Description
Clofibric acid is a peroxisome proliferator-activated receptor α (PPARα) agonist (EC
50 = 50 μM in a transactivation assay) and the active metabolite of clofibrate . It is formed from clofibrate by tissue and serum esterases. Dietary administration of clofibric acid (0.067-0.22%) reduces serum cholesterol, phospholipid, and triglyceride levels in rats. It decreases glutamate oxaloacetate transaminase (GOT) levels and increases glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) levels, markers of xenobiotic stress, in the plasma of carp (
C. carpio) when administered in tank water at a concentration of 10 μg/L. Clofibric acid has been found in wastewater effluent.
Chemical Properties
Pale Yellow Solid
Uses
A hypolipidemic compound
Uses
herbicide, antihyperlipoproteinemic, antineoplastic
Definition
ChEBI: A monocarboxylic acid that is isobutyric acid substituted at position 2 by a p-chlorophenoxy group. It is a metabolite of the drug clofibrate.
Biological Activity
PPAR agonist. Antihyperlipoproteinemic.
Synthesis
Step 2: Synthesis of 2-(4-chlorophenoxy)-2-methylpropionic acid
To a solution of ethyl 2-(4-chlorophenoxy)-2-methylpropionate (2.0 g, 8.24 mmol) in tetrahydrofuran (16 mL) was added sequentially water (4 mL) and lithium hydroxide monohydrate (0.69 g, 16.4 mmol) at room temperature. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the mixture was diluted with water and washed with dichloromethane (DCM). The aqueous phase was separated and acidified with 1 M aqueous hydrochloric acid to pH about 2, followed by extraction with dichloromethane (DCM, 2 times). The organic extracts were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 2-(4-chlorophenoxy)-2-methylpropionic acid (p-chlorophenoxyisobutyric acid) as a white solid (1.45 g, 82% yield).
1H NMR (400 MHz, chloroform-d): δ 1.62 (6H, s), 6.89 (2H, d, J = 9.0 Hz), 7.24 (2H, d, J = 9.0 Hz).
References
[1] Journal of Medicinal Chemistry, 2017, vol. 60, # 2, p. 681 - 694
[2] Patent: WO2009/105509, 2009, A1. Location in patent: Page/Page column 36-37
[3] Journal of Pharmaceutical Sciences, 1980, vol. 69, # 1, p. 92 - 93
[4] Patent: WO2008/104994, 2008, A2. Location in patent: Page/Page column 32-33
[5] Patent: US2009/197959, 2009, A1. Location in patent: Page/Page column 18
