Eli Lilly and Company

Robin D Cooper

Gary A Koppel

Nancy June Snyder

Michael J Rodriguez

Lawrence J McShane

Mark J Zweifel

Richard Craig Thompson

Bret E Huff

Stephen Charles Wilkie

Michael A Staszak

Thalia I Nicas

John T Quatroche

Douglas O Spry

Robert F Bruns, Jr

David C Hunden

Jeffrey J Skelton

David Kent Herron

John Michael Morin, Jr

Bruce Anthony Dressman

Stephen W Kaldor

Mitchell I Steinberg

Larry C Blaszczak

Jan R Turner

John Robert Rizzo

Edward R Lavagnino

Barbara S Briggs

Michael O Chaney

Adam Joseph Kreuzman

Bernard J Graves

Milton Joseph Zmijewski, Jr

Lynn R Peters

This invention provides methods and 2-(azetidin-2-on-1-yl)acetic acid derivatives for the antagonism of the vasopressin V,receptor.

Non-peptidyl vasopressin V1a antagonists

The present invention provides glycopeptide antibiotic derivative compounds. These derivative compounds possess antibacterial activity against a wide variety of bacteria, including activity against vancomycin-resistant isolates. Methods of making and using these glycopeptide antibiotic derivative compounds are also provided.

Glycopeptide antibiotic derivatives

The present invention is directed to deacyl teicoplanin, and to a process for preparing deacyl teicoplanin by reacting teicoplanin with ECB deacylase. Deacyl teicoplanin can be alkylated to produce compounds useful for their antibacterial activity.

Teicoplanin deacylation process and product

The present invention is directed to amides of antibiotic A82846B (also known as chloroorienticin A), and of N.sup.4 -derivatives of A82846B. The present amide compounds are useful as antibacterials, especially for the control of gram positive bacteria; the compounds are particularly useful for the control of resistant bacterial strains, such as vancomycin-resistant-enterococci ('VRE').

Amides

The present invention is directed to teicoplanin derivatives of the following general formula, wherein R.sup.1 and R.sup.2 are as defined in the specification. ##STR1## These derivatives are useful as antibiotics for the control of gram-positive bacteria.

Teicoplanin derivatives

The present invention provides glycopeptide antibiotic derivative compounds. These derivative compounds possess antibacterial activity aginst a wide variety of bacteria, including activity against vancomycin-resistant isolates. Methods of making and using these glycopeptide antibiotic derivative compounds are also provided.

This invention relates to a combinatorial process for synthesizing a library of azetidinone peptide-like compounds. The compounds are synthesized as mixtures from a common azetidinone intermediate. The compounds are biologically active as inhibitors of the Vasopressin (V1a) receptor.

Combinatorial process for synthesizing azetidinone analogs

2,5-Disubstituted oxazolidin-4-one-3-ylacetyl chlorides and 1,2,5-substituted imidazolidin-4-one-3-yl-acetyl chlorides function as chiral auxiliary moieties in the asymmetric cycloaddition with aldimines to provide cis-azetidinones. The azetidinones are useful intermediates in the preparation of antibiotics.

Chiral 3-(1,2,5-trisubstituted imidazolidinone) azetidinone antibiotic

3.beta.-Substituted succinimido)azetidinones represented by the formula ##STR1## wherein R and R.sub.1 are e.g. C.sub.1 -C.sub.5 alkanoyloxy, benzoyloxy, substituted benzoyloxy, or benzyloxy, or one of R and R.sub.1 is hydrogen and the other is as defined above; R.sub.2 is C.sub.1 -C.sub.4 alkoxycarbonyl or an arylvinyl group e.g. styrryl or 2-furylvinyl; and R.sub.3 is e.g. protected-carboxymethyl, or an NH protecting group; are provided via stereoselective cycloaddition of imines with chiral auxiliary 3,4-disubstituted succinimidoacetyl chlorides. The chiral auxiliary e.g., 3S,4S-dibenzoyloxy-and 3S,4S-diacetoxysuccinimidoacetyl chloride, is obtained from tartaric acid via anhydride and imide formation with retention of chirality. The chiral azetidinones obtained are useful intermediates to .beta.-lactam antibacterial compounds.

3.beta.-succinimidoazetidinones as chiral intermediates

Oxazolino-azetidinones are prepared by reaction of a phosphorus compound with a 3-exomethylenecepham sulfoxide.

Preparation of oxazolines

This invention provides a novel allylic chlorination process for inserting a chlorine atom on the saturated methyl group of a 3-methyl-2-but-3-enoate group on the ring nitrogen atom of a 2-azetidinone or thiazolinoazetidinone. The chloro-substituted compounds prepared thereby are novel intermediates used in preparation of cephalosporins.

Allylic chlorination process and compounds prepared thereby

Naphthylglycyl and tetrahydronaphthylglycyl cephalosporins are potent antibacterial agents and are particularly useful as oral treatments for upper respiratory infections.

Naphthylglycyl cephalosporin derivatives

7-(2-Benzothienyl)glycylamido cephalosporins have good gram positive activity and favorable pharmacokinetics and are orally effective.

Benzothienylglycyl cephalosporin derivatives

Thiazoline azetidinones are converted in good yield to 3-bromo-3-methylcephams by treatment with a bromine source and dimethyl sulfoxide.

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Indianapolis, IN, United States of America

Robin D Cooper