Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors.
A series of milnacipran analogs were synthesized and studied as monoamine transporter inhibitors, and several potent compounds with moderate lipophilicity were identified from the 1S,2R-isomers. Thus, 15l exhibited IC(50) values of 1.7nM at NET and 25nM at SERT, which were, respectively, 20- and 13-fold more potent than 1S,2R-milnacipran 1-II.
Tamiya
Junko
J
Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Dyck
Brian
B
Zhang
Mingzhu
M
Phan
Kasey
K
Fleck
Beth A
BA
Aparicio
Anna
A
Jovic
Florence
F
Tran
Joe A
JA
Vickers
Troy
T
Grey
Jonathan
J
Foster
Alan C
AC
Chen
Chen
C
D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D000078764:Milnacipran; D015394:Molecular Structure; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000928:Antidepressive Agents; D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors