Beyond Retigabine: Design, Synthesis, and Pharmacological Characterization of a Potent and Chemically Stable Neuronal Kv7 Channel Activator with Anticonvulsant Activity.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
25 08 2022
25 08 2022
Historique:
pubmed:
17
8
2022
medline:
27
8
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator clinically approved for seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon the recently described cryoEM structure of Kv7.2 complexed with retigabine and on previous structure-activity relationship studies, a small library of retigabine analogues has been designed, synthesized, and characterized for their Kv7 opening ability using both fluorescence- and electrophysiology-based assays. Among all tested compounds,
Identifiants
pubmed: 35972998
doi: 10.1021/acs.jmedchem.2c00911
pmc: PMC9421656
doi:
Substances chimiques
Anticonvulsants
0
Carbamates
0
KCNQ2 Potassium Channel
0
KCNQ3 Potassium Channel
0
Phenylenediamines
0
ezogabine
12G01I6BBU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11340-11364Références
Mol Pharmacol. 2015 Jan;87(1):31-8
pubmed: 25319542
Eur J Pharmacol. 2013 Jun 5;709(1-3):52-63
pubmed: 23562623
J Neurosci. 2015 Jun 10;35(23):8829-42
pubmed: 26063916
Front Physiol. 2017 Feb 06;8:43
pubmed: 28220076
J Biomol Screen. 2010 Apr;15(4):441-6
pubmed: 20208034
ACS Med Chem Lett. 2019 May 08;10(6):929-935
pubmed: 31223450
Pharmacol Rev. 2005 Dec;57(4):473-508
pubmed: 16382104
Metabolism. 2006 Jun;55(6):711-21
pubmed: 16713428
Pflugers Arch. 2020 Jul;472(7):881-898
pubmed: 32506321
J Biomol Screen. 1999;4(2):67-73
pubmed: 10838414
J Pharmacol Toxicol Methods. 2020 Jan - Feb;101:106653
pubmed: 31730935
Anal Biochem. 2011 Nov 1;418(1):66-72
pubmed: 21782781
Nat Commun. 2015 Sep 03;6:8116
pubmed: 26333338
J Neurosci. 2005 May 18;25(20):5051-60
pubmed: 15901787
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
ChemMedChem. 2019 May 6;14(9):952-964
pubmed: 30861620
J Comput Aided Mol Des. 2013 Mar;27(3):221-34
pubmed: 23579614
Epilepsy Res. 2012 Aug;101(1-2):135-40
pubmed: 22483539
Curr Neurol Neurosci Rep. 2007 Jul;7(4):348-54
pubmed: 17618543
Physiology (Bethesda). 2011 Oct;26(5):365-76
pubmed: 22013194
Clin Pharmacol. 2010;2:225-36
pubmed: 22291509
J Med Chem. 2006 Jan 26;49(2):534-53
pubmed: 16420040
Eur J Pharmacol. 2020 Nov 15;887:173440
pubmed: 32745603
J Membr Biol. 2020 Apr;253(2):167-181
pubmed: 32170353
Mol Pharmacol. 2016 Jun;89(6):667-77
pubmed: 27005699
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
J Biomol Screen. 2004 Dec;9(8):671-7
pubmed: 15634793
Chem Res Toxicol. 2019 Feb 18;32(2):294-303
pubmed: 30638013
Mol Cell. 2021 Jan 7;81(1):25-37.e4
pubmed: 33238160
Lancet Neurol. 2019 Apr;18(4):357-375
pubmed: 30773428
J Phys Chem B. 1998 Apr 30;102(18):3586-616
pubmed: 24889800
PLoS Biol. 2010 Jun 29;8(6):e1000412
pubmed: 20613859
Org Biomol Chem. 2014 Oct 14;12(38):7486-8
pubmed: 25156588
Physiol Behav. 2009 Dec 7;98(5):579-86
pubmed: 19772866
J Am Chem Soc. 2015 Jul 15;137(27):8700-3
pubmed: 26121223
Curr Opin Pharmacol. 2008 Feb;8(1):65-74
pubmed: 18061539
J Pharm Biomed Anal. 2012 Dec;71:148-51
pubmed: 22954446
J Pharmacol Exp Ther. 2008 Sep;326(3):818-28
pubmed: 18577704
J Pharmacol Exp Ther. 1998 May;285(2):724-30
pubmed: 9580619
J Med Chem. 2021 May 13;64(9):5816-5837
pubmed: 33929863
Mol Pharmacol. 2005 Apr;67(4):1009-17
pubmed: 15662042
J Med Chem. 2020 Jan 9;63(1):163-185
pubmed: 31815462
Epilepsia. 2015 Apr;56(4):647-57
pubmed: 25779225
ChemMedChem. 2013 Dec;8(12):1941-53
pubmed: 24150998
Science. 1998 Dec 4;282(5395):1890-3
pubmed: 9836639
Commun Biol. 2020 Jul 8;3(1):356
pubmed: 32641720
Ther Adv Drug Saf. 2015 Feb;6(1):15-9
pubmed: 25642319
Nucleic Acids Res. 2012 Jan;40(Database issue):D370-6
pubmed: 21890895
J Pharm Biomed Anal. 2014 Jun;94:71-6
pubmed: 24552644
J Med Chem. 2016 Mar 10;59(5):2179-91
pubmed: 26847872
Epilepsia. 2018 Oct;59(10):1908-1918
pubmed: 30146722
Chemistry. 2019 Apr 11;25(21):5433-5439
pubmed: 30829425
Arzneimittelforschung. 2000 Dec;50(12):1063-70
pubmed: 11190770
J Neurosci. 2015 Feb 4;35(5):2101-11
pubmed: 25653366
Cell Res. 2021 Jan;31(1):52-61
pubmed: 32884139
Epilepsy Res. 1996 Apr;23(3):211-23
pubmed: 8739124