14617-29-9

Upstream product

• 209528-69-8 methyl 3-(benzyloxy)-4-nitrobenzoate 
• 403-21-4 3-fluoro-4-nitrobenzoic acid 
• 100-51-6 benzyl alcohol 
• 713-52-0 methyl 3-hydroxy-4-nitrobenzoate 
• 100-39-0 benzyl bromide 

Downstream Products

• 228707-86-6 3-benzyloxy-4-nitro-N-(2-sulfamoylphenyl)benzamide 
• 1006030-88-1 methyl 3-propoxy-4-(3-benzyloxy-4-nitro-benzoylamino)-benzoate 
• 1006031-14-6 methyl 3-isopropoxy-4-(3-isopropoxy-4-(3-benzyloxy-4-nitro-benzoylamino)-benzoylamino)-benzoate 
• 1006031-15-7 methyl 3-isopropoxy-4-(3-propoxy-4-(3-benzyloxy-4-nitro-benzoylamino)-benzoylamino)-benzoate 
• 1006030-97-2 methyl 3-isopropoxy-4-(3-(2-naphthylmethoxy)-4-(3-benzyloxy-4-nitro-benzoylamino)-benzoylamino)-benzoate 
• 1006030-86-9 methyl 3-isopropoxy-4-(3-benzyloxy-4-nitro-benzoylamino)-benzoate 
• 1147133-76-3 C₂₇H₂₈N₂O₆ 
• 1379520-51-0 methyl 3-(benzyloxy)-4-(3-benzyloxy-4-nitrobenzamido)-benzoate 
• 14617-30-2 3-(benzyloxy)-4-nitrobenzoyl chloride 

Relevant academic research and scientific papers

Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors

ATP-competitive inhibitors of DNA gyrase and topoisomerase IV are among the most interesting classes of antibacterial drugs that are unrepresented in the antibacterial pipeline. We developed 32 new N-phenylpyrrolamides and evaluated them against DNA gyrase and topoisomerase IV from E. coli and Staphylococcus aureus. Antibacterial activities were studied against Gram-positive and Gram-negative bacterial strains. The most potent compound displayed an IC50 of 47 nm against E. coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12.5 μm against the Gram-positive Enterococcus faecalis. Some compounds displayed good antibacterial activities against an efflux-pump-deficient E. coli strain (MIC=6.25 μm) and against wild-type E. coli in the presence of efflux pump inhibitor PAβN (MIC=3.13 μm). Here we describe new findings regarding the structure–activity relationships of N-phenylpyrrolamide DNA gyrase B inhibitors and investigate the factors that are important for the antibacterial activity of this class of compounds.

BCL-2 INHIBITORS AND THEIR USE AS PHARMACEUTICALS

The disclosure is directed to, in part, to BCL-2 inhibitors, pharmaceutical compositions comprising the same, as well as methods of their use and preparation.

COMPOUNDS, COMPOSITIONS AND METHODS FOR STABILIZING TRANSTHYRETIN AND INHIBITING TRANSTHYRETIN MISFOLDING

Provided herein are compounds having activity against TTR related conditions, and pharmaceutically accepted salts and solvates thereof. Also provided are methods of using the compounds for inhibiting and preventing TTR aggregation and/or amyloid formation in the peripheral nerves, kidney, cardiac tissue, eye and CNS, and of treating a subject with peripheral TTR amyloidosis.

Design, Synthesis, and Conformational Analysis of Oligobenzanilides as Multifacial α-Helix Mimetics

The design, synthesis, and conformational analysis of an oligobenzanilide helix mimetic scaffold capable of simultaneous mimicry of two faces of an α-helix is reported. The synthetic methodology provides access to diverse monomer building blocks amenable to solid-phase assembly in just four synthetic steps. The conformational flexibility of model dimers was investigated using a combination of solid and solution state methodologies supplemented with DFT calculations. The lack of noncovalent constraints allows for significant conformational plasticity in the scaffold, thus permitting it to successfully mimic residues i, i+2, i+4, i+6, i+7, and i+9 of a canonical α-helix.

Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly wiTheR and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers.

Perturbation of the c-Myc-Max Protein-Protein Interaction via Synthetic α-Helix Mimetics

The rational design of inhibitors of the bHLH-ZIP oncoprotein c-Myc is hampered by a lack of structure in its monomeric state. We describe herein the design of novel, low-molecular-weight, synthetic α-helix mimetics that recognize helical c-Myc in its transcriptionally active coiled-coil structure in association with its obligate bHLH-ZIP partner Max. These compounds perturb the heterodimer's binding to its canonical E-box DNA sequence without causing protein-protein dissociation, heralding a new mechanistic class of "direct" c-Myc inhibitors. In addition to electrophoretic mobility shift assays, this model was corroborated by further biophysical methods, including NMR spectroscopy and surface plasmon resonance. Several compounds demonstrated a 2-fold or greater selectivity for c-Myc-Max heterodimers over Max-Max homodimers with IC50 values as low as 5.6 μM. Finally, these compounds inhibited the proliferation of c-Myc-expressing cell lines in a concentration-dependent manner that correlated with the loss of expression of a c-Myc-dependent reporter plasmid despite the fact that c-Myc-Max heterodimers remained intact. (Chemical Equation Presented).

GLP-1 receptor agonist compounds having stabilized regions

The disclosure provides GLP-1 receptor agonist compounds having stabilized regions corresponding to alpha-helical regions of the natural peptide compounds. The disclosure also provides benzamide-containing exendin-4 analogs and alkene-constrained exendin-4 analogs, both of which have stabilized regions corresponding to alpha-helical regions of exendin-4.

BRD4 Structure-Activity Relationships of Dual PLK1 Kinase/BRD4 Bromodomain Inhibitor BI-2536

A focused library of analogues of the dual PLK1 kinase/BRD4 bromodomain inhibitor BI-2536 was prepared and then analyzed for BRD4 and PLK1 inhibitory activities. Particularly, replacement of the cyclopentyl group with a 3-bromobenzyl moiety afforded the most potent BRD4 inhibitor of the series (39j) with a Ki = 8.7 nM, which was equipotent against PLK1. The superior affinity of 39j over the parental compound to BRD4 possibly derives from improved interactions with the WPF shelf. Meanwhile, substitution of the pyrimidine NH with an oxygen atom reversed the PLK1/BRD4 selectivity to convert BI-2536 into a BRD4-selective inhibitor, likely owing to the loss of a critical hydrogen bond in PLK1. We believe further fine-tuning will furnish a BRD4 "magic bullet" or an even more potent PLK1/BRD4 dual inhibitor toward the expansion and improved efficacy of the chemotherapy arsenal.

Conformational properties of O-alkylated benzamides

In this article, we report the synthesis, solid-state and solution-state conformational studies of O-alkylated aromatic benzamides based on two scaffolds. Intramolecular hydrogen bonding provides conformational pre-organization and side chains can interact with each other within a molecule. In the solid-state three-dimensional arrangement, the molecules further interact with each other through non-covalent interactions. Given, the demonstrated potential of this class of scaffolds to act as helix mimetics for the inhibition of protein-protein interactions (PPIs), these results provide key insight for future inhibitor design.

2-O-Alkylated para-benzamide α-helix mimetics: The role of scaffold curvature

The design and synthesis of a new 2-O-alklyated benzamide α-helix mimetic is described. Comparison with regioisomeric 3-O-alkylated benzamides permits a preliminary evaluation of the role that mimetic curvature has in determining molecular recognition properties.