Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitors.
Derivatives of milnacipran were synthesized and studied as monoamine transporter inhibitors. Potent analogs were discovered at NET (9k) and at both NET and SERT (9s and 9u). A pharmacophore model was established based on the conformational analysis of milnacipran in aqueous solution using NMR techniques and was consistent with the SAR results.
Chen
Chen
C
Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Dyck
Brian
B
Fleck
Beth A
BA
Foster
Alan C
AC
Grey
Jonathan
J
Jovic
Florence
F
Mesleh
Michael
M
Phan
Kasey
K
Tamiya
Junko
J
Vickers
Troy
T
Zhang
Mingzhu
M
D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology; D000478:Alkylation; D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D003521:Cyclopropanes / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D000078764:Milnacipran; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000081:Acetamides; D000577:Amides; D003521:Cyclopropanes; D007211:Indoles; D050493:Vesicular Monoamine Transport Proteins; C057812:indoline; D000078764:Milnacipran