Synthesis and pharmacological evaluation of 3-aryl-3-azolylpropan-1-amines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.
A series of 3-aryl-3-azolylpropan-1-amines was prepared and screened for its capability of inhibiting monoamine reuptake. Analogs with nanomolar potency, good human in vitro microsomal stability, and low drug-drug interaction potential were described. In vivo models were used to evaluate the compound 19r for antidepressive, anxiolytic, and analgesic activity.
Lee
Ki-Ho
KH
Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea. kiho.lee@sk.com
Park
Chun-Eung
CE
Min
Kyung-Hyun
KH
Shin
Yong-Je
YJ
Chung
Coo-Min
CM
Kim
Hui-Ho
HH
Yoon
Hae-Jeoung
HJ
Won-Kim
Ryu
Eun-Ju
EJ
Shin
Yu-Jin
YJ
Nam
Hyun-Sik
HS
Cho
Jeong-Woo
JW
Lee
Hee-Yoon
HY
D000700:Analgesics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D051379:Mice; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D009638:Norepinephrine / Q000378:metabolism*; D011437:Propylamines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013777:Tetrazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000700:Analgesics; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014179:Neurotransmitter Uptake Inhibitors; D011437:Propylamines; D013777:Tetrazoles; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine