Novel synthesis and pharmacological evaluation as alpha2-adrenoceptor ligands of O-phenylisouronium salts.
The synthesis of nine new mono- and bis-O-phenylisouronium compounds (2, 6b-10b and 12b-14b) and their Boc-protected isourea precursors (2a, 6a-10a and 12a-14a) is described. The carbodiimide 4, which was formed, had been suggested as the reactive intermediate species and driving force of the reaction. All final substrates were tested as potential alpha(2)-ARs ligands in human brain tissue by means of radioligand binding experiments and were compared to the potential antidepressant 1, as well as other related guanidine containing derivatives.
Goonan
Aine
A
School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
Kahvedzić
Amila
A
Rodriguez
Fernando
F
Nagle
Padraic S
PS
McCabe
Thomas
T
Rozas
Isabel
I
Erdozain
Amaia M
AM
Meana
J Javier
JJ
Callado
Luis F
LF
D058669:Adrenergic alpha-2 Receptor Antagonists; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000928:Antidepressive Agents; D008024:Ligands; D012492:Salts; D013440:Sulfides; D014508:Urea