- Design, Synthesis and Biological Evaluation of Novel Nonsteroidal Progesterone Receptor Antagonists Based on Phenylamino-1,3,5-triazine Scaffold
-
We report here the development of phenylamino-1,3,5-triazine derivatives as novel nonsteroidal progesterone receptor (PR) antagonists. PR plays key roles in various physiological systems, including the female reproductive system, and PR antagonists are promising candidates for clinical treatment of multiple diseases. By using the phenylamino-1,3,5-triazine scaffold as a template structure, we designed and synthesized a series of 4-cyanophenylamino-1,3,5-triazine derivatives. The synthesized compounds exhibited PR antagonistic activity, and among them, compound 12n was the most potent (IC50=0.30μM); it also showed significant binding affinity to the PR ligand-binding domain. Docking simulation supported the design rationale of the compounds. Our results suggest that the phenylamino-1,3,5-triazine scaffold is a versatile template for development of nonsteroidal PR antagonists and that the developed compounds are promising lead compounds for further structural development of nonsteroidal PR antagonists.
- Kaitoh, Kazuma,Nakatsu, Aki,Mori, Shuichi,Kagechika, Hiroyuki,Hashimoto, Yuichi,Fujii, Shinya
-
p. 566 - 575
(2019/07/22)
-
- Design and synthesis of 1,3,5-triazine derivatives as novel inverse agonists of nuclear retinoic acid receptor-related orphan receptor-γ
-
1,3,5-Triazine structure is a versatile chemical species for development of functional molecules, including biologically active compounds. We report herein the design, synthesis and biological evaluation of novel inverse agonists of nuclear retinoic acid receptor-related orphan receptor-γ (RORγ), in which the 2-anilino-1,3,5-triazine moiety was used as a scaffold for structural development. Among the synthesized compounds, 13b exhibited potent and selective inverse agonistic activity toward RORγ, being more potent than the lead compound T0901317 (7). The results suggest that the 2-anilino-1,3,5-triazine moiety is a useful scaffold for development of inhibitory ligands of nuclear receptors.
- Kaitoh, Kazuma,Toyama, Hirozumi,Hashimoto, Yuichi,Fujii, Shinya
-
p. 547 - 556
(2019/05/21)
-