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N ‐(Imidazolidin‐2‐ylidene)‐1‐arylmethanamine Oxides: Synthesis, Structure and Pharmacological Evaluation
Author(s) -
Saczewski Jarosław,
Hudson Alan,
Laird Shayna,
Rybczyńska Apolonia,
Boblewski Konrad,
Lehmann Artur,
Ma Daqing,
Maze Mervyn,
Watts Helena,
Gdaniec Maria
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201100028
Subject(s) - chemistry , oxime , biphenyl , tautomer , imidazoline receptor , stereochemistry , chemical synthesis , in vivo , in vitro , medicinal chemistry , organic chemistry , pharmacology , medicine , biochemistry , microbiology and biotechnology , biology
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.