Ciprofibrate

Ciprofibrate is a peroxisome proliferator-activated receptor agonist.Target: PPARCiprofibrate is a hypolipidemic compound that can induce proliferation of peroxisomes in liver cells of rats. Known to be a PPARα (peroxisome proliferator-activated receptor α) agonist [1, 2].

Ciprofibrate is a monocarboxylic acid, a member of cyclopropanes and an organochlorine compound. It has a role as an antilipemic drug.

The above crude 265K cyclization product (IV) and 400Kg of ethanol were withdrawn in a 1000 L reaction ax, Open mechanical agitation, One-time pumping has been equipped with a good solution of sodium hydroxide (40Kg sodium hydroxide dissolved in 195Kg water), Room temperature reaction 30 min (HPLC monitoring).After completion of the reaction, the ethanol was concentrated under reduced pressure.100Kg of water was poured into the concentrated ax, the aqueous phase was washed twice with 90Kg ethyl acetate, the aqueous phase was cooled to T' 10C, and concentrated hydrochloric acid was slowly added dropwise to pH = 3-4.The aqueous phase was extracted three times with 200 Kg of ethyl acetate. The organic phase was synthesized, washed with 200 Kg of saturated brine, dried over 30 Kg of anhydrous sodium sulfate, filtered and concentrated to give crude cyproterone.The crude ciprofibrate was decolored with 10 Kg of activated carbon, 87 Kg of toluene and 275 Kg of n-hexane mixed solvent232Kg light yellow ciprofibric products (), the yield of 92percent, the total yield of 88percent.The above 274Kg of the cyclized product crude and 500Kg of ethanol were pumped into a 1000L reaction ax and mechanical stirring was started. A good aqueous sodium hydroxide solution (41Kg sodium hydroxide dissolved in 200Kg water) was drawn in one time and reacted at room temperature for 30min monitor). After the reaction was completed, the ethanol was concentrated under reduced pressure. The concentrated ax was cooled to 10 ° C, concentrated hydrochloric acid was slowly dropped acidified to pH = 3-4. The aqueous phase was extracted three times with 200Kg of ethyl acetate, and the organic phase was synthesized, washed with 200Kg of saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated to obtain crude ciprofibrate. The crude ciprofibrate was decolorized with lOKg of activated carbon, and recrystallized from a mixed solvent of 200Kg of toluene and 200Kg of n-hexane to obtain 260Kg of light yellow ciprofibrate (V) in a yield of 91percent. The total yield86percentThe above-mentioned 209 g of the cyclized product crude product was dissolved in 400 mL of methanol, A one-time addition of the aqueous sodium hydroxide solution (34 g of sodium hydroxide dissolved in 140 mL of water)The reaction mixture was stirred at room temperature for 30 min (TLC monitoring).After completion of the reaction, the methanol was concentrated under reduced pressure. To the concentrated residue was added 100 mL of water, the aqueous phase was washed twice with 80 mL of ethyl acetate and the aqueous phase was cooled to T≤ 10 , slowly dropping concentrated hydrochloric acid to pH = 3-4. The extract was extracted with 150 mL of ethyl acetate three times to synthesize the organic phase with 150 mLSaturated with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give crude cyproterone. The ciprofloxacin crude product with 6g liveThe charcoal was decolorized and recrystallized from a mixed solvent of toluene 100 mL and n-hexane 300 mL to obtain 180 g of a pale yellow ciprofibrate product(V), the yield of 90percent, the total yield of 71percent.At 0 °C to 5g 2- methyl-2- (4-vinyl-phenoxy) propionic acid (III) was dissolved 40mL DCM + 4mLTHF, addthe magnesium 0.57g, 3.67g CClThe alcoholysis reaction: 1 mol of 4-(2, 2-dichlorocyclopropyl)phenyl acetate, 300 g of methanol, was added to a 1L reaction flask.0.3 mol of potassium carbonate was reacted at 20° C. for 10 hours, and there was no raw material in the HPLC control, and was concentrated under reduced pressure to obtain about 250 g of an oil.Alkylation: Into a 2L clean reaction flask, 1.8 mol of ethyl bromoisobutyrate was added, 2 mol of potassium carbonate, 600 g of alcohol solution.The product was warmed at reflux for 24 hours. The raw material in HPLC was controlled to be 99percent.

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor involved in the regulation of lipid homeostasis. Activation of PPARα results in expression of a variety of genes, particularly those involved in fatty acid β-oxidation, binding, and transport. Ciprofibrate activates PPARα with an EC50 value of 20 μM and only marginally affects PPARγ (EC50 = >300 μM). It has been shown to lower adipose tissue weight and reduce plasma insulin concentrations in obese rats and has been used clinically in the treatment of dyslipidemia. Ciprofibrate reportedly stimulates cholesteryl ester transfer protein expression and improves the flow of cholesterol through the indirect reverse cholesterol transport system, preserving plasma HDL.

Molecular Weight:289.15
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:288.0319997
Monoisotopic Mass:288.0319997
Topological Polar Surface Area:46.5
Heavy Atom Count:18
Complexity:333
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes