1-methyl-5-(tritylamino)pyrazole-4-carbaldehyde | 474956-63-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-methyl-5-(tritylamino)pyrazole-4-carbaldehyde
• 英文别名: 1-methyl-5-(tritylamino)-1H-pyrazole-4-carbaldehyde；1-Methyl-5-triphenylmethylaminopyrazole-4-carbaldehyde
• CAS: 474956-63-3
• 化学式: C₂₄H₂₁N₃O
• 分子量: 367.45
• InChiKey: AYAMPQPIIJSCJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  535.2±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-methyl-5-(tritylamino)pyrazole-4-carbaldehyde 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 3-hydroxy-3-[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]propanenitrile
  参考文献：
  名称：

  WO2007/119511

  摘要：

  公开号：
• 作为产物：
  描述：

  三苯基氯甲烷 、 5-氨基-1-甲基-1H-吡唑-4-甲醛 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 70.0h， 以92%的产率得到1-methyl-5-(tritylamino)pyrazole-4-carbaldehyde
  参考文献：
  名称：

  Structural requirements for the stability of novel cephalosporins to AmpC β-lactamase based on 3D-structure

  摘要：

  AmpC beta-lactamase is one of the leading causes of Pseudomonas aeruginosa (P. aeruginosa) resistance to cephalosporins. FR259647 is a cephalosporin having a novel pyrazolium substituent at the 3-position and exhibits excellent activity (MIC = 1 mu g/mL) against the AmpC beta-lactamase overproducing P. aeruginosa FP1380 strain in comparison with the third-generation cephalosporins FK518 [Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 454; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 455; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 456; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 457] (MIC = 16 mu g/mL) and ceftazidime (CAZ) (MIC = 128 mu g/mL). The stability of FR259647 and FK518 to AmpC beta-lactamase was evaluated using MIC assays against both the P. aeruginosa PAO1 strain and a PAO1 mutant strain overproducing AmpC beta-lactamase as a differential assay, which indicates that the main difference derives from their stability to AmpC beta-lactamase. A structural analysis using computer simulations indicated that the difference in stability may be due to steric hindrance of the 3-position substituents causing differential affinity. This steric hindrance may disturb entry of the cephalosporins into the binding pocket. We predicted the possibility of inhibition of entry as a potential means of enhancing stability by conformational analysis. In order to validate this speculation, novel FR259647 derivatives 4-9 were designed, calculated, synthesized, and evaluated. As a result, we demonstrated that their probability of entry correlated with the MIC ratio of the mutant strain to the parent strain and supports the validity of our model. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.074

文献信息

• Cephem compounds
  申请人：——

  公开号：US20040248875A1

  公开（公告）日：2004-12-09

  The present invention relates to a compound of the formula [I]: wherein A is lower alkylene or lower alkenylene; R1 is lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl or protected amino(lower)alkyl, and R2 is hydrogen or amino protecting group, or R1 and R2 are bonded together and form lower alkylene; R3 and R5 are independently amino or protected amino; and R4 is carboxy or protected carboxy, or a pharmaceutically acceptable salt thereof, a process for preparing a compound of the formula [I], and a pharmaceutical composition comprising a compound of the formula [I] in admixture with a pharmaceutically acceptable carrier. 1

  本发明涉及一种化合物，其化学式为[I]：其中，A为较低的烷基或烯基烷基；R1为较低的烷基、羟基(较低)烷基、保护羟基(较低)烷基、氨基(较低)烷基或保护氨基(较低)烷基，R2为氢或氨基保护基，或R1和R2结合形成较低的烷基；R3和R5独立地为氨基或保护氨基；R4为羧基或保护羧基，或其药学上可接受的盐，以及制备化学式[I]的化合物的方法和包含化学式[I]的化合物与药学上可接受的载体混合的制药组合物。
• Cephem Compounds and Use as Antimicrobial Agents
  申请人：Yamanaka Toshio

  公开号：US20090012054A1

  公开（公告）日：2009-01-08

  The present invention provides a compound of the formula [I]: wherein R1 is lower alkyl, etc. and R2 is hydrogen, etc., or R1 and R2 are bonded together to form lower alkylene; R3 is a group represented by wherein R6 and R7 are independently optionally protected amino, etc.; m and n are independently an integer of 0 to 6; R8 and R9 are independently optionally protected amino, etc., and q and r are independently an integer of 0 to 6, or R8 and R9, together with the adjacent alkylene(s) and the nitrogen atom, form saturated nitrogen-containing heterocycle optionally having substituent(s); R4 is lower alkyl, etc.; and R5 is amino, etc., or a pharmaceutically acceptable salt thereof.

  本发明提供了一种化合物，其化学式为[I]：其中R1是低碳基等，R2是氢等，或者R1和R2结合形成低碳基烯；R3是一个由表示的基团，其中R6和R7分别是可选的保护氨基等；m和n分别是0到6的整数；R8和R9分别是可选的保护氨基等，q和r分别是0到6的整数，或者R8和R9与相邻的烷基和氮原子结合形成饱和的含氮杂环，该杂环可以有取代基；R4是低碳基等；R5是氨基等，或其药学上可接受的盐。
• CEPHEM COMPOUNDS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP1392704A1

  公开（公告）日：2004-03-03
• CEPHEM COMPOUNDS AND USE AS ANTIMICROBIAL AGENTS
  申请人：Astellas Pharma Inc.

  公开号：EP1994035A1

  公开（公告）日：2008-11-26
• US7179801B2
  申请人：——

  公开号：US7179801B2

  公开（公告）日：2007-02-20