5-cyclopropyl-2-(3-fluoro-phenyl)-2,4-dihydro-pyrazol-3-one | 1057093-28-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-cyclopropyl-2-(3-fluoro-phenyl)-2,4-dihydro-pyrazol-3-one
• 英文别名: 5-cyclopropyl-2-(3-fluorophenyl)-4H-pyrazol-3-one
• CAS: 1057093-28-3
• 化学式: C₁₂H₁₁FN₂O
• 分子量: 218.231
• InChiKey: UUYMDAZPWSYZHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-cyclopropyl-2-(3-fluoro-phenyl)-2,4-dihydro-pyrazol-3-one 、 乙烯磺酰氟 在 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以75%的产率得到5-cyclopropyl-7-(3-fluorophenyl)-4,7-dihydro-3H-[1,2]oxathiino[6,5-c]pyrazole 2,2-dioxide
  参考文献：
  名称：

  The structure-based optimization of δ-sultone-fused pyrazoles as selective BuChE inhibitors

  摘要：

  Structure-based optimization was conducted to improve the potency and selectivity of BuChE inhibitors with delta-sulfonolactone-fused pyrazole scaffold. By mimicking the hydrophobic interactions of donepezil at PAS, the introduction of a tertiary benzylamine at 5-position can significantly increase BuChE inhibitory activity. Compounds C4 and C6 were identified as high selective nanomolar BuChE inhibitors (IC50 = 8.3 and 7.7 nM, respectively), which exhibited mild antioxidant capacity, nontoxicity, lipophilicity and neuroprotective activity. Kinetic studies showed that BuChE inhibition of compound C6 was mixed-type against BuChE (K-i = 24 nM) and >2000-fold selectivity for BuChE over AChE. The proposed binding mode of new inhibitors was consistent with the results of structure-activity relationship analysis. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112273
• 作为产物：
  描述：

  (3-氟苯基)肼盐酸盐(1:1) 、 3-环丙基-3-羰基-丙酸乙酯 在 碳酸氢钠 、 溶剂黄146 作用下， 反应 1.5h， 生成 5-cyclopropyl-2-(3-fluoro-phenyl)-2,4-dihydro-pyrazol-3-one
  参考文献：
  名称：

  The structure-based optimization of δ-sultone-fused pyrazoles as selective BuChE inhibitors

  摘要：

  Structure-based optimization was conducted to improve the potency and selectivity of BuChE inhibitors with delta-sulfonolactone-fused pyrazole scaffold. By mimicking the hydrophobic interactions of donepezil at PAS, the introduction of a tertiary benzylamine at 5-position can significantly increase BuChE inhibitory activity. Compounds C4 and C6 were identified as high selective nanomolar BuChE inhibitors (IC50 = 8.3 and 7.7 nM, respectively), which exhibited mild antioxidant capacity, nontoxicity, lipophilicity and neuroprotective activity. Kinetic studies showed that BuChE inhibition of compound C6 was mixed-type against BuChE (K-i = 24 nM) and >2000-fold selectivity for BuChE over AChE. The proposed binding mode of new inhibitors was consistent with the results of structure-activity relationship analysis. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112273

文献信息

• New pyrazolones as 11b-HSD1 inhibitors for diabetes
  申请人：Amrein Kurt

  公开号：US20070049574A1

  公开（公告）日：2007-03-01

  Compounds of formula as well as pharmaceutically acceptable salts and esters thereof, wherein R 1 to R 4 have the significance given in claim 1 can be used in the form of pharmaceutical compositions.

  公式化合物以及医药可接受的它们的盐和酯，其中R1至R4的意义如权利要求1中所给出，可以用作药物组合物。
• PYRAZOLONE DERIVATIVES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1924562A2

  公开（公告）日：2008-05-28
• US7652057B2
  申请人：——

  公开号：US7652057B2

  公开（公告）日：2010-01-26
• [EN] PYRAZOLONE DERIVATIVES<br/>[FR] DERIVES DE PYRAZOLONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2007025880A2

  公开（公告）日：2007-03-08

  [EN] Compounds of formula (I) as well as pharmaceutically acceptable salts and esters thereof, wherein R¹ to R⁴ have the significance given in claim 1 can be used in the form of pharmaceutical compositions.
  [FR] L'invention concerne des composés de formule (I) ainsi que des sels et des esters pharmaceutiquement acceptables de ceux-ci, formule dans laquelle R¹ à R⁴ ont les significations indiquées à la revendication 1, ces composés pouvant être utilisés sous forme de compositions pharmaceutiques.
• The structure-based optimization of δ-sultone-fused pyrazoles as selective BuChE inhibitors
  作者：Ziwen Zhang、Jingli Min、Mengdie Chen、Xia Jiang、Yingying Xu、Huali Qin、Wenjian Tang

  DOI：10.1016/j.ejmech.2020.112273

  日期：2020.9

  Structure-based optimization was conducted to improve the potency and selectivity of BuChE inhibitors with delta-sulfonolactone-fused pyrazole scaffold. By mimicking the hydrophobic interactions of donepezil at PAS, the introduction of a tertiary benzylamine at 5-position can significantly increase BuChE inhibitory activity. Compounds C4 and C6 were identified as high selective nanomolar BuChE inhibitors (IC50 = 8.3 and 7.7 nM, respectively), which exhibited mild antioxidant capacity, nontoxicity, lipophilicity and neuroprotective activity. Kinetic studies showed that BuChE inhibition of compound C6 was mixed-type against BuChE (K-i = 24 nM) and >2000-fold selectivity for BuChE over AChE. The proposed binding mode of new inhibitors was consistent with the results of structure-activity relationship analysis. (C) 2020 Elsevier Masson SAS. All rights reserved.