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Usage

Uses

Used in Medicinal Chemistry:
4-Cyano-2-Methyl-1H-indole is utilized as a building block for the synthesis of various pharmaceutical compounds. Its unique structure and properties allow it to be a valuable component in the development of new drugs with potential therapeutic effects.
Used in Pharmaceutical Compounds Synthesis:
In the pharmaceutical industry, 4-Cyano-2-Methyl-1H-indole is used as a key intermediate in the synthesis of a wide range of pharmaceutical compounds. Its presence in these compounds can contribute to their biological activities and pharmacological effects, making it an essential component in drug discovery and development processes.
Used in Biological Activity and Pharmacological Effect Studies:
4-Cyano-2-Methyl-1H-indole is also employed in research studies focused on exploring its potential biological activities and pharmacological effects. Its unique chemical structure makes it an interesting target for scientists to investigate its interactions with biological systems and its potential role in treating various diseases and conditions.

Upstream product

• 74-88-4 methyl iodide 
• 877203-66-2 2-(2-bromophenyl)-3-methyl-2H-azirine 
• 21906-31-0 1-(2-bromophenyl)propane-2-one 
• 6127-18-0 4-bromo-2-methyl-1H-indole 
• 1232861-11-8 4-bromo-2-methyl-1-(phenylsulfonyl)-1H-indole 
• 412048-77-2 1‐(benzenesulfonyl)‐4‐bromo‐1H‐indole 
• 52488-36-5 4-bromo-1H-indole 
• 557-21-1 zinc(II) cyanide 
• 16136-52-0 4-cyanoindole 

Downstream Products

• 1542705-83-8 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 
• 1542705-58-7 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]-pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide 
• 1542705-09-8 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile 
• 1542706-02-4 1-(4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-2-methyl-1H-indole-4-carboxamide 
• 1542705-59-8 1-[4-(benzylamino)-5,6,7,8-tetrahydroquinazolin-2-yl]-2-methyl-1H-indole-4-carbonitrile 

Relevant academic research and scientific papers

Development of Red-Shifted and Fluorogenic Nucleoside and Oligonucleotide Diarylethene Photoswitches

The reversible modulation of fluorescence signals by light is of high interest for applications in super-resolution microscopy, especially on the DNA level. In this article we describe the systematic variation of the core structure in nucleoside-based diarylethenes (DAEs), in order to generate intrinsically fluorescent photochromes. The introduction of aromatic bridging units resulted in a bathochromic shift of the visible absorption maximum of the closed-ring form, but caused reduced thermal stability and switching efficiency. The replacement of the thiophene aryl unit by thiazol improved the thermal stability, whereas the introduction of a benzothiophene unit led to inherent and modulatable turn-off fluorescence. This feature was further optimized by introducing a fluorescent indole nucleobase into the DAE core, resulting in an effective photoswitch with a fluorescence quantum yield of 0.0166 and a fluorescence turn-off factor of 3.2. The site-specific incorporation into an oligonucleotide resulted in fluorescence-switchable DNA with high cyclization quantum yields and switching efficiency, which may facilitate future applications.

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.

Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)

The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-5083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell death. In tumor bearing mice, oral administration of 71 causes rapid accumulation of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. 71 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors.

SERINE/THREONINE PAK1 INHIBITORS

Compounds having the formula I wherein A, Z, R1a, R1b, R2, R3, R4, R5, R6, R7, R9, R10, Ra, Rb and n are as defined herein are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.