1716-12-7

Usage

Uses

Used in Pharmaceutical Industry:
Sodium 4-phenylbutyrate is used as an antineoplastic agent for its potent differentiating capacity in multiple hematopoietic and solid tumor cell lines. It acts as an inducer of tumor cytostasis and differentiation, as well as a transcriptional regulator, improving the targeting of δF508-CFTR for ubiquitination and degradation by reducing the expression of HSC70 in epithelial cells.
Used in Cancer Research:
Sodium 4-phenylbutyrate is used as a histone-deacetylase inhibitor, which has been shown to increase fetal hemoglobin production in vitro and in vivo. It is also used as an endoplasmic reticulum (ER) stress inhibitor to study the role of ER stress in the expression of betatrophin.
Used in Urea Cycle Disorder Treatment:
Sodium 4-phenylbutyrate is used as a treatment for urea cycle disorders, where it stimulates urinary nitrogen excretion and is formulated under the brand name Buphenyl (Medicis).
Used in Infection Research:
Sodium 4-phenylbutyrate is used in cancer and infection research due to its inhibitory effects on various tumors and its role in ER stress.

Biological Activity

Sodium 4-Phenylbutyrate is a histone deacetylase inhibitor that displays anticancer activity. Inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. Also inhibits protein isoprenylation, depletes plasma glutamine, increases production of fetal hemoglobin through transcriptional activation of the γ-globin gene and affects hPPARγ activation.

Biochem/physiol Actions

Sodium phenylbutyrate is a histone deacetylase inhibitor.

References

1) Engelhard et al. (1998), Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration and invasiveness of malignant glioma cells; J. Neuro-Oncol., 37 97 2) Appelskog et al. (2004), Histone deacetylase inhibitor 4-phenylbutyrate suppresses GAPDH mRNA expression in glioma cells; Int. J. Oncol., 24 1419

InChI:InChI=1/C10H12O2.Na/c1-2-9(10(11)12)8-6-4-3-5-7-8;/h3-7,9H,2H2,1H3,(H,11,12);/q;+1/p-1

Upstream product

• 1821-12-1 4-Phenylbutyric acid 
• 1449300-08-6 4-phenyl-N-(quinolin-8-yl)butanamide 
• 578-66-5 8-amino quinoline 
• 108-86-1 bromobenzene 

Relevant academic research and scientific papers

Intermolecular Reductive Heck Reaction of Unactivated Aliphatic Alkenes with Organohalides

A general intermolecular reductive Heck reaction of organohalides with both terminal and internal unactivated aliphatic alkenes has been first realized in high yield with complete anti-Markovnikov selectivity. The challenging vinyl bromides, aryl chlorides, and polysubstituted internal alkenes were first applied. More than 100 remote carbofunctionalized alkyl carboxylic acid derivatives were rapidly synthesized from easily accessible starting materials. The synthesis of drug molecules has further demonstrated the wide synthetic utility of this scalable strategy. Preliminary mechanistic studies are consistent with the proposed catalytic cycle.

Preparation method of sodium phenylbutyrate

The invention discloses a preparation method of sodium phenylbutyrate. The preparation method comprises the steps that in the inert atmosphere, materials and anhydrous 2,3-butanediol are added into areaction vessel, and mixing is conducted uniformly, wherein the related materials include allyl palladium (II) chloride dimer, 2-(dicyclohexylphosphino)-1-phenyl-1H-pyrrole, N-(8-aminoquinoline)butyl-3-enamide, lithium acetate, bromobenzene, cyanoacetic acid and water; the reaction vessel is placed in an oil bath at 125-135 DEG, a vigorous stirring reaction is conducted for 12 hours, a reaction product is purified through a silica gel column, and a compound with a guiding group is obtained; the compound is added into an ethanol solvent containing sodium hydroxide, the mixture is heated to 130-140 DEG C, a reflux reaction is conducted for 12 hours, the reaction product is subjected to vacuum distillation to remove the solvent, extraction is conducted, a water layer is collected, vacuum distillation is conducted to remove water, and a sodium phenylbutyrate preparation is obtained. The method has the advantages of being high in reaction site selectivity and yield, mild in reaction condition and simple in reaction and aftertreatment purification process.

Preparation method for sodium phenylbutyrate

The invention discloses a preparation method for sodium phenylbutyrate. The method comprises the following steps: (1) purification of 4-phenylbutyric acid: 1) under the catalysis of a catalyst, reacting industrial grade phenylbutyric acid in alcoholic solvents, and treating a reacted system to obtain the 4-phenylbutyric acid; 2) in the existence of an alkali catalyst or an acidic catalyst, performing hydrolysis reaction on the 4-phenylbutyric acid in a solvent to obtained purified phenylbutyric acid, namely, the industrial grade phenylbutyric acid is purified; (2) preparation of the sodium phenylbutyrate: enabling the phenylbutyric acid which is purified by the step 1) to react with a sodium reagent to obtain the sodium phenylbutyrate. According to the preparation method disclosed by the invention, alcohols (methyl alcohol and ethyl alcohol) serve as reaction solvents, so that the preparation method is more environmentally -friendly and green compared with a synthesis method in the prior art; the preparation of high-purity methyl alcohol is realized through a three-step conventional reaction; the purity of the sodium phenylbutyrate prepared by the preparation method reaches 99.5 percent or above, and single impurities are controlled to be within 0.1 percent.

Use of 4-phenylbutyric acid and/or salts thereof for enhancing stress tolerance in plants

The invention relates to the use of 4-phenylbutyric acid and/or salts thereof, of the formula (I) for enhancing stress tolerance in plants to abiotic stress, preferably drought stress, and to the associated enhancement in plant growth and/or increase in plant yield.

Effects of structure variation on solution properties of hydrotropes: Phenyl versus cyclohexyl chain tips

The physicochemical behavior of the phenyl-n-alkanoate (PhenCx) and cyclohexyl-n-alkanoate (CyclohexCx) series has been investigated, supporting previous work on the understanding of hydrotropes (Hopkins Hatzopoulos, M.; Eastoe, J.; Dowding, P.J.; Rogers, S. E.; Heenan, R.; Dyer, R. Langmuir2011, 27, 12346-12353). Electrical conductivity, surface tension, 1H NMR, and small-angle neutron scattering (SANS) were used to study adsorption and aggregation in terms of critical aggregation concentration (cac). The PhenCx series exhibited very similar d log(cac)/dn to n-alkylbenzoates (CnBenz), exhibiting two branches of behavior, with a common inflection point at four linear carbons, whereas the CyclohexCx series showed no break point. Electrical conductivity and 1H NMR concentration scans indicate a difference in physicochemical behavior between higher and lower homologues in both the PhenCx and CyclohexCx series. Surface tension measurements with compounds belonging to either group gave typical Gibbs adsorption profiles, having d log(cac)/dn curves consistent with limiting headgroup areas in the region of (35-55 A2) indicating monolayer formation. SANS profiles showed no evidence for aggregates below the electrical conductivity determined cac values, inferring an "on-off" mode of aggregation. Analyses of SANS profiles was consistent with charged ellipsoidal aggregates, persisting from lower through to higher homologues in both the PhenCx and CyclohexCx series.

Vibrational spectroscopic studies of cocrystals and salts. 3. cocrystal products formed by benzenecarboxylic acids and their sodium salts

X-ray powder diffraction, differential scanning calorimetry, infrared absorption spectroscopy, and Raman spectroscopy have been used to study the phenomenon of salt formation in four benzenecarboxylic acids (benzoic acid, phenylacetic acid, hydrocinnamic acid, and 4-phenylbutanoic acid), and in the 1:1 stoichiometric products formed by the cocrystallization of a free acid and a sodium salt. Assignments were derived for the observed peaks in both infrared absorption and Raman spectra of the reactants and their products. In all instances, it was observed that the energy of the antisymmetric stretching mode of the carbonyl group of the free benzenecarboxylic acid invariably shifted to higher energies when that acid formed a cocrystal with a sodium salt of another benzenecarboxylic acid. In addition, the symmetric stretching mode of the benzenecarboxylic acid carbonyl group disappeared in the Raman spectrum of its sodium salt and was also absent in the Raman spectrum of the cocrystal product. It was also found that the antisymmetric carboxylate anion stretching mode, the symmetric carboxylate anion stretching mode, the out-of-plane carboxylate deformation mode, and the vibrational modes associated with the phenyl ring and alkane side chains were not useful spectroscopic tools to differentiate cocrystal and sodium salt, as the observed differences of these vibrational modes did not exhibit significantly consistent differences between the various forms.

Use of highly concentrated formulations of 4-phenylbutyrate for treatment of certain disorders

A highly concentrated preparation of sodium 4-phenylbutyrate in an aqueous medium as an alternative for present high dosage therapeutic treatments of certain disorders is provided, specifically for the treatment of spinal muscular atrophy (SMA), central nervous system (CNS) cancer, myelodysplastic syndrome (MS), acute leukemia, glioblastoma multiforme, amyotrophic lateral sclerosis (ALS), and colon cancer.

Process for preparation of liquid dosage form containing sodium 4-phenylbutyrate

A process for preparing a stable aqueous dosage form of sodium 4-phenylbutyrate, including such dosage forms in a highly concentrated solution, as well as methods for making 4-phenylbutyrate and 4-phenylbutyric acid, and for using 4-phenylbutyrate. The stable aqueous dosage forms do not freeze at 0° C.