2936-08-5

Usage

Uses

2,2-Di-n-propylacetyl chloride is used to produce 1,2-bis-(2-propyl-valerylamino)-ethan.

Upstream product

• 99-66-1 valproic acid 
• 7719-09-7 thionyl chloride 
• 17022-31-0 ethyl 2-propylpentanoate 

Downstream Products

• 99174-91-1 2-bromo-2-propyl pentanoic acid ethyl ester 
• 2936-09-6 2-Propyl-valeriansaeure-anilid 
• 50390-47-1 1-phenyl-2-propyl-pentan-1-one 
• 2936-18-7 2-Propyl-valeriansaeure-<3-morpholino-propylamid> 
• 22632-59-3 methyl 2-propylvalerate 
• 2936-11-0 2-Propyl-valeriansaeure-propylamid 
• 3116-28-7 2-Propyl-valeriansaeure-cyclohexylamid 
• 3116-25-4 2-Propyl-valeriansaeure-p-anisidid 
• 3116-29-8 N-(2-hydroxyethyl)-2-propylpentanamide 
• 3116-30-1 2-Propyl-valeriansaeure-dipropylamid 
• 4344-69-8 2-Propyl-valeriansaeure-<3,4-dimethyl-anilid> 
• 22635-29-6 N,N-Dimethyl-di-n-propylessigsaeureamid 
• 2936-12-1 2-Propyl-valeriansaeure-isopropylamid 
• 2936-13-2 2-Propyl-valeriansaeure-butylamid 

Relevant academic research and scientific papers

Incorporation of [3H]valproic acid into lipids in GT1-7 neurons

Valproic acid (2-propylpentanoic acid, valproate, VPA), an 8-carbon, branched chain fatty acid, is effectively used in the treatment of mania and epilepsy. The biochemical mechanisms by which this drug has its therapeutic effects are not yet established. The purpose of this study was to partially characterize the incorporation of [3H]VPA into phospholipids of GT1-7 neurons, an immortalized hypothalamic cell line. GT1-7 neurons were grown to confluence in culture dishes, and then were incubated with various concentrations of [3H]VPA between 10 and 400 μg/mL for various times up to 20 hr. Total lipids were extracted and phospholipids were separated from neutral lipids using TLC. Our results indicate that [3H]VPA (10 μg/mL) was incorporated into phospholipids of GT1-7 neurons in a time-dependent and saturable manner over 300 min. Subsequent separation of the lipid fraction by TLC indicated that 44.4% of the radioactivity taken up by the cells was incorporated into phospholipids and neutral lipids. One of the phospholipids migrated with a slightly lower R(f) value than authentic phosphatidylcholine. Our results show that the incorporation of VPA into phospholipids and glycerides was linear with VPA concentrations from 10 to 400 μg/mL. Finally, we synthesized 1-acyl-2-valproyl-sn-glycero-3-phosphocholine and validated its structure with nuclear magnetic resonance and electrospray mass spectrometry to verify the structure of this compound, confirming that this compound is structurally possible. We conclude that VPA is incorporated into lipids in GT1-7 neurons and discuss the possible effects of valproyl phospholipids on neuronal functional properties. Copyright (C) 1998 Elsevier Science, Inc.

Synthesis and pharmacological activity of two derivatives of the amide of valproic acid

Valproic acid (VPA), a synthetic branched-chain fatty acid, and its pro-drug the primary amide (VPD) are effective and widely used anti-epileptic agents. Although the use of VPA has grown in recent years, major side effects are still associated with this drug. We presume that it is possible, without loosing the VPD pharmacological profile, to obtain new compounds by undertaking substitutions in the CONH group. N,N'-bis-(2-propylpentanoyl)-1,2-ethane-diamine (3) and N,N'-bis-(2-propylpentanoyl)-1,3-propane-diamine (4) were obtained from VPA (1) using a method reported in the literature. The chemical structures of the new compounds were demonstrated by elemental analysis, IR, and 1H NMR spectroscopy. Both compounds are less toxic and more effective in protecting the animals from death caused by PTZ than VPD after intraperitoneal administration to mice.

Novel phosphinic and phosphonic acid analogues of the anticonvulsant valproic acid

1-Propylbutylphosphinic acid 2, (1-propylbutyl)methylphosphinic acid 3 and 1-propylbutylphosphonic acid 4 have been synthesized as bioisosteres of the corresponding carboxylic acid valproate 1, which is a potent anticonvulsant. The novel phosphinic and phosphonic acids were tested for their anticonvulsant activity and were found to be inactive. (C) 2000 Elsevier Science Ltd.

Novel valproic aminophenol amides with enhanced glial cell viability effect

New valproic acid derivatives were synthesized by coupling valproyl chloride with ortho-aminophenols, resulting in seven N-(ortho-hydroxyphenyl)valproamides. These amides share similar structural characteristics and exhibit tuneable electronic and steric contributions either without particular substituents, or through the inclusion of electro-donating (-Me), electro-withdrawing (-NO2) or pi electro-donating/sigma electro-withdrawing (-Cl) substituents at the aromatic ring. The identity of such derivatives was evidenced through spectroscopic characterization using FTIR, 1H, 13C and HETCOR NMR, as well as by analyzing their melting points. In particular, for three derivatives it was feasible to determine their chemical structures in the crystal phase; all three behaved in a similar fashion and exhibited very similar conformations independent of the attached substituents. The base compound was found to exhibit 15.8 times more activity in C6 cells and 4.4 times more activity in U373 cells compared with VPA. In general, the parent compound, or those having-Me as a substituent, presented a greater effect on C6 cells than U373 cells. However, those with-NO2 and-Cl substituents, as well as VPA, required similar doses for the IC50 in both cell lines. Modification of the base compound with a-Me or-NO2 substituent increased the effect on cell viability to ca. 20 times that of VPA in both C6 and U373, indicating that a larger structure causes an important enhancement in the inhibition of cell viability. In both cell lines,-Cl containing derivatives were the most active compounds. For these derivatives, an activity increase of ca. 59 and 47 times that of VPA was observed for C6 and U373 cells, respectively. An important perspective is that VPA analogues possessing an aromatic ring with a-Cl substituent may become central structures in the search for more potent pharmaceutical prototypes.

Practical aspects of cyclic voltammetry: How to estimate reduction potentials when irreversibility prevails

What is the best approach for estimating standard electrochemical potentials, E(0), from voltammograms that exhibit chemical irreversibility? The lifetimes of the oxidized or reduced forms of the majority of known redox species are considerably shorter than the voltammetry acquisition times, resulting in irreversibility and making the answer to this question of outmost importance. Halfwave potentials, E(1/2), provide the best experimentally obtainable representation of E(0). Due to irreversible oxidation or reduction, however, the lack of cathodic or anodic peaks in cyclic voltammograms renders E(1/2) unattainable. Therefore, we evaluate how closely alternative potentials, readily obtainable from irreversible voltammograms, estimate E(0). Our analysis reveals that, when E(1/2) is not available, inflection-point potentials provide the best characterization of redox couples. While peak potentials are the most extensively used descriptor for irreversible systems, they deviate significantly from E(0), especially at high scan rates. Even for partially irreversible systems, when the cathodic peak is not as pronounced as the anodic one, the half-wave potentials still provide the best estimates for E(0). The importance of these findings extends beyond the realm of electrochemistry and impacts fields, such as materials engineering, photonics, cell biology, solar energy engineering and neuroscience, where cyclic voltammetry is a key tool.

N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed in silico with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells

Epigenetic alterations are associated with cancer and their targeting is a promising approach for treatment of this disease. Among current epigenetic drugs, histone deacetylase (HDAC) inhibitors induce changes in gene expression that can lead to cell death in tumors. Valproic acid (VPA) is a HDAC inhibitor that has antitumor activity at mM range. However, it is known that VPA is a hepatotoxic drug. Therefore, the aim of this study was to design a set of VPA derivatives adding the arylamine core of the suberoylanilide hydroxamic acid (SAHA) with different substituents at its carboxyl group. These derivatives were submitted to docking simulations to select the most promising compound. The compound 2 (N-(2-hydroxyphenyl)-2-propylpentanamide) was the best candidate to be synthesized and evaluated in vitro as an anti-cancer agent against HeLa, rhabdomyosarcoma and breast cancer cell lines. Compound 2 showed a better IC50 (μM range) than VPA (mM range) on these cancer cells. And also, 2 was particularly effective on triple negative breast cancer cells. In conclusion, 2 is an example of drugs designed in silico that show biological properties against human cancer difficult to treat as triple negative breast cancer.

Molecular modeling and LC–MS-based metabolomics of a glutamine-valproic acid (Gln-VPA) derivative on HeLa cells

Abstract: Glutaminase plays an important role in carcinogenesis and cancer cell growth. This biological target is interesting against cancer cells. Therefore, in this work, in silico [docking and molecular dynamics (MD) simulations] and in vitro methods (antiproliferative and LC–MS metabolomics) were employed to assay a hybrid compound derived from glutamine and valproic acid (Gln-VPA), which was compared with 6-diazo-5-oxo-l-norleucine (DON, a glutaminase inhibitor) and VPA (contained in Gln-VPA structure). Docking results from some snapshots retrieved from MD simulations show that glutaminase recognized Gln-VPA and DON. Additionally, Gln-VPA showed antiproliferative effects in HeLa cells and inhibited glutaminase activity. Finally, the LC–MS-based metabolomics studies on HeLa cells treated with either Gln-VPA (IC60 = 8?mM) or DON (IC50 = 3.5?mM) show different metabolomics behaviors, suggesting that they modulate different biological targets of the cell death mechanism. In conclusion, Gln-VPA is capable of interfering with more than one pharmacological target of cancer, making it an interesting drug that can be used to avoid multitherapy of classic anticancer drugs. Graphic abstract: [Figure not available: see fulltext.].

PROCESS FOR THE PREPARATION OF EFLORNITHINE DERIVATIVES AND THEIR PHARMACEUTICAL ACCEPTABLE SALTS THEREOF

This invention relates to a process of large scale manufacturing of 2-Amino-2-(difluoromethyl)-5-(2-propylpentanamido) pentanoic acid derivatives and their pharmaceutically acceptable salts, polymorphs, stereoisomers, enantiomers thereof, by two step process. It further discloses the use of 2-Amino-2-(difluoromethyl)-5-(2-propylpentanamido) pentanoic acid derivatives and their pharmaceutically acceptable forms thereof for the treatment of cancer, trypanosomiasis and excessive hair growth.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER

The compositions and compounds of formula I and formula II which includes nucleic acid synthesis inhibitor conjugates or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These conjugates may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for oral administration, intravenous, solution, syrup, sachet, transdermal administration, or injection. Such compositions may be used to treatment of cancer or its associated complications.

Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.