ethyl 5-isobutyl-1-phenyl-1H-pyrazole-3-carboxylate | 1155683-15-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-isobutyl-1-phenyl-1H-pyrazole-3-carboxylate
• 英文别名: ethyl 5-(2-methylpropyl)-1-phenylpyrazole-3-carboxylate
• CAS: 1155683-15-0
• 化学式: C₁₆H₂₀N₂O₂
• 分子量: 272.347
• InChiKey: KTZBJPCTYDJEEE-UHFFFAOYSA-N

物化性质

• 沸点：
  392.3±30.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-isobutyl-1-phenyl-1H-pyrazole-3-carboxylate 在 盐酸 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-((4-cyanopiperidin-4-yl)methyl)-5-isobutyl-1-phenyl-1H-pyrazole-3-carboxamide hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-piperidinecarboxylate and 4-piperidinecyanide derivatives for T-type calcium channel blockers

  摘要：

  To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives were prepared and evaluated for in vitro and in vivo activity against alpha(1G) calcium channel. Among them, several compounds showed good T-type calcium channel inhibitory activity and minimal off-target activity over hERG channel (% inhibition at 10 mu M = 61.85-71.99, hERG channel IC50 = 1.57 +/- 0.14-4.98 +/- 0.36 mu M). Selected compound 31a was evaluated on SNL model of neuropathic pain and showed inhibitory effect on mechanical allodynia. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.087
• 作为产物：
  描述：

  4-甲基-2-戊酮 在 sodium 作用下， 以 乙醇 为溶剂， 反应 4.25h， 生成 ethyl 5-isobutyl-1-phenyl-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Ｔ-형 칼슘 채널에 활성을 가지는 피롤리딘 또는 피페리딘 화합물

  摘要：

  本发明涉及对T型钙通道具有活性的吡啶或哌啶化合物，更具体地说，根据本发明，化学式1所示的吡啶或哌啶化合物对T型钙通道具有优异的抑制作用，可用于治疗或预防癫痫、高血压等脑部疾病，心脏疾病如心绞痛，慢性疼痛，神经性疼痛等疼痛性疾病，以及与癌症相关的疾病。

  公开号：

  KR20200022710A

文献信息

• COMPOUNDS CAPABLE OF INHIBITING VOLTAGE GATED CALCIUM ION CHANNEL, AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20150329533A1

  公开（公告）日：2015-11-19

  Disclosed herein are an N-(pyrazolylmethyl)arylsulfonamide derivative useful as a calcium ion channel blocker, a pharmaceutically acceptable salt thereof, and the medicinal use thereof as a therapeutic agent using its calcium ion channel blocking effect.

  本文披露了一种N-(吡唑甲基)芳基磺酰胺衍生物，可用作钙离子通道阻滞剂，其药用盐，以及利用其钙离子通道阻滞效应作为治疗剂的药用。
• NOVEL PYRAZOLYLMETHYLAMINE COMPOUNDS AS CALCIUM CHANNEL MODULATORS AND PREPARATION METHOD THEREOF
  申请人：NAM Ghilsoo

  公开号：US20100094006A1

  公开（公告）日：2010-04-15

  The present invention relates to pyrazolylmethylamine-piperazine derivatives and their pharmaceutically acceptable salts effective as calcium channel modulators and a method of manufacturing the same. The present invention also relates to the medicinal use of the above compounds as therapeutic treatment of diseases due to their effect as calcium channel modulators.

  本发明涉及吡唑甲基胺基哌嗪衍生物及其药用盐，其作为钙通道调节剂具有有效性，以及其制造方法。本发明还涉及上述化合物的药用作用，用于治疗因其作为钙通道调节剂而产生的疾病。
• Synthesis and biological evaluation of pyrrolidine-based T-type calcium channel inhibitors for the treatment of neuropathic pain
  作者：Hak Kyun Yang、Woo Seung Son、Keon Seung Lim、Gun Hee Kim、Eun Jeong Lim、Changdev G. Gadhe、Jae Yeol Lee、Kyu-Sung Jeong、Sang Min Lim、Ae Nim Pae

  DOI：10.1080/14756366.2018.1513926

  日期：2018.1.1

  T-type channel inhibitors showed promising in vivo efficacy in neuropathic pain animal models and are being investigated in clinical trials. Herein we report development of novel pyrrolidine-based T-type calcium channel inhibitors by pharmacophore mapping and structural hybridisation followed by evaluation of their Cav3.1 and Cav3.2 channel inhibitory activities. Among potent inhibitors against both

  神经性疼痛的治疗是迫切的医疗需求之一，T型钙通道是神经性疼痛的有希望的治疗靶点。几种有效的T型通道抑制剂在神经性疼痛动物模型中显示出有希望的体内功效，并且正在临床试验中进行研究。在本文中，我们报告了通过药效基团定位和结构杂交，然后对其Cav3.1和Cav3.2通道抑制活性进行评估的新型基于吡咯烷的T型钙通道抑制剂的开发。根据体内药代动力学研究，在针对Cav3.1和Cav3.2通道的有效抑制剂中，一种基于体外ADME特性的有前途的化合物20n在大鼠中显示出令人满意的血浆和脑暴露。
• Synthesis and T-type calcium channel-blocking effects of aryl(1,5-disubstituted-pyrazol-3-yl)methyl sulfonamides for neuropathic pain treatment
  作者：Jung Hyun Kim、Gyochang Keum、Hesson Chung、Ghilsoo Nam

  DOI：10.1016/j.ejmech.2016.07.032

  日期：2016.11

  A novel series of aryl(1,5-disubstituted pyrazol-3-yl)methyl sulfonamide derivatives was designed, synthesized, and evaluated for T-type calcium channel (ctiG and chm) inhibitory activity. We identified several compounds, 9a, 9b, 9g, and 9h that displayed good T-type channel inhibitory potency with low hERG channel and CYP450 inhibition. Among them, 9a and 9b exhibited neuropathic pain alleviation effects in mechanical and cold allodynia induced in the SNL rat model. Compounds 9a and 9b displayed better efficacy than mibefradil and gabapentin against cold allodynia. In particular, compound 9a seemed to be valuable as shown fast acting performance in mechanical neuropathic pain model. (C) 2016 Elsevier Masson SAS. All rights reserved'.
• Neuropathic pain-alleviating effects of pyrazole-conjugated arylsulfonamides as 5-HT6 receptor antagonists
  作者：Jin Ri Hong、Hyunah Choo、Ghilsoo Nam

  DOI：10.1016/j.bmcl.2017.07.031

  日期：2017.9

  A novel series of arylsulfonylaminomethyl-3-(1-phenyl-5-isopropyl)pyrazoles was evaluated for serotonin receptor subtype 6 (5-HT6R) antagonistic effects in vitro. We also investigated their neuropathic pain-alleviating effects in vivo using a rat spinal nerve ligation (SNL) model. Bicyclic aromatic sulfonamino groups, such as naphthalene and quinolin-substituted derivatives, showed good 5-HT6 inhibitory activity in vitro. Among them, selected compounds, 12 and 13, having 8-quinoylsulfonamino groups, showed potent neuropathic pain-alleviating effects in the rat model. (C) 2017 Elsevier Ltd. All rights reserved.