Design and synthesis of new potent, silent 5-HT1A antagonists by covalent coupling of aminopropanol derivatives with selective serotonin reuptake inhibitors.
Hybrid molecules built up by covalent coupling of aminopropanol derivatives (especially pindolol) with antidepressant drugs like fluoxetine, paroxetine or milnacipran were found to be potent and silent 5-HT1A antagonists (KB < 1 nM for 7c and 9a).
Perez
M
M
Medicinal Chemistry, Centre de Recherche Pierre Fabre, Castres, France. michel.perez@pierre-fabre.com
Pauwels
P J
PJ
Pallard-Sigogneau
I
I
Fourrier
C
C
Chopin
P
P
Palmier
C
C
Colovray
V
V
Halazy
S
S
D000818:Animals; D015195:Drug Design; D051379:Mice; D010394:Penbutolol / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism
D010394:Penbutolol; D010869:Pindolol; D011433:Propranolol; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors