- Design, Synthesis and Biological Evaluation of Novel Nonsteroidal Progesterone Receptor Antagonists Based on Phenylamino-1,3,5-triazine Scaffold
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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
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p. 566 - 575
(2019/07/22)
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- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 00796-00797
(2018/11/22)
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- Antiviral activities of some new 2,4,6-trisubstituted 1,3,5-triazines having alkoxy and/or alkylamino groups
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We report the preparation of C3-and CS-symmetrical 2,4,6-trisubstituted 1,3,5-triazine derivatives having alkoxy and/or alkylamino groups and results of biological evaluation of their anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity against Vero cells. New targeted symmetrical molecules were obtained by using a method starting with 2,4,6-trichloro-1,3,5-triazine (1). Among the synthesized compounds, CS-symmetrical tri-aliphatic alkylamino-substituted compound 6s showed high anti-HSV-1 activity (EC50 = 5.4 μM) and low cytotoxicity (CC50 > 200 μM). The results of an SAR study suggested that the presence of two hydrogen bond donor protons of sec-amine functionality in the molecule is an important structural factor for expression of potential anti-HSV-1 activities.
- Mibu, Nobuko,Yokomizo, Kazumi,Yuzuriha, Ai,Otsubo, Marie,Kawaguchi, Yuna,Sano, Marina,Sakai, Izumi,Nakayama, Keita,Zhou, Jian-Rong,Sumoto, Kunihiro
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p. 1653 - 1677
(2017/09/20)
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- Synthesis and antiviral evaluation of some C3-symmetrical trialkoxy-substituted 1,3,5-triazines and their molecular geometry
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As one of our projects, we here report some new molecular modifications of 2,4,6-trichloro-1,3,5-triazine (TCTAZ: 1) to symmetrical 2,4,6-trialkoxy- or 2,4,6-triaryloxy-substituted 1,3,5-triazine (TAZ) molecules, as well as the results of anti-herpes simplex virus type 1 (anti-HSV-1) activity evaluation of synthesized 2,4,6-trisubstituted TAZ derivatives. Among the tested 2,4,6-trisubstituted TAZ derivatives, we reconfirmed that a C3-symmetrical TAZ derivative, 4e, shows the highest level of anti-HSV-1 activity with a good selectivity index. In this paper, we also report the results of the preparation of newly targeted TAZ derivatives and the structure-activity relationships (SARs) of these trialkoxy-substituted TAZ derivatives and related compounds. The sugar recognition properties of C3-symmetrical TAZ derivative 4e are also described.
- Mibu, Nobuko,Yokomizo, Kazumi,Aki, Hatsumi,Ota, Norimasa,Fujii, Hiroyuki,Yuzuriha, Ai,Saneyoshi, Shiori,Tanaka, Aoi,Koga, Airi,Zhou, Jianrong,Miyata, Takeshi,Sumoto, Kunihiro
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p. 935 - 944
(2016/02/03)
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- NOVEL ORALLY BIOAVAILABLE BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME
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The present invention includes compositions that are useful in the prevention and/or treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of preventing and/or treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition of the invention.
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Page/Page column 149-150
(2014/06/11)
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- Selective mono- or dialkoxylation of 2,4,6-trichloro-1,3,5-triazine in solid-liquid phase transfer conditions
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In solid-liquid phase transfer conditions, both the primary and the secondary alcohols react cleanly with 2,4, 6-trichloro-1,3,5-triazine to give the corresponding mono or dialkoxy derivatives depending on the reagent molar ratio.
- Menicagli,Malanga,Peluso
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p. 2153 - 2158
(2007/10/02)
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