42225-04-7

Usage

Chemical Properties

White solid

InChI:InChI=1/C10H12N2S/c1-6-2-3-7-8(5-11)10(12)13-9(7)4-6/h6H,2-4,12H2,1H3/t6-/m1/s1

Upstream product

• 589-92-4 1-methylcyclohexan-4-one 
• 109-77-3 malononitrile 

Downstream Products

• 1243985-34-3 2-(4-chlorophenyl)-7-methyl-5,6,7,8-tetrahydro[b]benzothieno[2,3-d]pyrimidin-4-amine 
• 1243985-35-4 2-(2-chlorophenyl)-7-methyl-5,6,7,8-tetrahydro[b]benzothieno[2,3-d]pyrimidin-4-amine 
• 1243985-31-0 7-methyl-2-phenyl-5,6,7,8-tetrahydro[b]benzothieno[2,3-d]pyrimidin-4-amine 
• 1243985-32-1 7-methyl-2-(4-methylphenyl)-5,6,7,8-tetrahydro[b]benzothieno[2,3-d]pyrimidin-4-amine 
• 1243985-33-2 2-(4-methoxyphenyl)-7-methyl-5,6,7,8-tetrahydro[b]benzothieno[2,3-d]pyrimidin-4-amine 
• 375355-54-7 C₁₈H₁₇N₃OS₂ 

Relevant academic research and scientific papers

Novel tetrahydrobenzo[b]thiophen-2-yl)urea derivatives as novel α-glucosidase inhibitors: Synthesis, kinetics study, molecular docking, and in vivo anti-hyperglycemic evaluation

α-Glucosidase inhibitors, which can inhibit the digestion of carbohydrates into glucose, are one of important groups of anti-type 2 diabetic drugs. In the present study, we report our effort on the discovery and optimization of α-glucosidase inhibitors with tetrahydrobenzo[b]thiophen-2-yl)urea core. Screening of an in-house library revealed a moderated α-glucosidase inhibitors, 5a, and then the following structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased inhibitory activity against α-glucosidase than the parental compound 5a (IC50 of 26.71 ± 1.80 μM) and the positive control acarbose (IC50 of 258.53 ± 1.27 μM). Among them, compounds 8r (IC50 = 0.59 ± 0.02 μM) and 8s (IC50 = 0.65 ± 0.03 μM) were the most potent inhibitors, and showed selectivity over α-amylase. The direct binding of both compounds with α-glucosidase was confirmed by fluorescence quenching experiments. Kinetics study revealed that these compounds were non-competitive inhibitors, which was consistent with the molecular docking results that compounds 8r and 8s showed high preference to bind to the allosteric site instead of the active site of α-glucosidase. In addition, compounds 8r and 8s were not toxic (IC50 > 100 μM) towards LO2 and HepG2 cells. Finally, the in vivo anti-hyperglycaemic activity assay results indicated that compounds 8r could significantly decrease the level of plasma glucose and improve glucose tolerance in SD rats treated with sucrose. The present study provided the tetrahydrobenzo[b]thiophen-2-yl)urea chemotype for developing novel α-glucosidase inhibitors against type 2 diabetes.

Synthesis and biological evaluation of new antitubulin agents containing 2-(30,40,50-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Scaffold

Two novel series of compounds based on the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 4,5,6,7-tetrahydrobenzo[b]thiophene molecular skeleton, characterized by the presence of a 30,40,50-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(30,40,50-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivative 3a and its 6-ethoxycarbonyl homologue 3b as new antiproliferative agents that inhibit cancer cell growth with IC50 values ranging from 1.1 to 4.7 μM against a panel of three cancer cell lines. Their interaction with tubulin at micromolar levels leads to the accumulation of cells in the G2/M phase of the cell cycle and to an apoptotic cell death. The cell apoptosis study found that compounds 3a and 3b were very effective in the induction of apoptosis in a dose-dependent manner. These two derivatives did not induce cell death in normal human peripheral blood mononuclear cells, suggesting that they may be selective against cancer cells. Molecular docking studies confirmed that the inhibitory activity of these molecules on tubulin polymerization derived from binding to the colchicine site.

Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis from Mycobacterium tuberculosis

The enhanced intracellular survival (Eis) protein of Mycobacterium tuberculosis (Mtb) is a versatile acetyltransferase that multiacetylates aminoglycoside antibiotics abolishing their binding to the bacterial ribosome. When overexpressed as a result of promoter mutations, Eis causes drug resistance. In an attempt to overcome the Eis-mediated kanamycin resistance of Mtb, we designed and optimized structurally unique thieno[2,3-d]pyrimidine Eis inhibitors toward effective kanamycin adjuvant combination therapy. We obtained 12 crystal structures of enzyme-inhibitor complexes, which guided our rational structure-based design of 72 thieno[2,3-d]pyrimidine analogues divided into three families. We evaluated the potency of these inhibitors in vitro as well as their ability to restore the activity of kanamycin in a resistant strain of Mtb, in which Eis was upregulated. Furthermore, we evaluated the metabolic stability of 11 compounds in vitro. This study showcases how structural information can guide Eis inhibitor design.

An innovative synthesis of tertiary hydroxyl thieno[2,3-d]pyrimidinone skeleton: Natural-like product from the tandem reaction of o-aminothienonitrile and carbonyl compound

A straightforward base accelerant tandem protocol for the synthesis of the tertiary hydroxyl natural-like thieno[2,3-d]pyrimidinone skeleton was developed from the cyclocondensation of o-aminothienonitrile and carbonyl compound. The reaction process includes PDF conversion and photo-catalytic oxygenation. This synthetic strategy offers an alternative method for regioselective construction of tertiary hydroxylated thieno[2,3-d]pyrimidinone architectures with kinetic, thermodynamic control, and six-member ring effect.

Solvent-free synthesis of 2-aminothiophene-3-carbonitrile derivatives using high-speed vibration milling

The solvent-free synthesis of 2-aminothiophene-3-carbonitrile derivatives by high-speed vibration milling using the inexpensive and environmentally friendly Et2NH as a catalyst was studied. The reaction conditions were optimised and the derivatives were obtained in good yield. This method has advantages in terms of short reaction time and facile conditions.

Identification of 5,6-substituted 4-aminothieno[2,3-d]pyrimidines as LIMK1 inhibitors

4-Aminobenzothieno[3,2-d]pyrimidines were previously identified in a high throughput screening campaign as LIMK1 inhibitors. Scaffold reversal led to the identification of a series of simple 5,6-substituted 4-aminothieno[2,3-d] pyrimidines with low micromolar inhibition of LIMK1.

An efficient one-pot synthesis of substituted 2-aminothiophenes via three-component gewald reaction catalyzed by l -proline

An efficient one-pot procedure for the direct catalytic synthesis of substituted 2-aminothiophenes catalyzed by l-proline under mild reaction conditions has been developed. A variety of functionalized 2-aminothiophene scaffolds were assembled in high yields by this catalytic protocol. Low catalyst loading, simple procedure, and high yields are the important attributes of this methodology.