1608986-16-8

Basic information

• Product Name: (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid
• Synonyms: (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid;Bortezomib (2R)-Acid
• CAS NO: 1608986-16-8
• Molecular Formula: C14H14N3O3
• Molecular Weight: 272.27926
• Mol File: 1608986-16-8.mol
• Article Data: 27

Chemical Properties

• Appearance: /
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid(1608986-16-8)
• EPA Substance Registry System: (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid(1608986-16-8)

Safety Data

• Hazardous Substances Data: 1608986-16-8(Hazardous Substances Data)

Usage

Description

(R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid, also known as N-(2-Pyrazinylcarbonyl)-D-phenylalanine, is a chiral compound derived from L-phenylalanine through a series of chemical reactions involving dipeptidyl boronic acid ester intermediates. It is characterized by its unique molecular structure, which features a phenyl group and a pyrazine-2-carboxamido group attached to a chiral carbon center.

Uses

Used in Pharmaceutical Industry:
(R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid is used as a starting intermediate for the synthesis of Bortezomib (B675700), a potent proteasome inhibitor. Bortezomib is a therapeutic agent that targets the ubiquitin-proteasome pathway, which plays a crucial role in the regulation of cellular processes such as cell cycle progression, apoptosis, and immune responses. By inhibiting this pathway, Bortezomib exhibits anti-cancer properties and is particularly effective against multiple myeloma and other malignancies.
In the synthesis of Bortezomib, (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid serves as a key building block, providing the necessary structural elements for the final drug molecule. Its chiral nature is essential for the biological activity of Bortezomib, as the (R)-enantiomer is the active form responsible for the proteasome inhibition.
Furthermore, the development of (R)-3-phenyl-2-(pyrazine-2-carboxaMido)propanoic acid as a starting intermediate for Bortezomib synthesis highlights its potential in the field of medicinal chemistry. Its unique structure and reactivity make it a valuable compound for the design and synthesis of novel therapeutic agents targeting various diseases, including cancer.

Upstream product

• 179324-69-7 velcade 
• 73058-37-4 N-(2-pyrazinylcarbonyl)-L-phenylalanine methyl ester 
• 98-97-5 2-pyrazylcarboxylic acid 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 16480-57-2 L-phenylalanine sodium salt 
• 7364-51-4 N,O-bis(trimethylsilyl)phenylalanine 
• 103435-88-7 pyrazinecarboxylic acid imidazolide 
• 19847-10-0 pyrazinoyl chloride 
• 63-91-2 L-phenylalanine 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 18414-58-9 diphenylmethylsilanecarboxylic acid 
• 32111-21-0 2-iodopyrazine 
• 15100-75-1 L-phenylalanine tert-butyl ester hydrochloride 
• 306990-94-3 (1H-benzo[d][1,2,3]triazol-1-yl)(pyrazin-2-yl)methanone 

Downstream Products

• 1621908-72-2 N-[(1S)-1-[[[(1R)-1-[(3aS,4R,6R,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborol-2-yl]-3-methylbutyl]-amino]carbonyl]-2-phenyl]-2-pyrazincarboxamide 
• 1194235-41-0 N-(2-pyrazinecarbonyl)-L-phenylalanine-L-phenylalanine-L-leucineboronic acid 
• 1194235-25-0 N-(2-pyrazinecarbonyl)-L-phenylalanine-L-leucine 
• 1132709-14-8 [(1S)-1-[[(2S)-3-phenyl-2-[(pyrazine-2-carbonyl)amino]-1-oxopropyl]amino]-3-methylbutyl]boronic acid 
• 1132709-16-0 bortezomib 

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.

Structure-Based Design of Selective LONP1 Inhibitors for Probing in Vitro Biology

LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression of LONP1 promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Despite the importance of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Our efforts led to several nanomolar LONP1 inhibitors with little to no activity against the 20S proteasome that serve as tool compounds to investigate LONP1 biology.

PYRAZINOIC ACID CONJUGATES AND HYBRID CONJUGATES

Pyrazinamide (PZA) conjugates and hybrids are provided herein. The PZA conjugates are useful for treating bacterial infections. In one embodiment, the PZA conjugates are useful for treating tuberculosis.