260443-89-8

Basic information

• Product Name: NSC-703786
• Synonyms: 4-(5-Fluoro-2-benzothiazolyl)-2-methyl-benzenamine;5F203;5F-203;NSC-703786;5-fluoro 203;4-(5-fluoro-1,3-benzothiazol-2-yl)-2-methylaniline
• CAS NO: 260443-89-8
• Molecular Formula: C₁₄H₁₁FN₂S
• Molecular Weight: 258.3139432
• Mol File: 260443-89-8.mol

Chemical Properties

• Appearance: white to beige/
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble20mg/mL, clear
• CAS DataBase Reference: NSC-703786(CAS DataBase Reference)
• NIST Chemistry Reference: NSC-703786(260443-89-8)
• EPA Substance Registry System: NSC-703786(260443-89-8)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 260443-89-8(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
NSC-703786 is used as a cytotoxic agent for its ability to activate AhR signaling, leading to the transcription of CYP1A1 and the formation of DNA adducts. This process results in cell cycle arrest, making it a potential therapeutic option for various types of cancer.
Used in Drug Delivery Systems:
In the pharmaceutical industry, NSC-703786 is used as a key component in the development of novel drug delivery systems. These systems aim to improve the bioavailability, delivery, and therapeutic outcomes of the compound by employing various organic and metallic nanoparticles as carriers. This approach can enhance the efficacy of NSC-703786 in cancer treatment and potentially reduce side effects.
Used in Research and Development:
NSC-703786 is also utilized in the field of research and development, particularly in the study of AhR signaling and its role in cancer biology. By understanding the molecular mechanisms underlying the compound's cytotoxic effects, researchers can develop more targeted and effective cancer therapies.

Upstream product

• 260443-96-7 5-fluoro-2-(3-methyl-4-nitrophenyl)benzothiazole 
• 1003-99-2 2-bromo-5-fluoroaniline 
• 35675-46-8 3-methyl-4-nitro-benzoyl chloride 
• 260444-01-7 N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzothioamide 
• 343975-60-0 N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzamide 
• 343975-42-8 N-(3-fluoro-phenyl)-3-methyl-4-nitro-thiobenzamide 
• 3113-71-1 3-methyl-4-nitrobenzoic acid 

Relevant articles and documents

Recyclable copper-catalyzed cyclization of o-haloanilides and metal sulfides: An efficient and practical access to substituted benzothiazoles

An efficient heterogeneous copper-catalyzed cyclization of o-haloanilides and metal sulfides has been achieved via the C–S coupling in DMF at 80 or 140 °C in the existence of an MCM-41-bound NHC-Cu(I) catalyst and then intramolecular condensation, delivering a wide range of substituted benzothiazoles in mostly good to high yields. This new MCM-41-NHC-CuI complex can facilely be obtained by a two-step procedure starting from easily accessible and inexpensive reagents and reused more than seven times without any significant loss of its catalytic efficiency. The present protocol has been successfully applied to the gram-scale synthesis of two antitumor agents 5F203 and PMX 610.

Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; Synthesis of 5F203 hydrogels for local delivery

Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R2 > 0.7). Time-dependent appearance of γ-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines.

Bioactivation of fluorinated 2-aryl-benzothiazole antitumor molecules by human cytochrome P450s 1A1 and 2W1 and deactivation by cytochrome P450 2S1

Both 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) and 5-fluoro-2-(3,4-dimethoxyphenyl)-benzothiazole (GW 610) contain the benzothiazole pharmacophore and possess potent and selective in vitro antitumor properties. Prior studies suggested the involvement of cytochrome P450 (P450) 1A1 and 2W1-mediated bioactivation in the antitumor activities and P450 2S1-mediated deactivation of 5F 203 and GW 610. In the present study, the biotransformation pathways of 5F 203 and GW 610 by P450s 1A1, 2W1, and 2S1 were investigated, and the catalytic parameters of P450 1A1- and 2W1-catalyzed oxidation were determined in steady-state kinetic studies. The oxidations of 5F 203 catalyzed by P450s 1A1 and 2W1 yielded different products, and the formation of a hydroxylamine was observed for the first time in the latter process. Liquid chromatography-mass spectrometry (LC-MS) analysis with the synthetic hydroxylamine and also a P450 2W1/5F 203 incubation mixture indicated the formation of dGuo adduct via a putative nitrenium intermediate. P450 2W1-catalyzed oxidation of GW 610 was 5-fold more efficient than the P450 1A1-catalyzed reaction. GW 610 underwent a two-step oxidation process catalyzed by P450 1A1 or 2W1: a regiospecific O-demethylation and a further hydroxylation. Glutathione (GSH) conjugates of 5F 203 and GW 610, presumably through a quninoneimine and a 1,2-quinone intermediate, respectively, were detected. These results demonstrate that human P450s 1A1 and 2W1 mediate 5F 203 and GW 610 bioactivation to reactive intermediates and lead to GSH conjugates and a dGuo adduct, which may account for the antitumor activities of 5F 203 and GW 610 and also be involved in cell toxicity. P450 2S1 can catalyze the reduction of the hydroxylamine to the amine 5F 203 under anaerobic conditions and, to a lesser extent, under aerobic conditions, thus attenuating the anticancer activity.

Metabolically stabilized benzothiazoles for imaging of amyloid plaques

Six new N-11C-labeled aminophenylbenzothiazoles substituted with fluorine in different positions have been synthesized and evaluated as amyloid-β binding ligands. Our structure-property relationship studies show that the substitution pattern of

Substituted 2-arylbenzazole compounds and their use as antitumour agents

Substituted 2-phenylbenzazole compounds of formula (I) wherein X represents S or O and Q represents a direct bond, —CH2— or —CH═Ch—, exhibt selective antiproliferactive activity in respect of mammalian tumour cells. At least in preferred enbodiments the b

Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)benzothiazoles

Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted-phenyl)benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and 7-fluorobenzothiazoles were formed from the established Jacobsen cyclization of precursor 3-

The regiospecific synthesis of 5- and 7-monosubstituted and 5,6- disubstituted 2-arylbenzothiazoles

The regiospecific synthesis of a range of antitumour 2- arylbenzothiazoles substituted in the benzothiazole ring is described. In this procedure a bromine atom situated ortho to the anilido nitrogen is used to direct a regiospecific cyclisation where, in the absence of bromine, a mixture of regioisomers is produced. The chemistry described is applicable to the synthesis of 2-arylbenzothiazoles bearing both electron-withdrawing (- NO2) and electron-donating (-NH2) substituents on the aryl ring.