N-[1-(3,4-difluorobenzyl)-1H-pyrazol-3-yl]-2-(4-isopropylphenyl)acetamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-[1-(3,4-difluorobenzyl)-1H-pyrazol-3-yl]-2-(4-isopropylphenyl)acetamide
• 英文别名: N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(4-propan-2-ylphenyl)acetamide
• 化学式: C₂₁H₂₁F₂N₃O
• 分子量: 369.414
• InChiKey: VOSFWDZWOGANJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-异丙基苯乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 2.0h， 生成 N-[1-(3,4-difluorobenzyl)-1H-pyrazol-3-yl]-2-(4-isopropylphenyl)acetamide
  参考文献：
  名称：

  Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies

  摘要：

  We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.

  DOI：

  10.1021/acs.jmedchem.7b01236

文献信息

• [EN] PYRAZOLE COMPOUNDS AND THEIR USE AS T-TYPE CALCIUM CHANNEL BLOCKERS<br/>[FR] COMPOSÉS DE PYRAZOLE ET LEUR UTILISATION EN TANT QUE BLOQUEURS DES CANAUX CALCIQUES DE TYPE T
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2015186056A1

  公开（公告）日：2015-12-10

  The invention relates to compounds of formula (I) Formula (I) wherein X, Y, R1, R2, (R4)n, and (R5)m are as defined in the description, and to pharmaceutically acceptable salts of such compounds. These compounds are useful as calcium T-channel blockers.

  这项发明涉及式(I)的化合物。式(I)中X、Y、R1、R2、(R4)n和(R5)m的定义如描述中所述，并且涉及这些化合物的药用盐。这些化合物可用作钙T通道阻滞剂。
• Pyrazole compounds and their use as T-type calcium channel blockers
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：US10065929B2

  公开（公告）日：2018-09-04

  The invention relates to compounds of formula (I) wherein X, Y, R1, R2, (R4)n, and (R5)m are as defined in the description, and to pharmaceutically acceptable salts of such compounds. These compounds are useful as calcium T-channel blockers.

  本发明涉及式 (I) 的化合物 其中X、Y、R1、R2、(R4)n和(R5)m如描述中所定义，并涉及此类化合物的药学上可接受的盐。这些化合物可用作钙 T 通道阻滞剂。
• PYRAZOLE COMPOUNDS AND THEIR USE AS T-TYPE CALCIUM CHANNEL BLOCKERS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP3152199A1

  公开（公告）日：2017-04-12
• US9932314B2
  申请人：——

  公开号：US9932314B2

  公开（公告）日：2018-04-03
• Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies
  作者：Olivier Bezençon、Bibia Heidmann、Romain Siegrist、Simon Stamm、Sylvia Richard、Davide Pozzi、Olivier Corminboeuf、Catherine Roch、Melanie Kessler、Eric A. Ertel、Isabelle Reymond、Thomas Pfeifer、Ruben de Kanter、Michael Toeroek-Schafroth、Luca G. Moccia、Jacques Mawet、Richard Moon、Markus Rey、Bruno Capeleto、Elvire Fournier

  DOI：10.1021/acs.jmedchem.7b01236

  日期：2017.12.14

  We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.