Mercachem BV

Nijmegen, Netherlands

Mercachem BV

Nijmegen, Netherlands
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Veerman J.J.N.,Mercachem BV | Bruseker Y.B.,Mercachem BV | Van Esseveldt B.C.J.,Mercachem BV | Glen R.,Peakdale Molecular Ltd. | And 8 more authors.
Heterocycles | Year: 2016

Three methods were developed for the synthesis of substituted 5,6-dihydro-4H-[1,2,4]oxadiazines. The desired oxadiazine rings were synthesised via reductive amination, addition to an iminium ion intermediate and by condensation of a diamine with an imidate. For all methods the scope with respect to the substituents that could be introduced was explored. It was found that the imidate condensation route was the most versatile and the products could be isolated in yields up to 91%. This route is also suitable for the introduction of chirality on the C5 and C6 position of the oxadiazine rings. © 2016 The Japan Institute of Heterocyclic Chemistry.

De Koning H.P.,University of Glasgow | Gould M.K.,University of Glasgow | Sterk G.J.,Mercachem BV | Tenor H.,Nycomed GmbH | And 3 more authors.
Journal of Infectious Diseases | Year: 2012

The development of drugs for neglected infectious diseases often uses parasite-specific enzymes as targets. We here demonstrate that parasite enzymes with highly conserved human homologs may represent a promising reservoir of new potential drug targets. The cyclic nucleotide-specific phosphodiesterases (PDEs) of Trypanosoma brucei, causative agent of the fatal human sleeping sickness, are essential for the parasite. The highly conserved human homologs are well-established drug targets. We here describe what is to our knowledge the first pharmacological validation of trypanosomal PDEs as drug targets. High-throughput screening of a proprietary compound library identified a number of potent hits. One compound, the tetrahydrophthalazinone compound A (Cpd A), was further characterized. It causes a dramatic increase of intracellular cyclic adenosine monophosphate (cAMP). Short-term cell viability is not affected, but cell proliferation is inhibited immediately, and cell death occurs within 3 days. Cpd A prevents cytokinesis, resulting in multinucleated, multiflagellated cells that eventually lyse. These observations pharmacologically validate the highly conserved trypanosomal PDEs as potential drug targets. © 2012 The Author.

Baramov T.,Bayer AG | Baramov T.,Leibniz Institute for Catalysis at the University of Rostock | Loos P.,Bayer AG | Loos P.,Leibniz Institute for Catalysis at the University of Rostock | And 9 more authors.
Advanced Synthesis and Catalysis | Year: 2016

A carbon nanotube supported catalyst containing cobalt/cobalt oxide (Co/Co3O4) nanoparticles encapsulated within a shell of nitrogen-doped graphene layers (Co3O4/NGr@CNT) was prepared. It shows excellent chemoselectivity in the hydrogenation of 1-iodo-4-nitrobenzene, which contains an iodine substituent highly sensitive against hydrodehalogenation. In contrast to traditional activated charcoal-supported catalysts such as Pt-V/C or the closely related Vulcan carbon black supported Co3O4/NGr@C, the advantageous morphological properties of the CNT support allow for the application of the new Co3O4/NGr@CNT as a fixed bed catalyst in a continuous flow reactor. Under optimized conditions, no dehalogenation side products could be detected. This remarkable selectivity in combination with its mechanical stability under operation conditions render Co3O4/NGr@CNT a catalyst particularly relevant for application in continuous processes based on a packed bed reactor. (Figure presented.). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

News Article | October 27, 2016

NEW YORK & NIJMEGEN, The Netherlands--(BUSINESS WIRE)--X-Rx, Inc, a biotechnology company focused on the creation of small molecule drug candidates, and Mercachem BV, a leading chemistry CRO with expertise in medicinal and process chemistry, today reported progress with two discovery-stage oncology programs from the portfolio of X-Rx. The programs target Mcl1, an anti-apoptotic target that is over-expressed in many liquid and solid tumor types, and TAK1, a member of the mitogen-activated protei

Leenders R.,Mercachem BV | Heeres J.,Janssen Research Foundation | Vandenput D.,Mercachem BV | Guillemont J.,Johnson and Johnson Pharmaceutical Research and Development | Lewi P.,Janssen Research Foundation
Synthetic Communications | Year: 2011

Sterically hindered electron-deficient anilines are coupled to the 6-position of the purine core only when activated as their corresponding TFA-amide. The free anilines did not react under all conditions tested. After aqueous work-up, the TFA-group is lost. This procedure provides a new tool in the construction of purines functionalized with a sterically hindered electron-deficient aniline in the 6-position. Copyright © 2011 Taylor & Francis Group, LLC.

Kubas H.,Merz Pharmaceuticals GmbH | Meyer U.,Merz Pharmaceuticals GmbH | Hechenberger M.,Merz Pharmaceuticals GmbH | Klein K.-U.,Merz Pharmaceuticals GmbH | And 5 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013

The metabotropic glutamate receptor subtype 5 has evolved into a promising target for the treatment of various diseases of the central nervous system, such as Fragile X and l-DOPA induced dyskinesia. One of the most advanced clinical compound is Novartis' AFQ-056 (Mavoglurant), which served us as a template for a scaffold hopping approach, generating a structurally diverse set of potent analogs. Both the limited aqueous solubility and the relatively poor metabolic stability of AFQ-056 were improved with hexahydrocyclopenta[c]pyrrole derivative 54a, which proved to be a valuable candidate for further development. © 2013 Elsevier Ltd. All rights reserved.

Leenders R.,Mercachem BV | Heeres J.,Janssen Research Foundation | Vandenput D.,Mercachem BV | Zijlmans R.,Mercachem BV | And 2 more authors.
European Journal of Organic Chemistry | Year: 2010

An optimized procedure is given for the synthesis of novel 3-(arylamino)-1,2,4-triazin-5-one building blocks from commercially available material. By employing these building blocks, a practical protocol is described for the functionalization of the 5-position of the triazine core with anilines or phenols. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

Leenders R.,Mercachem BV | Heeres J.,Janssen Research Foundation | Guillemont J.,Johnson and Johnson Pharmaceutical Research and Development | Lewi P.,Janssen Research Foundation
Tetrahedron Letters | Year: 2010

A method is described to couple sterically-hindered electron-poor anilines to the 4-position of the pyrimidine core using a pyrimidine-2,4-bis(trifluoromethanesulfonate). © 2009 Elsevier Ltd. All rights reserved.

Enders D.,RWTH Aachen | Del Signore G.,RWTH Aachen | Del Signore G.,Mercachem BV | Raabe G.,RWTH Aachen
Turkish Journal of Chemistry | Year: 2013

The asymmetric synthesis of α-(heteroaryl)alkylamines was accomplished by employing a diastereoselective nucleophilic 1,2-addition of lithiated aromatic heterocycles to aldehyde SAMP-hydrazones, followed by BH 3·THF or SmI2 promoted removal of the chiral auxiliary. The CBz or benzoyl-protected amines were obtained in good yields (40%-78%) and excellent enantiomeric excesses (ee = 88%-99%). The methodology can be applied to the synthesis of highly enantioenriched α-amino acids (ee = 90%-99%). © TÜBITAK.

Merkx R.,Netherlands Cancer Institute | De Bruin G.,Netherlands Cancer Institute | Kruithof A.,Netherlands Cancer Institute | Van Den Bergh T.,Mercachem B.V. | And 4 more authors.
Chemical Science | Year: 2013

We developed a scalable synthesis of γ-thiolysine starting straight from lysine. The application of γ-thiolysine was compared to δ-thiolysine in the chemical synthesis of K48 and K33 linked diubiquitin conjugates. Both γ- and δ-thiolysine were found to perform equally efficiently as handles for non-enzymatic ubiquitination. This journal is © 2013 The Royal Society of Chemistry.

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