Abstract: Disclosed are multibinding compounds which are &bgr;2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor.

Abstract: A method of synthesis of a material corresponding to the general formula: R3—X—H characterized in that it comprises a material corresponding to the following general formula: being cleaved as indicated enzymatically or non-enzymatically using acid catalysis in the presence of a nucleophile, wherein: R1 represents a group providing the site for exo-enzyme or acid hydrolysis; R2 represents an intermediate linked to a solid support; R3 represents a carbohydrate, (oligo-)saccharide, (glyco-)peptide, (glyco-)lipid or an organic molecule which is at least one of heterocyclic and aromatic in structure; X represents O, N(H), N(R″), C(O)O, S, C(O)N(H) or C(O)N(R″), R″ being a non-interfering group; and Support represents a solid support.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. In one particular embodiment, an array of rotated cyclic polymers is formed. In another embodiment, an array of polymers is formed based on a target polymer. The array includes systematically substituted versions of the target molecule. In another embodiment, rotated and systematically substituted cyclic polymers are formed on a substrate.

Abstract: The present invention provides complex compounds reminiscent of natural products and libraries thereof, as well as methods for their production. The inventive compounds and libraries of compounds are reminiscent of natural products in that they contain one or more stereocenters, and a high density and diversity of functionality. In general, the inventive libraries are synthesized from diversifiable scaffold structures, which are synthesized from readily available or easily synthesizable template structures. In certain embodiments, the inventive compounds and libraries are generated from diversifiable scaffolds synthesized from a shikimic acid based epoxyol template. In other embodiments, the inventive compounds and libraries are generated from diversifiable scaffolds synthesized from the pyridine-based template isonicotinamide. The present invention also provides a novel ortho-nitrobenzyl photolinker and a method for its synthesis.

Abstract: The present invention relates to a compound of the formula These modified streptavidin compounds have are useful as part of a delivery system to deliver a molecule to a target site for use in diagnosis or therapy.

Abstract: This invention relates to novel multibinding compounds (agents) that are H1 histamine receptor antagonists and pharmaceutical compositions comprising such compounds. Accordingly, the multibinding compounds and pharmaceutical compositions of this invention are useful in the treatment and prevention of allergic diseases such as rhinitis, urticaria, asthma, and anaphylaxis, and the like.

Abstract: A general stochastic method for synthesizing random oligomers can be used to synthesize compounds to screen for desired properties. The use of identification tags on the oligomers facilitates identification of oligomers with desired properties.

Abstract: Disclosed are multibinding compounds which inhibit cyclooxygenase-2 (COX-2), an enzyme which catalyzes the first committed step in the biosynthesis of prostaglandins. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a moiety capable of binding to COX-2. The multibinding compounds of this invention are useful in the treatment inflammation, pain, fever and the like.

Abstract: Disclosed are multibinding compounds which are antibiotics effective against bacterial infections, in particular, Gram-negative bacterial infections. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a polymyxin, circulin or octapeptin antibiotic or other suitable compound which binds to the LPS present in bacteria, in particular, Gram-negative bacteria. The multibinding compounds of this invention are useful for the prophylaxis and treatment of various bacterial infections caused by bacteria.

Abstract: Method for preparing a combinatorial chemistry library of compounds of the formula R1—C(═O)—NH—R2, wherein R1 and R2 are as defined in the specification, which comprises acylating a combinatorial chemistry intermediate of the formula 1A wherein Y1, Y2, X, n, R1 and R2 are as defined in the specification to produce a compound of the formula wherein Y1, R1, R2 and X are as defined in the specification, followed by acidolytic cleavage of the resin bound linker to release the compound of the formula R1—C(═O)—NH—R2.

Abstract: This invention describes self assembled monolayers (SAMs) manufactured by imprinting reactive peptides onto solid supports. The invention further relates to methods of preparing and using these improved SAMs.

Abstract: The present invention is directed to multibinding compounds which are &bgr;2 adrenergic receptor agonists and are therefore useful in the treatment and prevention of respiratory diseases such asthma, bronchitis, and the like. They are also useful in the treatment of nervous system injury and premature labor.

Abstract: Methods for solid phase and combinatorial synthesis using a resin activation/capture approach are provided. In particular, methods for the production of dihydropyridones, N-acyidihydropyridones, tetrahydropyridones, pyridines, aminopyridines, N-acyltetrahydropyridines and tetrahydropyridines compounds and libraries containing such compounds are provided. Methods for screening the libraries and compounds and pharmaceutical compositions containing compounds prepared by the methods are provided.

Abstract: Novel solid phase reaction supports are disclosed. The solid phase reaction supports include (a) a solid phase carrier having a multiplicity of NH2 functional groups; (b) a coupling compound covalently bonded to an NH2 group of the solid phase carrier; and (c) a receptor compound coupled to the solid phase carrier through the coupling compound. The coupling compound is preferably ascorbic acid, dehydroascorbic acid or a diketo compound structurally similar to ascorbic acid or dehydroascorbic acid. The solid phase carrier is preferably made of cellulose.

Abstract: The invention provides spiro[pyrrolidine-2,3′-oxindole] compounds and libraries of these compounds produced by the stereo- and regio-selective reaction of variously substituted isatins, &agr;-amino acids, and dipolarophiles (e.g., trans-chalcones, acrylate esters, or vinyl oxindoles). The new libraries can be assayed using any of many known screening procedures for activity, e.g., biological activity. For example, the libraries can be screened for activity as drugs (e.g., anticancer drugs, antibiotics, antiviral drugs, antiinflammatory drugs, analgesics, immunomodulators, neuroleptics, sedatives, stimulants, or diagnostic aids), bioseparation agents, or pesticides (e.g., herbicides, insecticides, or rodenticides).

Abstract: The present invention is directed to multibinding compounds which are &bgr;3 adrenergic receptor agonists and are therefore useful in the treatment and prevention of metabolic disorders such as obesity, diabetes, and the like.

Abstract: Disclosed are multibinding compounds which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-COA reductase), the rate limiting enzyme in cholesterol biosynthesis. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a moiety capable of binding to HMG-CoA reductase and the distance between ligands is at least 10 Å. The multibinding compounds of this invention are useful in the treatment and prevention of hypercholesterolemia, hyperlipidemia, atherosclerosis and the like.

Abstract: Novel solid phase reaction supports are disclosed. The solid phase reaction supports include (a) a solid phase carrier having a multiplicity of NH2 functional groups of the Formula (I): in which R1 and R2 are each H, or R1 is H and R2 is an alkyl or acyl substituent with a degree of substitution ≦1 or R1 is an alkyl or acyl substituent with a degree of substitution ≦1, and R2 is H, or R1 and R2 are each a substituent with a degree of substitution ≦2 and R3 is an aromatic substituent containing at least one free amino group having a substitution degree ≦1; (b) a coupling compound covalently bonded to an NH2 group of the solid phase carrier; and (c) a receptor compound coupled to the solid phase carrier through the coupling compound.

Abstract: Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc.

Abstract: The present invention is directed to novel methods for identifying small molecule ligands that are capable of binding with high affinity to a biological target molecule of interest. High affinity binding ligands identified by the described methods find use, for example, as small molecule lead compounds that may they themselves be, or may give rise to, novel therapeutic drugs. More specifically, the subject invention is directed to methods for identifying a ligand that binds to a target biological molecule of interest, wherein a population of small organic compounds are selected and then “pre-screened” to identify those that are capable of binding to the molecular target.