5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists

A Slassi; L Edwards; A O'Brien; C Q Meng; T Xin; C Seto; D K Lee; N MacLean; D Hynd; C Chen; H Wang; R Kamboj; S Rakhit

doi:10.1016/s0960-894x(00)00322-x

5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists

Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9. doi: 10.1016/s0960-894x(00)00322-x.

Authors

A Slassi¹, L Edwards, A O'Brien, C Q Meng, T Xin, C Seto, D K Lee, N MacLean, D Hynd, C Chen, H Wang, R Kamboj, S Rakhit

Affiliation

¹ NPS Allelix Corp., Mississauga, Ontario, Canada. slassi@allelix.com

PMID: 10937729
DOI: 10.1016/s0960-894x(00)00322-x

Abstract

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.

MeSH terms

Animals
In Vitro Techniques
Protein Binding
Rabbits
Receptor, Serotonin, 5-HT1D
Receptors, Serotonin / drug effects*
Receptors, Serotonin / metabolism
Saphenous Vein / drug effects
Serotonin Receptor Agonists / chemistry
Serotonin Receptor Agonists / metabolism
Serotonin Receptor Agonists / pharmacology*
Tryptamines / chemistry*
Tryptamines / metabolism

Substances

Receptor, Serotonin, 5-HT1D
Receptors, Serotonin
Serotonin Receptor Agonists
Tryptamines