Evolution of a 4-Benzyloxy-benzylamino Chemotype to Provide Efficacious, Potent, and Isoform Selective PPARα Agonists as Leads for Retinal Disorders.
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:
26 03 2020
26 03 2020
Historique:
pubmed:
26
2
2020
medline:
4
9
2020
entrez:
26
2
2020
Statut:
ppublish
Résumé
Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in retinal Müller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPARα with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal diseases in animal models. As such, PPARα is a promising drug target for diabetic retinopathy and age-related macular degeneration. Herein, we report proof-of-concept in vivo efficacy in an streptozotocin-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead
Identifiants
pubmed: 32096640
doi: 10.1021/acs.jmedchem.9b01189
pmc: PMC7365701
mid: NIHMS1577324
doi:
Substances chimiques
Benzylamines
0
PPAR alpha
0
Streptozocin
5W494URQ81
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2854-2876Subventions
Organisme : NEI NIH HHS
ID : R01 EY018659
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY028279
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028949
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY019309
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103640
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY012231
Pays : United States
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