Tagworks Pharmaceuticals B.v.

Koninklijke Philips Corporation N.v.

U.S. Philips Corporation

Duphar International Research Bv

Marion Laboratories

Minoryx Therapeutics S.l.

The Horticulture and Food Research Institute of New Zealand Limited

Syncom B.v.

Wolter Ten Hoeve

Marc Stefan Robillard

Ronny Mathieu Versteegen

Raffaella Rossin

Hendricus Marie Janssen

Edsko E Havinga

Hans Wynberg

Hans Wijnberg

Dagobert Michel De Leeuw

Adam R Brown

Johannes Nicolaas Koek

Anita Pomp

Bart-Hendrik Huisman

Ana Maria García Collazo

Sander De Wilde

Knut H Chmii

Johannes B M Rewinkel

Henricus Marie Janssen

Johan Lub

Egbert Willem Meijer

Margaretha Maria De Kok

Gerardus L Rikken

Chris G Kruse

Robert B Koolstra

Sandra Martina Van Den Bosch

David R Borcherding

Louis F Pauli

Peter Tobias Herwig

Albert Jos Jan Marie Van Breemen

Knut H Chmil

Arthur Henry Antoon Marie Van Onzen

Freek Johannes Maria Hoeben

William Thomas Jones

Jantje R Thiecke

Alphons Dufourny

Sjef Nijhuis

Gerrit A Barf

Freek Johannes Hoeben

Ana Maria Garcia Collazo

Johannes BM Rewinkel

Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct Cbound to a Trigger T, the kit having a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine having a Construct Cbound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of the Construct.

Cleavable tetrazine used in bio-orthogonal drug activation

The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

Bio-orthogonal drug activation

The disclosure provides a process of making the compound of Formula I, and pharmaceutically acceptable salts thereof; and the process of making the intermediate of Formula III; wherein PG is as defined as set forth in the specification.

Process for preparing 5-[[4-[2-[5-(1-hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]-methyl]-2,4-thiazolidinedione and salts thereof

The disclosure provides a process of making the compound of Formula I, and pharmaceutically acceptable salts thereof: and the process of making the intermediate of Formula III: wherein PG is as defined as set forth in the specification. 

Process for preparing 5-[[4-[2-[5-(1-hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione and salts thereof

Disclosed is the use of the reactive components of the inverse electron-demand Diels Alder reaction for chemical masking and unmasking in vitro. This can be applied in complex chemical reactions and, particularly in the synthesis of biomolecules, e.g. on solid supports. The reactive components are a dienophile, particularly a trans-cyclooctene, and a diene, particularly a tetrazine.

Chemically cleavable group

Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has one or more axial substituents.

Pretargeting kit, method and agents used therein

The synthesis of a precursor oligocene, particularly pentacene, is a two-step process. In the first step the Diels-Alder adduct of the a,b-dihydro-a,b-etheno-oligocene with a 1,1-dialkoxy-cyclopentadiene is formed. In the second step this Diels-Alder adduct is converted into the precursor oligocene, in that first the corresponding keto-compound is formed, which may be eliminated thereafter. The resulting precursor oligocene can be converted to the oligocene with a heat treatment, particularly after providing a solution hereof on a substrate. It is suitable for use as semiconductor material in a thin-film transistor. Formula (I). 

Method of preparation of a precursor oligocene

A polymer comprising structural units of the formula I is prepared according to a novel method, in which the starting compound R'S&#x2014;(CHR')&#x2014;Ar&#x2014;(CHR)&#x2014;SRis polymerized with a base, preferably in an aprotic solvent. The polymer comprises 50 to 1000 structural units of the formula I. The solution comprising the polymer thus prepared has a lower viscosity than a solution of a similar polymer with a greater chain length. The solution comprising the polymer thus prepared may be applied as a layer on a substrate. Electronic components with layers prepared with the polymer of the invention show better properties. 

Method of preparing a polymer, method of preparing a compounds, compounds, polymers, and method of manufacturing an electronic device

The invention relates to a method of preparing thiophene-containing or furan-containing conjugated compounds such as polythiophene. The method uses a precursor compound having tetrahydrothiophene or tetrahydrofuran precursor units having arylthio or alkylthio substituents. The precursor units can be thermally converted into thiophene or furan units. Due to the presence of the precursor units the precursor compound is soluble and can, unlike the corresponding conjugated compound, be processed from solution.

Method of preparing a thiophene-containing or furan-containing conjugated compound and precursor compound and use thereof for making semiconductor device

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Assen, Netherlands

Wolter Ten Hoeve