7160-97-6

Usage

Uses

Used in Pharmaceutical Industry:
2,3,4,5-Tetrahydro-1,5-benzoxazepine is used as a potential therapeutic agent for neurological and psychiatric disorders due to its activity as a serotonin receptor agonist. This property makes it a candidate for the treatment of various conditions that involve the serotonin system, such as depression, anxiety, and other mood disorders.
Used in Antidepressant Development:
2,3,4,5-Tetrahydro-1,5-benzoxazepine is used as a novel antidepressant agent, given its potential to modulate neurotransmitter systems in the brain. Its role in influencing mood and behavior positions it as a promising candidate for the development of new antidepressant medications.
Used in Anxiolytic Agent Research:
2,3,4,5-Tetrahydro-1,5-benzoxazepine is used as a potential anxiolytic agent, indicating its capacity to alleviate anxiety symptoms. 2,3,4,5-Tetrahydro-1,5-benzoxazepine's interaction with serotonin receptors suggests that it could be a valuable addition to the arsenal of treatments for anxiety disorders.
Used in Neurotransmitter Modulation Studies:
2,3,4,5-Tetrahydro-1,5-benzoxazepine is used as a research tool in the study of neurotransmitter modulation, particularly in the context of mood and behavior. Its pharmacological properties make it a valuable compound for understanding the complex interactions within the brain's neurotransmitter systems.

Upstream product

• 18845-22-2 3-(3-chloropropyl)-3H-benzooxazol-2-one 
• 24541-01-3 chroman-4-one oxime 
• 24541-01-3 (4E)-2,3-dihydro-4H-chromen-4-one oxime 
• 491-37-2 2,3-dihydro-4H-1-benzopyran-4-one 
• 6303-99-7 3-(o-aminophenoxy)propionic acid 
• 95-55-6 2-amino-phenol 
• 109-64-8 1,3-dibromo-propane 
• 1304141-71-6 3,4-dihydro-N-hydroxy-2H-1-benzopyran-4-amine 
• 56182-22-0 1-(but-3-en-1-yloxy)-2-nitrobenzene 
• 847256-46-6 3-(2-nitrophenoxy)-propanal 
• 50911-59-6 3-(2-chlorophenoxy)-1-propanamine 
• 704-48-3 2,3,4,5-tetrahydro-1,5-benzoxazepin-4-one 
• 37576-01-5 2-(3-chloro-propylamino)-phenol 
• 810681-77-7 1-(2-azidopropoxy)-2-chlorobenzene 

Downstream Products

• 1092844-55-7 5-(4-cyano-3-methylbenzoyl)-2,3,4,5-tetrahydro-1,5-benzoxazepine 
• 54252-69-6 5-(2-dimethylamino-5-nitro-benzoyl)-2,3,4,5-tetrahydro-benzo[b][1,4]oxazepine 
• 54252-70-9 5-(2-methylamino-5-nitro-benzoyl)-2,3,4,5-tetrahydro-benzo[b][1,4]oxazepine 
• 137975-83-8 1-(4-Aminobenzoyl)-1,2,3,4-tetrahydro-5,1-benzoxazepine 
• 33703-28-5 5-(3,4-dimethoxy-phenethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]oxazepine 
• 54252-67-4 5-(2-chloro-5-nitro-benzoyl)-2,3,4,5-tetrahydro-benzo[b][1,4]oxazepine 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of brain penetrant benzazepine-based histone deacetylase 6 inhibitors for alleviating stroke-induced brain infarction

Histone deacetylase 6 (HDAC6) has become a promising therapeutic target for central nervous system diseases due to its more complex protein structure and biological functions. However, low brain penetration of reported HDAC6 inhibitors limits its clinical application in neurological disorders. Therefore, the benzazepine, a brain-penetrant rigid fragment, was utilized to design a series of selective HDAC6 inhibitors to improve brain bioavailability. Various synthetic strategies were applied to assemble the tetrahydro-benzazepine ring, and 22 compounds were synthesized. Among them, compound 5 showed low nanomolar potency and strong isozyme selectivity for the inhibition of HDAC6 (IC50 = 1.8 nM, 141-fold selectivity over HDAC1) with efficient binding patterns like coordination with the zinc ion and π-π stacking effect. Western blot results showed it could efficiently transport into SH-SY5Y cells and selectively enhance the acetylation level of α-tubulin with a moderate effect on Histone H3. Notably, pharmacokinetic studies demonstrated that compound 5 (brain/plasma ratio of 2.30) had an excellent ability to penetrate the blood-brain barrier of C57 mice. In male rats with transient middle cerebral artery occlusion (MCAO), compound 5 significantly reduced the cerebral infarction from 21.22% to 11.47% and alleviated neurobehavioral deficits in post-ischemic treatment, which provided a strong rationale for pursuing HDAC6-based therapies for ischemic stroke.

[1,5]-Hydride shift-cyclization versus C(sp2)-H functionalization in the knoevenagel-cyclization domino reactions of 1,4- And 1,5-Benzoxazepines

Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 μM IC50 value.

4 - Substituted benzene sulfonamide derivative and its preparation method and application

The present invention discloses a class of new 4-substituted benzene sulfonamide derivatives represented by a formula (I), wherein the 4-substituted benzene sulfonamide derivatives have good antitumor activity, and each group is defined in the specification. The present invention further discloses a preparation method of the derivative, a pharmaceutical composition containing the derivative, and applications of the 4-substituted benzene sulfonamide derivative and the pharmaceutical composition containing the derivative as the antitumor drug. The formula I is defined in the specification.

Synthesis, anti-cancer evaluation of benzenesulfonamide derivatives as potent tubulin-targeting agents

A series of benzenesulfonamide derivatives were synthesized and evaluated for their anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferative and tubulin polymerization. Compound BA-3b proved to be the most potent compound with IC50value ranging from 0.007 to 0.036 μM against seven cancer cell lines, and three drug-resistant cancer cell lines, which indicated a promising anti-cancer agent. The target tubulin was also verified by dynamic tubulin polymerization assay and tubulin intensity assay.

Ring-expansion reaction of oximes with aluminum reductants

The ring-expansion reactions of heterocyclic ketoximes and carbocyclic ketoximes with several reductants such as AlHCl2, AlH3 (alane), LiAlH4, LiAlH(OtBu)3, and (MeOCH 2CH2O)2AlH2Na (Red-Al) were examined. Among reductants, AlHCl2 (LiAlH4:AlCl 3 = 1:3) in cyclopentyl methyl ether (CPME) has been found to be a suitable reagent for the reaction, and the rearranged cyclic secondary amines were obtained in good to excellent yields.

Regiospecific rearrangement of hydroxylamines to secondary amines using diisobutylaluminum hydride

A systematic investigation of a reductive ring-expansion reaction of N-monosubstituted hydroxylamines with diisobutylaluminum hydride (DIBALH) was carried out. The reaction regiospecifically provided a variety of bicyclic or tricyclic heterocycles or linear secondary amines containing nitrogen attached to an aromatic ring. The Japan Institute of Heterocyclic Chemistry.

Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism

(Chemical Equation Presented) A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic ringswith diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b] [1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6- hexahydroazepino[3,2-b]-indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]-azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee-Yang-Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because the potential energy curve along the intrinsic reaction coordinate (IRC) had twomaxima (saddle points; TS1 and TS2) and the partial phenonium cation intermediate C. In addition to cyclic ketoximes fused to aromatic rings, the reactions of various cyclic and acyclic ketoximeswere examined to investigate preference of migrating group. It was found that themore electron-rich group migrated preferentially to give the corresponding secondary amines.

Regiospecific synthesis of unsubstituted basic skeletons of heterocycles containing nitrogen neighboring an aromatic ring by the reductive ring expansion reaction using diisobutylaluminum hydride

A systematic investigation of reductive ring expansion reaction of oximes with diisobutylaluminum hydride (DIBAH) was performed. The reaction regiospecifically provided a variety of unsubstituted bicyclic heterocycles 3a-3g or tricyclic heterocycles 3h, 3j-3l that contained nitrogen attached to an aromatic ring.

GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO

GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates, and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists

Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.