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
• Article Data: 12

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

2-Methyl-4-nitroindole is a useful synthetic intermediate in the synthesis of AZD1981, a CRTH2 receptor antagonist used in patients with moderate to severe COPD. 2-Methyl-4-nitroindole is also used as a reagent in the preparation of anti-angiogenic pyrroloazaflavones.

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

• 944055-59-8 3-[(2-methyl-4-nitroindol-3-yl)-p-chlorophenylmethyl]-4H-chromen-4-one 
• 944055-60-1 3-[(2-methyl-4-nitroindol-3-yl)-o-fluorophenylmethyl]-4H-chromen-4-one 
• 944055-61-2 3-[(2-methyl-4-nitroindol-3-yl)-o-(trifluoromethyl)phenylmethyl]-4H-chromen-4-one 
• 628737-12-2 3-(4-chlorophenylsulfanyl)-2-methyl-4-nitro-1H-indole 
• 182234-10-2 2-methyl-4-amino-1H-indole 
• 1542711-71-6 2-methyl-4-nitro-1-(phenylsulfonyl)-1H-indole 
• 1542711-73-8 2-methyl-1-(phenylsulfonyl)-1H-indol-4-amine 
• 1542711-75-0 C₁₅H₁₂ClNO₄S₂ 
• 1542711-77-2 2-methyl-1-(phenylsulfonyl)-1H-indole-4-sulfonamide 
• 1542706-38-6 1-[4-(benzylamino)-5H,7H,8H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-1H-indole-4-sulfonamide 
• 1542711-81-8 4-iodo-2-methyl-1-(phenylsulfonyl)-1H-indole 
• 1542711-83-0 2-methyl-4-(methylsulfonyl)-1-(phenylsulfonyl)-1H-indole 
• 1542706-42-2 N-benzyl-2-(2-methyl-4-(methylsulfonyl)-1H-indol-1-yl)-5,6,7,8-tetrahydroquinazolin-4-amine 

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.

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.

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.