Publications by authors named "Cedric Callens"

7 Publications

  • Page 1 of 1

Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships.

J Med Chem 2019 06 23;62(12):5863-5884. Epub 2019 May 23.

Cancer Research UK Centre for Cancer Therapeutics , The Institute of Cancer Research , 15 Cotswold Road , London SM2 5NG , United Kingdom.

Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing an aminomethylenethiophene (AMT) scaffold. High-throughput screening provided the initial hits. Structure-activity relationship (SAR) studies led to the discovery of AMT inhibitors with sub-micromolar half-maximal inhibitory concentrations (IC) in a LOX enzyme activity assay. Further SAR optimization yielded the orally bioavailable LOX inhibitor CCT365623 with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.
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http://dx.doi.org/10.1021/acs.jmedchem.9b00335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937593PMC
June 2019

Amino acid-based reoxidants for aminohydroxylation: application to the construction of amino acid-amino alcohol conjugates.

Angew Chem Int Ed Engl 2011 Nov 23;50(46):10957-60. Epub 2011 Sep 23.

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, OX1 3TA, UK.

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http://dx.doi.org/10.1002/anie.201103293DOI Listing
November 2011

Recent developments in methodology for the direct oxyamination of olefins.

Chemistry 2011 Jan 16;17(1):58-76. Epub 2010 Dec 16.

Department of Chemistry, Chemical Research Laboratory, University of Oxford, UK.

1,2-Amino alcohols are high-value, versatile functional groups that are found in scores of biologically active molecules and other interesting synthetic targets such as ligands and auxiliaries. Given their prominent position within organic compounds of import, it is no surprise to note that many routes have been developed to access this motif and there are many different starting points from which a synthetic chemist might embark on a synthesis. However, one particular approach stands out from the others, and this is the direct conversion of an alkene to a vicinal amino alcohol derivative (oxyamination). Research in this field has been particularly active in recent years and many interesting new methodologies have been reported. The purpose of this review is to give the reader a tour of the methods that have emerged in the last few years so one can appreciate the myriad of different metals and reagents that can accomplish the oxyamination of alkenes. There are still many challenges to be overcome and, herein, we also outline the areas that are ripe for further development and which bode well for the future.
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http://dx.doi.org/10.1002/chem.201002323DOI Listing
January 2011

A novel oxidative cyclisation onto vinyl silanes.

Chem Commun (Camb) 2010 Oct 6;46(39):7310-2. Epub 2010 Sep 6.

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.

A novel osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendant vinyl silane affords THFs that contain silicon functionality at the ring junction. When the cyclisation occurs onto a vinyl benzyldimethylsilyl group, the resulting silyl group can act as a masked hydroxyl group and undergo a Fleming-Tamao type oxidation at a later stage to form the corresponding lactol. The scope of this reaction can also be extended beyond 1,2-diols and applied to the cyclisation of α-hydroxy-sulfonamides and α-hydroxy-amides.
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http://dx.doi.org/10.1039/c0cc01342kDOI Listing
October 2010

Substituted pyrroles via olefin cross-metathesis.

Org Lett 2010 Sep;12(18):4094-7

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.

Olefin cross-metathesis (CM) provides a short and convenient entry to diverse trans-γ-aminoenones. When exposed to either acid or Heck arylation conditions, these intermediates are converted to mono-, di-, or trisubstituted pyrroles. The value of this chemistry is demonstrated by its application to the tetrasubstituted pyrrole subunit of Atorvastatin.
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http://dx.doi.org/10.1021/ol101681rDOI Listing
September 2010

New modes for the osmium-catalyzed oxidative cyclization.

Org Lett 2010 Mar;12(5):1060-3

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, United Kingdom.

The osmium-catalyzed oxidative cyclization of amino alcohol initiators formally derived from 1,4-dienes is an effective method for the construction of pyrrolidines, utilizing a novel reoxidant (4-nitropyridine N-oxide = NPNO). The cyclization of enantiopure syn- and anti-amino alcohols gives rise to enantiopure cis- and trans-2,5-disubstituted pyrrolidines, respectively. Moreover, the cyclization of bis-homoallylic amines bearing an exocyclic chelating group is shown to be a complementary method for trans-pyrrolidine formation.
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http://dx.doi.org/10.1021/ol100046aDOI Listing
March 2010

Tethered aminohydroxylation (TA) reaction of amides.

Org Lett 2009 Jun;11(11):2305-7

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.

The first examples of amide-tethered aminohydroxylation reactions, catalyzed by osmium, showing that the use of N-O-based reoxidants are essential for success, are reported. The system that is described is compatible with a variety of different alkene substitution patterns and ring sizes and works with low loadings in both cyclic and acyclic systems. The levels of diastereoselectivity that were observed for substituents at both the allylic and homallylic position bode well for the use of stereoselective TA reactions in organic synthesis.
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http://dx.doi.org/10.1021/ol900631yDOI Listing
June 2009