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.

Article Details

Citation

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%).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Sumatriptan5-hydroxytryptamine receptor 1DEC 50 (nM)5.3N/AN/ADetails