40358-33-6

Usage

Uses

Used in Pharmaceutical Industry:
2,3,4,5-Tetrahydro-1,5-benzothiazepine is used as a reactant for the preparation of substituted 3,3-difluoro-2-oxindoles via intramolecular C-H difluoroalkylation. This application is significant because the resulting 3,3-difluoro-2-oxindoles can be further utilized in the development of various pharmaceutical compounds, potentially leading to new drugs with improved therapeutic properties.
Additionally, due to its unique chemical structure, 2,3,4,5-tetrahydro-1,5-benzothiazepine may also be employed as a scaffold in the design of novel bioactive molecules targeting specific receptors or enzymes in the human body. This can contribute to the discovery of new drugs for the treatment of various diseases and conditions.

InChI:InChI=1/C9H11NS/c1-2-5-9-8(4-1)10-6-3-7-11-9/h1-2,4-5,10H,3,6-7H2

Upstream product

• 137-07-5 2-amino-benzenethiol 
• 109-64-8 1,3-dibromo-propane 
• 15857-68-8 thiochroman-4-one oxime 
• 3528-17-4 2,3-dihydro-4H-[1]benzothiopyran-4-one 
• 26235-49-4 N-(thiochroman-4-yl)hydroxylamine 
• 68253-35-0 indan-1-one oxime 
• 6320-02-1 o-bromothiophenol 
• 15857-68-8 (E)-thiochroman-4-one oxime 

Downstream Products

• 58121-91-8 2,3,4,5-Tetrahydro-1,5-benzothiazepin hydrochloride 
• 92962-62-4 N-benzoyl-2,3,4,5-tetrahydro-1,5-benzothiazepine 
• 384832-29-5 5-(4-Cyano-3-methylbenzoyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine 

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.

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.

An efficient synthesis of benzene fused six-, seven- and eight-membered rings containing nitrogen and sulfur by benzyne ring closure reaction

3,4-Dihydro-2-H-benzo[1,4]thiazines (3a-c), 2,3,4,5-tetrahydro[b]-[1,4] thiazapines (3d-f) and 2,3,4,5-tetrahydro-2H-benzo[b][1,4]thiazocines (3g-i) were prepared by the cyclization of the respective 2-bromophenylsulfanyl derivatives of ethylamine (1a-c), propylamine (2d-f) and butylamine (2g-i).

Process for preparing 3-fluoro-4,6-dichlorotoluene

3-Fluoro-4,6-dichlorotoluene is prepared with reduced formation of 3-fluoro-2,6-dichlorotoluene by chlorinating 3-fluorotoluene in the presence of a catalyst system to give a mixture containing 3-fluoro-6-chlorotoluene and 3-fluoro-4-chlorotoluene and chlorinating this in the presence of another catalyst system to give 3-fluoro-4,6-dichlorotoluene.