Publications by authors named "Serge Pieters"

10 Publications

  • Page 1 of 1

Factors affecting flavor perception in space: Does the spacecraft environment influence food intake by astronauts?

Compr Rev Food Sci Food Saf 2020 11 18;19(6):3439-3475. Epub 2020 Sep 18.

Department of Experimental Psychology, University of Oxford, Oxford, UK.

The intention to send a crewed mission to Mars involves a huge amount of planning to ensure a safe and successful mission. Providing adequate amounts of food for the crew is a major task, but 20 years of feeding astronauts on the International Space Station (ISS) have resulted in a good knowledge base. A crucial observation from the ISS is that astronauts typically consume only 80% of their daily calorie requirements when in space. This is despite daily exercise regimes that keep energy usage at very similar levels to those found on Earth. This calorie deficit seems to have little effect on astronauts who spend up to 12 months on the ISS, but given that a mission to Mars would take 30 to 36 months to complete, there is concern that a calorie deficit over this period may lead to adverse effects in crew members. The key question is why astronauts undereat when they have a supply of food designed to fully deliver their nutritional needs. This review focuses on evidence from astronauts that foods taste different in space, compared to on Earth. The underlying hypothesis is that conditions in space may change the perceived flavor of the food, and this flavor change may, in turn, lead to underconsumption by astronauts. The key areas investigated in this review for their potential impact on food intake are the effects of food shelf life, physiological changes, noise, air and water quality on the perception of food flavor, as well as the link between food flavor and food intake.
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http://dx.doi.org/10.1111/1541-4337.12633DOI Listing
November 2020

Design and synthesis of a novel series of cyanoindole derivatives as potent γ-secretase modulators.

Bioorg Med Chem Lett 2019 07 15;29(14):1737-1745. Epub 2019 May 15.

Jubilant Biosys Ltd, Bangalore, Karnataka, India.

The discovery, design and synthesis of a new series of GSMs is described. The classical imidazole heterocycle has been replaced by a cyano group attached to an indole nucleus. The exploration of this series has led to compound 26-S which combined high in vitro and in vivo potency with an acceptable drug-like profile.
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http://dx.doi.org/10.1016/j.bmcl.2019.05.023DOI Listing
July 2019

2,4-Diaminoquinazolines as Dual Toll-like Receptor (TLR) 7/8 Modulators for the Treatment of Hepatitis B Virus.

J Med Chem 2018 07 17;61(14):6236-6246. Epub 2018 Jul 17.

Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30 , 2340 Beerse , Belgium.

A novel series of 2,4-diaminoquinazolines was identified as potent dual Toll-like receptor (TLR) 7 and 8 agonists with reduced off-target activity. The stereochemistry of the amino alcohol was found to influence the TLR7/8 selectivity with the ( R) isomer resulting in selective TLR8 agonism. Lead optimization toward a dual agonist afforded ( S)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexanol 31 as a potent analog, being structurally different from previously described dual agonists ( McGowan J. Med. Chem. 2016 , 59 , 7936 ). Pharmacokinetic and pharmacodynamic (PK/PD) studies revealed the desired high first pass profile aimed at limiting systemic cytokine activation. In vivo pharmacodynamic studies with lead compound 31 demonstrated production of cytokines consistent with TLR7/8 activation in mice and cynomolgus monkeys and ex vivo inhibition of hepatitis B virus (HBV).
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http://dx.doi.org/10.1021/acs.jmedchem.8b00643DOI Listing
July 2018

Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists.

Bioorg Med Chem Lett 2018 02 16;28(4):711-719. Epub 2018 Jan 16.

Janssen Infectious Diseases Diagnostics BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.

The discovery of a novel series of highly potent quinazoline TLR 7/8 agonists is described. The synthesis and structure-activity relationship is presented. Structural requirements and optimization of this series toward TLR 7 selectivity afforded the potent agonist 48. Pharmacokinetic and pharmacodynamic studies highlighted 48 as an orally available endogenous interferon (IFN-α) inducer in mice.
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http://dx.doi.org/10.1016/j.bmcl.2018.01.014DOI Listing
February 2018

Identification and Optimization of Pyrrolo[3,2-d]pyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for the Treatment of Hepatitis B.

J Med Chem 2017 07 14;60(14):6137-6151. Epub 2017 Jul 14.

Janssen Pharmaceutica , N. V. Turnhoutseweg 30, 2340 Beerse, Belgium.

Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 activity, which may be detrimental to the tolerability of the candidate drug. Oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (ISG) response in mice and cynomolgus monkeys. We aimed for a high first pass effect, limiting cytokine induction systemically, and demonstrated the potential for the immunotherapy of viral hepatitis.
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http://dx.doi.org/10.1021/acs.jmedchem.7b00365DOI Listing
July 2017

Novel Pyrimidine Toll-like Receptor 7 and 8 Dual Agonists to Treat Hepatitis B Virus.

J Med Chem 2016 09 23;59(17):7936-49. Epub 2016 Aug 23.

Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.

Toll-like receptor (TLR) 7 and 8 agonists can potentially be used in the treatment of viral infections and are particularly promising for chronic hepatitis B virus (HBV) infection. An internal screening effort identified a pyrimidine Toll-like receptor 7 and 8 dual agonist. This provided a novel alternative over the previously reported adenine and pteridone type of agonists. Structure-activity relationship, lead optimization, in silico docking, pharmacokinetics, and demonstration of ex vivo and in vivo cytokine production of the lead compound are presented.
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http://dx.doi.org/10.1021/acs.jmedchem.6b00747DOI Listing
September 2016

Anilinotriazoles as potent gamma secretase modulators.

Bioorg Med Chem Lett 2014 Dec 18;24(24):5805-5813. Epub 2014 Oct 18.

Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address:

The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.
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http://dx.doi.org/10.1016/j.bmcl.2014.10.024DOI Listing
December 2014

Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X7 Antagonists.

ACS Med Chem Lett 2013 Apr 12;4(4):419-22. Epub 2013 Mar 12.

Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.

The synthesis and preclinical characterization of two novel, brain penetrating P2X7 compounds will be described. Both compounds are shown to be high potency P2X7 antagonists in human, rat, and mouse cell lines and both were shown to have high brain concentrations and robust receptor occupancy in rat. Compound 7 is of particular interest as a probe compound for the preclinical assessment of P2X7 blockade in animal models of neuro-inflammation.
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http://dx.doi.org/10.1021/ml400040vDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027403PMC
April 2013

Design and synthesis of a novel series of bicyclic heterocycles as potent γ-secretase modulators.

J Med Chem 2012 Nov 8;55(21):9089-106. Epub 2012 Jun 8.

Janssen Research & Development, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.

The design and the synthesis of several chemical subclasses of imidazole containing γ-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo potency. This has resulted in the identification of benzimidazole 44a as a GSM with low nanomolar potency in vitro. In mouse, rat, and dog, this compound displayed the typical γ-secretase modulatory profile by lowering Aβ42 and Aβ40 levels combined with an especially pronounced increase in Aβ38 and Aβ37 levels while leaving the total levels of amyloid peptides unchanged.
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http://dx.doi.org/10.1021/jm201710fDOI Listing
November 2012

2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-site APP cleaving enzyme): Use of structure based design to convert a micromolar hit into a nanomolar lead.

J Med Chem 2007 Sep 8;50(18):4261-4. Epub 2007 Aug 8.

Johnson & Johnson Pharmaceutical Research and Development, LLC, Spring House, Pennsylvania 19477, USA.

A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 microM to 11 nM K(i)) by substitution into the unoccupied S(1)' pocket.
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http://dx.doi.org/10.1021/jm0705408DOI Listing
September 2007