3-Dimensional Pharmaceuticals, Inc.

Janssen Pharmaceutica Nv

Other

Ortho-Mcneil Pharmaceutical Corp.

Dimensional Pharmaceuticals, Inc.

Roger Francis Bone

Richard M Soll

Francis Raymond Salemme

Aihua Wang

John Curtis Spurlino

Tianbao Lu

Dimitris K Agrafiotis

Bruce Edward Tomczuk

Nalin L Subasinghe

Kristi A Leonard

Michael W Pantoliano

Alexander W Rhind

Carl R Illig

Joseph Kent Barbay

Brett A Tounge

Barry A Springer

Kenneth Rhodes

Lawrence C Kuo

Frank A Lewandowski

Cynthia M Milligan

Robert Scannevin

Richard Scott Alexander

Matthew J Todd

Paul F Jackson

Diane M Maguire

Celine Schalk-Hihi

Ingrid Christa Deckman

Andrés Avelino Trabanco-Suárez

José Maria Cid-Núñez

Kenneth Jerome Wilson

Roy E Twyman

M Jonathan Rudolph

Hilde Lavreysen

Marc André Ceusters

Brian D Klein

James B Hoffman

Stefan Maria Christiaan Pype

Nancy Eulalie Sylvain Van Osselaer

H Steven White

Troy L Randle

Scott L Klein

Jeremy Mark Travins

Shelley K Ballentine

Heather Rae Hufnagel

Carl L Manthey

Ehab Khalil

Farah Ali

Carl L Illig

Carl Crysler

Beverley Moore

The present invention relates to combinations comprising a positive allosteric modulator ('PAM') of metabotropic glutamatergic receptor subtype 2 ('mGluR2') or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A (&#x201c;SV2A&#x201d;) ligand.

Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use

The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues. The present invention also relates to the use of small-molecule allosteric processing inhibitors for the treatment of diseases mediated by inappropriate matrix metalloproteinase (MMP) activity.

Methods of treatment using allosteric processing inhibitors for matrix metalloproteinases

Methods for designing, selecting and/or optimizing allosteric processing inhibitors for matrix metalloproteinases

Crystal structure of the pro form of a matrix metalloproteinase and an allosteric processing inhibitor

The present invention is directed to conjugated complement cascade inhibitors, and a method of treating a patient using a conjugated complement cascade inhibitor.

Conjugated complement cascade inhibitors

Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I:wherein R, R, R, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed for in vivo imaging of thrombi.

Cyclic oxyguanidine pyrazinones as protease inhibitors

The present invention provides an assay apparatus for that includes a temperature adjusting means for simultaneously heating a plurality of samples, and a receiving means for receiving spectral emission from the samples while the samples are being heated. In further aspects of the invention, the receiving means can be configured to receive fluorescent emission, ultraviolet light, and visible light. The receiving means can be configured to receive spectral emission from the samples in a variety of ways, e.g., one sample at a time, simultaneously from more than one sample, or simultaneously from all of the samples. The temperature adjusting means can be configured with a temperature controller for changing temperature in accordance with a predetermined profile.

Microplate thermal shift assay apparatus for ligand development and multi-variable protein chemistry optimization

Cyclic oxyguanidine protease inhibitors

Compounds and compositions for treating C1s-mediated diseases and conditions

Methods of treating C1s-mediated diseases and conditions and compositions thereof

A computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.

Method of generating chemical compounds having desired properties

An automatic, partially automatic, and/or manual iterative system, method and/or computer program product for generating chemical entities having desired or specified physical, chemical, functional, and/or bioactive properties. The present invention identifies a set of compounds for analysis; collects, acquires or synthesizes the identified compounds; analyzes the compounds to determine one or more physical, chemical and/or bioactive properties (structure-property data); and uses the structure-property data to identify another set of compounds for analysis in the next iteration. An Experiment Planner generates Selection Criteria and/or one or more Objective Functions for use by a Selector. The Selector searches the Compound Library to identify a subset of compounds (a Directed Diversity Library) that maximizes or minimizes the Objective Functions. The compounds listed in the Directed Diversity Library are then collected, acquired or synthesized, and are analyzed to evaluate their properties of interest. In one embodiment, when a compound in a Directed Diversity Library is available in a Chemical Inventory, the compound is retrieved from the Chemical Inventory instead of re-synthesizing the compound. The Analysis Module receives the compounds of the Directed Diversity Library from the Chemical Inventory and/or the Synthesis Module, analyzes the compounds and outputs Structure-Property data. The Structure-Property data is provided to the Experiment Planner and is also stored in the Structure-Property database. The Experiment Planner defines one or more new Selection Criteria and/or Objective Functions for the next iteration of the invention. In one embodiment, a Structure-Property Model Generator generates Structure-Property Models and provides them to the Experiment Planner which uses the Models to generate subsequent Selection Criteria and/or Objective Function.

System, method and computer program product for identifying chemical compounds having desired properties

Described are compounds of the Formula VII:

Heterocyclic protease inhibitors

Growing community of inventors

Bridgewater, NJ, United States of America

Roger Francis Bone