2-Dimethylaminomethyl-3-(3-hydroxymethyl-6-nitro-chroman-5-ylamino)-propan-1-ol | 705286-11-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-Dimethylaminomethyl-3-(3-hydroxymethyl-6-nitro-chroman-5-ylamino)-propan-1-ol
• 英文别名: 2-[(dimethylamino)methyl]-3-[[3-(hydroxymethyl)-6-nitro-3,4-dihydro-2H-chromen-5-yl]amino]propan-1-ol
• CAS: 705286-11-9
• 化学式: C₁₆H₂₅N₃O₅
• 分子量: 339.392
• InChiKey: WLXDDZUTIGUIAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-Dimethylaminomethyl-3-(3-hydroxymethyl-6-nitro-chroman-5-ylamino)-propan-1-ol 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 44.0h， 生成 3-(2-Amino-8-hydroxymethyl-8,9-dihydro-7H-chromeno[5,6-d]imidazol-1-yl)-2-dimethylaminomethyl-propan-1-ol
  参考文献：
  名称：

  SAR by MS:  Discovery of a New Class of RNA-Binding Small Molecules for the Hepatitis C Virus:  Internal Ribosome Entry Site IIA Subdomain

  摘要：

  A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub-micromolar affinity is reported. The benzimidazole 'hit' 1 with a K-D similar to 100 mu M to a 29-mer RNA model of Domain IIA was identified from a 180000-member library using mass spectrometry-based screening methods. Further MS-assisted SAR (structure-activity relationships) studies afforded benzimidazole derivatives with sub-micromolar binding affinity for the IIA RNA construct. The optimized benzimidazoles demonstrated activity in a cellular replicon assay at concentrations comparable to their K-D for the RNA target.

  DOI：

  10.1021/jm050815o
• 作为产物：
  描述：

  2-hydroxymethyl-3-dimethylaminopropionitrile 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 potassium carbonate 、 三乙胺 、 calcium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 88.0h， 生成 2-Dimethylaminomethyl-3-(3-hydroxymethyl-6-nitro-chroman-5-ylamino)-propan-1-ol
  参考文献：
  名称：

  SAR by MS:  Discovery of a New Class of RNA-Binding Small Molecules for the Hepatitis C Virus:  Internal Ribosome Entry Site IIA Subdomain

  摘要：

  A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub-micromolar affinity is reported. The benzimidazole 'hit' 1 with a K-D similar to 100 mu M to a 29-mer RNA model of Domain IIA was identified from a 180000-member library using mass spectrometry-based screening methods. Further MS-assisted SAR (structure-activity relationships) studies afforded benzimidazole derivatives with sub-micromolar binding affinity for the IIA RNA construct. The optimized benzimidazoles demonstrated activity in a cellular replicon assay at concentrations comparable to their K-D for the RNA target.

  DOI：

  10.1021/jm050815o

文献信息

• Benzimidazoles and analogs thereof as antivirals
  申请人：Swayze E. Eric

  公开号：US20050124638A1

  公开（公告）日：2005-06-09

  Provided are compounds of the formula: wherein R N1 is a substituent of formula G 1 -NX 1 X 2 , wherein G 1 is an optionally further substituted alkylene, which optionally forms, together with R N2 , a cyclic group, and each of X 1 and X 2 is independently H or an N-substituent, or X 1 and X 2 together form a heterocyclic ring, or X 1 together with G 1 forms a cyclic group and X 2 is H or an N-substituent; and each of Z 1 , Z 2 , Z 3 and Z 4 is H or a substituent, or two of Z 1 , Z 2 , Z 3 and Z 4 together form an optionally substituted ring, and further wherein at least one of Z 1 , Z 2 , Z 3 and Z 4 is other than H, and salts thereof, pharmaceutical compositions and methods of using the compounds. The compounds have antiviral activity.

  提供的化合物的公式为：其中RN1是公式G1-NX1X2的取代基，其中G1是可选择进一步取代的烷基，可选地与RN2一起形成环状基团，而X1和X2各自独立地为H或N取代基，或者X1和X2一起形成杂环环，或者X1与G1一起形成环状基团，而X2为H或N取代基；而Z1、Z2、Z3和Z4中的每一个都是H或取代基，或者Z1、Z2、Z3和Z4中的两个一起形成可选择取代的环，此外，至少有一个Z1、Z2、Z3和Z4不是H，以及其盐，药物组合物和使用该化合物的方法。这些化合物具有抗病毒活性。
• SAR by MS:  Discovery of a New Class of RNA-Binding Small Molecules for the Hepatitis C Virus:  Internal Ribosome Entry Site IIA Subdomain
  作者：Punit P. Seth、Alycia Miyaji、Elizabeth A. Jefferson、Kristin A. Sannes-Lowery、Stephen A. Osgood、Stephanie S. Propp、Ray Ranken、Christian Massire、Rangarajan Sampath、David J. Ecker、Eric E. Swayze、Richard H. Griffey

  DOI：10.1021/jm050815o

  日期：2005.11.1

  A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub-micromolar affinity is reported. The benzimidazole 'hit' 1 with a K-D similar to 100 mu M to a 29-mer RNA model of Domain IIA was identified from a 180000-member library using mass spectrometry-based screening methods. Further MS-assisted SAR (structure-activity relationships) studies afforded benzimidazole derivatives with sub-micromolar binding affinity for the IIA RNA construct. The optimized benzimidazoles demonstrated activity in a cellular replicon assay at concentrations comparable to their K-D for the RNA target.