Synthesis of aryl-1,2,4-triazine-3,5-diones as antagonists of the gonadotropin-releasing hormone receptor

doi:10.1016/j.bmcl.2005.06.057

Bioorganic & Medicinal Chemistry Letters

Volume 15, Issue 19, 1 October 2005, Pages 4363-4366

https://doi.org/10.1016/j.bmcl.2005.06.057 Get rights and content

Abstract

Several efficient synthetic routes for 2-, 4-, and 6-aryl-1,2,4-triazine-3,5-diones were developed. Derivatives were synthesized and studied as gonadotropin-releasing hormone antagonists in an effort to understand structure–activity relationships of the monocyclic compounds.

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Moreover, in the past few years, numerous small molecules possessing a 1,2,4-triazine scaffold have been shown to exhibit a great variety of pharmacological effects. Several reports have been published on the application of these compounds, such as 5-lipoxygenase (5-LOX) inhibitors [9,10], herbicides, bactericides, fungicides, antimicrobials [11,12] and gonadotropin-releasing hormone receptor (GnRH-R) antagonists [13]. Even for fused 1,2,4-triazine compounds not only antitumor and antimetastatic activity against a broad spectrum of cancer cells could be noted but also kinase inhibiting activities [1,14–17].
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Synthesis of aryl-1,2,4-triazine-3,5-diones as antagonists of the gonadotropin-releasing hormone receptor

Abstract

Graphical abstract

Annu. Rep. Med. Chem.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

J. Org. Chem.

Mol. Endocrinol.

J. Med. Chem.