289472-81-7

Basic information

• Product Name: N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide
• Synonyms: N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide;2-PyrazinecarboxaMide, N-[(1S)-2-[[(1S)-1-hydroxy-3-Methylbutyl]aMino]-2-oxo-1-(phenylMethyl)ethyl]-;(S)-Hydroxy Des(boric Acid) BortezoMib;(N-[(1S)-1-hydroxy-3-Methylbutyl]-Nα-(pyrazin-2-ylcarbonyl)-L-phenylalaninaMide;Bortezomib Impurity D;Bortezomib USP Related Compoud J;N-[(1S)-2-[[(1S)-1-hydroxy-3-methylbutyl]amino]-2-oxo-1-(phenylmethyl)ethyl]-2-Pyrazinecarboxamide;N-[(1S)-2-[[(1S)-1-hydroxy-3-methylbutyl]amino]-2-oxo-1-(phenylmethyl)ethyl]-pyrazi
• CAS NO: 289472-81-7
• Molecular Formula: C19H24N4O3
• Molecular Weight: 356.41886
• Product Categories: Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 289472-81-7.mol

Chemical Properties

• Boiling Point: 672.0±55.0 °C(Predicted)
• Appearance: /
• Density: 1.199±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 11.90±0.46(Predicted)
• CAS DataBase Reference: N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide(CAS DataBase Reference)
• NIST Chemistry Reference: N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide(289472-81-7)
• EPA Substance Registry System: N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide(289472-81-7)

Safety Data

• Hazardous Substances Data: 289472-81-7(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Industry:
N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide is used as an impurity in the synthesis of Bortezomib (B675700), a first-in-class proteasome inhibitor approved by the US FDA for the treatment of multiple myeloma, a type of blood cancer. Its role in the synthesis process is crucial for the development of this groundbreaking drug.
2. Used in Cancer Treatment:
As a component in the synthesis of Bortezomib, N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide contributes to the development of a drug that targets the ubiquitin-proteasome pathway, a critical cellular process involved in the regulation of protein homeostasis. By inhibiting the 26S proteasome, Bortezomib disrupts the balance of protein synthesis and degradation, leading to the accumulation of misfolded proteins and ultimately inducing cell death in cancer cells.
3. Used in Drug Development Research:
The unique molecular structure of N-((S)-1-(((S)-1-Hydroxy-3-Methylbutyl)aMino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxaMide may also make it a valuable compound for further research in drug development. Its chiral centers and functional groups could potentially be exploited to design new drugs with improved efficacy and selectivity, targeting various diseases and conditions.

Upstream product

• 179324-69-7 velcade 
• 289472-78-2 Pyrazine-2-carboxylic acid [(S)-1-((R)-1-hydroxy-3-methyl-butylcarbamoyl)-2-phenyl-ethyl]-amide 

Downstream Products

• 289472-80-6 Pyrazine-2-carboxylic acid ((S)-1-carbamoyl-2-phenyl-ethyl)-amide 

Relevant articles and documents

Stress degradation study of bortezomib: Effect of co-solvent, isolation and characterization of degradation products by UHPLC-Q-TOF-MS/MS and NMR and evaluation of the toxicity of the degradation products

Bortezomib (BTZ) is a first-in-class, potent reversible inhibitor of proteasome used in the treatment of multiple myeloma, the second most common hematological cancer. Stress degradation studies were performed to investigate the inherent stability of the drug according to ICH recommended guidelines Q1A (R2). Stress experiments were carried out in two ways using acetonitrile and methanol as co-solvents under various conditions. A selective stability-indicating LC-MS method has been developed to separate all degradation products of the drug on a Hibar-Purospher STAR, C18 (250 × 4.6 mm, 5 μm) column using a mobile phase consisting of 0.1% formic acid and acetonitrile in the gradient mode. BTZ was found to undergo degradation under acidic, basic, neutral hydrolysis and oxidative conditions, whereas it was stable under other conditions. Thirteen degradation products (DP-1-DP-13) were identified using acetonitrile as a co-solvent. Additionally, three (DP-14-DP-16) degradation products were found where methanol was used as a co-solvent. A total of 16 (DP-1-DP-16) degradation products were characterized by liquid chromatography-tandem mass spectrometry (LC-ESI-Q-TOF/MS/MS) and high-resolution mass spectrometry (HRMS). Major degradation products, DP-3, DP-6, DP-9, DP-10, DP-11 and DP-12, formed under oxidation conditions were isolated using preparative HPLC and characterized by 1D and 2D NMR experiments. Furthermore, in vitro cytotoxicity of isolated DPs was tested on normal cell lines such as CHO-K1, HEK-293 and NRK-49F by MTT assays. This study revealed that they were around 2-6 times less toxic as compared with the standard control of the drug and DP-10 showed relatively more toxicity than other isolated DPs against rat kidney cells at 18.20 μM. In silico toxicity studies suggested that BTZ and its DPs can be hepatotoxic and genotoxic resulting in severe toxicity.

Degradation pathways of a peptide boronic acid derivative, 2-Pyz-(CO)-Phe-Leu-B(OH)2

The peptide boronic acid derivative 2-Pyz-(CO)-Phe-Leu-B(OH)2 is a potent inhibitor of 20S proteasome and a proposed anticancer agent. During preformulation studies, the compound presented erratic stability behavior. Efforts were made to isolate and identify the degradation products, thereby helping to identify possible mechanisms for the degradation. The reaction of 2-Pyz-(CO)-Phe-Leu-B(OH)2 with hydrogen peroxide not only provided a convenient way to isolate the initial degradation products seen from hydrolysis in aqueous buffers but also showed that the major, initial degradation pathway was probably oxidative in nature. The isolated degradation products were characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, and optical rotation dispersion. In the presence of hydrogen peroxide, the boronic acid group was cleaved from 2-Pyz-(CO)-Phe-Leu-B(OH)2 to give an alcohol with an apparent retention of the original stereochemistry. Subsequent isomerization and further hydrolysis were then seen. Surprisingly, added ascorbate and EDTA accelerated rather than inhibited degradation. Degradation of 2-Pyz-(CO)-Phe-Leu-B(OH)2 under acidic and basic conditions seemed to be mediated by an initial oxidative degradation pathway similar to that seen with the peroxide. (C) 2000 Wiley-Liss, Inc.