6629-55-6Relevant academic research and scientific papers
Elongation of the Hydrophobic Chain as a Molecular Switch: Discovery of Capsaicin Derivatives and Endogenous Lipids as Potent Transient Receptor Potential Vanilloid Channel 2 Antagonists
Schiano Moriello, Aniello,López Chinarro, Silvia,Novo Fernández, Olalla,Eras, Jordi,Amodeo, Pietro,Canela-Garayoa, Ramon,Vitale, Rosa Maria,Di Marzo, Vincenzo,De Petrocellis, Luciano
, p. 8255 - 8281 (2018/09/25)
The transient receptor potential vanilloid type-2 (TRPV2) protein is a nonselective Ca2+ permeable channel member of the TRPV subfamily, still considered an orphan TRP channel due to the scarcity of available selective and potent pharmacological tools and endogenous modulators. Here we describe the discovery of novel synthetic long-chain capsaicin derivatives as potent TRPV2 antagonists in comparison to the totally inactive capsaicin, the role of their hydrophobic chain, and how the structure-activity relationships of such derivatives led, through a ligand-based approach, to the identification of endogenous long-chain fatty acid ethanolamides or primary amides acting as TRPV2 antagonists. Both synthetic and endogenous antagonists exhibited differential inhibition against known TRPV2 agonists characterized by distinct kinetic profiles. These findings represent the first example of both synthetic and naturally occurring TRPV2 modulators with efficacy in the submicromolar/low-micromolar range, which will be useful for clarifying the physiopathological roles of this receptor, its regulation, and its targeting in pathological conditions.
Alkylaluminium Dichloride Induced Friedel-Crafts Acylation of Unsaturated Carboxylic Acids and Alcohols
Metzger, Juergen O.,Biermann, Ursula
, p. 645 - 650 (2007/10/02)
The ethylaluminium dichloride induced Friedel-Crafts acylation of unsaturated carboxylic acids, for example 10-undecenoic acid (1a) and oleic acid (5a), and of the respective alcohols 1b and 5b with acyl chlorides and cyclic acyl anhydrides gave the corresponding long-chain β,γ-unsaturated ketones 3, 6/7, 11 and 13/14 with ω-carboxy and ω-hydroxy functions, respectively.The intramolecular cyclization of petroselinic acid chloride (17) yielded (E)-2-dodecylidenecyclohexanone (18).Catalytic hydrogenation gave the respective saturated ketones 4, 8/9, 12, 15/16 and 19.Key Words: Friedel-Crafts acylation / β,γ-Unsaturated keto carboxylic acids and alcohols
