N,N-diethyl-3β-hydroxy-5-cholenamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: N,N-diethyl-3β-hydroxy-5-cholenamide
• 英文别名: (R)-N,N-diethyl-4-((3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide；3β-hydroxy-cholen-(5)-oic acid-(24)-diethylamide；3β-Hydroxy-cholen-(5)-saeure-(24)-diaethylamid；3β-Hydroxy-N.N-diaethyl-cholen-(5)-amid-(24)；(4R)-N,N-diethyl-4-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanamide
• 化学式: C₂₈H₄₇NO₂
• 分子量: 429.687
• InChiKey: UHXLQEAPQSOPCF-JDTILAPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3B-羟基-D5-胆烯酸 在 吡啶 、 氢氧化钾 、 氯化亚砜 作用下， 生成 N,N-diethyl-3β-hydroxy-5-cholenamide
  参考文献：
  名称：

  Kuwada; Yago, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1937, vol. 57, p. 963,966; dtsch. Ref. S. 271

  摘要：

  DOI：

文献信息

• [EN] MRNAS ENCODING IMMUNE MODULATING POLYPEPTIDES AND USES THEREOF<br/>[FR] ARNM CODANT DES POLYPEPTIDES DE MODULATION IMMUNITAIRE ET LEURS UTILISATIONS
  申请人：MODERNA TX INC

  公开号：WO2021076805A1

  公开（公告）日：2021-04-22

  The disclosure features lipid nanoparticle (LNP) compositions comprising immune modulating polypeptides and uses thereof. The LNP compositions of the present disclosure comprise mRNA therapeutics encoding immune modulating polypeptides, e.g., interleukin 2 (IL- 2) and/or granulocyte macrophage colony stimulating factor (GM-CSF). The LNP compositions of the present disclosure can stimulate T regulatory cells, e.g., increase the level and/or activity of T regulatory cells in vivo or ex vivo.

  披露了包含免疫调节多肽的脂质纳米粒子（LNP）组合物及其用途。本公开的LNP组合物包括编码免疫调节多肽的mRNA治疗药物，例如白细胞介素2（IL-2）和/或粒细胞巨噬细胞集落刺激因子（GM-CSF）。本公开的LNP组合物可以刺激T调节细胞，例如在体内或体外增加T调节细胞的水平和/或活性。
• Structural requirements of cholenamide derivatives as the LXR ligands
  作者：Kana Saida–Tamiya、Minoru Tamiya、Genki Sekiya、Kazunori Isobe、Takaaki Kitazawa、Nobuhisa Isaka、Ayako Matsukawa、Kohichi Kawahara、Akihiko Komuro、Masaji Ishiguro

  DOI：10.1016/j.bmcl.2019.03.051

  日期：2019.6

  A study of the structural requirements of cholic acid derivatives as liver X receptor (LXR) ligands was performed. A model of cholenamide derivative 1 complexed with LXR showed that the C24 carbonyl oxygen forms a hydrogen bond with His435 located close to Trp457. The N,N-dimethyl group is located in a hydrophobic pocket. Based on these data, we designed compounds with high affinity for LXRs. Cholenamide

  对胆酸衍生物作为肝X受体（LXR）配体的结构要求进行了研究。与LXR络合的胆酰胺衍生物1的模型显示，C24羰基氧与位于Trp457附近的His435形成氢键。N，N-二甲基位于疏水口袋中。基于这些数据，我们设计了对LXR具有高亲和力的化合物。由3β-乙酰基-Δ5-胆酸20合成胆酰胺衍生物1-11，由醇25合成内酰胺12-19。在报告基因分析中，叔酰胺3和4表现出更高的活性，具有疏水残基的化合物表现出最高的活性所有衍生品。发现C23的立体化学是EC50和基因反式激活的重要决定因素，因为每种异构体均表现出不同的活性。
• STEROL ANALOGS AND USES THEREOF
  申请人：ModernaTX, Inc.

  公开号：US20220402965A1

  公开（公告）日：2022-12-22

  The invention relates to compositions and methods for the preparation, manufacture, and therapeutic use of compositions comprising mRNA and a lipid nanoparticle comprising a compound of the invention and an ionizable lipid.

  本发明涉及包含mRNA和脂质纳米粒子的组合物的制备、制造和治疗用途的方法和组合物，所述脂质纳米粒子包括本发明的化合物和可离子化脂质。
• Structure–activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect
  作者：Fumika Karaki、Kenji Ohgane、Kosuke Dodo、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2013.06.022

  日期：2013.9

  A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site. (C) 2013 Elsevier Ltd. All rights reserved.
• COMPOSITIONS AND METHODS FOR DELIVERY OF AGENTS TO IMMUNE CELLS
  申请人：ModernaTX, Inc.

  公开号：US20190314291A1

  公开（公告）日：2019-10-17

  The disclosure features immune cell delivery lipid nanoparticle (LNP) compositions that allow for enhanced delivery of agents, e.g., nucleic acids, such as therapeutic and/or prophylactic RNAs, to immune cells, in particular T cells, as well as B cells, dendritic cells and monocytes. The LNPs comprise an effective amount of an immune cell delivery potentiating lipid such that delivery of an agent by an immune cell delivery LNP is enhanced as compared to an LNP lacking the immune cell delivery potentiating agent. Methods of using the immune cell delivery LNPs for delivery of agents, e.g., nucleic acid delivery, for protein expression, for modulating immune cell activity and modulating immune responses are also disclosed.