Local anesthetic activity of new amidoxime derivatives

Abstract

Three series of amidoxime derivatives including nitrous derivatives of a-chloro-a-isonitrosoacetone and hydrochlorides of O-aroyl-b-aminopropioamidoximes and 3-[b-(piperidin-1-yl)]ethyl-5-aryl-1,2,4-oxadiazoles were tested for conduction, infiltration, and terminal anesthesia. There are four interesting "hit" compounds, i.e., the hydrochloride of O-m-chlorophenyl-b-(benzimidazol-1-yl)propioamidoxime (VII), the hydrochlo-, which exhibit higher activity than the reference drugs (trimecaine, lidocaine, novocaine, kazcaine). As a whole, all tested compounds were active in conduction and infiltration anesthesia (at the level of the reference drugs) and did not show activity in terminal anesthesia. Compounds VII -X are of interest for further testing under condition and infiltration anesthesia conditions. Amidoximes are an attractive class of compounds with respect to their versatile reactivity at the imine and amine N atoms and the oxime O atom. As a result, various heterocyclic and linear derivatives containing pharmacophores that exhibit a broad spectrum of biological activity can be prepared [1]. These include antituberculosis, antimicrobial, antiviral, insecticidal, fungicidal, herbicidal, antidepressant, antihistamine, anti-inflammatory, local anesthetic, pyretic, etc. Several amidoximes are already used as drugs or are being tested in various phases of incorporation into medical 468 0091-150X/11/4508-0468 Note: p 1 , correlation coefficient relative to trimecaine; p 2 , relative to lidocaine; p 3 , relative to novocaine; p 4 , relative to kazcaine.

Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties

“…In the 13 C spectra of the compounds 4a-e, 5a-e and 6, all signals of aliphatic and aromatic protons were recorded in the expected regions.…”

“…The practical interest in the class of β-aminopropioamidoxime derivatives is supported by their pronounced local anesthetic, antitubercular, and antidiabetic activities [ 13 , 14 , 15 , 16 ].…”

“…In addition, spiropyrazolinium structures-2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-ene-5-ammonium arylsulfonates are formed at arylsulfochlorination of β-aminopropioamidoximes (Scheme 4) [12]. The practical interest in the class of β-aminopropioamidoxime derivatives is supported by their pronounced local anesthetic, antitubercular, and antidiabetic activities [13][14][15][16].…”

Amidoxime Derivatives with Local Anesthetic, Antitubercular, and Antidiabetic Activity

“…We developed new β-aminopropioamidoximes and studied their neurotropic properties. Herein we present results from a study of the local anesthetic activities of three chemical groups of new amidoxime derivatives [4].…”

“…Herein we present results from a study of the local anesthetic activities of three chemical groups of new amidoxime derivatives (1-10)[4].The first group includes derivatives of α-chloro-α-isonitrosoacetone such as 3acetyl-5,5-bis(hydroxymethyl)-5,6-dihydro-4H-1,2,4-oxadiazine(1) and the antiisomer of N-(4-methylphenyl)acetylformamidoxime thiosemicarbazone (2). The second group includes the hydrochlorides of O-aroyl-β-aminopropioamidoximes with piperidine (3), morpholine (4-6), and benzimidazole (7 and 8)intheβ-position.…”