Lincomycin nucleotides
AssigneeThe Upjohn Company
InventorsAlexander D. Argoudelis, David W. Stroman
Life of this patent
Estimating the term…
Abstract
Novel and useful ribonucleotides of analogs of the well known antibiotics lincomycin and clindamycin. These ribonucleotides are unexpectedly highly active against Streptococcus hemolyticus and Staphylococcus aureus in vivo.
Claims29
The 3-(5'-ribonucleotide) of a compound having the formula
- wherein R.sub.1, which can be singly or multiply substituted in any position of the pyridine ring not already substituted by R.sub.2, is selected from the group consisting of hydrogen, alkyl and substituted alkyl wherein the alkyl portion is from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof, cycloalkyl and substituted cycloalkyl of from 3 to 8 carbon atoms inclusive, substituted oxygen, substituted nitrogen, halogen, phenyl, and substituted phenyl, --(CH.sub.2).sub.n --OH, --(CH.sub.2).sub.n --NR.sub.4 R.sub.5, and branched chain isomers thereof, wherein n is an integer of from 1 to 8, inclusive, R.sub.4 and R.sub.5 are H or alkyl of from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof;
- wherein R.sub.2, which can be singly substituted in any position of the pyridine ring not already substituted by R.sub.1, is ##STR7## and X is the amino function of a compound selected from the group consisting of 7(S)-halo-methyl 1-thio-.alpha.-lincosaminide and 7(R)-halo-methyl 1-thio-.alpha.-lincosaminide;
- and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR9## wherein R.sub.1, which can be singly or multiply substituted in the 3, 4, 5, or 6 position of the pyridine ring, is selected from the group consisting of hydrogen, alkyl and substituted alkyl wherein the alkyl portion is from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof, cycloalkyl of from 3 to 8 carbon atoms, inclusive and substituted cycloalkyl, substituted oxygen, substituted nitrogen, halogen, phenyl, and substituted phenyl, --(CH.sub.2).sub.n --OH, --(CH.sub.2).sub.n --NR.sub.4 R.sub.5, and branched chain isomers thereof, wherein n is an integer of from 1 to 8, inclusive, R.sub.4 and R.sub.5 are H or alkyl of from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof;
- wherein Y is selected from the group consisting of 7(S)-halo and 7(R)-halo;
- and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR10## wherein R.sub.1, which can be singly or multiply substituted in the 3, 4, 5, 7, 8 or 9 position of the ring, is selected from the group consisting of hydrogen, alkyl and substituted alkyl wherein the alkyl portion is from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof, cycloalkyl of from 3 to 8 carbon atoms, inclusive and substituted cycloalkyl, substituted oxygen, substituted nitrogen, halogen, phenyl, and substituted phenyl, --(CH.sub.2).sub.n --OH, --(CH.sub.2).sub.n --NR.sub.4 R.sub.5, and branched chain isomers thereof, wherein n is an integer of from 1 to 8, inclusive, R.sub.4 and R.sub.5 are H or alkyl of from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof;
- wherein R.sub.3 is selected from the group consisting of H, CH.sub.3, C.sub.2 H.sub.5, and --CH.sub.2 --CH.sub.2 --OH;
- wherein n is an integer of from 1 to 4, inclusive, wherein Y is selected from the group consisting of 7(S)-halo and 7(R)-halo;
- and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR11## and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR12## the 2-palmitate;
- and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR13## wherein X is selected from the group consisting of 7(S)-halo-methyl 1-thio-.alpha.-lincosaminide and 7(R)-halo-methyl 1-thio-.alpha.-lincosaminide;
- and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR17## and the pharmaceutically acceptable salts thereof.
The 3-(5'-ribonucleotide) of a compound having the formula ##STR20## wherein R.sub.1, which can be singly or multiply substituted in any position of the pyridine ring not already substituted by R.sub.2, is selected from the group consisting of hydrogen, alkyl and substituted alkyl wherein the alkyl portion is from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof, cycloalkyl of from 3 to 8 carbon atoms, inclusive and substituted cycloalkyl, substituted oxygen, substituted nitrogen, halogen, phenyl, and substituted phenyl, --(CH.sub.2).sub.n --OH, --(CH.sub.2).sub.n --NR.sub.4 R.sub.5, and branched chain isomers thereof, wherein n is an integer of from 1 to 8, inclusive, R.sub.4 and R.sub.5 are H or alkyl of from 1 to 8 carbon atoms, inclusive, and isomeric forms thereof;
- wherein R.sub.2, which can be singly substituted in any position of the pyridine ring not already substituted by R.sub.1, is ##STR21## and X is the amino function of a compound selected from the group consisting of 7(S)-halo-methyl 1-thio-.alpha.-lincosaminide and 7(R)-halo-methyl 1-thio-.alpha.-lincosaminide;
- and the pharmaceutically acceptable salts thereof.
A compound of the formula ##STR23## wherein R is ##STR24##
A compound of the formula ##STR25## wherein R is ##STR26##
A compound of the formula ##STR27## wherein R is ##STR28##
A compound of the formula ##STR29## wherein R is ##STR30##
Dependencies are inferred from the claim text.