137107-28-9

Upstream product

• 524-38-9 N-hydroxyphthalimide 
• 823-78-9 meta-bromobenzyl bromide 
• 591-17-3 meta-bromotoluene 
• 3132-99-8 m-bromobenzoic aldehyde 
• 15852-73-0 (3-Bromophenyl)methanol 

Downstream Products

• 159023-41-3 O-(3-bromobenzyl)hydroxylamine hydrochloride 
• 83670-46-6 O-(3-bromobenzyl)hydroxylamine 

Relevant academic research and scientific papers

O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.

NBu4NI-catalyzed intermolecular C-O cross-coupling reactions: Synthesis of alkyloxyamines

A practical and simple nBu4NI-catalyzed C-O bond formation for the synthesis of alkyloxyamines was achieved under metal-free conditions. The reaction is applicable to the coupling of a range of benzylic and allylic hydrocarbons with N-hydroxyphthalimide and is tolerant of various functional groups. The reaction mechanism was primarily investigated and a radical process was proposed.

4-Alkyloxyimino-cytosine nucleotides: Tethering approaches to molecular probes for the P2Y6 receptor

4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N4 and γ-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y6R potency generally better than γ-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y6R expressed in 1321N1 human astrocytoma cells with an EC50 of 9 nM, and exhibited high selectivity for this receptor over other uridine nucleotide-activated P2Y receptors. Flow cytometry detected specific labeling with 16 to P2Y 6R-expressing but not to wild-type 1321N1 cells. Additionally, confocal microscopy indicated both internalized 16 (t1/2 of 18 min) and surface-bound fluorescence. Known P2Y6R ligands inhibited labeling. Theoretical docking of 16 to a homology model of the P2Y6R predicted electrostatic interactions between the fluorophore and extracellular portion of TM3. Thus, we have identified the N4-benzyloxy group as a structurally permissive site for synthesis of functionalized congeners leading to high affinity molecular probes for studying the P2Y6R.