Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors.
A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26nM at NET and SERT, respectively.
Vickers
Troy
T
Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Dyck
Brian
B
Tamiya
Junko
J
Zhang
Mingzhu
M
Jovic
Florence
F
Grey
Jonathan
J
Fleck
Beth A
BA
Aparicio
Anna
A
Johns
Michael
M
Jin
Liping
L
Tang
Hui
H
Foster
Alan C
AC
Chen
Chen
C
D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D000078764:Milnacipran; D015394:Molecular Structure; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors