N-(3-(trans-4-ethylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: N-(3-(trans-4-ethylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acetamide
• 英文别名: N-[3-(trans-4-ethylcyclohexyl)-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl]acetamide
• 化学式: C₁₇H₂₂N₄O₃
• 分子量: 330.387
• InChiKey: DWMVHVIOKXDVAN-AULYBMBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.18
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  96.85
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2-氨基-3-羧酸甲酯-5-硝基吡啶 在 palladium 10% on activated carbon 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.08h， 生成 N-(3-(trans-4-ethylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acetamide
  参考文献：
  名称：

  Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease

  摘要：

  Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.

  DOI：

  10.1021/acs.jmedchem.9b01852

文献信息

• TREATMENT OF CHAGAS DISEASE
  申请人：UNIVERSITY OF DUNDEE

  公开号：US20170114029A1

  公开（公告）日：2017-04-27

  The invention provides compounds of the formula: wherein L 1 and L 2 are independently selected from O and S; R 1 is C 3 -C 6 straight or branched alkyl, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, adamantly, phenyl or saturated heterocyclyl, any of which being optionally substituted; R 2 is H, methyl or ethyl; R 5 is NRxCORy, NRxRy, CH 2 COCH 3 , CH 2 C≡N, or a 5- or 6-membered heteroaryl group which is optionally substituted; X, Y and Z are independently N or CH; Rx is independently H or C 1 -C 4 alkyl; Ry is independently H, CrC4alkyl, phenyl or benzyl, either of which is optionally substituted; n is 0-3; salts, hydrates and N-oxides, wherein the optional substituents are further defined in the claims. The compounds have utility in the prophylaxis or treatment of trypanosomal diseases, such as T. cruzi (Chagas disease).
• Discovery and Optimization of a Compound Series Active against <i>Trypanosoma cruzi</i>, the Causative Agent of Chagas Disease
  作者：Justin R. Harrison、Sandipan Sarkar、Shahienaz Hampton、Jennifer Riley、Laste Stojanovski、Christer Sahlberg、Pia Appelqvist、Jessey Erath、Vinodhini Mathan、Ana Rodriguez、Marcel Kaiser、Dolores Gonzalez Pacanowska、Kevin D. Read、Nils Gunnar Johansson、Ian H. Gilbert

  DOI：10.1021/acs.jmedchem.9b01852

  日期：2020.3.26

  Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.