63998-82-3Relevant academic research and scientific papers
Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability
Kinney, William A.,McDonnell, Mark E.,Zhong, Hua Marlon,Liu, Chaomin,Yang, Lanyi,Ling, Wei,Qian, Tao,Chen, Yu,Cai, Zhijie,Petkanas, Dean,Brenneman, Douglas E.
, p. 424 - 428 (2016/05/19)
Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.
Synthesis of Cannabinoids Carrying ω-Carboxy Substituents: The Cannabidiols, Cannabinol and Δ1- and Δ6-Tetrahydrocannabinols of this Series
Crombie, Leslie,Crombie, W. Mary L.,Tuchinda, Patoomratana
, p. 1255 - 1262 (2007/10/02)
A convenient synthesis of methyl 5-(3,5-dihydroxyphenyl)pentanoate adaptable for isotopic side-chain labelling is reported.Using acid-catalysed terpenylations involving (1S,4R)-(+)-trans-p-menthadienol, conditions for making (3R,4R)-o- and p-cannabidiols,
