Synthesis and properties of novel alkoxy- and phenoxyalkyl ethers of secondary and tertiary ethynylpiperidin-4-ols possessing unusual analgesic, anti-bacterial, anti-spasmotic, and anti-allergic properties as well as low toxicity

Abstract EN

Methodology was developed to obtain a series of unusual alkoxy-and phenoxyalkyl ethers of secondary and tertiary ethynylpiperidin-4-ols representative examples of which were evaluated for analgesic, anti-bacterial, anti-spasmodic, and anti-allergic activity.

Twenty-two new compounds were prepared and identified by elemental and spectra analyses.

Etherification of 4-hydroxypiperidin-4-ols was accomplished via Williamson ether-type syntheses in dry DMF.

Side reactions of the bromides used appeared to involve complex processes with DMF under a variety of conditions employed which led to modest yields of products.

Since all target molecules were oils at room temperature, conversions to P-cyclodextrins were accomplished and served as vehicles for pharmacological screening.

Several ethyl-substituted agents displayed deep analgesic activity in the "tail flick" model although some alkoxy- and phenoxy ethers from secondary alcohols were less effective as analgesics (Table 1).

Interestingly, LD50 values for the agents.