Drug discovery: phosphinolactone, in vivo bioisostere of the lactol group.
In drug discovery, structural modifications over the lead molecule are often crucial for the development of a drug. Herein, we reported the first in vivo bioisosteric effect of phosphinolactone function in relation to the lactol group constituting the bioactive molecule: Hydroxybupropion. The preparation of phosphinolactone analogues and their antidepressant evaluation towards forced swimming test in mice showed that biological activity was regained and even strengthen.
Volle
Jean-Noël
JN
Institut Charles Gerhardt Montpellier, ENSCM, 8 rue de l'Ecole Normale, 34296, Montpellier Cedex 5, France. jean-noel.volle@enscm.fr
Filippini
Damien
D
Krawczy
Bartlomiej
B
Kaloyanov
Nikolay
N
Van der Lee
Arie
A
Maurice
Tangui
T
Pirat
Jean-Luc
JL
Virieux
David
D
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D055808:Drug Discovery; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010721:Phosphinic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013550:Swimming
D000928:Antidepressive Agents; D007783:Lactones; D010721:Phosphinic Acids