereby inhibiting viral replication. Longer peptides containing the foregoing pentapeptide sequence are more potent inhibitors.

Inhibitor of ribonucleotide reductase

Phosphate derivatives of substituted butyl guanines which have antiviral activity against DNA viruses, such as herpes viruses and HTLV-III.

Phosphate derivatives of substituted butyl guanines, antiviral

Disclosed are N-acyl derivatives of the antibiotic thienamycin having the following structural formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen and acyl. Such derivatives and their pharmaceutically acceptable salts, are useful as antibiotics. Also disclosed are processes for the preparation of such derivatives, pharmaceutical compositions comprising such derivatives, and methods of treatment comprising administering such derivatives and compositions when an antibiotic effect is indicated.

N-acyl derivatives of thienamycin

A series of peptides has been found to inhibit the activity of the ribonucleotide reductase enzyme of herpes simplex virus in vitro thereby inhibiting viral replication.

A process for preparing 9-substituted guanine-containing acyclonucleosides comprising selective alkylation at the 9-position of the purine by utilizing a blocking group at the 6-position.

Regioselective synthesis of 9-substituted purine acyclonucleoside

This application discloses antibacterial cephems of the formula: ##STR1## wherein R.sub.1 represents hydrogen, alkyl, alkenyl, heterocyclylalkyl, or aralkyl; R.sub.3 is a 5- or 6-membered heterocyclic ring selected from: ##STR2## and X is sulfur or oxygen. Included also are pharmaceutically acceptable salts and esters of such compounds; pharmaceutical compositions thereof, and methods of treatment comprising such compositions when an antibiotic effect is needed.

Antibacterial 7.beta.-heterocyclic-cephem

This invention relates to a new class of penicillins (I) and their pharmaceutically acceptable salts and esters which are useful as antibiotics: ##STR1## wherein the stylized radical (hereafter referred to as R'): ##STR2## attached to the 6-amino nitrogen moiety of the penicillin (or ring analogue thereof) nucleus represents a mono- or polycyclic N-containing heterocyclic group; X is S, SO, CH.sub.2, or O; m is 0, 1 or 2; R is, inter alia, hydrogen, substituted and unsubstituted: alkyl, aryl, alkenyl, heterocyclylalkyl, heterocyclylalkenyl, aralkenyl, aralkyl, --NR.sub.2, COOR, CONR.sub.2, --OR, or CN; R.sup.2 is H, or lower alkoxyl.

6-N-Heterocyclyl penicillins

Disclosed are N-acyl and carboxyl derivatives of the antibiotic thienamycin, which has the following structure: ##STR1## Such derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such derivatives, pharmaceutical compositions comprising such derivatives and methods of treatment comprising administering such derivatives and compositions when an antibiotic effect is indicated.

N- And carboxyl derivatives of thienamycin

Novel cephalosporin compounds having a substituted or unsubstituted vinyl group at the 3-position are prepared by the reaction of a phosphoranylidene compound with a compound containing a carbonyl group. The novel cephalosporin compounds are active against a range of gram-negative and gram-positive microorganisms and are of value in human and veterinary medicine.

Cephalosporin compounds

This invention relates to a new class of thienamycins (I) and their pharmaceutically acceptable salts and esters which are useful as antibiotics: ##STR1## wherein the stylized radical (hereafter referred to as R'): ##STR2## attached to the amino nitrogen group of thienamycin represents a mono- or polycyclic N-containing heterocyclic group; R is, inter alia, hydrogen, substituted and unsubstituted: alkyl, aryl, alkenyl, heterocyclylalkenyl, aralkenyl, heterocyclylalkyl, aralkyl, --NR.sub.2, COOR, CONR.sub.2, --OR, or CN.

Antibiotic N-heterocyclyl thienamycin

Disclosed are antibiotic cephalosporins (I) of the formula: ##STR1## Wherein the stylized radical attached to the 7-amino nitrogen of the cephalosporin moiety represents a nitrogen-containing heterocyclic group (mono- or polycyclic); R is, inter alia, hydrogen, alkyl, heterocyclylalkyl, aryl, alkenyl, aralkyl, --NR.sub.2, --OR, COOR, CONR.sub.2 or CN; A is conventionally known in the cephalosporin art; and R.sup.2 is H, or lower alkoxyl. Also disclosed are the pharmaceutically acceptable salt and ester derivatives of I; processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

7-N-Heterocyclyl cephalosporins

This invention relates to a new class of penicillins (I) and their pharmaceutically acceptable salts which are useful as antibiotics: ##STR1## wherein the stylized radical (hereafter referred to as R'): ##STR2## attached to the 6-amino nitrogen moiety of the penicillin nucleus represents a mono- or polycyclic N-containing heterocyclic group; and R is, inter alia, hydrogen, substituted and unsubstituted: alkyl, aryl, alkenyl, heterocyclylalkyl, heterocyclylalkenyl, aralkenyl, aralkyl, --NR.sub.2, COOR, CONR.sub.2,--OR, or CN.

6-N-Heterocyclyl-3-tetrazolyl-penicillins

Disclosed are antibiotic cephalosporins (I) of the formula: ##STR1## wherein the stylized radical attached to the 7-amino nitrogen of the cephalosporin moiety represents a nitrogen-containing heterocyclic group (mono- or polycyclic); R is, inter alia, hydrogen, alkyl, heterocyclylalkyl, aryl, alkenyl, aralkyl, --NR.sub.2, --OR, COOR, CONR.sub.2 or CN; A is H or is conventionally known in the cephalosporin art; R.sup.2 is H, or loweralkoxyl; p is 1 or 2; and R.degree. is H or CH.sub.3. Also disclosed are the pharmaceutically acceptable salt and ester derivatives of I; processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

7-N-Heterocyclyl cephalosporins and antibiotic pharmaceutical

Disclosed are antibiotic cephalosporins (I) of the formula: ##STR1## Wherein the stylized radical attached to the 7-amino nitrogen of the cephalosporin moiety represents a nitrogen-containing heterocyclic group (mono- or polycyclic); R is, inter alia, hydrogen, alkyl, heterocyclylalkyl, aryl, alkenyl, aralkyl, -NR.sub.2, -OR, COOR, CONR.sub.2 or CN; R.degree. is hydrogen or methyl; and R.sup.2 is H, or loweralkoxyl. Also disclosed are the pharmaceutically acceptable salt and ester derivatives of I; processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

Disclosed are antibiotic cephalosporins (I) of the formula: ##STR1## Wherein the stylized radical attached to the 7-amino nitrogen of the cephalosporin moiety represents a nitrogen-containing heterocyclic group (mono- or polycyclic); R is, inter alia, hydrogen, alkyl, heterocyclylalkyl, aryl, alkenyl, aralkyl, --NR.sub.2, --OR, COOR, CONR.sub.2 or CN; R.sup.o is H or CH.sub.3 ; and R.sup.2 is H, or loweralkoxyl: Also disclosed are the pharmaceutically acceptable salt and ester derivatives of I; processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

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Matawan, NJ, United States of America

John Hannah