5-tert-butyl-2-(3-chloro-4-fluorophenyl)pyrazol-3-amine | 1001522-07-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-tert-butyl-2-(3-chloro-4-fluorophenyl)pyrazol-3-amine
• CAS: 1001522-07-1
• 化学式: C₁₃H₁₅ClFN₃
• 分子量: 267.734
• InChiKey: DCHMROCQYRCPHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-tert-butyl-2-(3-chloro-4-fluorophenyl)pyrazol-3-amine 在 copper(l) iodide 、 lithium aluminium tetrahydride 、 亚硝酸特丁酯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.0h， 生成 N-((3-tert-butyl-1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(methylsulphonamido)phenyl)propanamide
  参考文献：
  名称：

  Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists

  摘要：

  A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methyl-sulfonamidophenyl) propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with K-i(CAP) = 0.1 nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.020
• 作为产物：
  描述：

  新戊酰基乙腈 、 3-氯-4-氟苯肼盐酸盐 以 乙醇 、 水 为溶剂， 生成 5-tert-butyl-2-(3-chloro-4-fluorophenyl)pyrazol-3-amine
  参考文献：
  名称：

  发现1-（1H-吲唑-4-基）-3-（（1-苯基-1H-吡唑-5-基）甲基）尿素作为有效和热中性TRPV1拮抗剂。

  摘要：

  研究了一系列1-吲唑-3-（1-苯基吡唑-5-基）甲基脲作为h TRPV1拮抗剂。系统地研究了吲唑A区和3-三氟甲基/叔丁基吡唑C区的结构-活性关系，以优化对辣椒素活化的拮抗作用。其中，拮抗剂26，50和51显示具有高度有效的拮抗作用ķ我（CAP） = 0.4-0.5纳米。此外，在小鼠体内的研究表明，这些衍生物均拮抗辣椒素诱导的体温过低，与它们的体外相符活动，并且他们自己没有诱发热疗。在福尔马林模型中，51以剂量依赖性方式显示出抗伤害感受活性。

  DOI：

  10.1016/j.bmcl.2020.127548

文献信息

• Synthesis and Biological Evaluation of Chromenylurea and Chromanylurea Derivatives as Anti-TNF-α agents that Target the p38 MAPK Pathway
  作者：Xingzhou Li、Xinming Zhou、Jing Zhang、Lili Wang、Long Long、Zhibing Zheng、Song Li、Wu Zhong

  DOI：10.3390/molecules19022004

  日期：——

  A series of 1-aryl-3-(2H-chromen-5-yl)urea and 1-aryl-3-(chroman-5-yl)urea derivatives were designed, synthesized and evaluated for their inhibitory activities towards TNF-α production in lipopolysaccharide-stimulated THP-1 cells. The most active compound, 40g, inhibited TNF-α release with an IC50 value of 0.033 μM, which is equipotent to that of BIRB796 (IC50 = 0.032 μM).

  设计、合成并评估了一系列1-芳基-3-(2H-色烯-5-基)脲和1-芳基-3-(色满-5-基)脲衍生物对脂多糖刺激的THP-1细胞中TNF-α产生抑制活性。活性最高的化合物40g能以0.033 μM的IC50值抑制TNF-α的释放，与BIRB796的效力相当（IC50 = 0.032 μM）。
• [EN] POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES<br/>[FR] DÉRIVÉS D'URÉE POLYAROMATIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES MUSCULAIRES
  申请人：ANAGENESIS BIOTECHNOLOGIES S A S

  公开号：WO2021013712A1

  公开（公告）日：2021-01-28

  The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.

  当前的发明提供尿素衍生物，特别是具有核心结构杂环基-NH-CO-NH-芳基-O-杂环基的化合物，用于治疗、改善、延缓、治愈和/或预防与肌肉细胞和/或卫星细胞相关的疾病或症状，如杜兴氏肌肉萎缩症、贝克氏肌肉萎缩症、虚弱或肌肉萎缩症。
• COMBINATION OF POLYAROMATIC UREA DERIVATIVES AND GLUCOCORTICOID OR HDAC INHIBITOR FOR THE TREATMENT OF DISEASES OR CONDITIONS ASSOCIATED WITH MUSCLE CELLS AND/OR SATELLITE CELLS
  申请人：Anagenesis Biotechnologies

  公开号：EP4029501A1

  公开（公告）日：2022-07-20

  The current invention provides compounds for treating, ameliorating, delaying, curing and/or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia, in combination with a corticosteroid or a HDAC inhibitor.

  本发明提供了一种与皮质类固醇或HDAC抑制剂联合使用的化合物，用于治疗、改善、延缓、治愈和/或预防与肌肉细胞和/或卫星细胞相关的疾病或病症，如杜氏肌萎缩症、贝克肌萎缩症、消瘦或肌肉萎缩症。
• Discovery of 1-(1H-indazol-4-yl)-3-((1-phenyl-1H-pyrazol-5-yl)methyl) ureas as potent and thermoneutral TRPV1 antagonists
  作者：Jin Mi Kang、Sun Ok Kwon、Jihyae Ann、Peter M. Blumberg、Heejin Ha、Young Dong Yoo、Robert Frank-Foltyn、Bernhard Lesch、Gregor Bahrenberg、Hannelore Stockhausen、Thomas Christoph、Jeewoo Lee

  DOI：10.1016/j.bmcl.2020.127548

  日期：2020.12

  A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure-activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Among them, the antagonists 26, 50 and 51 displayed highly potent antagonism with Ki(CAP)

  研究了一系列1-吲唑-3-（1-苯基吡唑-5-基）甲基脲作为h TRPV1拮抗剂。系统地研究了吲唑A区和3-三氟甲基/叔丁基吡唑C区的结构-活性关系，以优化对辣椒素活化的拮抗作用。其中，拮抗剂26，50和51显示具有高度有效的拮抗作用ķ我（CAP） = 0.4-0.5纳米。此外，在小鼠体内的研究表明，这些衍生物均拮抗辣椒素诱导的体温过低，与它们的体外相符活动，并且他们自己没有诱发热疗。在福尔马林模型中，51以剂量依赖性方式显示出抗伤害感受活性。
• Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists
  作者：Sunho Lee、Changhoon Kim、Jihyae Ann、Shivaji A. Thorat、Eunhye Kim、Jongmi Park、Sun Choi、Peter M. Blumberg、Robert Frank-Foltyn、Gregor Bahrenberg、Hannelore Stockhausen、Thomas Christoph、Jeewoo Lee

  DOI：10.1016/j.bmcl.2017.08.020

  日期：2017.9

  A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methyl-sulfonamidophenyl) propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with K-i(CAP) = 0.1 nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360. (C) 2017 Elsevier Ltd. All rights reserved.