73391-96-5

Usage

InChI:InChI=1/C10H12BrNO/c1-12(10(13)7-11)8-9-5-3-2-4-6-9/h2-6H,7-8H2,1H3

Upstream product

• 598-21-0 2-Bromoacetyl bromide 
• 103-67-3 benzyl-methyl-amine 

Downstream Products

• 1337537-45-7 N-benzyl-N-methyl-2-(4-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-1-yl)acetamide 
• 1013663-31-4 2-azido-N-benzyl-N-methylacetamide 
• 1181671-91-9 N-benzyl-N-methyl-2-(phenylamino)acetamide 
• 1394816-82-0 N-benzyl-N-methyl-2-dipropylaminoacetamide 
• 1394816-81-9 N-benzyl-N-methyl-2-dibenzylaminoacetamide 
• 1394816-80-8 N-benzyl-N-methyl-2-(benzylphenylamino)acetamide 
• 1394816-79-5 N-benzyl-N-methyl-2-[(4-nitrophenyl)methylamino]acetamide 
• 1394816-78-4 N-benzyl-N-methyl-2-[(4-chlorophenyl)methylamino]acetamide 

Relevant academic research and scientific papers

Acceleration of 1,3-Dipolar Cycloadditions by Integration of Strain and Electronic Tuning

The 1,3-dipolar cycloaddition between azides and alkynes provides new means to probe and control biological processes. A major challenge is to achieve high reaction rates with stable reagents. The optimization of alkynyl reagents has relied on two strateg

Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with PotentIn VitroAntiproliferative Activity

Heme oxygenase-1 (HO-1) promotes heme catabolism exercising cytoprotective roles in normal and cancer cells. Herein, we report the design, synthesis, molecular modeling, and biological evaluation of novel HO-1 inhibitors. Specifically, an amide linker in the central spacer and an imidazole were fixed, and the hydrophobic moiety required by the pharmacophore was largely modified. In many tumors, overexpression of HO-1 correlates with poor prognosis and chemoresistance, suggesting the inhibition of HO-1 as a possible antitumor strategy. Accordingly, compounds7iand7l-pemerged for their potency against HO-1 and were investigated for their anticancer activity against prostate (DU145), lung (A549), and glioblastoma (U87MG, A172) cancer cells. The selected compounds showed the best activity toward U87MG cells. Compound7lwas further investigated for its in-cell enzymatic HO-1 activity, expression levels, and effects on cell invasion and vascular endothelial growth factor (VEGF) extracellular release. The obtained data suggest that7lcan reduce cell invasivity acting through modulation of HO-1 expression.

Hydantoin analogs inhibit the fully assembled ClpXP protease without affecting the individual peptidase and chaperone domains

Proteolysis mediated by ClpXP is a crucial cellular process linked to bacterial pathogenesis. The development of specific inhibitors has largely focused on ClpP. However, this focus was challenged by a recent finding showing that conformational control by ClpX leads to a rejection of ClpP binders. Thus, we here follow up on a hit molecule from a high throughput screen performed against the whole ClpXP complex and demonstrate that stable inhibition with high potency is possible. Further investigations revealed that the small molecule binds to ClpP without affecting its activity. Likewise, the molecule does not inhibit ClpX and retains the overall oligomeric state of ClpXP upon binding. Structure activity relationship studies confirmed structural constraints in all three parts of the molecule suggesting binding into a defined stereospecific pocket. Overall, the inhibition of ClpXP without affecting the individual components represents a novel mechanism with perspectives for further optimization for in situ applications.

Catalytic Enantioselective Intramolecular C(sp3)?H Amination of 2-Azidoacetamides

An enantioselective ring-closing C(sp3)?H amination of 2-azidoacetamides is catalyzed by a chiral-at-metal ruthenium complex and provides chiral imidazolidin-4-ones in 31–95 % yield, with enantioselectivities of up to 95 % ee, and at catalyst loadings down to 0.1 mol % (turnover number (TON)=740). To our knowledge, this is the first example of a highly enantioselective C(sp3)?H amination with aliphatic azides. Mechanistic experiments reveal the importance of the amide group, which presumably enables initial bidentate coordination of the 2-azidoacetamides to the catalyst. DFT calculations show that the transition state leading to the major enantiomer features a better steric fit and favorable π–π stacking between the substrate and the catalyst framework.

Highly stereoselective intramolecular Buchner reaction of diazoacetamides catalyzed by a Ru(ii)-Pheox complex

This work reports the first efficient enantioselective intramolecular Buchner reaction of diazoacetamides. The Ru(ii)-Pheox catalyst was shown to be highly efficient in this transformation in terms of both the regio-and enantioselectivity (up to 99% ee) giving the desired products in quantitative yield.

Novel Multitarget-Directed Ligands Aiming at Symptoms and Causes of Alzheimer's Disease

Alzheimer's disease (AD) is a major public health problem, which is due to its increasing prevalence and lack of effective therapy or diagnostics. The complexity of the AD pathomechanism requires complex treatment, e.g. multifunctional ligands targeting both the causes and symptoms of the disease. Here, we present new multitarget-directed ligands combining pharmacophore fragments that provide a blockade of serotonin 5-HT6 receptors, acetyl/butyrylcholinesterase inhibition, and amyloid β antiaggregation activity. Compound 12 has displayed balanced activity as an antagonist of 5-HT6 receptors (Ki = 18 nM) and noncompetitive inhibitor of cholinesterases (IC50hAChE = 14 nM, IC50eqBuChE = 22 nM). In further in vitro studies, compound 12 has shown amyloid β antiaggregation activity (IC50 = 1.27 μM) and ability to permeate through the blood-brain barrier. The presented findings may provide an excellent starting point for further studies and facilitate efforts to develop new effective anti-AD therapy.

Synthesis and invitro Evaluation of West Nile Virus Protease Inhibitors Based on the 2-{6-[2-(5-Phenyl-4H-{1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide Scaffold

In recent years, clinical symptoms resulting from West Nile virus (WNV) infection have worsened in severity, with an increased frequency in neuroinvasive diseases among the elderly. As there are presently no successful therapies against WNV for use in humans, continual efforts to develop new chemotherapeutics against this virus are highly desired. The viral NS2B-NS3 protease is a promising target for viral inhibition due to its importance in viral replication and its unique substrate preference. In this study, a WNV NS2B-NS3 protease inhibitor with a 2-{6-[2-(5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide scaffold was identified during screening. Optimization of this initial hit by synthesis and screening of a focused compound library with this scaffold led to the identification of a novel uncompetitive inhibitor (1a24, IC50=3.4±0.2μM) of the WNV NS2B-NS3 protease. Molecular docking of 1a24 into the WNV protease showed that the compound interferes with productive interactions of the NS2B cofactor with the NS3 protease and is an allosteric inhibitor of the WNV NS3 protease.

α-Aminoamides as ligands in Goldberg amidations

α-Aminoamides are shown to be useful as ligands in Goldberg amidations. A number of α-aminoamides are examined and the importance of substitution on the α-aminoamides is explored. Acetamide is focused on as the nucleophilic coupling partner due to its low cost, stability and convenience as a protecting group. The initial substrate scope for these catalysts is explored and includes electronically activated and deactivated aryl bromides, however o-substituted aryl bromides are problematic.

Ru(II)-Pheox catalyzed N-H insertion reaction of diazoacetamides: Synthesis of N-substituted α-aminoamides

An efficient protocol for the preparation of α-aminoamides was developed via the Ru(II)-dm-Pheox catalyzed N-H insertion reaction of various diazoacetamides with several amines, including aniline. This catalytic N-H insertion reaction was also applied to the synthesis of 2-(2-methylquinolin-4- ylamino)-N-phenylacetamide, a potential antileishmanial agent.

Synthesis and structure-activity relationship studies in translocator protein ligands based on a pyrazolo[3,4-b]quinoline scaffold

As a further development of our large program focused on the medicinal chemistry of translocator protein [TSPO (18 kDa)] ligands, a new class of compounds related to alpidem has been designed using SSR180575, emapunil, and previously published pyrrolo[3,4-b]quinoline derivatives 9 as templates. The designed compounds were synthesized by alkylation of the easily accessible 4-methyl-2-phenyl-1H-pyrazolo[3,4-b]quinolin-3(2H)-one derivatives 13-15 with the required bromoacetamides. Along with the expected 2-(4-methyl-3-oxo-2- phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-1-yl)acetamide derivatives 10, 2-(4-methyl-3-oxo-2-phenyl-2H-pyrazolo[3,4-b]quinolin-9(3H)-yl)acetamide isomers 11 were isolated and characterized. The high TSPO affinity shown by new pyrazolo[3,4-b]quinoline derivatives 10 and especially 11 leads the way to further expand the chemical diversity in TSPO ligands and provides new templates and structure-affinity relationship data potentially useful in the design of new anxiolytic and neuroprotective agents.