N-(5-((dibenzylamino)methyl)-4-oxo-4,7-dihydro-3H-pyrrolo-[2,3-d]pyrimidin-2-yl)octanamide | 88523-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: N-(5-((dibenzylamino)methyl)-4-oxo-4,7-dihydro-3H-pyrrolo-[2,3-d]pyrimidin-2-yl)octanamide
• 英文别名: Octanoic acid{5-[(dibenzylamino)-methyl]-4-oxo-4,7-dihydro-3h-pyrrolo[2,3-d]pyrimidin-2-yl}-amide；N-[5-[(dibenzylamino)methyl]-4-oxo-3,7-dihydropyrrolo[2,3-d]pyrimidin-2-yl]octanamide
• CAS: 88523-20-0
• 化学式: C₂₉H₃₅N₅O₂
• 分子量: 485.629
• InChiKey: QWQAKESRAMSQNY-UHFFFAOYSA-N

物化性质

• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  89.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(5-((dibenzylamino)methyl)-4-oxo-4,7-dihydro-3H-pyrrolo-[2,3-d]pyrimidin-2-yl)octanamide 在 苄基三乙基氯化铵 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 0.67h， 以76%的产率得到octanoic acid {4-chloro-5-[(dibenzylamino)-methyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-amide
  参考文献：
  名称：

  [EN] NOVEL HETEROCYCLIC COMPOUNDS AS HSP90-INHIBITORS
  [FR] NOUVEAUX COMPOSES HETEROCYCLIQUES UTILISES EN TANT QU'INHIBITEURS DE LA PROTEINE HSP90

  摘要：

  公开号：

  WO2005028434A3
• 作为产物：
  描述：

  2-氨基-4-羟基吡咯并[2,3-d]嘧啶 在 吡啶 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 24.5h， 生成 N-(5-((dibenzylamino)methyl)-4-oxo-4,7-dihydro-3H-pyrrolo-[2,3-d]pyrimidin-2-yl)octanamide
  参考文献：
  名称：

  新型5,6-二取代吡咯并[2,3- d ]嘧啶衍生物作为广谱抗增殖剂：合成，基于细胞的测定，激酶谱和分子对接研究

  摘要：

  两个新的系列5-subtituted和5,6-二取代的吡咯并[2,3的d ]嘧啶octamides（4A - ö和6A -克）和它们的相应的游离胺5A -米和图7a -克已被合成和生物学评价具有抗三种人类癌细胞系的抗增殖活性。5,6-二取代的辛酰胺6d – g以及胺衍生物7b在测试的癌细胞中均显示出最佳的抗癌活性，其单摩尔微摩尔GI 50值优于被测癌细胞，并且具有较低的细胞毒性作用（GI 50 > 10.0 µM）针对HFF-1正常细胞。已经建立了结构活性关系（SAR）研究，并揭示了C2的末端辛酰胺部分以及吡咯并[2,3- d ]嘧啶的C5和C6与氟苄基哌嗪的分解是关键的结构特征，是获得最佳抗增殖活性的前提。此外，测试了最活跃的成员6f在NCI上对一组60个癌细胞系的抗增殖活性，并在多个癌细胞上显示了亚微摩尔GI 50和TGI值的独特的广谱抗癌活性。化合物6f的激酶谱在10 µM浓度下，超

  DOI：

  10.1016/j.bmc.2018.10.004

文献信息

• Ricin inhibitors and methods for use thereof
  申请人：Research Development Foundation

  公开号：US06562969B1

  公开（公告）日：2003-05-13

  Ricin A-chain is an N-glycosidase that attacks ribosomal RNA at a highly conserved adenine residue. Crystallographic studies show that not only adenine and formycin, but also pterin-based rings can bind in the ricin active site. For a better understanding of the recognition mode between ricin, and adenine-like rings, the interaction energies and geometries were calculated for a number of complexes. Shiga toxin, a compound essentially identical to the protein originally isolated from Shigella dysenteniae, has an active protein chain that is a homologue of the ricin active chain, and catalyzes the same depurination reaction. The present invention is drawn to identifying inhibitors of ricin and Shiga toxin, using methods molecular mechanics and ab initio methods and using the identified inhibitors as antidotes to ricin or Shiga toxin, or to facilitate immunotoxin treatment by controlling non-specific cytotoxicity.

  Ricin A链是一种N-糖苷酶，攻击核糖体RNA上高度保守的腺嘌呤残基。晶体学研究显示，不仅腺嘌呤和福尔酰胺，还有以黄素为基础的环可以结合在 ricin 的活性位点上。为了更好地理解 ricin 与腺嘌呤类环之间的识别模式，对多个复合物的相互作用能量和几何构型进行了计算。Shiga毒素是一种与最初从志贺氏痢疾杆菌中分离的蛋白质本质上相同的化合物，具有与 ricin 活性链同源的活性蛋白链，并催化相同的去嘌呤反应。本发明涉及利用分子力学和从头算方法识别 ricin 和 Shiga 毒素的抑制剂，并将识别的抑制剂用作 ricin 或 Shiga 毒素的解毒剂，或通过控制非特异性细胞毒性促进免疫毒素治疗。
• [EN] TREATMENTS FOR AUTOIMMUNE DISEASE<br/>[FR] TRAITEMENTS POUR MALADIES AUTOIMMUNES
  申请人：PROVOST FELLOWS & SCHOLARS COLLEGE OF THE HOLY UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

  公开号：WO2016050806A1

  公开（公告）日：2016-04-07

  The invention relates to a novel approach to the treatment of autoimmune diseases, particularly multiple sclerosis.In a further embodiment of the invention there is provided a molecule capable of acting as substrate for the queuine-insertase enzyme complex and where said molecule is not a substrate for Hypoxanthine- guanine phosphoribosyltransferase and said molecule has the effect of lowering interferon gamma, for use in the treatment of auto-immune diseases. Preferably the autoimmune disease is multiple sclerosis.

  该发明涉及一种治疗自身免疫疾病，特别是多发性硬化症的新方法。在该发明的另一实施例中，提供了一种能够作为排队嘌呤插入酶复合物底物的分子，该分子不是次黄嘌呤-鸟嘌呤磷酸核糖转移酶的底物，该分子具有降低干扰素γ的作用，用于治疗自身免疫疾病。最好是多发性硬化症。
• [EN] SUBSTITUTED PYRIMIDINE DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE DISEASES<br/>[FR] DÉRIVÉS DE PYRIMIDINE SUBSTITUÉS UTILES DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES
  申请人：PROVOST FELLOWS & SCHOLARS COLLEGE OF THE HOLY UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

  公开号：WO2016050804A1

  公开（公告）日：2016-04-07

  The present invention describes compounds of formula (I) (I) Wherein: R1 is selected from H and CH3 R2 is selected from H, C4H9 alkyl, C6H13 alkyl and C3H6-phenyl, said phenyl optionally substituted by OH or OCH3, (1R,2S,5S)-5-methylcyclopent-3-ene-1,2-diol X is O or S Y is C, N or S. These compounds have been identified as novel compounds useful in the treatment of multiple sclerosis and other autoimmune diseases.

  本发明描述了化合物的结构为（I）（I）其中：R1可选择H和CH3；R2可选择H、C4H9烷基、C6H13烷基和C3H6-苯基，所述苯基可选择OH或OCH3取代，（1R,2S,5S）-5-甲基环戊-3-烯-1,2-二醇；X可选择O或S；Y可选择C、N或S。这些化合物已被确认为新型化合物，可用于治疗多发性硬化症和其他自身免疫性疾病。
• Pyrrolopyrimidines and Related Analogs as HSP90-Inhibitors
  申请人：Kasibhatla R. Srinivas

  公开号：US20070173483A1

  公开（公告）日：2007-07-26

  Pyrrolopyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Methods of synthesis and use of such compounds are also described and claimed.

  本文描述并证明吡咯并嘧啶及相关类似物作为热休克蛋白90（HSP90）抑制剂在治疗和预防各种HSP90介导的疾病中具有效用，例如增殖性疾病。本文还描述和声明了这些化合物的合成和使用方法。
• Queuine Analogues Incorporating the 7‐Aminomethyl‐7‐deazaguanine Core: Structure–Activity Relationships in the Treatment of Experimental Autoimmune Encephalomyelitis
  作者：Michelle Cotter、Sreeja Varghese、Franciane Chevot、Claire Fergus、Vincent P. Kelly、Stephen J. Connon、J. Mike Southern

  DOI：10.1002/cmdc.202300207

  日期：2023.9

  A library of queuine analogues targeting the modification of tRNA isoacceptors for Asp, Asn, His and Tyr catalysed by queuine tRNA ribosyltransferase (QTRT, also known as TGT) was evaluated in the treatment of a chronic multiple sclerosis model: murine experimental autoimmune encephalomyelitis. Several active 7‐deazaguanines emerged, together with a structure–activity relationship involving the necessity for a flexible alkyl chain of fixed length.

  摘要 针对奎宁 tRNA 核糖转移酶（QTRT，又称 TGT）催化的 tRNA 对 Asp、Asn、His 和 Tyr 的异接受体的修饰，我们评估了一个奎宁类似物库，用于治疗慢性多发性硬化症模型：小鼠实验性自身免疫性脑脊髓炎。结果发现了几种具有活性的 7-脱氮鸟嘌呤，同时还发现了一种结构-活性关系，即必须有固定长度的柔性烷基链。