Isis Pharmaceuticals, Inc.

Peter W Davis

David J Ecker

Oscar L Acevedo

Phillip Dan Cook

Jacqueline R Wyatt

Normand Hebert

John S Kiely

Eric E Swayze

Thomas W Bruice

Timothy A Vickers

Kevin P Anderson

Ronnie C Hanecak

Susan M Freier

Yogesh S Sanghvi

Kelly G Sprankle

Vickie L Brown-Driver

Robert Jay Tinder

Normand Herbert

The present invention provides monocyclic, bicyclic and oligomeric amine compounds with at least two sites of diversity. These compounds are formed from monocyclic scaffolds which can be cyclized to form bicyclic amine scaffolds. These can then be reacted with building blocks to form the amine compounds of the invention. This invention further provides libraries or monocyclic, bicyclic and oligomeric amine compounds. Also provided are methods for preparing monocyclic, bicyclic and oligomeric amine compounds and libraries thereof. The present invention also provides pharmaceutical compositions of the monocyclic, bicyclic and oligomeric amine compounds.

Amine compounds and combinatorial libraries comprising same

Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.

Chemical reaction apparatus and methods

Novel ethylene glycol compounds bearing various functional groups are used to prepare oligomeric structures. The ethylene glycol monomers can be joined via standard phosphate linkages including phosphodiester and phosphorothioate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.

Phosphate linked oligomers formed of monomeric diols and processes for preparing same

Amide compounds of formula (I), combinatorial libraries of amide compounds and methods of preparing the same are provided. Libraries of the invention are useful for screening in biological assays in order to identify pharmaceutically useful compounds.

Amide compound libraries

Chemical synthesis apparatus employing a droplet generator

The present invention provides methods of analyzing and evaluating phosphorus bearing monomeric units as to their suitability for use in preparing randomer oligomer libraries. The invention further provides methods for preparing such randomer oligomer libraries from the selected monomers.

Random oligonucleotide libraries and methods of making the same

Chemical reaction apparatus for performing multiple reaction on a

Phosphate linked oligomers

Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled oligomers are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.

Methods for synthetic unrandomization of oligomer fragments

Synthetic unrandomization of oligomer fragments

Method of making oligonucleotide libraries

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Carlsbad, CA, United States of America

Peter W Davis