779357-85-6

Usage

Chemical Properties

Off-White Solid

InChI:InChI=1/C15H28BNO2.ClH/c1-9(2)6-13(17)16-18-12-8-10-7-11(14(10,3)4)15(12,5)19-16;/h9-13H,6-8,17H2,1-5H3;1H/t10-,11-,12+,13-,15-;/m0./s1

Upstream product

• 514820-48-5 1,1,1-trimethyl-N-{(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}-N-(trimethylsilyl)silanamine 
• 87304-47-0 2-[(1S)-1-chloro-3-methylbutyl]-(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborole 
• 85167-14-2 (3aS,4S,6S,7aR)-2-[(1S)-1-chloro-3-methylbutyl]-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole 
• 87249-60-3 (3aS,4S,6S,7aR)-2-(dichloromethyl)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole 
• 18680-27-8 pinanediol 
• 84110-34-9 2-(2-methylpropyl)-(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborole 
• 179324-86-8 (1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]butan-1-amine 
• 7785-70-8 (+)-α-pinene 
• 7647-01-0 hydrogenchloride 
• 7785-26-4 (-)-α-pinene 
• 20536-51-0 (+)-α-pinanediol 
• 22422-34-0 (1R,2R,3S,5R)-2,3-pinane diol 
• 1173167-09-3 2-methyl-4-chloro-butylboronic acid-(-)-α-pinanediol ester 
• 29333-10-6 (1S,2R,3R, 5S)-pinanediol 

Downstream Products

• 1613134-42-1 N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-1-{2-[(2,3,4-trimethoxyphenyl)formamido]ethyl}-1H-1,2,3-triazole-4-carboxamide 
• 1564251-60-0 C₃₂H₄₉BN₂O₇ 
• 1564251-59-7 C₃₁H₄₇BN₂O₇ 

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.

Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids

Boronic acids are an increasingly important compound class for many applications, including C-C bond formation reactions, medicinal chemistry, and diagnostics. The deprotection of boronic ester intermediates is frequently a problematic and inefficient step in boronic acid syntheses. We describe an approach that highly facilitates this transformation by leveraging the volatility of methylboronic acid and its diol esters. The method is performed under mild conditions, provides high yields, and eliminates cumbersome and problematic purification steps.

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.

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.

Discovery of novel 20S proteasome inhibitors by rational topology-based scaffold hopping of bortezomib

A series of structurally novel proteasome inhibitors 1–12 have been developed based rational topology-based scaffold hopping of bortezomib. Among these novel proteasome inhibitors, compound 10 represents an important advance due to the comparable proteasome-inhibitory activity (IC50 = 9.7 nM) to bortezomib (IC50 = 8.3 nM), the remarkably higher BEI and SEI values and the effectiveness in metabolic stability. Therefore, compound 10 provides an excellent lead suitable for further optimization.

Boric acid compounds, and preparation method and use thereof

The invention relates to the fields of pharmaceutical chemistry and medicine therapeutics, concretely relates to a new boric acid compounds, and a preparation method and a use thereof, and especially relates to new substituted five-membered heterocyclic boric acid and substituted benzo five-membered boric acid compounds, and a preparation method thereof. A result of bioactive screening test of the substituted five-membered heterocyclic boric acid and substituted benzo five-membered boric acid compounds having a structure represented by a formula shown in the description shows that the compounds have a proteasome inhibition effect, and can be further used for preparing medicines for treating proteasome correlated diseases.

Boric acid compound used as 20S proteasome inhibitor, and preparation method thereof

The invention relates to the fields of pharmaceutical chemistry and medicine therapeutics, concretely relates to new boric acid compounds, and a preparation method and a use thereof, and especially relates to a boric acid compound used as a 20S proteasome inhibitor, and a preparation method thereof. The invention also discloses a boric acid compound represented by formula I, and a preparation method thereof. A result of bioactive screening test shows that the compound prepared in the invention has a proteasome inhibition function, and can be further used for preparing medicines for treating proteasome correlated diseases.

Preparation of (1R)-(S)-pinane diol-1-amino-3-methyl-butane-1-borate and a salt thereof

The invention discloses a method for preparing (1R)-(S)-pinanediol-1-amino-3-methylbutane-1-borate ester and a salt thereof. The method for preparing (1R)-(S)-pinanediol-1-amino-3-methylbutane-1-borate ester comprises step A and step B in the following synthetic route, wherein in the formula, X represents a halogen atom and M represents an alkali metal. (1R)-(S)-pinanediol-1-amino-3-methylbutane-1-borate ester is subjected to a salt forming reaction with an organic acid or an inorganic aid, and an acidic salt of (1R)-(S)-pinanediol-1-amino-3-methylbutane-1-borate ester is obtained. The method of the invention can help to synthesize high-purity bortezomib or other boropeptide compounds in low cost, is accord with industrial production requirements and has practical value.

Proteasome inhibitor delanzomib for use in the treatment of lupus

The present invention provides a method for treating lupus in a subject, comprising the step of administering to the subject Compound A.

PROTEASOME INHIBITORS AND PROCESSES FOR THEIR PREPARATION, PURIFICATION AND USE

The invention provides boronic esters of Formula (I) wherein R1, R2, R3, and R4 are as described herein, and methods for the preparation and purification thereof.