1494675-86-3

Basic information

• Product Name: ZA7371
• Synonyms: N-(2-Hydroxyethyl)-1-[(6-methoxy-5-methylpyrimidin-4-yl)methyl]-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide;DprE1-IN-1 ZA7371;ZA7371;DprE1-IN-1;AZ-7371;AZ-7371(DprE1-IN-1);TBA-7371
• CAS NO: 1494675-86-3
• Molecular Formula: C18H21N5O3
• Molecular Weight: 355.39104
• Mol File: 1494675-86-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 691.6±55.0 °C(Predicted)
• Appearance: /
• Density: 1.34±0.1 g/cm3(Predicted)
• PKA: 12.79±0.46(Predicted)
• CAS DataBase Reference: ZA7371(CAS DataBase Reference)
• NIST Chemistry Reference: ZA7371(1494675-86-3)
• EPA Substance Registry System: ZA7371(1494675-86-3)

Safety Data

• Hazardous Substances Data: 1494675-86-3(Hazardous Substances Data)

Usage

General Description

ZA7371 is a chemical compound that has been identified as a noncompetitive antagonist of the glutamate receptor ion channel. It is a potent inhibitor of both the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses in the central nervous system. ZA7371 has shown potential for neuroprotective and anti-seizure effects in preclinical studies, making it a promising candidate for the treatment of neurological disorders such as epilepsy and neurodegenerative diseases. Additionally, its selective targeting of glutamate receptor ion channels makes it a valuable tool for studying the role of these receptors in normal and pathological brain function. Further research and development of ZA7371 may lead to new therapeutic options for conditions involving glutamate receptor dysfunction.

Upstream product

• 1494676-28-6 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid ethyl ester 
• 533910-45-1 6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid ethyl ester 
• 533910-51-9 ethyl 3-(dimethylamino)-2-(5-methyl-3-nitropyridin-2-yl)acrylate 
• 533910-49-5 ethyl 2-(5-methyl-3-nitropyridin-2-yl)acetate 
• 23056-40-8 2-chloro-5-methyl-3-nitro-pyridine 
• 533910-47-3 2-(5-Methyl-3-nitro-pyridin-2-yl)-malonic acid diethyl ester 
• 1494676-19-5 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid 
• 141-43-5 ethanolamine 

Relevant articles and documents

1,4-azaindole, A potential drug candidate for treatment of tuberculosis

New therapeutic strategies against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis are urgently required to combat the global tuberculosis (TB) threat. Toward this end, we previously reported the identification of 1,4-azaindoles, a promising class of compounds with potent antitubercular activity through noncovalent inhibition of decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1). Further, this series was optimized to improve its physicochemical properties and pharmacokinetics in mice. Here, we describe the short-listing of a potential clinical candidate, compound 2, that has potent cellular activity, drug-like properties, efficacy in mouse and rat chronic TB infection models, and minimal in vitro safety risks. We also demonstrate that the compounds, including compound 2, have no antagonistic activity with other anti-TB drugs. Moreover, compound 2 shows synergy with PA824 and TMC207 in vitro, and the synergy effect is translated in vivo with TMC207. The series is predicted to have a low clearance in humans, and the predicted human dose for compound 2 is ≤1 g/day. Altogether, our data suggest that a 1,4-azaindole (compound 2) is a promising candidate for the development of a novel anti-TB drug. Copyright

Lead optimization of 1,4-azaindoles as antimycobacterial agents

In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-β-d-ribose-2′- epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies.