title: Lipoic acid analogs with enhanced pharmacological activity.
abstract: Lipoic acid (1,2-dithiolane-3-pentanoic acid) is a pharmacophore with unique antioxidant and cytoprotective properties. We synthesized a library based upon the condensation of natural and unnatural amino acids with the carboxylic acid moiety of lipoic acid. SAR studies were conducted using a cardiac ischemia-reperfusion animal model. Cytoprotective efficacy was associated with the R-enantiomer of the dithiolane. Potency of library compounds was dictated by the acidic strength of the adduct. α-N-[(R)-1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine, designated CMX-2043, was chosen for further pharmacologic evaluation.
authors: Ischemix, LLC, 63 Great Road, Maynard, MA 01759, United States. Electronic address: skates@ischemix.com.
authors: Steven A
authors: SA
authors: Kates
authors: Ischemix, LLC, 63 Great Road, Maynard, MA 01759, United States.
authors: Ralph A
authors: RA
authors: Casale
authors: Ischemix, LLC, 63 Great Road, Maynard, MA 01759, United States.
authors: Alexander
authors: A
authors: Baguisi
authors: Ischemix, LLC, 63 Great Road, Maynard, MA 01759, United States.
authors: Reinier
authors: R
authors: Beeuwkes
mesh_terms: D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004151:Dipeptides; C000602148:alpha-N-(1,2-dithiolane-3-pentanoyl)glutamylalanine; D008063:Thioctic Acid
keywords: Amino acids; Ischemia-reperfusion; Lipoic acid; Polymerization; SAR studies