6786-30-7

Usage

Uses

Used in Pharmaceutical Industry:
3,4-Dihydro-2H-benzo[b]oxepin-5-one is used as a potential therapeutic agent for the treatment of anxiety and sleep disorders due to its sedative and anxiolytic properties. Its ability to modulate the central nervous system makes it a promising candidate for the development of drugs targeting these conditions.
Used in Neurological Disorders Research:
3,4-Dihydro-2H-benzo[b]oxepin-5-one is used as a research compound for investigating its potential anticonvulsant and antipsychotic activities. Its effects on the nervous system make it a valuable tool for studying the underlying mechanisms of these disorders and developing novel treatment strategies.
Used in Drug Development:
3,4-Dihydro-2H-benzo[b]oxepin-5-one is used as a chemical scaffold for the development of new drugs with potential applications in various therapeutic areas. Its unique structure and biological activities provide a foundation for the design and synthesis of novel compounds with improved pharmacological properties and therapeutic efficacy.

InChI:InChI=1/C10H10O2/c11-9-5-3-7-12-10-6-2-1-4-8(9)10/h1-2,4,6H,3,5,7H2

Upstream product

• 6303-58-8 4-phenyloxybutanoic acid 
• 90919-14-5 1-[2-(2-chloroethoxy)phenyl]ethanone 
• 52191-14-7 2-(2-acetylphenoxy)-1-bromoethane 
• 118-93-4 o-hydroxyacetophenone 
• 2364-59-2 γ-phenoxybutyric acid ethyl ester 
• 108-95-2 phenol 
• 114524-36-6 methyl γ-phenoxycrotonate 
• 5139-89-9 4-phenoxybutyryl chloride 
• 20426-87-3 (±)-2,3,4,5-tetrahydro-1-benzoxepin-5-ol 
• 21273-27-8 methyl 2-methyl-3-phenoxybutanoate 

Downstream Products

• 33177-03-6 9-methyl-7,12-dihydro-6H-benzo[2,3]oxepino[4,5-b]indole 
• 17517-61-2 8-phenyl-6,7-dihydro-benzo[2,3]oxepino[4,5-b]quinoline 
• 33177-06-9 12-benzyl-7,12-dihydro-6H-benzo[2,3]oxepino[4,5-b]indole 
• 33177-07-0 12-benzyl-7,12-dihydro-6H-benzo[2,3]oxepino[4,5-b]indole-9-carboxylic acid ethyl ester 
• 90094-05-6 4-[1-(4-Chloro-phenyl)-meth-(E)-ylidene]-3,4-dihydro-2H-benzo[b]oxepin-5-one 
• 90094-01-2 4-[1-Phenyl-meth-(E)-ylidene]-3,4-dihydro-2H-benzo[b]oxepin-5-one 
• 90094-04-5 4-[1-(4-Dimethylamino-phenyl)-meth-(E)-ylidene]-3,4-dihydro-2H-benzo[b]oxepin-5-one 
• 6169-78-4 2,3,4,5-tetrahydro-benzo[b]oxepine 
• 14949-49-6 2,3-dihydro-1-benzoxep-4-ene 
• 20426-78-2 4-bromo-3,4-dihydro-1(2H)-benzoxepin-5-one 
• 127283-63-0 3,4-dihydro-7-nitro-1-benzoxepine-5(2H)-one 
• 138802-05-8 3,4-dihydro-9-nitro-1-benzoxepine-5(2H)-one 
• 1027917-14-1 1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-6-oxa-1,2-diaza-benzo[e]azulene-3-carboxylic acid ethyl ester 
• 20426-80-6 3,4-dihydro-2H-1-benzopyran-4-carboxylic acid 

Relevant academic research and scientific papers

An arylative ring expansion cascade of fused cyclobutenes via short-lived intermediates with planar chirality

An arylative ring expansion cascade has been developed for the synthesis of medium-sized carbocycles from fused cyclobutenes. This reaction proceeds through a short-lived cis,trans-cycloalkadiene intermediate that is formed by thermal 4η electrocyclic ring opening. Chirality transfer experiments provide direct evidence for the transient generation of the intermediate.

Benzoxepine-5-ketone compound as well as preparation method and application thereof

The invention relates to a benzoxazepine-5-ketone compound as well as a preparation method and application thereof. The benzoxazepine-5-ketone compound has a structure as shown in a formula (I) defined in the description. The benzoxazepine-5-ketone compound can block the excessive generation of pro-inflammatory factors in the brain, and provides a feasible alternative treatment strategy for treating AIS.

Synthesis and Target Identification of Benzoxepane Derivatives as Potential Anti-Neuroinflammatory Agents for Ischemic Stroke

Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti-inflammation in LPS-induced neuroinflammatory mice model and cerebral ischemic injury through anti-neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti-inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti-neuroinflammatory effect in vitro and in vivo by inhibiting PKM2-mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation-related diseases.

Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity

Estrogen receptor α (ERα) is an important target for the design of drugs such as tamoxifen (2a) and fulvestrant (5). Three series of ER-ligands based on the benzoxepin scaffold structure were synthesized: series I containing an acrylic acid, series II with an acrylamide, and series III with a saturated carboxylic acid substituent. These compounds were shown to be high affinity ligands for the ER with nanomolar IC50 binding values. Series I acrylic acid ligands were generally ERα selective. In particular, compound 13e featuring a phenylpenta-2,4-dienoic acid substituent was shown to be antiproliferative and downregulated ERα and ERβ expression in MCF-7 breast cancer cells. Interestingly, from series III, the phenoxybutyric acid derivative compound 22 was not antiproliferative and selectively downregulated ERβ. A docking study of the benzoxepin ligands was undertaken. Compound 13e is a promising lead for development as a clinically relevant SERD, while compound 22 will be a useful experimental probe for helping to elucidate the role of ERβ in cancer cells.

Light Harvesting for Rapid and Selective Reactions: Click Chemistry with Strain-Loadable Alkenes

Intramolecular strain is a powerful driving force for rapid and selective chemical reactions, and it is the cornerstone of strain-induced bioconjugation. However, the use of molecules with built-in strain is often complicated as a result of instability or selectivity issues. Here, we show that such strain, and subsequent cycloadditions, can be mediated by visible light via the harvesting of photochemical energy. Through theoretical investigations and molecular engineering of strain-loadable cycloalkenes, we demonstrate the rapid chemoselective cycloaddition of alkyl azides with unstrained cycloalkenes via the transiently (reversibly) formed trans-cycloalkene. We assess this system via the rapid bioconjugation of azide-functionalized insulin. An attractive feature of this process is the cleavable nature of the linker, which makes a catch-and-release strategy possible. In broader terms, we show that conversion of photochemical energy to intramolecular ring strain is a powerful strategy that can facilitate complex chemical transformations, even in biomolecular systems. Probing, isolating, and/or manipulating biologically relevant macromolecules is central to the study of their function in living systems. However, the synthetic tools available for performing the chemistry necessary for such studies are often difficult to use or limited in utility. In the approach presented here, light is converted to molecular strain energy, which can in turn be used for performing rapid and highly selective chemistry on macromolecular systems. Because it involves chemically stable and chemoselective reactions, this research not only opens up new possibilities for biomolecular functionalization and manipulation but also promises to make such experiments accessible to a broader class of researchers. The central concept of strain-loadable alkenes is general and provides a firm foundation for light-activated chemistry in complex environments. Strain-loadable alkenes are cycloalkenes that, when irradiated in the presence of a visible-light-absorbing photocatalyst, undergo double-bond isomerization. Because of engineered geometrical constraints, this isomerization results in significant molecular strain. Weaver and colleagues exploit this strain to dramatically accelerate the cycloaddition with azides, which are otherwise unreactive, in mixed molecular environments.

Sodium Bromide-Catalyzed Oxidation of Secondary Benzylic Alcohols Using Aqueous Hydrogen Peroxide as Terminal Oxidant

A halide salt, hydroperoxide and AcOH catalyst system was applied to the oxidation of secondary benzylic alcohols. This simple system can be applied to a variety of secondary benzylic alcohols and scaled up for gram-scale preparation. High secondary benzylic alcohol selectivity of the present method is demonstrated in hydroxyketone synthesis. Based on several experimental results, a catalytic cycle for our oxidation is proposed.

Discovery of Lu AA33810: A highly selective and potent NPY5 antagonist with in vivo efficacy in a model of mood disorder

The structure-activity relationship of a series of tricyclic-sulfonamide compounds 11-32 culminating in the discovery of N-[trans-4-(4,5-dihydro-3,6- dithia-1-aza-benzo[e]azulen-2-ylamino)-cyclohexylmethyl]-methanesulfonamide (15, Lu AA33810) is reported. Compound 15 was identified as a selective and high affinity NPY5 antagonist with good oral bioavailability in mice (42%) and rats (92%). Dose dependent inhibition of feeding was observed after i.c.v. injection of the selective NPY5 agonist ([cPP1-7,NPY19-23,Ala 31,Aib32,Gln34]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress.

Structure-based design of thienobenzoxepin inhibitors of PI3-kinase

Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xenogra

BENZOPYRAN AND BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Synthesis, biological evaluation, structural-activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators

The estrogen receptors ERα and ERβ are recognized as important pharmaceutical targets for a variety of diseases including osteoporosis and breast cancer. A series of novel benzoxepin-derived compounds are described as potent selective modulators of the human estrogen receptor modulators (SERMs). We report the antiproliferative effects of these compounds on human MCF-7 breast tumor cells. These heterocyclic compounds contain the triarylethylene arrangement as exemplified by tamoxifen, conformationally restrained through the incorporation of the benzoxepin ring system. The compounds demonstrate potency at nanomolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity together with low nanomolar binding affinity for the estrogen receptor. The compounds also demonstrate potent antiestrogenic properties in the human uterine Ishikawa cell line. The effect of a number of functional group substitutions on the ER binding properties of the benzoxepin molecular scaffold is examined through a detailed docking and 2D-QSAR computational investigation. The best QSAR model developed for ERαβ selectivity yielded R2 of 0.84 with an RMSE for the training set of 0.30. The predictive quality of the model was Q2 of 0.72 and RMSE of 0.18 for the test set. One particular compound (26b) bearing a 4-fluoro substituent, exhibits 15-fold selectivity for ERβ and both our docking and QSAR studies converge on the correlation between enhanced lipophilicity and enhanced ERβ binding for this benzoxepin ring scaffold.