5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists.
A series of 5-alkyltryptamines (6) and the corresponding conformationally constrained analogues (8) have been synthesized. The structure activity relationships (SAR) at the 5-position of the indole skeleton and the ethylamine side chain have been studied. Functional activities were assessed using isolated rabbit saphenous vein. Potent, selective ligands were found (6e, Ki 2.5 nM, 5-HT1B/5-HT1D 125-fold) that have potential for treating acute migraine.
NPS Allelix Corp., Mississauga, Ontario, Canada. slassi@allelix.com
A
A
Slassi
L
L
Edwards
A
A
O'Brien
C Q
CQ
Meng
T
T
Xin
C
C
Seto
D K
DK
Lee
N
N
MacLean
D
D
Hynd
C
C
Chen
H
H
Wang
R
R
Kamboj
S
S
Rakhit
D000818:Animals; D066298:In Vitro Techniques; D011485:Protein Binding; D011817:Rabbits; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014363:Tryptamines / Q000737:chemistry* / Q000378:metabolism
D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines