2-iodo-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)benzamide | 1073143-37-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-iodo-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)benzamide
• 英文别名: N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-iodobenzamide
• CAS: 1073143-37-9
• 化学式: C₁₆H₁₀F₆INO₂
• 分子量: 489.156
• InChiKey: HWMSFWPDEHJRQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-iodo-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)benzamide 在 4-二甲氨基吡啶 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 tert-butyl (4-(1,1,1,3,3,3-hexafluoro-2-((4-methoxybenzyl)oxy)propan-2-yl)phenyl)(2-iodobenzoyl)carbamate
  参考文献：
  名称：

  LXR Antagonists with a 5-Substituted Phenanthridin-6-one Skeleton: Synthesis and LXR Transrepression Activities of Conformationally Restricted Carba-T0901317 Analogs

  摘要：

  DOI：

  10.3987/com-07-s(n)7
• 作为产物：
  描述：

  2-(4-氨基苯)-1,1,1,3,3,3-六氟-2-丙醇 、 邻碘苯甲酰氯 生成 2-iodo-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)benzamide
  参考文献：
  名称：

  LXR Antagonists with a 5-Substituted Phenanthridin-6-one Skeleton: Synthesis and LXR Transrepression Activities of Conformationally Restricted Carba-T0901317 Analogs

  摘要：

  DOI：

  10.3987/com-07-s(n)7

文献信息

• [EN] ROR GAMMA AGONISTS AS ENHANCERS OF PROTECTIVE IMMUNITY<br/>[FR] AGONISTES DE ROR GAMMA EN TANT QUE ACTIVTATEURS DE L'IMMUNITÉ PROTECTRICE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2017079120A1

  公开（公告）日：2017-05-11

  The T cell specific RORgamma isoform RORgammat has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated anti-tumor efficacy, RORgammat controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Agonists of RORgammat have been shown to increase the basal activity of RORgammat enhancing TH17 cell proliferation. Here we show that activation of RORgammat using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance anti-tumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORgammat should activate Tc17/TH17 cells, decrease the population of Tregs, repress PD-1, and produce IL17 in situ, an immune factor associated with good prognosis in cancer.

  T细胞特异性RORgamma亚型RORgammat已被证明是启动TH17和TC17细胞分化程序的关键谱系定义转录因子，这些细胞表现出抗肿瘤功效，RORgammat控制增强免疫的基因网络，包括增加IL17产生和减少免疫抑制。已经证明RORgammat的激动剂可以增加RORgammat的基础活性，增强TH17细胞增殖。在这里，我们展示了使用合成激动剂激活RORgammat会驱动TH17细胞增殖，同时降低免疫检查点蛋白PD-1的水平，这一机制应该增强抗肿瘤免疫，同时减弱肿瘤相关的适应性免疫抵抗。有趣的是，推测的内源性激动剂会驱动TH17细胞增殖，但不会抑制PD-1。这些发现表明，RORgammat的合成激动剂应该能够激活Tc17/TH17细胞，减少Tregs的数量，抑制PD-1，并在原位产生IL17，这是与癌症良好预后相关的免疫因子。
• [EN] MODULATORS OF THE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTORS<br/>[FR] MODULATEURS DES RÉCEPTEURS ORPHELINS LIÉS AU RÉCEPTEUR DE L'ACIDE RÉTINOÏQUE
  申请人：GRIFFIN PATRICK R

  公开号：WO2011115892A1

  公开（公告）日：2011-09-22

  The invention provides small molecule modulators of retinoic acid receptor-related orphan receptors such as RORα RORβ, or RORγ. Compounds of the invention can be effective modulators at concentrations ineffective to act on LXR receptors, or on other nuclear receptors, or other biological targets. Methods of modulation the RORs and methods of treating metabolic disorders, immune disorders, cancer, and CNS disorders wherein modulation of an ROR is medically indicated are also provided.

  这项发明提供了调节视黄酸受体相关孤儿受体的小分子调节剂，如RORα、RORβ或RORγ。该发明的化合物可以在无法对LXR受体或其他核受体或其他生物靶点产生作用的浓度下起到有效的调节作用。还提供了调节RORs的方法以及治疗代谢紊乱、免疫紊乱、癌症和中枢神经系统紊乱的方法，其中调节ROR在医学上是指示的。
• Structural development studies of anti-hepatitis C virus agents with a phenanthridinone skeleton
  作者：Masahiko Nakamura、Atsushi Aoyama、Mohammed T.A. Salim、Mika Okamoto、Masanori Baba、Hiroyuki Miyachi、Yuichi Hashimoto、Hiroshi Aoyama

  DOI：10.1016/j.bmc.2010.02.057

  日期：2010.4

  A phenanthridinone skeleton was derived from our previous researches on thalidomide and retinoids as a multi-template for generation of anti-viral lead compounds. Structural development studies focusing on anti-hepatitis C virus activity afforded 5-butyl-2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenanthridin-6(5H)-one (10) and 5-butylbenzo[b] phenanthridin-6(5H)-one(39), which showed EC50 values of approximately 3.7 and 3.2 mu M, respectively. (C) 2010 Elsevier Ltd. All rights reserved.