Bicyclo[2.2.1]heptanes as novel triple re-uptake inhibitors for the treatment of depression.
A series of substituted naphthyl containing chiral [2.2.1] bicycloheptanes were prepared utilizing asymmetric Diels-Alder chemistry. This paper describes structure-activity relationships in this series. The N-methyl 2-naphthyl analogue (16d) and its des-methyl analogue (17d) are active triple re-uptake inhibitors both in vivo and in vitro.
Axford
Lorraine
L
Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK.
Boot
John R
JR
Hotten
Terrence M
TM
Keenan
Martine
M
Martin
Fionna M
FM
Milutinovic
Sandra
S
Moore
Nick A
NA
O'Neill
Michael F
MF
Pullar
Ian A
IA
Tupper
David E
DE
Van Belle
Kristel R
KR
Vivien
Vincent
V
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D001643:Bridged Bicyclo Compounds; D014179:Neurotransmitter Uptake Inhibitors; C116378:bicyclo(2.2.1)heptene