A convenient one-pot synthesis of asymmetric 1,3,5-triazine-2,4,6-triones and its application towards a novel class of gonadotropin-releasing hormone receptor antagonists.
A convenient one-pot synthetic route was developed for the preparation of asymmetric 1,3-dialkyl-1,3,5-triazine-2,4,6-triones from readily available alkyl- or aryl-isocyanates, primary amines and N-chlorocarbonyl isocyanate in excellent yields. Subsequent alkylation with N-protected amino alcohols afforded the desired 1,3,5-triazine-2,4,6-triones in good yields. This methodology was applied to the synthesis of a chemical library acting as antagonists of the hGnRH receptor.
Guo
Zhiqiang
Z
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA. zguo@neurocrine.com
Wu
Dongpei
D
Zhu
Yun-Fei
YF
Tucci
Fabio C
FC
Pontillo
Joseph
J
Saunders
John
J
Xie
Qiu
Q
Struthers
R Scott
RS
Chen
Chen
C
D000478:Alkylation; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis*; D011485:Protein Binding; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis*
D007659:Ketones; D011966:Receptors, LHRH; D014227:Triazines