1494675-86-3

Usage

Uses

Used in Pharmaceutical Industry:
ZA7371 is used as a neuroprotective agent for its potential to protect neurons from damage in neurodegenerative diseases. Its ability to inhibit glutamate receptor-mediated responses may help in reducing excitotoxicity, a key factor in the progression of such diseases.
Used in Epilepsy Treatment:
ZA7371 is used as an anti-seizure medication for its potential to reduce seizure activity. By inhibiting the overactivation of glutamate receptors, it may help in controlling the excessive neuronal firing associated with epileptic seizures.
Used in Neurological Research:
ZA7371 is used as a research tool for studying the role of glutamate receptor ion channels in normal and pathological brain function. Its selective targeting of these receptors allows researchers to investigate their involvement in various neurological processes and disorders.
Used in Drug Development:
ZA7371 is used as a lead compound in the development of new therapeutic options for conditions involving glutamate receptor dysfunction. Further research and optimization of its chemical structure may lead to the discovery of more effective and safer drugs for the treatment of neurological disorders.

Upstream product

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

Relevant academic research and scientific papers

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

AZAINDOLE COMPOUNDS, SYNTHESIS THEREOF, AND METHODS OF USING THE SAME

The invention provides compounds of formula (I) and methods of treating a Mycobacterium infection or tuberculosis, or inhibiting DprE1 with the same.

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.

Azaindoles: Noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo

We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-β-D-ribose2′-epimerase (DprE1). With "drug-like" properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis.