Cover Page
The handle http://hdl.handle.net/1887/44705 holds various files of this Leiden University dissertation
Author: Janssen, Freek J.
Title: Discovery of novel inhibitors to investigate diacylglycerol lipases and α/β hydrolase domain 16A
Issue Date: 2016-12-01
Discovery of novel inhibitors to investigate diacylglycerol lipases and α/β hydrolase domain 16A
PROEFSCHRIFT ter verkrijging van
de graad van Doctor aan de Universiteit van Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,
volgens het besluit van het College voor Promoties te verdedigen op donderdag 1 december 2016
klokke 12:30 uur
door
Freek J. Janssen geboren te Geldrop in 1988
Promotiecommissie
Promotor Prof. dr. H.S. Overkleeft
Co‐promotor Dr. M. van der Stelt
Overige leden Prof. dr. M. Maccarrone Prof. dr. C. A. A. van Boeckel Prof. dr. A. K. H. Hirsch Prof. dr. J. Brouwer Dr. S. van Kasteren
Printed by: Gildeprint Cover design: DE-SIGN-NIS
“Remember that wherever your heart is, there you will find your treasure.”
Paulo Coelho, The Alchemist
Table of contents
Chapter 1 7
General introduction
Chapter 2 17
Potent sn-1 diacylglycerol lipase α inhibitor discovered by in silico screening
Chapter 3 33
Comprehensive analysis of structure-activity relationships of α-ketoheterocycles as sn-1 diacylglycerol lipase α inhibitors
Chapter 4 59
α-Ketoheterocycles as highly selective and drug-like sn-1 diacylglycerol lipase α inhibitors
Chapter 5 81
Discovery of glycine sulfonamides as dual inhibitors of sn-1 diacylglycerol lipase α and α/β hydrolase domain 6
Chapter 6 109
Discovery of sulfonyl-1,2,4-triazole ureas as sn-1 diacylglycerol lipase α inhibitors by HTS-ABPP
Chapter 7 141
Discovery of 1,2,4-triazole ureas sulfonamides ureas as in vivo active α/β hydrolase domain 16A inhibitors
Chapter 8 161
Inhibitors of diacylglycerol lipases in neurodegenerative and metabolic disorders
Chapter 9 175
Summary and future prospects
