Icn Pharmaceuticals, Inc.

Isis Pharmaceuticals, Inc.

Valeant Pharmaceuticals North America

Ribapharm Inc.

Kandasamy Ramasamy

Devron R Averett

Robert C Tam

Guangyi Wang

Wilfried E Seifert

Phillip Dan Cook

David J Ecker

Zhi Hong

Andrew Mamoru Kawasaki

Natarajan Raju

Oscar L Acevedo

Charles John Guinosso

Johnson Lau

Roland K Robins, Deceased

Arthur F Lewis

Vjera Pejanovic

Rajanikanth Bandaru

Ramesh Bharadwaj

Robert Orr

Colin Granger

Novel nucleoside analog compounds are disclosed. The novel compounds or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Type 1 and Type 2 activity.

Nucleoside analogs with carboxamidine modified monocyclic base

C-nucleosides are synthesized by a method in which a sugar is derivatized in a single step to provide a heterocycle at the C position, and then the heterocycle is aromatized in another single step. In one class of preferred embodiments a cyano sugar is converted into thiocarboxamide, and subsequently condensed to form an azole ring. In a second class of preferred embodiments a cyano sugar is condensed with an amino acid to provide the azole ring. In a third class of preferred embodiments a halo sugar is condensed with a preformed heterocycle to provide the azole ring.

Method of producing tiazofurin and other C-nucleosides

Monocyclic L-nucleosides, analogs and uses thereof

Moncyclic L-nucleosides analogs

Nucleosides and other compounds to selectively modulate Th1 and Th2 responses relative to each other in the treatment of disease. In one aspect of the invention, administration of a nucleoside or other compound reduces the dosage at which a primary drug is administered. In another aspect of the invention, an abnormality reflected in increased response in one group of cytokines is treated by administering a nucleoside or other compound that increases response in another group of cytokines. In yet another aspect of the invention, a patient is prophylactically treated by administering a nucleoside or other compound that selectively reduces Th1 activity without significantly reducing Th2 activity. In yet another aspect of the invention, a nucleoside or other compound is administered to a patient at a dose that reduces the patient's GTP pool to a degree that selectively reduces one of the Th1 or Th2 responses without significantly reducing the other response. Controlled release dosage forms are particularly contemplated to achieve that result.

Cytokine related treatments of disease

Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferrably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferrably accomplished. Therapeutics, diagnostics and research methods and also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

Compound for detecting and modulating RNA activity and gene expression

A quaternary ammonium cholinergic agent is complexed with a multivalent anion, or with multiple monovalent anions. The complex may be administered orally to a patient to treat pain, or for some other purpose. Numerous modifications are contemplated, including modifications to the ring structure of the compound, substitution and functionalization of the ring. Other contemplated modifications include the use of different anions, including various monovalent and polyvalent anions, and both organic and inorganic anions. The compounds have utility as cholinergic agents, and especially in the treatment of mysasthenia gravis, chest pain, and carpal tunnel syndrome.

Multivalent salts of pyridostigmine and related compounds

Novel monocyclic L-Nucleoside compounds have the general formula ##STR1## Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th1 and Th2 response.

Monocyclic L-Nucleosides, analogs and uses thereof

The present invention provides various novel oligonucleotide analogs having one or more properties that make the subject compounds superior to conventional oligonucleotides for use in procedures employing oligonucleotides. The compounds of the invention are oligonucleotide analogs in which the furanose ring of a naturally occurring nucleic acid is replaced with an amino acid or a modified amino alcohol residue. Some embodiments of the novel compounds of the invention are particularly useful for the antisense control of gene expression. The compounds of the invention may also be used as nucleic acid hybridization probes or as primers. Another aspect of the invention is to provide monomeric precursors of the oligonucleotide analogs of the invention. These monomeric precursors may be used to synthesize the subject polynucleotide analogs. Another aspect of the invention is to provide formulations of the subject polynucleotide analogs that are designed for the treatment or prevention of disease conditions. Yet another aspect of the invention is to provide methods for treating or preventing diseases, particularly viral infections and cell growth disorders. The subject disease treatment methods comprise the step of administering an effective amount of the subject polynucleotide analogs for use as antisense inhibitors.

Oligonucleotide analogs with an amino acid or a modified amino alcohol

Novel procedures for obtaining ribo-C-nucleosides, including especially 2-.beta.-D-ribofuranosylthiazole-4-carboxylamide (tiazofirin) and 2-.beta.-D-ribofuranosylselenazole-4-carboxylamide (sylenazofurin) and synthesis intermediates thereof. The novel procedures involve introducing a cyano group at the 1' position of a ribose, directly or indirectly converting the cyano group to HN.dbd.C--OR.sub.1 or thicarboxylamide wherein R.sub.1 is a lower alkyl, forming the group which substituted for the cyano group into a heterocyclic ring containing an ester, and converting the ester into an amide.

Procedures for obtaining ribo-C-nucleosides

A number of modified nucleosides are disclosed composed of modified sugar moieties which contain substituents at C1 and C4 positions, or branched substituents at C3 and C5 positions of deoxyribose or ribose. Each nucleoside is converted to or properly protected and then converted to the corresponding phosphoramidites. These phosphoramidites are used to assemble oligonucleotides in which there is at least one forenoted nucleosides. These sugar modified oligonucleotides have the potential to be used as antisense therapies since they are expected to enhance nuclease resistance and cellular uptake while they maintain sequence-specificity and affinity to nucleic acid targets in vitro or in vivo.

Growing community of inventors

Laguna Hills, CA, United States of America

Kandasamy Ramasamy