3484-10-4

Basic information

• Product Name: 2-Methyl-4-nitroindole
• Synonyms: 2-Methyl-4-nitroindole;2-Methyl-4-nitro-1H-indole;4-Nitro-2-Methyl-1H-indole
• CAS NO: 3484-10-4
• Molecular Formula: C₉H₈N₂O₂
• Molecular Weight: 176.17202
• Product Categories: Heterocycles series;Pyrroles & Indoles
• Mol File: 3484-10-4.mol

Chemical Properties

• Melting Point: 192-194 °C
• Boiling Point: 365.6°Cat760mmHg
• Flash Point: 174.9°C
• Appearance: /
• Density: 1.355g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.694
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 15.34±0.30(Predicted)
• CAS DataBase Reference: 2-Methyl-4-nitroindole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methyl-4-nitroindole(3484-10-4)
• EPA Substance Registry System: 2-Methyl-4-nitroindole(3484-10-4)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 3484-10-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-Methyl-4-nitroindole is used as a synthetic intermediate for the development of AZD1981, a CRTH2 receptor antagonist. 2-Methyl-4-nitroindole is particularly beneficial for patients suffering from moderate to severe Chronic Obstructive Pulmonary Disease (COPD). By targeting the CRTH2 receptor, AZD1981 helps in managing the symptoms and improving the quality of life for COPD patients.
Additionally, 2-Methyl-4-nitroindole is used as a reagent in the preparation of anti-angiogenic pyrroloazaflavones. These compounds exhibit potential anti-cancer properties by inhibiting the formation of new blood vessels, which is a critical process for tumor growth and metastasis. The use of 2-Methyl-4-nitroindole in the synthesis of these anti-angiogenic agents contributes to the development of novel therapeutic strategies for cancer treatment.

Synthesis Reference(s)

Tetrahedron Letters, 40, p. 5395, 1999 DOI: 10.1016/S0040-4039(99)01014-X

InChI:InChI=1/C9H8N2O2/c1-6-5-7-8(10-6)3-2-4-9(7)11(12)13/h2-5,10H,1H3

Upstream product

• 133053-71-1 N-(2-methyl-3-nitro-phenyl)-acetimidic acid ethyl ester 
• 67-64-1 acetone 
• 99-09-2 3-nitro-aniline 
• 95-92-1 oxalic acid diethyl ester 
• 603-83-8 3-nitro-o-tolylamine 
• 133053-71-1 N-(2-Methyl-3-nitro-phenyl)-acetimidic acid ethyl ester 

Downstream Products

• 182234-10-2 2-methyl-4-amino-1H-indole 
• 1542706-42-2 N-benzyl-2-(2-methyl-4-(methylsulfonyl)-1H-indol-1-yl)-5,6,7,8-tetrahydroquinazolin-4-amine 
• 1542711-83-0 2-methyl-4-(methylsulfonyl)-1-(phenylsulfonyl)-1H-indole 
• 1542711-81-8 4-iodo-2-methyl-1-(phenylsulfonyl)-1H-indole 
• 1542706-38-6 1-[4-(benzylamino)-5H,7H,8H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-1H-indole-4-sulfonamide 
• 1542711-77-2 2-methyl-1-(phenylsulfonyl)-1H-indole-4-sulfonamide 
• 1542711-75-0 C₁₅H₁₂ClNO₄S₂ 
• 1542711-73-8 2-methyl-1-(phenylsulfonyl)-1H-indol-4-amine 
• 1542711-71-6 2-methyl-4-nitro-1-(phenylsulfonyl)-1H-indole 
• 1000604-27-2 1-(3-isopropyl-4-triisopropylsilanyloxybenzyl)-2-methyl-4-nitro-1H-indole 
• 628737-12-2 3-(4-chlorophenylsulfanyl)-2-methyl-4-nitro-1H-indole 

Relevant articles and documents

Discovery of novel pyrimidine molecules containing boronic acid as VCP/p97 Inhibitors

Valine-containing protein (VCP) is a member of the adenosine triphosphate family involved in a variety of cellular activities. VCP/p97 is capable of maintaining protein homeostasis and mediating the degradation of misfolded polypeptides by the ubiquitin–proteasome system (UPS). In this manuscript, a series of novel p97 inhibitors with pyrimidine as core structure were designed, synthesized and biologically evaluated. Based on the enzymatic results, a detailed structure–activity relationship discussion of the synthesized compounds was carried out. Furthermore, cellular activities of the compounds with enzymatic potency of less than 200 nM were investigated by using A549 and RPMI8226 cell lines. Among the screened inhibitors, compound 17 (IC50, 54.7 nM) showed good enzymatic activity. Investigation of cellular activities with non-small cell lung cancer A549 and multiple myeloma (MM) RPMI8226 further confirmed the potency of 17 with the IC50 values of 2.80 μM and 0.86 μM, respectively. Compound 17 is now being developed as a candidate. Finally, docking studies were carried out to explore the possible binding mode between the active inhibitor 17 and p97.

SMALL MOLECULE DIRECT INHIBITORS OF KEAP1-NRF2 PROTEIN-PROTEIN INTERACTION

This patent document diclsoes novel compounds and methods of preventing or treating diseases or conditions related to Keapl-Nrf2 interaction activity by use of the novel compounds. As direct inhibitors of Keapl-Nrf2 interaction, the compounds disclosed herein are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential dmg candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, Parkinson's, and inflammatory bowel disease including ulcerative colitis.

Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of non-small cell lung cancer

Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new molecule entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymatic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymatic inhibitory activity (IC50, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC50, 1.61 μM). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, respectively and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for intravenous treatment of non-small cell lung cancer.

1,2,4-TRIAZINE-6-CARBOXAMIDE DERIVATIVE

The present invention provides a compound represented by the following general formula (I) or a salt thereof which has a Syk inhibitory effect (in the formula R1 represents a hydrogen atom or an optionally Ra-substituted C1-C6 alkyl group; A represents a hydrogen atom, an optionally Ra-substituted C1-C8 alkyl group, an optionally Ra-substituted C2-C6 alkenyl group, an optionally Ra-substituted C2-C6 alkynyl group, an optionally Rb-substituted C3-C10 cycloalkyl group, an optionally Rb-substituted C6-C14 aromatic hydrocarbon group, an optionally Rb-substituted 4- to 10-membered unsaturated heterocyclic group, or an optionally Rb-substituted 4-to 10-membered saturated heterocyclic group, or optionally forms a 4- to 10-membered unsaturated heterocyclic ring or a 4- to 10-membered saturated heterocyclic ring together with R1 and the nitrogen atom bonded thereto; R2 represents a hydrogen atom or an optionally Ra-substituted C1-C6 alkyl group; and B represents an optionally Rc-substituted unsaturated heterocyclic group).

INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS

Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.

Synthesis, in vitro and in vivo preliminary evaluation of anti-angiogenic properties of some pyrroloazaflavones

This work investigated the in vitro and in vivo anti-angiogenic activity of some pyrroloazaflavones, exactly 2-phenyl-1H-pyrrolo[2,3-h]quinolin-4(7H)ones, with vinblastine as reference compound. Growth inhibitory activity, migration, and capillary-like structures formation were determined in human umbilical vein endothelial cell cultures, and Matrigel plug assay was carried out to evaluate in vivo effects on angiogenesis. Collectively, our results indicate that some pyrroloazaflavone derivatives, at non-cytotoxic concentrations and like vinblastine are able: (i) to exert in vitro anti-angiogenic activity and (ii) to counteract in vitro and in vivo the pro-angiogenic effects of fibroblast growth factor-2 (FGF-2).

NOVEL 6-5 BICYCIC HETEROCYCLIC DERIVATIVE AND MEDICAL USE THEREOF

An object of the present invention is to provide a medicament as a thyroid hormone receptor ligand which is sufficient in drug efficacy and safety, and has the excellent action as a drug. The present invention provides a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: [wherein [Chemical Formula 2] is a single bond or a double bond; A is -CH2- or -CO-; X, Y, and Z are each independently a nitrogen atom or a carbon atom; R1 is a hydrogen atom or an aralkyl group; R2 is an alkyl group or an aralkyl group, etc.; R3 is a hydrogen atom or an alkyl group, etc.; R4 is a hydrogen atom or an alkyl group; R5 is a hydrogen atom, an alkyl group or a halo lower alkyl group, etc.; R6 is a hydrogen atom or an alkyl group; R7 is a hydrogen atom, etc.; R8 is a hydrogen atom, or an alkyl group, etc.; and E is -NHCO-G-COR12, etc. (wherein G is a single bond or an alkylene group, and R12 is a hydroxy group or an alkoxy group)].

Synthesis of 4- and 6-substituted nitroindoles

Enolizable ketones react with m-nitroaniline in the presence of strong base such as t-BuOK to give 4- and 6-substituted nitroindoles. The reaction proceeds via oxidative nucleophilic substitution of hydrogen in m-nitroaniline with enolate anions in positions ortho to the amino group giving anionic σH adducts that are additionally stabilized by intramolecular interaction between the amino and the carbonyl group. Spontaneous oxidation of the σH adducts followed by the Bayer type condensation of the produced ortho-aminonitrobenzyl ketones gives 4- and 6-substituted nitroindoles. The scope of this reaction and its basic mechanistic features are discussed.

4-indole derivatives as serotonin agonists and antagonists

The present invention relates to compounds of the formula

A novel method of indole ring system construction: One-pot synthesis of 4- and 6-nitroindole derivatives via base promoted reaction between 3- nitroaniline and ketones

Base promoted condensation of ketones RCOCH2R' with 3-nitroaniline results in formation of the corresponding 4- and 6-nitro-2-R-3-R'-indoles. This multistep process apparently includes oxidative nucleophilic substitution of hydrogen in the arom