American Cyanamid Company

Merck Sharp + Dohme Corp.

Lawrence Livermore National Security, LLC

Trius Therapeutics, Inc.

John M Finn

Michael E Jung

Xiaoming Li

Junhu Zhang

Zhiyong Chen

Leslie William Tari

Thanh To Lam

Michael Trzoss

Felice C Lightstone

Sergio E Wong

Daniel Bensen

Suk Joong Lee

Toan B Nguyen

Robert Haselbeck

Karen Joy Shaw

Douglas W Phillipson

Vickie L Brown-Driver

Mark Hilgers

Mark Stidham

Kedar Gc

Min Teng

Robert F Doehner, Jr

David W Ladner

Allen Borchardt

Paul Aristoff

Barrington Cross

Marinus Los

Jerry L Johnson

Peter J Wepplo

Victor M Kamhi

Robert J Duguid

Charles Malcolm Langevine

Shin-Shyong Tseng

D Keith Hester, Ii

Voon Ong

Disclosed herein are compounds having the structure of Formula I and pharmaceutically suitable salts, esters, and prodrugs thereof that are useful as antibacterially effective tricyclic gyrase inhibitors. In addition, species of tricyclic gyrase inhibitors compounds are also disclosed herein. Related pharmaceutical compositions, uses and methods of making the compounds are also contemplated.

Tricyclic Gyrase inhibitors

Disclosed herein are compounds having the structure of Formula I and pharmaceutically suitable salts, esters, and prodrugs thereof that are useful as antibacterially effective tricyclic gyrase inhibitors. Related pharmaceutical compositions, uses and methods of making the compounds are also contemplated.

Tricyclic gyrase inhibitors

Dosage forms or pharmaceutical compositions comprise a compound having the structure of Formula IV:  wherein n is a non-negative integer; wherein each Z is an oxazolidinone-containing moiety having antibiotic activity in vivo upon cleaving, wherein M is independently ORor NRR; wherein Rand Rare independently selected from the group consisting of H, an optionally-substituted hydrocarbyl residue or a pharmaceutically acceptable cation; wherein the compound in the dosage form or a pharmaceutical composition is present in an amount effective for treating or preventing an antibacterial infection in a mammalian subject. Methods of preparing and using these dosage forms or pharmaceutical compositions are also disclosed.

Oxazolidinone containing dimer compounds, compositions and methods to make and use

The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a &#x3b2;-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.

Identification and application of antibiotic synergy

The invention provides a method for generating and selecting drug-sensitizing antisense DNA fragments. In one embodiment, the method includes identifying a gene of interest using knowledge of bacterial physiology, biochemistry, genetics, genomics, and other means. The method includes PCR amplification of a gene of interest using genomic DNA as a template; fragmentation of the DNA by sonication or other means; selecting DNA fragments no longer than 400 base pairs; ligating the DNA fragments into a suitable expression plasmid with a selectable marker; transforming the plasmids containing the DNA fragments into the organism from which the gene of interest originated; and selecting clones from transformed cells that show a phenotypic difference of the clone grown in the presence of the inducer relative to the phenotype in the absence of inducer.

Method for identifying drug-sensitizing antisense DNA fragments and use thereof

The present invention provides arylthioalkyl- and arylthioalkenylphosphonic acids and derivatives thereof having the structural formula I ##STR1## Further provided are compositions and methods comprising those compounds for the control of undesirable plant species.

Arylthioalkyl- and arylthioalkenylphosphonic acids and derivatives

5-Heterocyclic 2-(2-imidazolin-2-yl)pyridine compounds which are effective for the control of undesirable plant species are described. Also described are a method for the herbicidal use of said compounds and a method for their preparation.

5-heterocyclic 2-(2-imidazolin-2-yl)pyridines, useful as herbicidal

There are provided alkyl esters of 5-heterocyclic-pyridine-2,3-dicarboxylic acids useful as intermediates for the preparation of highly effective 5-heterocyclic-2-(2-imidazolin-2-yl)pyridine herbicidal agents and methods for the preparation thereof.

Alkyl esters of 5-heterocyclic-pyridine-2,3-dicarboxylic acids and

There are provided novel 5(and/or 6)substituted 2-(2-imidazolin-2-yl) and 2-(2-imidazolidinyl)nicotinic acids, esters and salts, which are useful as herbicidal agents. There are also provided novel substituted pyrrolopyridine acetonitriles, pyrrolopyridine acetamides, imidazopyrrolopyridinediones and carbamoylnicotinic acid esters, that are useful as intermediates for the preparation of the above said herbicidal agents.

5 (and/or 6) substituted 2-(2-imidazolin-2-yl)nicotinic acids, esters

5-Heterocyclic 2-(2-imidazolin-2-yl)pyridine compounds represented by formulas II and III ##STR1## which are effective for the control of undesirable plant species are described. Also described is a method for the herbicidal use of said compounds.

5-heterocyclic 2-(2-imidazolin-2-yl)-pyridines as herbicides

There are provided novel (2-imidazolin-2-yl) fused heteropyridine compounds, and intermediate compounds for the preparation thereof, and a method for controlling a wide variety of annual and perennial plant species therewith.

(2-imidazolin-2-yl) fused heteropyridine compounds, intermediates for

Alkyl esters of 5-heterocyclic-pyridine-2,3-dicarboxylic acids

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Mercerville, NJ, United States of America

John M Finn