N‐(Imidazolidin‐2‐ylidene)‐1‐arylmethanamine Oxides: Synthesis, Structure and Pharmacological Evaluation

Abstract

A high yielding three-step procedure was applied for the synthesis of N-(imidazolidin-2-ylidene)-1-arylmethanamine oxides 3 (α-aminonitrones) starting from the easily accessible imidazolidin-2-one O-benzyl oxime 1. The α-aminonitrone-α-iminohydroxyloamine tautomerism of these products was studied theoretically and the structures of the synthesised compounds were confirmed by single crystal X-ray crystallographic analysis. The compounds were evaluated in vitro for their binding affinities to α(1) and α(2) adrenoceptors as well as imidazoline I(1) and I(2) receptors. The highest potencies at the α(2) adrenergic receptors were observed for compounds bearing biphenyl (4h, K(i) = 9 nM) and naphthyl (4i, K(i) = 92 nM) moieties. Compounds 4h and 4i were further tested in vivo for their cardiovascular and sedative-hypnotic effects in rats.

Synthesis and reactivity of heterocyclic hydroxylamine-O-sulfonates

“…accidental, because subsequent studies have proven that analogous benzylation of 2-benzyloxyiminoimidazolidine assumes a similar course [38]. The results of our quantum chemical calculations suggest that the benzylation reaction of D proceeds under frontier orbital control.…”

<i>In Silico</i> Prediction of <i>N</i>-Nitrosamine Formation Pathways of Pharmaceutical Products

“…Gliclazide impurity B, Indapamide impurity A, and Indapamide impurity C were prepared according to the reported method. [24][25][26] In Silico Prediction of Degradation Pathway of Compounds Degradation products from gliclazide and indapamide were predicted by Zeneth ® (Version 9.0, KB 2022.1.2) (Lhasa Limited, Leeds, U.K.). In silico prediction was performed With the default parameters, including all the transformations (condensations and additions, eliminations and fragmentations, hydrolysis, isomerisations and rearrangements, oxidations and photochemical reactions) with the exception that pathway likelihood was selected as multiplied step likelihood (conditions; pH 1, 7, or 14 at 80 °C, maximum number of steps in a pathway: 4, maximum number of degradants was 1000, minimum score in multiplied step pathways: 0).…”

The 2-substituted imidazoline ring linked to an aromatic moiety by a biatomic bridge: a bioversatile scaffold

“…Particularly interesting was the derivative 11, which showed high affinity for I 2 -IBS and good selectivity over I 1 -IBS and α-ARs. Due to low lipophilicity, such a compound is not expected to cross the blood brain barrier and, therefore, might find application for the treatment of vascular hyperplasia [18].…”