Author Topic: 4-alkylanilines to 5-alkyltryptamines  (Read 4430 times)

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pHarmacist

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4-alkylanilines to 5-alkyltryptamines
« on: September 12, 2003, 12:51:00 PM »
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)

DOI:

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.



Anyone smoked 5-tert-butyl-DMT?  8)


Rhodium

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4-Phthalimidobutanal Diethylacetal
« Reply #1 on: September 12, 2003, 08:31:00 PM »
Ah, interesting use of that 4-phthalimidobutanal diethyl acetal... They aren't telling how they arrived at the 4-aminobutyraldehyde diethyl acetal though - is it commercially available, or can it be made from GABA easily??

4-Phthalimidobutanal Diethyl Acetal

4-Phthalimidobutanal diethyl acetal (7) was prepared by treating 4-aminobutyraldehyde diethyl acetal (8.33 g, 90% pure, 46.5 mmol) with N-carbethoxyphthalimide (10.73 g, 48.95 mmol) in water (75 mL) in the presence of NaHCO3 (3.93 g, 46.82 mmol) for 2 h at room temperature. The reaction mixture was extracted with CH2Cl2 (3x100 mL). The combined organic layers were washed with 5% NaHCO3 solution, dried over K2CO3, filtered, and concentrated to give relatively pure 7 (13.2 g, 45.3 mmol) as a colorless oil in 97% yield.

I believe that it would be interesting to test 5-Ethyl-DMT, this as it has been shown that 5,N,N-Trimethyltryptamine is active, at least by smoking it.