N-{3-[4-(aminomethyl)phenyl]-1H-5-pyrazolyl}-4-(4-methylpiperazino)benzamide | 1391621-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-{3-[4-(aminomethyl)phenyl]-1H-5-pyrazolyl}-4-(4-methylpiperazino)benzamide
• 英文别名: N-[5-[4-(aminomethyl)phenyl]-1H-pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
• CAS: 1391621-86-5
• 化学式: C₂₂H₂₆N₆O
• 分子量: 390.488
• InChiKey: JCWRBGRCGSKVEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  90.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{3-[4-(aminomethyl)phenyl]-1H-5-pyrazolyl}-4-(4-methylpiperazino)benzamide 、 氯甲酸苯酯 在 吡啶 作用下， 生成 phenyl N-[[4-[3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-1H-pyrazol-5-yl]phenyl]methyl]carbamate
  参考文献：
  名称：

  3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

  摘要：

  A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.05.116
• 作为产物：
  描述：

  benzyl N-[4-(5-amino-1H-3-pyrazolyl)benzyl]carbamate 在 吡啶 、 盐酸 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 生成 N-{3-[4-(aminomethyl)phenyl]-1H-5-pyrazolyl}-4-(4-methylpiperazino)benzamide
  参考文献：
  名称：

  3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

  摘要：

  A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.05.116

文献信息

• PYRAZOLE COMPOUNDS AND THIAZOLE COMPOUNDS AS PROTEIN KINASES INHIBITORS
  申请人：Jiaang Weir-Torn

  公开号：US20120225880A1

  公开（公告）日：2012-09-06

  A compound of formula (I): wherein A, B, D, X, Y, R 1 , R 2 , R 3 , m, p, and q are defined herein. Also disclosed is a method for inhibiting FMS-like tyrosine kinase 3, aurora kinase, or vascular endothelial growth factor receptor.

  其中A、B、D、X、Y、R1、R2、R3、m、p和q的化合物的化学式（I）： 还公开了一种抑制FMS样酪氨酸激酶3、极光激酶或血管内皮生长因子受体的方法。
• Discovery of 3-phenyl-1H-5-pyrazolylamine derivatives containing a urea pharmacophore as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)
  作者：Wen-Hsing Lin、John T.-A. Hsu、Shu-Yi Hsieh、Chiung-Tong Chen、Jen-Shin Song、Shih-Chieh Yen、Tsu Hsu、Cheng-Tai Lu、Chun-Hwa Chen、Ling-Hui Chou、Yung-Ning Yang、Ching-Hui Chiu、Ching-Ping Chen、Ya-Ju Tseng、Kuei-Jung Yen、Ching-Fang Yeh、Yu-Sheng Chao、Teng-Kuang Yeh、Weir-Torn Jiaang

  DOI：10.1016/j.bmc.2013.03.083

  日期：2013.6

  which we found to be potent inhibitors of FLT3 and VEGFR2. Some inhibited growth of FLT3-mutated MOLM-13 cells more strongly than the FLT3 inhibitors sorafenib (2) and ABT-869 (3). In preliminary in vivo toxicity studies of the four most active compounds, 10f was found to be the least toxic. A further in vivo efficacy study demonstrated that 10f achieved complete tumor regression in a higher proportion

  临床前研究和早期临床试验表明，FLT3抑制剂是治疗急性髓细胞性白血病的可行疗法。但是，由于不完全抑制FLT3，早期的临床数据令人难以理解。我们已经开发出3-苯基-1 H -5-吡唑烷基胺作为激酶抑制剂的有效模板。结构与活性的关系导致发现磺胺，氨基甲酸酯和脲系列的FLT3抑制剂。先前的研究表明，磺酰胺4和氨基甲酸酯5系列是有效的和选择性的FLT3抑制剂，具有良好的体内功效。在这里，我们描述了尿素系列，我们发现它是FLT3和VEGFR2的有效抑制剂。一些药物比FLT3抑制剂索拉非尼（2）和ABT-869（3）更能抑制FLT3突变的MOLM-13细胞的生长。在对四种活性最高的化合物的体内毒性初步研究中，发现10f毒性最低。进一步的体内功效研究表明，与4和5相比，10f在MOLM-13异种移植小鼠中实现的肿瘤完全消退（70％比10％和40％）。这些结果表明化合物10f 具有改善的药理学和选择性，并
• US9255072B2
  申请人：——

  公开号：US9255072B2

  公开（公告）日：2016-02-09
• 3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)
  作者：John T.-A. Hsu、Teng-Kuang Yeh、Shih-Chieh Yen、Chiung-Tong Chen、Shu-Yi Hsieh、Tsu Hsu、Cheng-Tai Lu、Chun-Hwa Chen、Ling-Hui Chou、Ching-Hui Chiu、Yun-I Chang、Ya-Ju Tseng、Kuei-Rong Yen、Yu-Sheng Chao、Wen-Hsing Lin、Weir-Torn Jiaang

  DOI：10.1016/j.bmcl.2012.05.116

  日期：2012.7

  A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells. (C) 2012 Published by Elsevier Ltd.