Design, synthesis and biological activity of novel dimethyl-[2-[6-substituted-indol-1-yl]-ethyl]-amine as potent, selective, and orally-bioavailable 5-HT(1D) agonists.
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Isaac M, Slassi M, Xin T, Arora J, O'Brien A, Edwards L, MacLean N, Wilson J, Demschyshyn L, Labrie P, Naismith A, Maddaford S, Papac D, Harrison S, Wang H, Draper S, Tehim A
Design, synthesis and biological activity of novel dimethyl-[2-[6-substituted-indol-1-yl]-ethyl]-amine as potent, selective, and orally-bioavailable 5-HT(1D) agonists.
Bioorg Med Chem Lett. 2003 Dec 15;13(24):4409-13.
- PubMed ID
- 14643336 [ View in PubMed]
- Abstract
A novel series of highly potent human 5-HT(1D) agonists, dimethyl-[2-[6-substituted-indol-1-yl]-ethyl]-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K(i)=2.4 nM) agonist at the human 5-HT(1D) receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F(po)=51%).
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Sumatriptan 5-hydroxytryptamine receptor 1D EC 50 (nM) 5.3 N/A N/A Details