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3H-Imidazo[4,5-b]pyridine-6-carboxylic acid derivatives as rexinoids with reduced teratogenicity.
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2019-05-28 , DOI: 10.1016/j.bmcl.2019.05.050 Yuta Takamura 1 , Manami Takahashi 1 , Midori Nishii 2 , Osamu Shibahara 1 , Masaki Watanabe 1 , Michiko Fujihara 2 , Hiroki Kakuta 1
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2019-05-28 , DOI: 10.1016/j.bmcl.2019.05.050 Yuta Takamura 1 , Manami Takahashi 1 , Midori Nishii 2 , Osamu Shibahara 1 , Masaki Watanabe 1 , Michiko Fujihara 2 , Hiroki Kakuta 1
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Several retinoid X receptor (RXR) ligands (rexinoids), such as bexarotene (1), exhibit teratogenicity, which is a serious impediment to their clinical application. We considered that rexinoids with a lower level of maximal RXR transcription activation (i.e., partial agonists) and lower lipid solubility might show weaker adverse side effects. Based on this idea, we modified our previously reported pentamethyltetralin-type RXR partial agonists 5 and 6 to reduce their lipophilicity. Here, we report a new RXR partial agonist, 3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (8, CATF-PMN), which showed greatly reduced teratogenicity in zebrafish embryos.
中文翻译:
3H-咪唑并[4,5-b]吡啶-6-羧酸衍生物,类视黄醇,致畸性降低。
几种类维生素X受体(RXR)配体(类维生素),例如贝沙罗汀(1),具有致畸性,严重阻碍了其临床应用。我们认为具有最高RXR转录激活水平较低(即部分激动剂)和较低脂质溶解度的类维生素可能显示出较弱的不良副作用。基于这个想法,我们修改了我们先前报道的五甲基四氢萘型RXR部分激动剂5和6,以降低它们的亲脂性。在这里,我们报告了一种新的RXR部分激动剂,3-(3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基)-2-(三氟甲基)-3H-咪唑[ 4,5-b]吡啶-6-羧酸(8,CATF-PMN),在斑马鱼胚胎中显示出大大降低的致畸性。
更新日期:2019-05-28
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
3H-咪唑并[4,5-b]吡啶-6-羧酸衍生物,类视黄醇,致畸性降低。
几种类维生素X受体(RXR)配体(类维生素),例如贝沙罗汀(1),具有致畸性,严重阻碍了其临床应用。我们认为具有最高RXR转录激活水平较低(即部分激动剂)和较低脂质溶解度的类维生素可能显示出较弱的不良副作用。基于这个想法,我们修改了我们先前报道的五甲基四氢萘型RXR部分激动剂5和6,以降低它们的亲脂性。在这里,我们报告了一种新的RXR部分激动剂,3-(3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基)-2-(三氟甲基)-3H-咪唑[ 4,5-b]吡啶-6-羧酸(8,CATF-PMN),在斑马鱼胚胎中显示出大大降低的致畸性。