178455-03-3

Usage

Uses

Used in Pharmaceutical Industry:
(R)-BoroPhe-(+)-Pinanediol-HCl is used as a chiral auxiliary in the synthesis of pharmaceuticals for its ability to control stereochemistry, leading to the production of enantiomerically pure compounds. This ensures the desired biological activity and minimizes potential side effects associated with the presence of unwanted enantiomers.
Used in Agrochemical Industry:
(R)-BoroPhe-(+)-Pinanediol-HCl is used as a chiral building block in the development of agrochemicals, such as pesticides and herbicides, with high stereochemical purity. This allows for the creation of more effective and selective agents, reducing the environmental impact and improving crop protection.
Used in Fine Chemicals Industry:
(R)-BoroPhe-(+)-Pinanediol-HCl is utilized as a chiral intermediate in the synthesis of fine chemicals, including fragrances, flavors, and specialty chemicals. Its ability to control stereochemistry ensures the production of high-quality enantiomerically pure compounds with desired properties and applications.
Used in Asymmetric Catalysis:
(R)-BoroPhe-(+)-Pinanediol-HCl is employed as a ligand in asymmetric catalysis, where it helps to control the stereochemistry of the reaction, leading to the formation of enantiomerically enriched products. This is particularly useful in the synthesis of chiral compounds with specific biological activities or desired properties.
Used in Research and Development:
(R)-BoroPhe-(+)-Pinanediol-HCl is used as a research tool in the development of new synthetic methods and strategies for the preparation of chiral compounds. Its unique properties and versatility make it an invaluable asset in the exploration of novel asymmetric reactions and the discovery of new enantioselective catalysts.

Upstream product

• 87100-28-5 pinacol benzylboronate 
• 88824-37-7 (R)-(1-chloro-2-phenylethyl)boronic acid (1R,2R,3S,5R)-(-)-2,3-pinanediol ester 
• 88824-36-6 (-)-pinanediol phenylmethane-1-boronate 
• 100-39-0 benzyl bromide 
• 78922-83-5 (1-phenylmethyl)boronic acid (1S,2S,3R,5S)-(+)-2,3-pinanediol ester 
• 78902-03-1 1-(S)-chloro-2-phenylethylboronic acid (1S,2S,3R,5S)-(+)-pinane-2,3-glycol ester 
• 78902-04-2 (+)-pinanediol (1R)-1-(N,N-bis(trimethylsilyl)amino)-2-phenylethaneboronate 
• 20536-51-0 (+)-α-pinanediol 
• 7785-26-4 (-)-α-pinene 
• 7647-01-0 hydrogenchloride 

Downstream Products

• 1613134-56-7 1-[2-(2-methoxy-4-trifluoromethylbenzoylamino)ethyl]-1H-[1,2,3]triazole-4-carboxylic acid [(R)-2-phenyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0²'⁶]dec-4-yl)ethyl]amide 
• 1613134-49-8 1-[2-(2-fluoro-4-trifluoromethylbenzoylamino)ethyl]-2H-[1,2,3]triazole-4-carboxylic acid [(R)-2-phenyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0²'⁶]dec-4-yl)ethyl]amide 
• 1613134-43-2 1-[2-(2,3,4-trimethoxybenzoylamino)ethyl]-1H-[1,2,3]triazole-4-carboxylic acid [(R)-2-phenyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]dec-4-yl)ethyl]amide 

Relevant academic research and scientific papers

Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (β5i)

Proteasomes are broadly expressed key components of the ubiquitin-dependent protein degradation pathway containing catalytically active subunits (β1, β2, and β5). LMP7 (β5i) is a subunit of the immunoproteasome, an inducible isoform that is predominantly expressed in hematopoietic cells. Clinically effective pan-proteasome inhibitors for the treatment of multiple myeloma (MM) nonselectively target LMP7 and other subunits of the constitutive proteasome and immunoproteasome with comparable potency, which can limit the therapeutic applicability of these drugs. Here, we describe the discovery and structure-based hit optimization of novel amido boronic acids, which selectively inhibit LMP7 while sparing all other subunits. The exploitation of structural differences between the proteasome subunits culminated in the identification of the highly potent, exquisitely selective, and orally available LMP7 inhibitor 50 (M3258). Based on the strong antitumor activity observed with M3258 in MM models and a favorable preclinical data package, a phase I clinical trial was initiated in relapsed/refractory MM patients.

Boronic acid derivatives

The present invention relates to boronic acid derivatives; the present invention provides compounds of formula (I) or pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof, pharmaceutical compositions comprising these compounds, and u

Mercapto-amide boronic acid derivative and application thereof as MBL (metal beta-lactamase) and/or SBL (serine beta-lactamase) inhibitor

The invention provides a compound of a formula (I) shown in the specification, or a conformational isomer, or an optical isomer or a pharmaceutically acceptable salt thereof. The compound of the formula (I) shown in the specification has excellent broad-spectrum inhibitory activity on MBL (metal beta-lactamase) and/or SBL (serine beta-lactamase), and can be used for preparing MBL and/or SBL inhibitors. Moreover, the compound disclosed by the invention has excellent antibacterial activity on multiple drug-resistant bacteria and is capable of reversing drug resistance of carbapenem drug-resistant bacteria, and the antibacterial effect of the compound is prior to those of positive control products such as L-captopril and tazobactam. The compound disclosed by the invention has very great potential in preparation of MBL/SBL dual inhibitors and medicines reversing drug resistance of carbapenem drug-resistance bacteria.

Structure-based development of (1-(3′-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- And Serine-β-lactamases

The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.

Synthesis, in vitro and in vivo biological evaluation, and comprehensive understanding of structure-activity relationships of dipeptidyl boronic acid proteasome inhibitors constructed from β-amino acids

An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed fromβ -amino acids is reported. SAR analysis revealed that bicyclic groups at the R1 position, 3-F substituents at the Rsu

Synthesis, in vitro and in vivo biological evaluation, docking studies, and structure-activity relationship (SAR) discussion of dipeptidyl boronic acid proteasome inhibitors composed of β-amino acids

A series of novel dipeptidyl boronic acid proteasome inhibitors composed of β-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i was the most active. The IC50 value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active as the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC50 values nearly less than 5 μM against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in a similar way as bortezomib.

Design, synthesis, biological evaluation, and Structure-Activity Relationship (SAR) discussion of dipeptidyl boronate proteasome inhibitors, Part I: Comprehensive understanding of the SAR of α-amino acid boronates

New series of dipeptidyl boronate inhibitors of 20S proteasome were designed and synthesized. The comprehensive understanding of the SAR was obtained by utilizing the variation of four substituents. From the screened compounds in enzyme, novel inhibitors 49 and 50 were identified to be highly potent druglike candidates with IC50 values of 1.2 and 1.6 nM, respectively, which showed better activities than the drug bortezomib on the market. Two hematologic human tumor cell lines, HL-60 and U266, were significantly sensitive to both candidates and showed nearly the same potency as the standard bortezomib with IC50 values less than 10 nM. But as for most of the eight human solid tumor cell lines, both candidates were more potent than the standard with the IC50 value range of 9.8-70 nM. The activity evaluation of the stereoisomers showed that changing R-isomers to S-isomers greatly reduced the potency and even induced inactivity.