title: 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.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA. zguo@neurocrine.com
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Guo
authors.forename: Dongpei
authors.initials: D
authors.lastname: Wu
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Zhu
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xie
authors.forename: R Scott
authors.initials: RS
authors.lastname: Struthers
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: 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*
chemical_list: D007659:Ketones; D011966:Receptors, LHRH; D014227:Triazines