N-Methyl-5-tert-butyltryptamine: A Novel, Highly Potent 5-HT1D Receptor Agonist
Yao-Chang Xu,* John M. Schaus, Clint Walker, Joe Krushinski, Nika Adham, John M. Zgombick, Sidney X. Liang, Dan T. Kohlman, and James E. Audia
J. Med. Chem., 42 (3), 526-531, 1999 (http://pharmacist.the-hive.tripod.com/4alkyltryptamine.pdf)
(http://pharmacist.the-hive.tripod.com/4alkyltryptamine.pdf)
DOI:10.1021/jm9805945 (http://dx.doi.org/10.1021/jm9805945)
Abstract: It has been observed that reported 5-HT1D receptor agonists have at least one heteroatom (N, O, or S) on the 5-substituent of the indole. This has led to the hypothesis that a 5-substituent capable of participating in hydrogen bonding is critical for conveying high affinity. This article describes the synthesis and biological evaluation of a new series of 5-alkyltryptamine analogues, which does not have a heteroatom in the 5-substituent group. In contrast to the hypothesis, 5-alkyltryptamines all exhibit high binding affinities for the human 5-HT1D receptor. The size of the lipophilic alkyl group at the 5-position of the indole has significant impact on the 5-HT1D binding affinity. Compounds with a tert-butyl group at the 5-position such as 9d, 10, and 11 were identified. These analogues display high binding affinity (Ki < 1 nM) and moderate receptor selectivity in comparison with known antimigraine agents such as sumatriptan, naratriptan, rizatriptan, and VML-251.
(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000458614-file_bdhy.gif)
Anyone smoked 5-tert-butyl-DMT? 8)