1-{1-[(6-nitrobenzo[1,3]dioxol-5-yl)methyl]-1,2,3,6-tetrahydropyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 1-{1-[(6-nitrobenzo[1,3]dioxol-5-yl)methyl]-1,2,3,6-tetrahydropyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
• 英文别名: 1-[1-(6-Nitro-benzo[1,3]dioxol-5-ylmethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-1,3-dihydro-benzoimidazol-2-one；3-[1-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-3,6-dihydro-2H-pyridin-4-yl]-1H-benzimidazol-2-one
• 化学式: C₂₀H₁₈N₄O₅
• 分子量: 394.387
• InChiKey: BHTTXYGCLABXEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  99.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-硝基胡椒醛 、 1,3-二氢-1-(1,2,3,6-四氢-4-吡啶基)-2H-苯并咪唑-2-酮 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 以57.1%的产率得到1-{1-[(6-nitrobenzo[1,3]dioxol-5-yl)methyl]-1,2,3,6-tetrahydropyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  From Hit to Lead. Combining Two Complementary Methods for Focused Library Design. Application to μ Opiate Ligands

  摘要：

  Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.

  DOI：

  10.1021/jm010877o

文献信息

• Rearrangement of spiro-benzimidazolines: preparation of N-alkenyl- and N-alkyl-benzimidazol-2-ones
  作者：Jeffrey T. Kuethe、Jack Varon、Karla G. Childers

  DOI：10.1016/j.tet.2007.06.106

  日期：2007.11

  A synthetically useful protocol has been developed for the preparation of highly functionalized N-alkenyl-benzimidazol-2-ones. Reaction of commercially available o-phenylenediamines with variously substituted cyclic ketones provides spiro-benzimidazolines. Treatment of these spiro-benzimidazolines with triphosgene in the presence of potassium carbonate results in rapid rearrangement and formation of N-alkenyl-benzimidazol-2-ones in modest to excellent yield for the two-step sequence. Extension of this methodology toward the preparation of a m opiate receptor antagonist and droperidol, a potent antiemetic and antipsychotic agent, currently a marketed pharmaceutical is also described. Upon treatment of spiro-benzimidazolines with triphosgene in the presence of sodium triacetoxyborohydride, N-alkyl-benzimidazol-2-ones were formed. (C) 2007 Merck & Co., Inc. Published by Elsevier Ltd. All rights reserved.
• From Hit to Lead. Combining Two Complementary Methods for Focused Library Design. Application to μ Opiate Ligands
  作者：Rébecca Poulain、Dragos Horvath、Béatrice Bonnet、Christian Eckhoff、Béatrice Chapelain、Marie-Christine Bodinier、Benoît Déprez

  DOI：10.1021/jm010877o

  日期：2001.10.1

  Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.