10328-92-4

Basic information

• Product Name: N-METHYLISATOIC ANHYDRIDE
• Synonyms: N-methyl isotoic anhydride;Isatoic anhydride, N-Methyl-;N-Methylisatioc anhydride;1-Methyl-4H-3,1-benzoxazine-2,4(1H)dione;N-Methylisatoic acid anhydride;NSC 76087;N-Methylisatoic anhydride technical, 90%;Melanoma-derived growth regulatory protein precursor
• CAS NO: 10328-92-4
• Molecular Formula: C₉H₇NO₃
• Molecular Weight: 177.16
• EINECS: 233-714-8
• Product Categories: pharmacetical;Anhydride Monomers;Monomers;Polymer Science
• Mol File: 10328-92-4.mol

Chemical Properties

• Melting Point: 165 °C (dec.)(lit.)
• Boiling Point: 309.06°C (rough estimate)
• Flash Point: 133.7 ºC
• Appearance: brownish chunks
• Density: 1.3312 (rough estimate)
• Vapor Density: 6.1 (vs air)
• Vapor Pressure: 0.00135mmHg at 25°C
• Refractive Index: 1.5200 (estimate)
• Storage Temp.: -20°C
• PKA: -2.24±0.20(Predicted)
• Sensitive: Moisture Sensitive
• CAS DataBase Reference: N-METHYLISATOIC ANHYDRIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-METHYLISATOIC ANHYDRIDE(10328-92-4)
• EPA Substance Registry System: N-METHYLISATOIC ANHYDRIDE(10328-92-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• RTECS: DM3140000
• TSCA: Yes
• Hazardous Substances Data: 10328-92-4(Hazardous Substances Data)

Usage

Uses

Used in RNA Structure Analysis:
N-Methylisatoic anhydride is used as a 2'-OH selective acylation agent for RNAs, playing a crucial role in resolving secondary RNA structures. It is widely employed in the SHAPE (Selective 2'-Hydroxyl Acylation Analyzed by Primer Extension) technology, which aids in understanding the complex structures and functions of RNA molecules.
Used in Pharmaceutical Synthesis:
In the pharmaceutical industry, N-Methylisatoic anhydride is used as a key intermediate in the synthesis of various drug compounds. It is first condensed with ethanolamine to produce N-(2-hydroxyethyl)-2-methylaminobenzamide. Further cyclization with ethyl pyruvate results in the formation of quinazoline derivatives. These derivatives, upon hydrolysis and dehydrative cyclization with l-methyl-2-chloropyridinium iodide, yield the l,4-oxazines[3,4-]quinazoline, which are valuable in the development of new pharmaceuticals.

InChI:InChI=1/C9H7NO3/c1-10-7-5-3-2-4-6(7)8(11)13-9(10)12/h2-5H,1H3

Upstream product

• 68790-40-9 N-methoxycarbonyl-N-methyl-anthranilic acid 
• 79228-33-4 N-carbethoxy-N-methylanthranilic acid 
• 119-68-6 N-Methylanthranilic acid 
• 541-41-3 chloroformic acid ethyl ester 
• 118-92-3 anthranilic acid 
• 77-78-1 dimethyl sulfate 
• 75-44-5 phosgene 
• 79-22-1 methyl chloroformate 
• 118-48-9 isatoic anhydride 
• 74-88-4 methyl iodide 
• 2058-74-4 1-methyl-1H-indole-2,3-dione 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 100-61-8 N-methylaniline 
• 201230-82-2 carbon monoxide 

Downstream Products

• 85-91-6 Methyl N-methylanthranilate 
• 56042-84-3 N,N-dimethyl-2-N'-methylaminobenzamide 
• 99985-64-5 o-methylaminobenzoate d'isopropyle 
• 31358-73-3 phenyl 2-(methylamino)benzoate 
• 58589-05-2 N-methyl-2-(3-phenyl-1,2,4-oxadiazol-5-yl)aniline 
• 52068-94-7 2-Methylamino-N-[2-(4-sulfamoyl-phenyl)-ethyl]-benzamide 
• 7505-81-9 2-methylaminobenzamide 
• 87296-85-3 2-Methylamino-N-morpholin-4-yl-benzamide 
• 93574-01-7 dihydro-3-(2-methylaminobenzoyl)-2(3H)-furanone 
• 93574-05-1 5,5-Dimethyl-3-(2-methylamino-benzoyl)-dihydro-furan-2-one 
• 113001-42-6 N-(2-methylaminobenzoyl)indole 
• 158091-45-3 N-Methyl-N'-(2-picolyl)anthranilic amide 
• 90260-19-8 2-methylamino-N-(3-imidazol-1-ylpropyl)benzamide 
• 72502-82-0 N-(2-(1H-indol-3-yl)ethyl)-2-(methylamino)benzamide 

Relevant articles and documents

One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction

The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation.

Design, synthesis and docking studies of novel 1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamide derivatives as a potential anti-proliferative agents

A new series of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide hybrids 8a-l have been designed and synthesized using peptide coupling agents with substituted N-phenyl piperazines and piperidines with good to excellent yields. The synthesized compounds were evaluated for their in?vitro anti-proliferative activity against PANC 1, HeLa and MDA-MB-231. The compounds 8d, 8e, 8f, 8g, 8h and 8k exhibited considerable anti-proliferative activity with GI50values ranging from 0.15 to 1.4?μM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against tubulin protein.

Discovery of Evodiamine Derivatives as Highly Selective PDE5 Inhibitors Targeting a Unique Allosteric Pocket

Clinical use of phosphodiesterase-5 (PDE5) inhibitors is limited by several side effects due to weak isoform selectivity. Herein, a unique allosteric pocket of PDE5 is identified by molecular modeling and structural biology, which enables the discovery of highly selective PDE5 inhibitors from natural product evodiamine (EVO). The crystal structure of PDE5 with bound EVO derivative (S)-7e revealed that binding of (S)-7e to the novel allosteric pocket induced dramatic conformation changes in the H-loop with a maximum 24 ? movement of their Cα atoms. This movement directly blocks the binding of substrate/inhibitors to the PDE5 active site, which is different from all traditional PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil. These derivatives showed >570-fold selectivity over PDE6C and PDE11A and achieved potent efficacy for the effective treatment of pulmonary hypertension in vivo.

Synthesis, regioselectivity, and DFT analysis of new antioxidant pyrazolo[4,3-c]quinoline-3,4-diones

The condensation of hydrazine, N-methylhydrazine, and N-phenylhydrazine with ethyl 4-chloro-2-oxo- 1,2-dihydroquinoline-3-carboxylate derivatives has been investigated. As a result, 12 new antioxidant pyrazolo[4,3- c]quinolin-3,4-diones were obtained with good to high yields. When two cross-products could be possible, only one isomer bearing the methyl or the phenyl group at the N1 position is isolated and unequivocally characterized using 1D and 2D NMR techniques, FT-IR, and combustion analyses. DFT analysis of the reaction mechanism was carried out in the Pearson’s hard soft acid base framework, confirming the assigned structure to the observed pyrazolo[4,3-c]quinolin-3,4-diones. These calculations indicate a favored kinetic control for the synthesized pyrazolo[4,3- c]quinolin-3,4-diones compared to its possible regioisomer.

Synthesis and antimicrobial activity of novel 4-Hydroxy-2-quinolone analogs

Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug discovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long alkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized. The antibacterial and antifungal activities of these analogs against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were investigated. The structure-activity relationship study revealed that the length of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial activities. Particularly, the brominated analogs 3j with a nonyl side chain exhibited exceptional antifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 μg/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity against S. aureus, although not as potent, showed a similar trend to the antifungal activity. The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment.

Design, Synthesis, and in vitro antitubercular activity of 1,2,3-triazolyl-dihydroquinoline derivatives

In the quest for new active molecules against Mycobacterium tuberculosis, a series of dihydroquinoline derivatives possessing triazolo substituents were efficiently synthesized using click chemistry. The structure of 6l was evidenced by X-ray crystallographic study. The newly synthesized compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC27294). The compounds 6a, 6g, and 6j (MIC: 3.13?μg/ml) showed promising activity when compared to the first-line drug such as ethambutol. In addition, the structure and antitubercular activity relationship were further supported by in silico molecular docking studies of the active compounds against 3IVX.PDB (crystal structure of pantothenate synthetase in complex with 2-(2-(benzofuran-2-ylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acid).

A novel templates of piperazinyl-1,2-dihydroquinoline-3-carboxylates: Synthesis, anti-microbial evaluation and molecular docking studies

A series of piperazinyl-1,2-dihydroquinoline carboxylates were synthesized by the reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylates with various piperazines and their structures were confirmed by 1H NMR, 13C NMR, IR and mass spectral analysis. All the synthesized compounds were screened for their in vitro antimicrobial activities. Further, the in silico molecular docking studies of the active compounds was performed to explore the binding interactions between piperazinyl-1,2-dihydroquinoline carboxylate derivatives and the active site of the Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCQ). The docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9b and 10c were identified as promising antimicrobial lead molecules. This study might provide insights to identify new drug candidates that target the S. aureus virulence factor, dehydrosqualene synthase.

Electrosynthesis of N-methylisatin

Isatin in a solution of dry N,N-dimethylformamide/NaClO4 is electroreduced in the presence of CH3I. N-methylisatin (NMI) is obtained in quantitative molar yield and high current efficiency by controlled potential electrolysis (CPE). NMI and N-methylisatoic anhydride are the reaction products when CPE is performed in the absence of CH3I, but adding it once the CPE was completed. The water effect on the identity and yield of the reaction product(s) is investigated. Reaction pathways are proposed.

One-step Synthesis for the Preparation of Quinoline Alkaloid Analogues

(Matrix Presented) A new one-step methodology has been introduced for the synthesis of quinoline alkaloid analogues. The reaction is based on a modification of the Mukaiyama aldol condensation, making use of the high reactivity of lactones or anhrydrides. The reaction is general and allows for the construction of new hetero polycondenced molecules in a one-step synthesis.

MODIFIED PROTEINS AND PROTEIN DEGRADERS

Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.