911290-21-6

Basic information

• Product Name: 7-[ (3-chlorobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one
• Synonyms: 7-[ (3-chlorobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one
• CAS NO: 911290-21-6
• Molecular Weight: 335.186
• Mol File: 911290-21-6.mol

Chemical Properties

• CAS DataBase Reference: 7-[ (3-chlorobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 7-[ (3-chlorobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one(911290-21-6)
• EPA Substance Registry System: 7-[ (3-chlorobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one(911290-21-6)

Safety Data

• Hazardous Substances Data: 911290-21-6(Hazardous Substances Data)

Upstream product

• 25392-41-0 4-chloromethyl-7-hydroxycoumarin 
• 766-80-3 1-bromomethyl-3-chlorobenzene 
• 108-46-3 recorcinol 

Downstream Products

• 911290-17-0 4-(azidomethyl)-7-[(3-chlorobenzyl)oxy]-2H-chromen-2-one 
• 1270045-98-1 7-[(3-chlorobenzyl)oxy]-4-(1H-imidazol-1-ylmethyl)-2H-chromen-2-one 
• 1427204-00-9 C₁₈H₁₆ClNO₃ 
• 1427203-99-3 C₁₈H₁₆ClNO₃ 

Relevant articles and documents

Design, synthesis and biological evaluation of potential anti-AD hybrids with monoamine oxidase B inhibitory and iron-chelating effects

A series of active hybrids combining 3-hydroxypyridin-4(1H)-one and coumarin pharmacophores were designed and synthesized as potential agents for the treatment of Alzheimer's disease (AD). All the compounds exhibited excellent iron-chelating activities (p

Chasing ChEs-MAO B Multi-Targeting 4-Aminomethyl-7-Benzyloxy-2H-Chromen-2-ones

A series of 4-aminomethyl-7-benzyloxy-2H-chromen-2-ones was investigated with the aim of identifying multiple inhibitors of cholinesterases (acetyl- and butyryl-, AChE and BChE) and monoamine oxidase B (MAO B) as potential anti-Alzheimer molecules. Starting from a previously reported potent MAO B inhibitor (3), we studied single-point modifications at the benzyloxy or at the basic moiety. The in vitro screening highlighted triple-acting compounds (6, 8, 9, 16, 20) showing nanomolar and selective MAO B inhibition along with IC50 against ChEs at the low micromolar level. Enzyme kinetics analysis toward AChE and docking simulations on the target enzymes were run in order to get insight into the mechanism of action and plausible binding modes.

Fine molecular tuning at position 4 of 2H-chromen-2-one derivatives in the search of potent and selective monoamine oxidase B inhibitors

The effects on the inhibition potencies of monoamine oxidase isoforms A (MAO-A) and B (MAO-B) depending upon changes in the physicochemical properties (size, shape, H-bonding, lipophilicity, etc.) of substituents at the C4 position of 2H-chromen-2-one derivatives were extensively investigated, and the results significantly added to our knowledge on this class of MAO inhibitors. All the 67 examined compounds showed high MAO-B selectivity, some of them achieving potency in the low nanomolar range. In particular, the 7-metachlorobenzyloxy-4- oxyacetamido-2H-chromen-2-one (entry 62) showed single digit nanomolar MAO-B potency (IC50 = 3.1 nM) and high selectivity over the MAO-A isoform (selectivity ratio = 7244). The great variety of the investigated substituents at C4 of the 2H-chromen-2-one nucleus, combined with binding models generated from docking studies carried out on selected compounds, allowed us to shed light on the main molecular requirements for potent and selective MAO-B inhibition, highlighting the dominant role of the steric effects. Interestingly, many of the designed substituents could be metabolically related to each other (e.g., CH3/CH2OH/CHO/COOH; NH2/NHCH3, NHAc), and therefore the results obtained may help in predicting the in vivo activity of some putative metabolites of lead MAO-B inhibitors.

Discovery, biological evaluation, and structure-activity and -selectivity relationships of 6′-substituted (E)-2-(benzofuran-3(2H)-ylidene)-N- methylacetamides, a novel class of potent and selective monoamine oxidase inhibitors

The use of selective inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B) holds a therapeutic relevance in the treatment of depressive disorders and Parkinson's disease (PD), respectively. Here, the discovery of a new class of compounds acting as monoamine oxidase inhibitors (MAO-Is) and bearing a 6′-substituted (E)-2-(benzofuran-3(2H)-ylidene)-N-alkylacetamide skeleton is reported. 6′-Sulfonyloxy derivatives exhibited outstanding affinities to MAO-A (7.0 nM 50 49 nM, much higher than moclobemide) and a pronounced MAO-A/B selectivity. The corresponding 6′-benzyloxy derivatives showed potent MAO-B inhibition and inverted selectivity profile. The rigid E-geometry of the exocyclic double bond allowed a more efficient binding conformation compared to more flexible and less active 2-(1-benzofuran-3-yl)-N- methylacetamide isomers and 4-N-methylcarboxamidomethylcoumarin analogues. Focused structural modifications and docking simulations enabled the identification of key molecular determinants for high affinity toward both MAO isoforms. These novel MAO-Is may represent promising hits for the development of safer therapeutic agents with a potential against depression, PD, and other age-related neurodegenerative pathologies.

Design, synthesis, and biological evaluation of imidazolyl derivatives of 4,7-disubstituted coumarins as aromatase inhibitors selective over 17-α-hydroxylase/C17-20 lyase

The design, synthesis, and biological evaluation of a series of new aromatase (AR, CYP19) inhibitors bearing an imidazole ring linked to a 7-substituted coumarin scaffold at position 4 (or 3) are reported. Many compounds exhibited an aromatase inhibitory potency in the nanomolar range along with a high selectivity over 17-α-hydroxylase/C17-20 lyase (CYP17). The most potent AR inhibitor was the 7-(3,4-difluorophenoxy)-4-imidazolylmethyl coumarin 24 endowed with an IC50 = 47 nM. Docking simulations on a selected number of coumarin derivatives allowed the identification of the most important interactions driving the binding and clearly indicated the allowed and disallowed regions for appropriate structural modifications of coumarins and closely related heterocyclic molecular scaffolds.

Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: Development and biopharmacological profiling of 7-[(3-chlorobenzyl) oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor

In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)-methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.

Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs

Structures of human monoamine oxidase B (MAO B) in complex with safinamide and two coumarin derivatives, all sharing a common benzyloxy substituent, were determined by X-ray crystallography. These compounds competitively inhibit MAO B with Ki v

SUBSTITUTED AMINOALKYL- AND AMIDOALKYL-BENZOPYRAN DERIVATIVES

This invention is related to novel aminoalkyl- and amidoalkyl- b enzopyran derivatives of the following general formula (I) wherein: the group (a) is a substituent in position 6 or 7 wherein: R is amono- or bi-cyclic (C6-C10) aryl or