@misc{10481/77839,
year = {2022},
month = {10},
url = {https://hdl.handle.net/10481/77839},
abstract = {The soluble epoxide hydrolase (sEH) has been suggested as a pharmacological target for the treatment of several
diseases, including pain-related disorders. Herein, we report further medicinal chemistry around new benzohomoadamantane-based
sEH inhibitors (sEHI) in order to improve the drug metabolism and pharmacokinetics properties of a previous hit. After an extensive
in vitro screening cascade, molecular modeling, and in vivo pharmacokinetics studies, two candidates were evaluated in vivo in a
murine model of capsaicin-induced allodynia. The two compounds showed an anti-allodynic effect in a dose-dependent manner.
Moreover, the most potent compound presented robust analgesic efficacy in the cyclophosphamide-induced murine model of
cystitis, a well-established model of visceral pain. Overall, these results suggest painful bladder syndrome as a new possible indication
for sEHI, opening a new range of applications for them in the visceral pain field.},
organization = {Spanish Government	SAF2017-82771-R	
RTI2018-093955-B-C21	
PGC2018-102192-B-I00	
RTI2018-101032-J-I00	
Spanish MCIN/AEI},
organization = {ERDF A way of making Europe - MCIN/AEI	PID2020-118127RB-I00},
organization = {PID2019-106285RB},
organization = {ERDF A way of making Europe},
organization = {Xunta de Galicia},
organization = {European Commission	ED431G 2019/02},
organization = {ED431C 2018/21},
organization = {Fundacio Bosch i Gimpera},
organization = {Universitat de Barcelona (F2I grant)		
Generalitat de Catalunya	2017 SGR 106	
2017 SGR 1707},
organization = {European Research Council (ERC)
European Commission	ERC-2015-StG-679001-NetMoDEzyme	
European Commission	MSCA-IF-2014-EF661160-MetAccembly},
organization = {Universitat de Barcelona (APIF grant)},
organization = {Spanish Society of Medicinal Chemistry (SEQT) and Lilly		
FWO	12Y0720N},
organization = {Ministry of Science and Innovation, Spain (MICINN)
Spanish Government	RYC2020-029552-I},
organization = {United States Department of Health & Human Services},
organization = {National Institutes of Health (NIH) - USA	R35 ES03443	
P42 ES004699},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Neurological Disorders & Stroke (NINDS)	R01 DK107767	
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)	R01 DK103616},
publisher = {American Chemical Society},
title = {Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors},
doi = {10.1021/acs.jmedchem.2c00515},
author = {Codony, Sandra and Entrena Fernández, José Manuel and González Cano, Rafael and Cobos del Moral, Enrique José},
}