W. T. Ashton et al. / Bioorg. Med. Chem. Lett. 11 (2001) 2597–2602
2601
Table 3. Inhibition of GnRH receptor binding and PI turnover by
tryptamine derivatives with two-carbon tether to a heterocycle
Acknowledgements
We are grateful to Amy Bernick and Dr. Lawrence
Colwell for providing mass spectral data, to Robert
Frankshun, Amanda Makarewicz, Joseph Simeone,
Mamta Parikh, and Dr. Peter Lin for preparation of
certain intermediates, to Dr. Jonathan Young for sup-
plying conditions for the Fukuyama–Mitsunobu amine
alkylation methodology, and to Joseph Simeone and
Robert Bugianesi for permission to use their unpub-
lished data. We are indebted to Jinchang Chen and
Mellissa Creighton in Drug Metabolism for pharmaco-
kinetics support. For assistance in the animal experi-
ments, we also thank Klaus Schleim in Animal
Pharmacology, as well as Dr. Judy Fenyk-Melody, Dr.
William Feeney, Dr. Susan Iliff, Donald Hora, Paul
Cunningham, Bonnie Friscino, Alison Kulick, and
Allison Parlapiano in Comparative Medicine.
Compd
Het
hGnRH IC50 (nM)a PI turnover IC50 (nM)b
31
5.3
0.2
0.4
0.3
1.0
0.6
0.4
82
32
33
34
35
36
37
1.4
3.9
1.0
11
References and Notes
4.0
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Figure 1. Effect of oral 24 (administration at time=6 h indicated by
arrow) on LH release in a castrated male rat, as described in ref 21.