Arylsulfochlorination of β-aminopropioamidoximes giving 2-aminospiropyrazolylammonium arylsulfonates

Russian Chemical Bulletin - The reaction of P-(morpholin-1-yl)propioamidoxime with aromatic sulfonyl chlorides (p-XC6H4SO2Cl; X = CH3O, CH3, H, Br, Cl, NO2) in chloroform in the presence of...     

IR, UV and NMR studies of ��-cyclodextrin inclusion complexes of kazcaine and prosidol bases

The interaction of the analgesic prosidol [1-(2-ethoxyethyl)-4-phenyl-4-propionyl-oxypiperidine] and the anaesthetic kazcaine [1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine] with ??-cyclodextrin (??-CD) in aqueous solutions has been studied by nuclear magnetic resonance (NMR), ultraviolet (UV) and infrared (IR) spectroscopy. The composition and structure of the formed guest:??-CD inclusion complexes have been determined and were found to have a molar ratio of 1:2, with the guest molecule located in the cavity formed by two ??-CD molecules in head-to-head orientation, with the O(2), O(3) rims interacting. The phenyl and ethoxyethyl substituents of the guests are in contact with the ??-CD molecules. In contrast to prosidol?Cbase and kazcaine?Cbase the complexes with ??-CD show a higher analgesic and local anaesthetic activity.     

Unusual Conformational Behavior of 3,7-Dihetera(N,N-;N,O-;N,S-) Bicyclo[3.3.1]Nonan-9-Ols Via Nmr Analysis

Abstract

Based upon the analysis of ¹H NMR data, along with molecular modeling, it was shown that the reduction of 3,7-dihetera(N,N-; N,O-; N,S-)bicyclo[3.3.1]nonan-9-ones by LiAlH₄ led to a mixture of two stereoisomeric secondary alcohols with different orientations of the hydroxyl groups in one of the ring systems. Diaza derivatives in deuterochloroform exist in predominant chair-boat conformations. However, the replacement of nitrogen in one of the heterocycles by oxygen or sulfur led to stereoisomers one of which existed in chair-boat conformation and another in a chair–chair conformation. In all cases the boat conformation is stabilized by formation of an intramolecular hydrogen bond (IMHB) between a lone electron pair of the nitrogen atom and a proton on the pseudo axial hydroxyl group of the other ring.     

Cyclization of O-benzoyl-β-piperidinopropionamidoximes to form 5-phenyl-3-(β-piperidino)ethyl-1,2,4-oxadiazoles

The reactions of -piperidinopropionamidoxime with substituted benzoyl chlorides afforded O-benzoylation products, which underwent cyclization to form 5-phenyl-3-(-piperidino)ethyl-1,2,4-oxadiazoles upon heating in dimethylformamide in the presence of molecular sieves at 60 °C for 1—2.5 h. Heating of O-benzoyl--piperidinopropionamidoxime in dimethylformamide in the presence of K₂CO₃ at 85 °C for 4 h afforded a mixture of 5-phenyl-3-(-piperidino)ethyl-1,2,4-oxadiazole, benzoic acid, and N-(-piperidino)ethylurea.     

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

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-spasmotic, 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 β-cyclodextrins were accomplished and served as vehicles for pharmacological screening. Several ethynyl-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 exceeded that of a number of clinical agents including Dimedrole, Klemastine, Lidocaine, No-spa, Tramal, Streptomycin, and Euphilline. Three representative examples of the agents (Table 2) exhibited moderate anti-bacterial action against Escherichia coli, Salmonella chloerae suis, Salmonella typhimurium, and Staphylococcus aureus, but did not exceed that of Streptomycin. The absence of the ethynyl ether group resulted in no anti-bacterial activity in several ethers. A few agents possessed anti-spasmotic ability, especially the ethers of 1-(2-ethoxyethyl)-4-ethynyl-4-hydroxypiperidines in various preparations (Table 3), and included the systems of acetylcholine-induced spasms, the histamine-induced spasms, and the calcium chloride-induced spasms. Two examples void of the ethynyl group were not effective as anti-spasmotic compounds. A small survey of five agents for anti-allergic properties (Table 4) revealed that two with ethynyl groups were similar in activity with Dimedrole but less than that of Klemastine in screens using acetylcholine and histamine systems. Overall, these families of piperidines possess a wide variety of important biological properties which require further exploration.