(E)-(arylmethyleneaminoxy)acetamides as analogues of neuroleptic benzamides: synthesis and D2-dopaminergic binding affinity.
Some type B (E)-(arylmethyleneaminoxy)acetamides were synthesised as analogues of type A neuroleptic and antipsychotic benzamides, in which the aromatic group is substituted by a (methyleneaminoxy)methyl moiety (C = NOCH2, MAOMM). Theoretical studies were performed in order to verify whether conformational analogies could exist between type A and type B compounds. Type B compounds were tested for their D2-dopaminergic binding affinity which represents a valid indication of their potential neuroleptic and antipsychotic properties. Biological results indicate that the MAOMM is not able to substitute the aromatic group effectively in the field of neuroleptic benzamides. The results are discussed in the light of the structural analogies and the differences between the MAOMM and the aryl.
Macchia
M
M
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
Manera
C
C
Martinelli
A
A
Orlandini
E
E
Romagnoli
F
F
Rossello
A
A
Chiellini
G
G
D000081:Acetamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008787:Metoclopramide / Q000494:pharmacology; D008968:Molecular Conformation; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010091:Oximes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D000081:Acetamides; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010091:Oximes; D017448:Receptors, Dopamine D2; D008787:Metoclopramide