(S)-2-(4-(dimethylamino)benzamido)-N8-hydroxy-N1-(quinolin-8-yl)octanediamide

• 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: (S)-2-(4-(dimethylamino)benzamido)-N8-hydroxy-N1-(quinolin-8-yl)octanediamide
• 英文别名: (2S)-2-[[4-(dimethylamino)benzoyl]amino]-N'-hydroxy-N-quinolin-8-yloctanediamide
• 化学式: C₂₆H₃₁N₅O₄
• 分子量: 477.563
• InChiKey: AWLFNVKRXDPUCZ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-7-(4-(dimethylamino)benzamido)-8-oxo-8-(quinolin-8-ylamino)octanoic acid 在 盐酸羟胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以41%的产率得到(S)-2-(4-(dimethylamino)benzamido)-N8-hydroxy-N1-(quinolin-8-yl)octanediamide
  参考文献：
  名称：

  Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components

  摘要：

  Malaria is the most lethal parasite-mediated tropical infectious disease, killing 1-2 million people each year. An emerging drug target is the enzyme Plasmodium falciparum histone deacetylase 1 (PfHDAC1). We report 26 compounds designed to bind the zinc and exterior surface around the entrance to the active site of PfHDAC1, 16 displaying potent in vitro antimalarial activity (IC(50) < 100 nM) against P. falciparum. Selected compounds were shown to cause hyperacetylation of P. falciparum histones and be > 10-fold more cytotoxic towards P. falciparum than a normal human cell type (NFF). Twenty-two inhibitors feature cinnamic acid derivatives or non-steroidal anti-inflammatory drugs (NSAIDs) as HDAC-binding components. A homology model of PfHDAC1 enzyme gives new insights to interactions likely made by some of these inhibitors. Results support PfHDAC1 as a promising new antimalarial drug target. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.096

文献信息

• Design, Synthesis, Potency, and Cytoselectivity of Anticancer Agents Derived by Parallel Synthesis from α-Aminosuberic Acid
  作者：Pia Kahnberg、Andrew J. Lucke、Matthew P. Glenn、Glen M. Boyle、Joel D. A. Tyndall、Peter G. Parsons、David P. Fairlie

  DOI：10.1021/jm050214x

  日期：2006.12.1

  differentiating agents to selectively kill cancer cells or transform them to a nonproliferating or normal phenotype could lead to cell- and tissue-specific drugs without the side effects of current cancer chemotherapeutics. This may be possible for a new generation of histone deacetylase inhibitors derived from amino acids. Structure-activity relationships are now reported for 43 compounds derived from 2-aminosuberic

  上个世纪的化学疗法的特征是不能区分癌细胞和正常细胞类型的细胞毒性药物，因此伴有通常限制剂量的毒性副作用。分化剂选择性杀死癌细胞或将其转化为非增殖或正常表型的能力可能导致细胞和组织特异性药物的产生，而没有当前癌症化学疗法的副作用。对于衍生自氨基酸的新一代组蛋白脱乙酰基酶抑制剂来说，这可能是可能的。现已报道了43种衍生自2-氨基磺酸的化合物的结构-活性关系，这些化合物可杀死多种癌细胞，其中26种是针对MM96L黑色素瘤细胞（IC50 20 nM-1 microM）的有效细胞毒素，而17种在杀死MM96L黑色素瘤细胞方面的选择性比正常（新生儿包皮成纤维细胞，NFF）细胞高5到60倍。与先前报道的衍生自半胱氨酸的化合物相比，这表示效力增加了10至100倍，并且选择性提高了多达10倍（J. Med。Chem。2004，47，2984）。选择性也被低估了，因为正常细胞NFF很少被所有药物杀死，这些药物
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
• Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components
  作者：Nicole C. Wheatley、Katherine T. Andrews、Truc L. Tran、Andrew J. Lucke、Robert C. Reid、David P. Fairlie

  DOI：10.1016/j.bmcl.2010.09.096

  日期：2010.12

  Malaria is the most lethal parasite-mediated tropical infectious disease, killing 1-2 million people each year. An emerging drug target is the enzyme Plasmodium falciparum histone deacetylase 1 (PfHDAC1). We report 26 compounds designed to bind the zinc and exterior surface around the entrance to the active site of PfHDAC1, 16 displaying potent in vitro antimalarial activity (IC(50) < 100 nM) against P. falciparum. Selected compounds were shown to cause hyperacetylation of P. falciparum histones and be > 10-fold more cytotoxic towards P. falciparum than a normal human cell type (NFF). Twenty-two inhibitors feature cinnamic acid derivatives or non-steroidal anti-inflammatory drugs (NSAIDs) as HDAC-binding components. A homology model of PfHDAC1 enzyme gives new insights to interactions likely made by some of these inhibitors. Results support PfHDAC1 as a promising new antimalarial drug target. (C) 2010 Elsevier Ltd. All rights reserved.