Eli Lilly and Company

E. R. Squibb Sons, Inc.

Transcell Technologies, Inc.

Incara Research Laboratories

Intercardia, Inc.

Other

Princeton University

Advanced Medicine, Inc.

Michael J Sofia

Ramesh Kakarla

Dashan Liu

Scott A Biller

Nicole T Hatzenbuhler

Robert D Dillard

Tin Yau Chan

J Scott Sawyer

Rakesh K Jain

Anna K Chen

Thomas C Zebovitz

Rui Liang

Nigel Mark Allanson

Domingos J Silva

Eric M Gordon

Donald S Karanewsky

James A Clemens

Natan A Kogan

Michael C Badia

Diane T Stephenson

Helena R Axelrod

Clifford S Mintz

Daniel E Kahne

Suzanne Walker Kahne

Paul E Floreancig

S Richard Baker

A combinatorial chemical library of compounds structurally related to the moenomycin class of antibiotics has the formula

Combinatorial library of moenomycin analogs and methods of producing same

A combinatorial chemical library of compounds structurally related to the moenomycin class of antibiotics has the formula ##STR1## wherein D is a donor mono- or disaccharide, A is an acceptor monosaccharide, and P-R is a lipophosphoglycerate mimetic group. Members of the library have a glycosidic linkage between the anomeric carbon of D and the C2 carbon of A, and the D-A moiety is in turn covalently linked through the anomeric carbon of A to the P-R group. Members of the library exhibit their greatest structural diversity in terms of substitutions occurring at the C3 position of the A residue, substitutions at the C2 position of the D residue, and different P-R groups used in assembling the compounds. Members of the library are preferably synthesized by solid phase techniques involving stepwise coupling of the respective units to a support, functionalizing the A and/or D saccharides either before or after immobilizing them on the support, and cleaving the assembled compounds from the support. Preferred functionalities attached to the sugar residues are amides, carbamates, ureas, sulfonamides, substituted amines, esters, carbonates, and sulfates. Exemplary P-R groups are derivatives of homoserine, glyceric acid, salicylates and mandelic acid. Members of the library can be screened for anti-microbial activity by contacting them with a culture of microbes and monitoring the growth rate of the microbes.

The present invention relates to methods of preventing or treating an infection or disease caused by an infectious agent. The present invention also relates to the augmentation of the efficacy of existing anti-infective agents by the co-administration of the compounds described herein.

Polyamine conjugates for treatment of infection

The present invention relates to a process for the preparation and manufacture of 3-amino-substituted glycosylated bile acid derivatives. Intermediates and related compounds are also disclosed. In particular, the present invention permits the conversion of cholic acid esters to the 3-amino-7,12-bis(glucosyl)cholic acid esters via an azide intermediate. Conditions for the purification and isolation of the desired product is also disclosed to provide an overall manufacturing process suitable for large-scale production.

Process for the manufacture of 3-amino-substituted glycosylated bile

A process is disclosed for making a compound having a sulfoxide group comprising providing a first compound having a sulfide group and contacting said first compound with an oxidizing agent in the presence of silica and a carboxylic acid anhydride. In a particular embodiment of the invention, the high yield preparation of glycoside moieties having anomeric sulfoxides at ambient temperature is described.

Process for preparing sulfoxides

The present invention relates to a process for the preparation and manufacture of 3-amino-substituted glycosylated bile acid derivatives. Novel intermediates and related compounds are also disclosed. In particular, the present invention permits the conversion of cholic acid esters to the 3-amino-7,12-bis(glucosyl)cholic acid esters via an azide intermediate. Conditions for the purification and isolation of the desired product is also disclosed to provide an overall manufacturing process suitable for large-scale production.

Novel glycosylated steroid derivatives for facilitating the transport of compounds across biological membranes, either in admixture or as conjugates, are disclosed. A novel process for efficient synthesis of these glycosylated steroid derivatives, using activated glycosyl sulfoxide intermediates is provided. Methods for the permeabilization of membranes and the enhancement of the activity of predetermined compounds are also provided.

Glycosylated steroid derivatives for transport across biological

The present invention relates to a process for the preparation and manufacture of 3-amino-substituted glycosylated bile acid derivatives. Novel intermediates and related compounds are also disclosed.

This invention provides methods for the treatment or prevention of Alzheimer's disease in a mammal which comprises administering to a mammal in need thereof an effective amount of an inhibitor of phospholipase A.sub.2. This invention also provides a series of compounds which are useful as inhibitors of phospholipases A.sub.2, especially cytosolic phospholipase A.sub.2.

Phospholipase A.sub.2 inhibitors

This invention provides certain 1,2,4,5 substituted benzene derivatives containing 'acid' substituents derived from cyclic or heterocyclic moieties. These unique compounds are leukotriene B.sub.4 antagonists and formulations of these derivatives, and a method of using these derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.

Leukotriene B4 antagonists

Use of PLA.sub.2 inhibitors as treatment for alzheimer's disease

Antagonists having a substituted phenyl phenol or a substituted phenolic biphenyl structure, and various derivatives thereof, are specific leukotriene antagonists. Their structures, use and synthesis are disclosed. Also, pharmaceutical formulations are disclosed for use in applications treating diseases or conditions characterized by excessive release of leukotriene B.sub.4, one of the metabolites of arachidonic acid. The primary LTB.sub.4 antagonistic structures are represented as: ##STR1##

Substituted phenyl phenol leukotriene antagonists

This invention provides 1,2,4-trioxygenated benzene derivatives which are leukotriene B.sub.4 antagonists, formulations of those derivatives, and a method of using those derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.

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Lawrenceville, NJ, United States of America

Michael J Sofia