4815-28-5

Usage

Synthesis

The synthesis of?2-AMINO-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE is as follows:A solution of aminothiophene EO (prepared as described in Example C; 500mg, 2.8 mmol) in concentrated sulphuric acid (5ml) was stirred at room temperature for 65 hours. The reaction mixture was poured cautiously into ice-cold aqueous potassium carbonate, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over magnesium sulphate and evaporated to dryness under reduced pressure to give the desired product (383mg, 70%) as an off-white solid.

InChI:InChI=1/C9H12N2OS/c10-8(12)7-5-3-1-2-4-6(5)13-9(7)11/h1-4,11H2,(H2,10,12)

Upstream product

• 108-94-1 cyclohexanone 
• 107-91-5 cyanoacetic acid amide 
• 110-82-7 cyclohexane 
• 704-16-5 Cyanocarbamidomethylenecyclohexane 
• 5634-51-5 acetylcyanamide 
• 4651-91-6 3-cyano-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene 

Downstream Products

• 27285-09-2 2,4-Dioxo-1,2,3,4,5,6,7,8-octahydro-<1>-1-benzothieno<2,3-d>pyrimidine 
• 109164-37-6 4-((3-carbamoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-4-oxobutanoic acid 
• 19819-18-2 4-hydroxy-2-phenyl-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidine 
• 101130-10-3 2-styryl-5,6,7,8-tetrahydrobenzothieno<2,3-d>pyrimidin-4(3H)-one 
• 18002-03-4 2-benzyl-5,6-tetramethylenethieno<2,3-d>pyrimidin-4(3H)-one 
• 60442-59-3 2-(4-methoxyphenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one 
• 60442-52-6 2-(4-chloro-benzoylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid amide 
• 142995-02-6 2-(cyclohexanecarbonyl-amino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid amide 

Relevant academic research and scientific papers

Uses of 1-(3-cyano-4,5,6,7-tetrahydrobenzo[b]-thiophen-2-yl)-3-dodecanoylthiourea as a building block in the synthesis of fused pyrimidine and thiazine systems

The reaction of lauroyl isothiocyanate and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was used to synthesize the title compound 2. Compound 2 could serve as the main building block in the synthesis of many target heterocyclic systems. Various fused pyrimidines were synthesized in the reactions of compound 2 with sodium ethoxide, hydrazine hydrate, phenyl hydrazine, ethyl carbazate, thiourea, and/or 2-aminothiophenol. The structures of the synthesized compounds were confirmed by microanalytical and spectral data.

Identification of small-molecule inhibitors of USP2a

USP2a is a deubiquitinating protease that rescues its target proteins from destruction by the proteasome by reversing the process of protein ubiquitination. USP2a shows oncogenic properties in vivo and has been found to be a specific activator of cyclin D1. Many types of cancers are addicted to cyclin D1 expression. Targeting USP2a is a promising strategy for cancer therapy but little progress has been made in the field of inhibition of USP2a. Using NMR-based fragment screening and biophysical binding assays, we have discovered small molecules that bind to USP2a. Iterations of fragment combination and structure-driven design identified two 5-(2-thienyl)-3-isoxazoles as the inhibitors of the USP2a-ubiquitin protein-protein interaction. The affinity of these molecules for the catalytic domain of USP2a parallels their ability to interfere with USP2a binding to ubiquitin in vitro. Altogether, our results establish the 5-(2-thienyl)-3-isoxazole pharmacophore as an attractive starting point for lead optimization.

Design, synthesis, and biological evaluation of new thieno[2,3-d] pyrimidine derivatives as targeted therapy for PI3K with molecular modelling study

Cancer is one of the most aggressive diseases characterised by abnormal growth and uncontrolled cell division. PI3K is a lipid kinase involved in cancer progression which makes it fruitful target for cancer control. 28 new morpholine based thieno[2,3-d] p

Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase

Influenza viruses (Flu) are responsible for seasonal epidemics causing high rates of morbidity, which can dramatically increase during severe pandemic outbreaks. Antiviral drugs are an indispensable weapon to treat infected people and reduce the impact on

Design, molecular modeling and synthesis of metal-free sensitizers of thieno pyridine dyes as light-harvesting materials with efficiency improvement using plasmonic nanoparticles

Considering the thiophene unit as an electron-rich heterocycle, it is investigated with the aim of elucidating its potential efficiency for solar cell application. With the introduction of active substituents such as COOEt, CONH2 and CN into the thiophene segment, three novel thieno pyridine sensitizers (6a–c), based on donor-acceptor D-π-A construction, are designed and synthesized. The effect of the anchoring groups is investigated based on their molecular orbital’s (MO’s) energy gap (Eg). The electrostatic interaction between the synthesized dyes and metal nanoparticles, namely gold, silver and ruthenium, is believed to improve their performance as organic sensitizers. The dye-sensitized solar cells (DSSCs) are manufactured using the novel diazenyl pyridothiophene dyes, along with their metal nanoparticles conjugates as sensitizers, and were examined for efficiency improvement. Accordingly, using this modification, the photovoltaic performance was significantly improved. The promising results of conjugate (6b/AgNPs), compared with reported organic and natural sensitizers (JSC (1.136 × 10–1 mA/cm2), VOC (0.436 V), FF (0.57) and η (2.82 × 10–2%)), are attributed to the good interaction between the amide, methyl, amino and cyano groups attached to the thiophene pyridyl scaffolds and the surface of TiO2 porous film. Implementation of a molecular modeling study is performed to predict the ability of the thiophene moiety to be used in solar cell applications.

5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors

Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 μM, CC50 > 100 μM, F = 25%) and 19k (EC50 = 0.31 μM, CC50 > 100 μM, F = 46%), displayed overall lead profiles superior to reported CAEs 7–10 used in our studies.

Structure–activity relationships for inhibitors of Pseudomonas aeruginosa exoenzyme S ADP-ribosyltransferase activity

During infection, the Gram-negative opportunistic pathogen Pseudomonas aeruginosa employs its type III secretion system to translocate the toxin exoenzyme S (ExoS) into the eukaryotic host cell cytoplasm. ExoS is an essential in vivo virulence factor that enables P. aeruginosa to avoid phagocytosis and eventually kill the host cell. ExoS elicits its pathogenicity mainly via ADP-ribosyltransferase (ADPRT) activity. We recently identified a new class of ExoS ADPRT inhibitors with in vitro IC50 of around 20 μM in an enzymatic assay using a recombinant ExoS ADPRT domain. Herein, we report structure–activity relationships of this compound class by comparing a total of 51 compounds based on a thieno [2,3-d]pyrimidin-4(3H)-one and 4-oxo-3,4-dihydroquinazoline scaffolds. Improved inhibitors with in vitro IC50 values of 6 μM were identified. Importantly, we demonstrated that the most potent inhibitors block ADPRT activity of native full-length ExoS secreted by viable P. aeruginosa with an IC50 value of 1.3 μM in an enzymatic assay. This compound class holds promise as starting point for development of novel antibacterial agents.

New thiophene–acridine compounds: Synthesis, antileishmanial activity, DNA binding, chemometric, and molecular docking studies

In this study, we synthesized eight new compounds containing the 2-amino-cycloalkyl[b]thiophene and acridine moieties (ACT01 and ACS01-ACS07). None tested compounds presented human erythrocyte cytotoxicity. The new compounds presented antipromastigote activity, where ACS01 and ACS02 derivatives presented significant antileishmanial activity, with better performance than the reference drugs (tri and pentavalent antimonials), with respective IC50 values of 9.60?±?3.19 and 10.95?±?3.96?μm. Additionally, these two derivatives were effective against antimony-resistant Leishmania (Leishmania) amazonensis strains. In addition, binding and fragmentation DNA assays were performed. It was observed that the antileishmanial activity of ACS01 is not associated with DNA fragmentation of the promastigote forms. However, it interacted with DNA with a binding constant of 104?m?1. In partial least-squares studies, it was observed that the most active compounds (ACS01 and ACS02) showed lower values of amphiphilic moment descriptor, but there was a correlation between the lipophilicity of the molecules and antileishmanial activity. Furthermore, the docking molecular studies showed interactions between thiophene–acridine derivatives and the active site of pyruvate kinase enzyme with the major contribution of asparagine 152 residue for the interaction with thiophene moiety. Thus, the results suggested that the new thiophene–acridine derivatives are promising molecules as potential drug candidates.

ZnO-CeO2 nanocomposite: Efficient catalyst for the preparation of thieno[2,3-d]pyrimidin-4(3H)-one derivatives

The Zinc oxide-cerium oxide (ZnO-CeO2) nanocomposite was prepared by a coprecipitation method and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and particle size distribution analysis. The XRD p

Tetrahydro benzothiophene derivative and application thereof to preparation of glycogen synthase kinase 3 beta inhibitor

The invention discloses a tetrahydro benzothiophene derivative and the application thereof to the preparation of a glycogen synthase kinase 3 beta inhibitor. The tetrahydro benzothiophene derivative, pharmaceutically acceptable salt, optical active body or racemate thereof has a chemical structure as shown in a formula I. Experiments show that the compound has good GSK-3 beta inhibitory activity. In addition, the invention further provides a method for preparing a tetrahydro benzothiophene compound. The method is short in synthesis route, simple in preparation process and easy to operate, and can meet the requirements of large-scale industrial production.