The State University of New York

Yale University

Research Foundation of State of N.y.

Thomas J Bardos

Yung-Chi Cheng

Michael E Perlman

Alan C Schroeder

Simon M Efange

Joan E MacDiarmid

Tai-Shun Lin

Robert G Hughes, Jr

Steven J Kasper

Yau-Kwan Ho

This invention relates to nucleoside and acyclo analogs containing 5- or 6-substituted 2-pyrazinone-4-N-oxide. These compounds are useful for treating various conditions including viral infections, cancer, fungal infections, bacterial infections, microbial infections and related disease states. This invention also relates to pharmaceutical formulations containing these compounds. In addition, this invention relates to methods of treating the above-described conditions in animals and in particular, humans.

Pyrazinone N-oxide nucleosides and analogs thereof

The nuceoside 1-(2-Deoxy-.beta.-D-ribofuranosyl)-5-(iodo)-2-pyrimidinone possesses a high level of antiviral activity and a low level of toxicity to the host cell making it an especially effective therapeutic agent for HSV-2.

5-ioso-2-pyrimidinone nucleoside

A method of inhibiting the replication of tumor cells is disclosed wherein Novel bis (2,2-dimethyl-1-aziridinyl)phosphinic amide antineoplastic agents of the formula: ##STR1## wherein X is R and R' are each, independently, hydrogen, alkyl, substituted alkyl, phenyl and substituted phenyl, Y is alkyl or substituted alkyl of 1-10 carbon atoms and, Z is oxygen or sulfur is administered to tumor cells.

Novel bis(2,2-dimethyl-1-aziridinyl) phosphinic amides for use in the

Polyribonucleotide analogs which are partially substituted by the introduction of mercapto groups and fluorine at the 5-position of some of their cytosine and uracil bases possess effective in vivo antitumor activity. Double stranded complexes formed from such polynucleotides are especially active as interferon inducers.

Novel polynucleotide analogs, methods for inhibiting nucleic acid

Compounds for inhibiting the replication of DNA viruses which induce the formation of thymidine kinase enzyme of the formula: ##STR1## wherein R.sub.1 is a radical selected from the group consisting of chloro, iodo, hydroxy, alkoxyalkyl, hydroxyalkyl, methylamino, formyl, nitro, and unsubstituted hydrocarbon groups of 2 to about 3 carbon atoms or halosubstituted hydrocarbon groups of 1 to about 3 carbon atoms; R.sub.2 is hydrogen or hydroxy; and R.sub.3 is hydroxy, --OP(O)(OH).sub.2, amino, or --OCOR.sub.4 where R.sub.4 is alkyl or alkoxyalkyl of 2 to about 18 carbon atoms.

Novel 5-substituted 2-pyrimidinone nucleosides and methods of use

Novel phosphoaziridines of the formula: ##STR1## wherein Z is oxygen or sulfur, R.sub.1 is independently at each occurrence H or --CH.sub.3, R.sub.2 is independently at each occurrence --CH.sub.3 or nitrophenyl R.sub.5 ; R.sub.3 is --NHR.sub.4, --OR.sub.4, --SR.sub.4 or ##STR2## where R.sub.4 is a radical containing up to 30 atoms including at least one amine, ester, ether, alkyl, substituted alkyl, hydrogen, phenyl, substituted phenyl, carbamate, heterocyclic ring or R.sub.5 group; provided that, when R.sub.4 contains and R.sub.5 group, R.sub.4 has an alkyl group between the phosphorous and the R.sub.5 group; and R.sub.5 is a radical containing and electron affinic group comprising a quinone, or a heterocyclic or phenyl ring directly connected to a radical selected from the group consisting of nitro, nitroso, sulfinyl, sulfoxine, and N-oxide; provided that the compound contains at least one R.sub.5 radical and provided that when R.sub.1 is H, the R.sub.2 group on the same ring is R.sub.5 ; and the method for using the above compounds for the treatment of tumors.

Phosphoaziridine compounds useful for treatment of tumors

Novel bis(2,2-dimethyl-1-aziridinyl)phosphinic amide antineoplastic agents are disclosed of the formula: ##STR1## wherein R and R' are each, independently, hydrogen, alkyl, substituted alkyl, phenyl and substituted phenyl and, Z is oxygen or sulfur.

Bis(2,2-dimethyl-1-aziridinyl)phosphinic amides for use in the treatment

A method for inhibiting the replication of a DNA virus which induces formation of thymidine kinase enzyme, by exposing the virus to an effective concentration of a compound of the formula: ##STR1## wherein R.sub.1 is a radical selected from the group consisting of halogen, --SCH.sub.3, --OH, alkoxy, cyano, methylamino, carboxy, formyl, nitro and unsubstituted or halosubstituted hydrocarbon groups of 1 through 3 carbon atoms; R.sub.2 is hydrogen; halogen or hydroxy; and R.sub.3 is hydroxy, --OP(O)(OH).sub.2, amino, or --OOR.sub.4 where R.sub.4 is lower alkyl of 1 through 6 carbon atoms.

Growing community of inventors

Snyder, NY, United States of America

Thomas J Bardos