2876-17-7

Usage

Uses

Used in Pharmaceutical Industry:
1-Methoxyphenazine is used as an antipsychotic agent for the treatment of schizophrenia and other psychotic disorders. It is effective due to its action as a dopamine antagonist, which helps in reducing the intensity of psychotic symptoms.
1-Methoxyphenazine is also used as a sedative to provide relief from agitation and restlessness often associated with psychiatric conditions, enhancing patient comfort during treatment.
Furthermore, 1-Methoxyphenazine serves as an antiemetic, addressing issues of nausea and vomiting that may accompany certain psychiatric disorders or their treatments, thereby improving patient care and medication adherence.
While the provided materials do not specify additional industries or applications for 1-Methoxyphenazine, its primary use is within the pharmaceutical industry for psychiatric treatment, as described above. If there are other applications or industries where 1-Methoxyphenazine is utilized, they would need to be specified in the materials for accurate inclusion.

InChI:InChI=1/C13H10N2O/c1-16-12-8-4-7-11-13(12)15-10-6-3-2-5-9(10)14-11/h2-8H,1H3

Upstream product

• 528-71-2 phenazin-1-ol 
• 3577-37-5 1-chlorophenazine 
• 536-90-3 m-Anisidine 
• 98-95-3 nitrobenzene 
• 90-04-0 2-methoxy-phenylamine 
• 116668-84-9 3-nitroveratrole 
• 62-53-3 aniline 
• 74-88-4 methyl iodide 
• 7664-93-9 sulfuric acid 
• 16315-07-4 2,3-dinitroanisole 
• 87-66-1 2-hydroxyresorcinol 
• 60855-15-4 3-methoxy-[1,2]benzoquinone 
• 95-54-5 1,2-diamino-benzene 
• 1346682-87-8 3-chloro-1-methoxyphenazine 

Downstream Products

• 65162-13-2 1-methoxy-5-methylphenazinium methyl sulfate 
• 528-71-2 phenazin-1-ol 
• 3225-16-9 1-phenylphenazine 
• 39022-48-5 N-phenylphenazin-1-amine 
• 2881-89-2 1-Amino-4-methoxy-phenazin 

Relevant academic research and scientific papers

An Efficient Buchwald-Hartwig/Reductive Cyclization for the Scaffold Diversification of Halogenated Phenazines: Potent Antibacterial Targeting, Biofilm Eradication, and Prodrug Exploration

Bacterial biofilms are surface-attached communities comprised of nonreplicating persister cells housed within a protective extracellular matrix. Biofilms display tolerance toward conventional antibiotics, occur in ～80% of infections, and lead to >500000 deaths annually. We recently identified halogenated phenazine (HP) analogues which demonstrate biofilm-eradicating activities against priority pathogens; however, the synthesis of phenazines presents limitations. Herein, we report a refined HP synthesis which expedited the identification of improved biofilm-eradicating agents. 1-Methoxyphenazine scaffolds were generated through a Buchwald-Hartwig cross-coupling (70% average yield) and subsequent reductive cyclization (68% average yield), expediting the discovery of potent biofilm-eradicating HPs (e.g., 61: MRSA BAA-1707 MBEC = 4.69 μM). We also developed bacterial-selective prodrugs (reductively activated quinone-alkyloxycarbonyloxymethyl moiety) to afford HP 87, which demonstrated excellent antibacterial and biofilm eradication activities against MRSA BAA-1707 (MIC = 0.15 μM, MBEC = 12.5 μM). Furthermore, active HPs herein exhibit negligible cytotoxic or hemolytic effects, highlighting their potential to target biofilms.

Structure-Activity Relationships of a Diverse Class of Halogenated Phenazines That Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and Mycobacterium tuberculosis

Persistent bacteria, including persister cells within surface-attached biofilms and slow-growing pathogens lead to chronic infections that are tolerant to antibiotics. Here, we describe the structure-activity relationships of a series of halogenated phena

An umpolung strategy for rapid access to thermally activated delayed fluorescence (TADF) materials based on phenazine

Herein, Ag(I)-promoted regioselective intramolecular radical nucleophilic addition/rearrangement of 2-aryl diazaboroles has been accomplished for the first time to construct phenazine structures. This protocol is an umpolung strategy based on the classical electrophilic mechanism, and therefore, a reversed regioselectivity was observed, which provides an opportunity to prepare sterically hindered phenazines. The resulting thermally activated delayed fluorescence (TADF) materials based on phenazine exhibit emission bands from green to red with high quantum yields and moderate fluorescence lifetimes as solid films.

Biosynthetic Pathway Construction and Production Enhancement of 1-Hydroxyphenazine Derivatives in Pseudomonas chlororaphis H18

1-Hydroxyphenazine derivatives are phenazine family chemicals with broad-spectrum antibacterial and potential biological activities. However, the lack of variety and low titer hinder their applications. In this research, three enzymes PhzS (monooxygenase), NaphzNO1 (N-monooxygenase), and LaphzM (methyltransferase) were heterologously expressed in a phenazine-1-carboxylic acid generating strain Pseudomonas chlororaphis H18. Four phenazines, 1-hydroxyphenazine, 1-methoxyphenazine, 1-hydroxyphenazine N′ 10-oxide, and a novel phenazine derivative 1-methoxyphenazine N′ 10-oxide, were isolated, characterized in the genetically modified strains, and exhibited excellent antimicrobial activities. Next, we verified the hydroxyl methylation activity of LaphzM and elucidated the biosynthetic pathway of 1-methoxyphenazine N′ 10-oxide in vitro. Moreover, the titer of 1-hydroxyphenazine derivatives was engineered. The three compounds 1-methoxyphenazine, 1-hydroxyphenazine N′ 10-oxide, and 1-methoxyphenazine N′ 10-oxide all reach the highest titer reported to date. This work provides a promising platform for phenazine derivatives' combinatorial biosynthesis and engineering.

Design, synthesis and biological evaluations of diverse Michael acceptor-based phenazine hybrid molecules as TrxR1 inhibitors

A series of novel phenazine derivatives (1~27) containing the Michael acceptor scaffolds were designed and synthesized in this study. Some compounds exhibited selective cytotoxicity against Bel-7402 cancer cell line in vitro, in which compound 26 were found to have the best antiproliferative activity. Meanwhile, compound 26 showed no obvious cell toxicity against human normal liver epithelial L02 cells, which means this compound possessed a better safety potential. In the following research, compound 26 was verified to inhibit TrxR1 enzyme activity, ultimately resulting in cellular molecular mechanism events of apoptosis including growth of intracellular ROS level, depletion of reduced Trx1, liberation of ASK1 and up-regulation of p38, respectively. Together, all these evidences implicated that compound 26 acted as the TrxR1 inhibitor against Bel-7402 cells, and could activate apoptosis through the ROS-Trx-ASK1-p38 pathway.

Synthesis of phenazines from ortho-bromo azo compounds via sequential Buchwald-Hartwig amination under micellar conditions and acid promoted cyclization

Non-symmetric phenazines were synthesized via the Buchwald-Hartwig amination of ortho-bromoazobenzenes with anilines under micellar conditions, using the commercially available surfactant Kolliphor EL in water, followed by an acid-promoted 6π-electrocyclization-aromatization process. Two different synthetic pathways to obtain the ortho-bromo azo intermediates were explored, namely the palladium catalysed selective ortho bromination of azobenzenes and the diazo coupling of ortho-bromo diazonium salts with N,N-dimethylaniline, imidazole, phenol, sodium methanesulfinate and ethyl chloroformate.

Functional and Structural Analysis of Phenazine O -Methyltransferase LaPhzM from Lysobacter antibioticus OH13 and One-Pot Enzymatic Synthesis of the Antibiotic Myxin

Myxin is a well-known antibiotic that had been used for decades. It belongs to the phenazine natural products that exhibit various biological activities, which are often dictated by the decorating groups on the heteroaromatic three-ring system. The three rings of myxin carry a number of decorations, including an unusual aromatic N5,N10-dioxide. We previously showed that phenazine 1,6-dicarboxylic acid (PDC) is the direct precursor of myxin, and two redox enzymes (LaPhzS and LaPhzNO1) catalyze the decarboxylative hydroxylation and aromatic N-oxidations of PDC to produce iodinin (1.6-dihydroxy-N5,N10-dioxide phenazine). In this work, we identified the LaPhzM gene from Lysobacter antibioticus OH13 and demonstrated that LaPhzM encodes a SAM-dependent O-methyltransferase converting iodinin to myxin. The results further showed that LaPhzM is responsible for both monomethoxy and dimethoxy formation in all phenazine compounds isolated from strain OH13. LaPhzM exhibits relaxed substrate selectivity, catalyzing O-methylation of phenazines with non-, mono-, or di-N-oxide. In addition, we demonstrated a one-pot biosynthesis of myxin by in vitro reconstitution of the three phenazine-ring decorating enzymes. Finally, we determined the X-ray crystal structure of LaPhzM with a bound cofactor at 1.4 ? resolution. The structure provided molecular insights into the activity and selectivity of the first characterized phenazine O-methyltransferase. These results will facilitate future exploitation of the thousands of phenazines as new antibiotics through metabolic engineering and chemoenzymatic syntheses.

Synthesis and antichlamydial activity of novel phenazines

Background: Chlamydiae are widespread Gram-negative bacteria that cause a number of human diseases. Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen. Methods: Fourteen novel phenazine derivatives were efficiently synthesized via Buchwald-Hartwig cross coupling reaction and Suzuki reaction from 4-bromo-1-methoxyphenazine. All the derivatives displayed antichlamydial activity with IC50 values from 1.01-19.77 μM against Chlamydia trachomatis D and L2 for inhibiting progeny formation. Results: C-4 morpholinyl 8a and C-4 phenyl phenazine 9c exhibited stronger antichlamydial activity with no apparent cytotoxicity. Both phenazine derivatives inhibited chlamydial inclusions formation and growth in a dose-dependent manner. They inhibited Chlamydia infection by reducing elementary body infectivity and disturbing Chlamydia growth at the mid-stage of the chlamydial developmental cycle. Conclusion: Our findings suggest C-4 aryl and C-4 amino phenazine derivatives as promising lead molecules for antichlamydials development.

Reactivity and substituent effects in the cyclization of N-aryl-2-nitrosoanilines to phenazines

Reactivity of variously substituted N-aryl-2-nitrosoanilines in the reaction of cyclization leading to phenazine derivatives, carried out in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), was estimated on the base of the observed reaction times. A strong opposite effect of substituents located at position para to the nitroso group and those located para to the amino group in the side ring was observed. Mechanistic explanation, based on the electronic properties of the substituents and their mesomeric effects, was presented. The usefulness of the obtained data for the designed syntheses of phenazines was exposed.

N-Aryl-2-nitrosoanilines as intermediates in the synthesis of substituted phenazines from nitroarenes

N-Aryl-2-nitrosoanilines, available from the reaction of nitroarenes with anilide anions, undergo cycliza-tion to furnish substituted phenazines. The reaction is promoted by potassium carbonate in methanol, N,O-bis(trimethylsilyl) acetamide (BSA) in aprotic solvents, and by acetic acid. The method is illustrated by the synthesis of 1-methoxyphenazine, a precursor of pyocyanine, starting from the appropriate nitro-arene-aniline pairs.