Studies towards the next generation of antidepressants. Part 4: derivatives of 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine with affinity for the serotonin transporter and the 5-HT1A receptor.
Derivatives of the serotonin reuptake inhibitor 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine, in which serotonin 1A (5-HT(1A)) receptor pharmacophoric elements are incorporated, are reported. Analogs exhibiting affinity for both the serotonin transporter and the 5-HT(1A) receptor are described. Compounds containing 1-(4-indolyl)piperazine and 2-(1H-indol-4-yloxy)ethylamine are promising leads for further SAR studies.
Evrard
Deborah A
DA
Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. evrardd@wyeth.com
Zhou
Ping
P
Yi
Soo Y
SY
Zhou
Dahui
D
Smith
Deborah L
DL
Sullivan
Kelly M
KM
Hornby
Geoffrey A
GA
Schechter
Lee E
LE
Andree
Terrance H
TH
Mewshaw
Richard E
RE
D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D005021:Ethylamines; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010879:Piperazines; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000928:Antidepressive Agents; D003514:Cyclohexylamines; D005021:Ethylamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D044282:Receptor, Serotonin, 5-HT1A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human