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

• 73058-37-4 N-(2-pyrazinylcarbonyl)-L-phenylalanine methyl ester 
• 19847-10-0 pyrazinoyl chloride 
• 63-91-2 L-phenylalanine 
• 673-06-3 D-(R)-phenylalanine 
• 306990-94-3 (1H-benzo[d][1,2,3]triazol-1-yl)(pyrazin-2-yl)methanone 
• 98-97-5 2-pyrazylcarboxylic acid 
• 3081-28-5 D-phenylalanine tert-butyl ester 
• 179324-69-7 velcade 
• 150-30-1 Phenylalanine 
• 16874-17-2 L-phenylalanine tert-butyl ester 
• 18934-70-8 2-amino-3-phenyl-propionic acid isopropyl ester 
• 15100-75-1 L-phenylalanine tert-butyl ester hydrochloride 
• 18414-58-9 diphenylmethylsilanecarboxylic acid 
• 32111-21-0 2-iodopyrazine 

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 
• 1194235-25-0 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 
• 1194235-41-0 N-(2-pyrazinecarbonyl)-L-phenylalanine-L-phenylalanine-L-leucineboronic acid 

Relevant articles and documents

Development of peptidomimetic hydroxamates as PfA-M1 and PfA-M17 dual inhibitors: Biological evaluation and structural characterization by cocrystallization

Plasmodium parasites causing malaria have developed resistance to most of the antimalarials in use, including the artemisinin-based combinations, which are the last line of defense against malaria. This necessitates the discovery of new targets and the development of novel antimalarials. Plasmodium falciparum alanyl aminopeptidase (PfA-M1) and leucyl aminopeptidase (PfA-M17) belong to the M1 and M17 family of metalloproteases respectively and play critical roles in the asexual erythrocytic stage of development. These enzymes have been suggested as potential antimalarial drug targets. Herein we describe the development of peptidomimetic hydroxamates as PfA-M1 and PfA-M17 dual inhibitors. Most of the compounds described in this study display inhibition at sub-micromolar range against the recombinant PfA-M1 and PfA-M17. More importantly, compound 26 not only exhibits potent malarial aminopeptidases inhibitory activities (PfA-M1 Ki = 0.11 ± 0.0002 μmol/L, PfA-M17 Ki = 0.05 ± 0.005 μmol/L), but also possesses remarkable selectivity over the mammalian counterpart (pAPN Ki = 17.24 ± 0.08 μmol/L), which endows 26 with strong inhibition of the malarial parasite growth and negligible cytotoxicity on human cell lines. Crystal structures of PfA-M1 at atomic resolution in complex with four different compounds including compound 26 establish the structural basis for their inhibitory activities. Notably, the terminal ureidobenzyl group of 26 explores the S2′ region where differences between the malarial and mammalian enzymes are apparent, which rationalizes the selectivity of 26. Together, our data provide important insights for the rational and structure-based design of selective and dual inhibitors of malarial aminopeptidases that will likely lead to novel chemotherapeutics for the treatment of malaria.

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.

Design and synthesis of tripeptidyl furylketones as selective inhibitors against the β5 subunit of human 20S proteasome

A series of tripeptidic proteasome inhibitors with furylketone as C-terminus were designed and synthesized. Biochemical evaluations against β1, β2 and β5 subunits revealed that they acted selectively on β5 subunit with IC50s against chymotrypsin-like (CT-L) activity in micromolar range. LC-MS/MS analysis of the ligand-20S proteasome mixture showed that the most potent compound 11m (IC50 = 0.18 μM) made no covalent modification on 20S proteasome. However, it was identified acting in a slowly reversible manner in wash-out assay and the reversibility was much lower than that of MG132, suggesting the possibility of these tripeptidic furylketones forming reversible covalent bonds with 20S proteasome. Several compounds were selected for anti-proliferative assay towards multiple cancer cell lines, and compound 11m displayed comparable potency to positive control (MG132) in all cell lines tested. Furthermore, the pharmacokinetic (PK) data in rats indicated 11m behaved similarly (Cmax, 2007 μg/L; AUC0?t, 680 μg/L·h; Vss, 0.66 L/kg) to the clinical used agent carfilzomib. All these data suggest 11m is a good lead compound to be developed to novel anti-tumor agent.