5-[3-(benzyloxy)-4-methoxyphenyl]-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one | 1083088-65-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[3-(benzyloxy)-4-methoxyphenyl]-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one
• 英文别名: 3-(4-methoxy-3-phenylmethoxyphenyl)-4,4-dimethyl-1H-pyrazol-5-one
• CAS: 1083088-65-6
• 化学式: C₁₉H₂₀N₂O₃
• 分子量: 324.379
• InChiKey: MXUQUKFZLPYADF-UHFFFAOYSA-N

物化性质

• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[3-(benzyloxy)-4-methoxyphenyl]-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one 在 palladium 10% on activated carbon 、 甲酸铵 、 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 0.33h， 生成 5-[4-Methoxy-3-[2-(4-methoxyphenyl)ethoxy]phenyl]-4,4-dimethyl-2-propan-2-ylpyrazol-3-one
  参考文献：
  名称：

  Catechol Pyrazolinones as Trypanocidals: Fragment-Based Design, Synthesis, and Pharmacological Evaluation of Nanomolar Inhibitors of Trypanosomal Phosphodiesterase B1

  摘要：

  Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. We used homology modeling and docking studies to guide fragment growing into the parasite-specific P-pocket in the enzyme binding site. The resulting catechol pyrazolinones act as potent TbrPDEB1 inhibitors with IC50 values down to 49 nM. The compounds also block parasite proliferation (e.g., VUF13525 (20b): T. brucei rhodesiense IC50 = 60 nM, T. brucei brucei IC50 = 520 nM, T. cruzi = 7.6 mu M), inducing a typical multiple nuclei and kinetoplast phenotype without being generally cytotoxic. The mode of action of 20b was investigated with recombinantly engineered trypanosomes expressing a cAMP-sensitive FRET sensor, confirming a dose-response related increase of intracellular cAMP levels in trypanosomes. Our findings further validate the TbrPDEB family as antitrypanosomal target.

  DOI：

  10.1021/jm301059b
• 作为产物：
  描述：

  4-甲氧基-3-苯基甲氧基苯甲酰氯 在 一水合肼 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 水 为溶剂， 反应 18.0h， 生成 5-[3-(benzyloxy)-4-methoxyphenyl]-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one
  参考文献：
  名称：

  Catechol Pyrazolinones as Trypanocidals: Fragment-Based Design, Synthesis, and Pharmacological Evaluation of Nanomolar Inhibitors of Trypanosomal Phosphodiesterase B1

  摘要：

  Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. We used homology modeling and docking studies to guide fragment growing into the parasite-specific P-pocket in the enzyme binding site. The resulting catechol pyrazolinones act as potent TbrPDEB1 inhibitors with IC50 values down to 49 nM. The compounds also block parasite proliferation (e.g., VUF13525 (20b): T. brucei rhodesiense IC50 = 60 nM, T. brucei brucei IC50 = 520 nM, T. cruzi = 7.6 mu M), inducing a typical multiple nuclei and kinetoplast phenotype without being generally cytotoxic. The mode of action of 20b was investigated with recombinantly engineered trypanosomes expressing a cAMP-sensitive FRET sensor, confirming a dose-response related increase of intracellular cAMP levels in trypanosomes. Our findings further validate the TbrPDEB family as antitrypanosomal target.

  DOI：

  10.1021/jm301059b

文献信息

• [EN] NOVEL PYRAZOLONE-DERIVATIVES AND THEIR USE AS PD4 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE PYRAZOLONE ET LEUR UTILISATION COMME INHIBITEURS DE LA PD4
  申请人：NYCOMED GMBH

  公开号：WO2010055083A1

  公开（公告）日：2010-05-20

  The compounds of formula (1) wherein R1 represents a phenyl derivative of formulae (a), (b) or (c) R10 is 1-3C-alkyl and R11 is 1-3C-alkyl, or R10 and R11 together with the carbon atom, to which they are bonded, form a spiro-linked 3-, 4-, 5- or 6-membered hydrocarbon ring, A is C(O) or S(O)2, and R12 is phenyl, naphthalenyl, pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl, 1,6-naphthyridinyl, 1,8-naphthyridinyl, indolyl, phenyl substituted by R13, R14, R15 and R16, pyridinyl substituted by R17 and R18, naphthalenyl substituted by R19 and R20, quinolinyl substituted by R21 or indolyl substituted by R22, are novel effective inhibitors of the type 4 phosphodiesterase.

  式（1）中的化合物，其中R1代表式（a）、（b）或（c）的苯基衍生物，R10是1-3C-烷基，R11是1-3C-烷基，或者R10和R11与它们结合的碳原子一起形成螺环连接的3、4、5或6元烃环，A是C（O）或S（O）2，R12是苯基、萘基、吡啶基、喹啉基、异喹啉基、喹喙啉基、1,6-萘啶基、1,8-萘啶基、吲哚基、被R13、R14、R15和R16取代的苯基、被R17和R18取代的吡啶基、被R19和R20取代的萘基、被R21取代的喹啉基或被R22取代的吲哚基，是一种新型有效的第4型磷酸二酯酶抑制剂。
• PYRAZOLONE DERIVATIVES AS PDE4 INHIBITORS
  申请人：Schmidt Beate

  公开号：US20100120757A1

  公开（公告）日：2010-05-13

  The compounds of a certain formula 1, in which R1, R7, R8, R9 and n have the meanings as given in the description, are novel effective inhibitors of the type 4 phosphodiesterase.

  某种化学式为1的化合物，其中R1、R7、R8、R9和n的含义如描述所给，是一种新型有效的4型磷酸二酯酶抑制剂。
• NOVEL PYRAZOLONE-DERIVATIVES AND THEIR USE AS PDE-4 INHIBITORS
  申请人：Schlemminger Imre

  公开号：US20110218201A1

  公开（公告）日：2011-09-08

  The compounds of Formula (I), are novel effective inhibitors of the type 4 phosphodiesterase.

  化合物式(I)的化合物是一种新颖有效的第4型磷酸二酯酶抑制剂。
• Pyrazolone derivatives as PDE4 inhibitors
  申请人：Nycomed GmbH

  公开号：US08304436B2

  公开（公告）日：2012-11-06

  The compounds of a certain formula 1, in which R1, R7, R8, R9 and n have the meanings as given in the description, are novel effective inhibitors of the type 4 phosphodiesterase.

  某种化学式为1的化合物，其中R1、R7、R8、R9和n的含义如说明中所述，是一种新型有效的第4型磷酸二酯酶抑制剂。
• Pyrazolone-derivatives and their use as PDE-4 inhibitors
  申请人：Schlemminger Imre

  公开号：US08609848B2

  公开（公告）日：2013-12-17

  The compounds of Formula (I), are novel effective inhibitors of the type 4 phosphodiesterase.

  化合物I式，是一种新型有效的第4型磷酸二酯酶抑制剂。