1173167-10-6

Basic information

• Product Name: (1S)-1-chloro-2-(4-methylbenzyl)boronic acid (+)-pinanediol ester
• Synonyms: (1S)-1-chloro-2-(4-methylbenzyl)boronic acid (+)-pinanediol ester
• CAS NO: 1173167-10-6
• Molecular Weight: 332.678
• Mol File: 1173167-10-6.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: (1S)-1-chloro-2-(4-methylbenzyl)boronic acid (+)-pinanediol ester(CAS DataBase Reference)
• NIST Chemistry Reference: (1S)-1-chloro-2-(4-methylbenzyl)boronic acid (+)-pinanediol ester(1173167-10-6)
• EPA Substance Registry System: (1S)-1-chloro-2-(4-methylbenzyl)boronic acid (+)-pinanediol ester(1173167-10-6)

Safety Data

• Hazardous Substances Data: 1173167-10-6(Hazardous Substances Data)

Upstream product

• 89980-67-6 p-methylbenzylmagnesium bromide 
• 87249-60-3 (3aS,4S,6S,7aR)-2-(dichloromethyl)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole 
• 356570-52-0 4,4,5,5-tetramethyl-2-[(4-methylphenyl)methyl]-1,3,2-dioxaborolane 
• 75-09-2 dichloromethane 
• 104-81-4 4-Methylbenzyl bromide 

Relevant articles and documents

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

Compounds of formula (I) are inhibitors of LMP7 and can be employed, inter alia, for the treatment of an autoimmue disorder abnomality or hematological malignancies.

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.