5464-79-9

Usage

Uses

Used in Pharmaceutical Industry:
4-Methoxy-2-aminobenzothiazole is used as a research intermediate for the synthesis of benzothiazole and aminobenzothiazoles derivatives, which possess antibacterial and antifungal properties. These derivatives are crucial in the development of new drugs and therapies to combat bacterial and fungal infections.
Used in Chemical Industry:
4-Methoxy-2-aminobenzothiazole is used as a chemical intermediate in the synthesis of various compounds with potential applications in different industries. Its unique chemical structure allows for the creation of novel molecules with specific properties, such as enhanced stability, reactivity, or selectivity.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

An amine, organosulfide. Organosulfides are incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials generate heat and in many cases hydrogen gas. Many of these compounds may liberate hydrogen sulfide upon decomposition or reaction with an acid. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition 4-Methoxy-2-aminobenzothiazole emits very toxic fumes of NOx and SOx.

Fire Hazard

Flash point data for 4-Methoxy-2-aminobenzothiazole are not available. 4-Methoxy-2-aminobenzothiazole is probably combustible.

Biochem/physiol Actions

2-Amino-4-methoxybenzothiazole on condensation reaction with 4-acetamidobenzaldehyde affords tridentate Schiff bases. It reacts with 2,4,6-trichloro 1,3,5-triazine to give 2-(4-methoxybenzothiazol-2′-ylamino)-4-(phenylthioureido)-6-(substitutedthioureido)-1,3,5-triazines.

InChI:InChI=1/C8H8N2OS/c1-11-5-3-2-4-6-7(5)10-8(9)12-6/h2-4H,1H3,(H2,9,10)

Upstream product

• 1516-37-6 1-(2-methoxyphenyl)thiourea 
• 90-04-0 2-methoxy-phenylamine 
• 67-66-3 chloroform 
• 7726-95-6 bromine 
• 1147550-11-5 ammonium thiocyanate 
• 333-20-0 potassium thioacyanate 
• 134-29-2 2-methoxyaniline hydrochloride 

Downstream Products

• 7471-03-6 2-amino-4-hydroxybenzothiazole 
• 63205-32-3 3-benzyl-2-(4-methoxy-benzothiazol-2-ylimino)-5-methyl-thiazolidin-4-one 
• 35412-20-5 N-(4-methoxy-benzothiazol-2-yl)-benzamide 
• 68501-20-2 6-methoxy-4-phenyl-benzo[4,5]thiazolo[3,2-a]pyrimidin-2-one 
• 3507-27-5 2-chloro-4-methoxybenzo[d]thiazole 
• 73518-38-4 3-benzylidene-2-(4-methoxy-benzothiazol-2-yl)-2,3-dihydro-isoindol-1-one 
• 76273-59-1 (5-Methoxy-3-phenyl-4H-benzo[1,4]thiazin-2-yl)-phenyl-methanone 
• 383866-88-4 (4-Methoxy-benzothiazol-2-yl)-urea 
• 918154-61-7 3-(4-methoxy-1,3-benzothiazol-2-yl)-2-phenylquinazolin-4(3H)-one 
• 354760-24-0 4-methoxy-2-(trifluoromethyl)benzo[d]thiazole 
• 1309261-83-3 C₂₂H₁₆N₄O₂S 
• 1026915-82-1 2-methoxy-6-(methylthio)aniline 

Relevant academic research and scientific papers

Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers

Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.

Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers

Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.

SN-Donor methylthioanilines and copper(II) complexes: Synthesis, spectral properties, and in vitro antimicrobial activity

Methylthioanilines, a series of sulfur-nitrogen donor ligands substituted with OCH3, CH3, Cl, and Br, and their copper(II) complexes have been synthesized and characterized by 1H and 13C NMR, elemental analysis, FTIR, UV-Vis and EPR spectra, molar conductance, and magnetic susceptibility measurements. The NMR spectra of the ligands revealed that the para/ortho protons and para carbon were sensitive to the electronic effect of substituents. The CHNS analysis presented CuLCl2 (L = OCH3, CH3, Cl) and CuL2Cl2 (L = Br) stoichiometries for the copper complexes. FTIR spectra showed that the bidentate ligands were coordinated to the copper ion through their nitrogen and sulfur atoms. The electronic spectra have suggested square planar and octahedral geometries for these complexes. The EPR spectra demonstrated that the solid state copper(II) complexes possess dx2-y2 orbital ground state and g= > g > 2.0023 in a tetragonal environment. The compounds were evaluated for in vitro antimicrobial activity against S. aureus, B. subtilis, E. coli, and C. albicans. The copper complexes showed higher activity than the parent ligands against S. aureus and B. subtilis; the electron-donating OCH3 and CH3 derivatives were more active than the withdrawing Br- A nd Cl-substituted compounds.

Scalable synthesis and antibacterial evaluation of 2-(3-(N-(substituted phenyl)sulfamoyl)ureido)benzothiazoles

A new series of 2-(3-(N-(substituted phenyl)sulfamoyl)ureido)benzothiazoles was synthesized via a one-pot efficient and scalable method, involving the condensation of 2-aminobenzothiazoles derivatives, substituted anilines, and chlorosulfonyl isocyanate. The products were obtained in good yield with a simple workup, and their structures were confirmed from their spectral analyses. The synthesized compounds were further screened for their antibacterial activity against Gram-positive and Gram-negative pathogenic strains. The molecules show promising activity in the MIC value range of 2–0.25 μg/ml against selected bacterial strains, especially against nonfermentative carbapenem-resistant bacteria (Pseudo VIM-2 and Acinetobacter baumanni).

Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance

A series of 18β-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant.

Synthesis and molecular docking of new roflumilast analogues as preferential-selective potent PDE-4B inhibitors with improved pharmacokinetic profile

In the present work, we designed and synthesized new roflumilast analogues with preferential-selective PDE-4B inhibition activity and improved pharmacokinetic properties. The unsubstituted benzo[d]thiazol-2-yl and -6-yl benzamide derivatives (4a and 6a) showed both good potency and preferential selectivity for PDE-4B. More remarkably, 6c revealed 6 times preferential PDE-4B/4D selectivity with a significant increase of in vitro cAMP and good % inhibition of TNF-α concentration. In addition, the in vitro pharmacokinetics of 6c showed good metabolic stability with in vitro CLint (5.67 mL/min/kg) and moderate % plasma protein binding (53.71%). This was reflected onto increased in vivo exposure with a half-life greater than roflumilast by 3 folds (21 h) and a Cmax value of 113.958 ng/mL. Molecular docking attributed its good activity to its key binding interactions in PDE-4B active site with additional hydrogen bonding with amino acids lining the metal pocket. Summing up, 6c can be considered as suitable candidate for further investigation for the treatment of COPD.

NOVEL BENZOTHIAZOLE DERIVATIVES WITH ENHANCED BIOLOGICAL ACTIVITY

The present invention discloses novel conjugates of benzothiazole derivatives with cystine and glucosamine and their method of synthesis. Their method of synthesis is easy and eco-friendly, avoiding the use of hazardous materials or reactions, The compounds offer technical advantages of increased solubility, potency, selectivity and biological activity. The novel compounds show antibacterial, antifungal and anticancer activities. Formula, physico-chemical data and biological activity of the novel derivatives are as given in Tables 1 to 9.

BENZOTHIAZOLE DERIVATIVE AND ANTI-TUMOR USE THEREOF

The present invention relates to a benzothiazole derivative of formula 1 or a pharmaceutically acceptable salt thereof and a process for preparation thereof. The present invention also relates to a pharmaceutical composition comprising the compounds and the use of the compounds in the preparation of an anti-tumor medicament.

Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists

Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.

Probing the ATP-Binding Pocket of Protein Kinase DYRK1A with Benzothiazole Fragment Molecules

DYRK1A has emerged as a potential target for therapies of Alzheimer's disease using small molecules. On the basis of the observation of selective DYRK1A inhibition by firefly d-luciferin, we have explored static and dynamic structural properties of fragment sized variants of the benzothiazole scaffold with respect to DYRK1A using X-ray crystallography and NMR techniques. The compounds have excellent ligand efficiencies and show a remarkable diversity of binding modes in dynamic equilibrium. Binding geometries are determined in part by interactions often considered "weak", including "orthogonal multipolar" types represented by, for example, F-CO, sulfur-aromatic, and halogen-aromatic interactions, together with hydrogen bonds that are modulated by variation of electron withdrawing groups. These studies show how the benzothiazole scaffold is highly promising for the development of therapeutic DYRK1A inhibitors. In addition, the subtleties of the binding interactions, including dynamics, show how full structural studies are required to fully interpret the essential physical determinants of binding.