1125-01-5

Usage

Uses

Used in Pharmaceutical Industry:
3-azaspiro[5.5]undecane hydrochloride is used as a M2 proton channel blocker for inhibiting the influenza virus M2 protein (AM2). This application is particularly relevant in the development of antiviral drugs targeting the M2 protein, which plays a crucial role in the replication of the influenza virus.
Used in Chemical Synthesis:
3-azaspiro[5.5]undecane hydrochloride can be utilized as a building block or intermediate in the synthesis of more complex organic molecules, particularly those with potential pharmaceutical or chemical applications. Its unique structure and functional groups may offer novel opportunities for the development of new compounds with specific properties and activities.

InChI:InChI=1/C10H19N.ClH/c1-2-4-10(5-3-1)6-8-11-9-7-10;/h11H,1-9H2;1H

Upstream product

• 180-44-9 3-azaspiro[5.5]undecane 
• 1130-32-1 3-azaspiro[5.5]undecane-2,4-dione 

Relevant academic research and scientific papers

SPIRO-PIPERIDINE INHIBITORS

Provided are compounds that are capable of modulating the activity of the influenza A virus via interaction with the M2 transmembrane protein. Also provided are methods for treating an influenza A-affected disease state or infection comprising administering a composition comprising one or more compounds that have been identified as being capable of interaction with the M2 protein.

Discovery of spiro-piperidine inhibitors and their modulation of the dynamics of the M2 proton channel from influenza A virus

Amantadine has been used for decades as an inhibitor of the influenza A virus M2 protein (AM2) in the prophylaxis and treatment of influenza A infections, but its clinical use has been limited by its central nervous system (CNS) side effects as well as emerging drug-resistant strains of the virus. With the goal of searching for new classes of M2 inhibitors, a structure-activity relation study based on 2-[3-azaspiro(5,5)undecanol]-2-midazoline (BL-1743) was initiated. The first generation BL-1743 series of compounds has been synthesized and tested by two-electrode voltage-clamp (TEV) assays. The most active compound from this library, 3-azaspiro[5,5]undecane hydrochloride (9), showed an IC50 as low as0.92 ± 0.11 μM against AM2, more than an order of magnitude m ore potent than amantadine (IC50 = 16 μM). 15N and 13C solid-state NMR was employed to determine the effect of compound 9 on the structure and dynamics of the transmembrane domain of AM2 (AM2-TM) in phospholipid bilayers. Compared to amantadine, spiro-piperidine 9 (1) induces a more homogeneous conformation of the peptide,(2) reduces the dynamic disorder of the G34-I35 backbone near the water -filled central cavity of the helical bundle, and (3) influences the dynamics and magnetic environment of more residues within the transmembranehelices. These data suggest that spiro-piperidine 9 binds more extensiv ely with the AM2 channel, thus leading to stronger inhibitory potency.