4-NPBA4-nonylphenylboronic acid

Formula

C₁₅H₂₅BO₂

Molar mass

248.17 g·mol⁻¹

CAS

256383-45-6

PubChem CID

4589192

Origin

A wholly synthetic compound. Arylboronic acids are very widely used organic chemistry reagents, notably for cross-couplings, and this one was available as a catalogue product before being recognised as an enzyme inhibitor. It has no natural occurrence and no human use.

InChIKey

VONVJOGSLHAKOX-UHFFFAOYSA-N

Editorial estimate, not clinical.

4-nonylphenylboronic acid owes its entry into endocannabinoid pharmacology to a screening approach rather than to design work. Minkkilä and colleagues assessed in 2008 a series of commercial boronic acids, phenylic, heteroarylic, alkylic and alkenylic, for inhibition of the two enzymes that degrade the endocannabinoids. The general result was that these compounds preferentially inhibit fatty acid amide hydrolase, with effective concentrations ranging from the nanomolar to the low micromolar, and that eight of them also touch monoacylglycerol lipase in the micromolar range. The most potent proved to be the phenylboronic acid bearing a nonyl chain at the para position, with a median inhibitory concentration of 9.1 nanomolar at the amide hydrolase against 7.9 micromolar at monoacylglycerol lipase, that is a selectivity of about 870 times. The mechanism rests on a general property of boron. Electron-deficient, it accepts the lone pair of the catalytic serine and forms a tetrahedral adduct that reproduces the geometry of the transition state of the hydrolysis reaction, which constitutes a reversible but very tight inhibition, distinct from the irreversible covalent mechanism of the carbamates and ureas. That work founded the boronic acids as a class of amide hydrolase inhibitors and was extended by later work on boronic acids directed at other lipases, notably endothelial lipase.

An entirely chemical route, described here by class only. The molecule combines a benzene ring bearing a linear nonyl chain at the para position with a boronic acid function. The boron atom, electron-deficient, is the functional element: it forms with the catalytic serine of hydrolases a tetrahedral adduct that mimics the transition state of the enzymatic reaction.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Class

ECS modulator (research)

Origin

A wholly synthetic compound. Arylboronic acids are very widely used organic chemistry reagents, notably for cross-couplings, and this one was available as a catalogue product before being recognised as an enzyme inhibitor. It has no natural occurrence and no human use.

Status

Unscheduled

1. 1.Minkkilä et coll. 2008 : découverte des acides boroniques comme inhibiteurs puissants de la FAAHPMID 18983140