3-氨基-5-叔丁基-2-环己基-2H-吡唑 | 1026246-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-氨基-5-叔丁基-2-环己基-2H-吡唑
• 英文名称: 3-(tert-butyl)-1-cyclohexyl-1H-pyrazol-5-amine
• 英文别名: 1-Cyclohexyl-3-(1,1-dimethylethyl)-1h-pyrazol-5-amine；5-tert-butyl-2-cyclohexylpyrazol-3-amine
• CAS: 1026246-38-7
• 化学式: C₁₃H₂₃N₃
• 分子量: 221.346
• InChiKey: QMLZEHKWXQWKHR-UHFFFAOYSA-N

物化性质

• 沸点：
  366.0±30.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-氨基-5-叔丁基-2-环己基-2H-吡唑 在 copper(l) iodide 、 lithium aluminium tetrahydride 、 亚硝酸特丁酯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 1.0h， 生成
  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：

  cyclohexanone hydrazone 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 3-氨基-5-叔丁基-2-环己基-2H-吡唑
  参考文献：
  名称：

  Pyrazole Urea-Based Inhibitors of p38 MAP Kinase:  From Lead Compound to Clinical Candidate

  摘要：

  We report on a series of N-pyrazole, N'-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5'-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

  DOI：

  10.1021/jm020057r

文献信息

• [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。
• SUBSTITUTED PYRAZOLO[3,4-b]PYRIDIN-6-CARBOXYLIC ACIDS AND METHOD OF USE
  申请人：AbbVie S.à.r.l.

  公开号：US20170101406A1

  公开（公告）日：2017-04-13

  The present invention provides for compounds of formula (I) wherein R 1 , R 2 , R 3 , and R 4 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjögren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

  本发明提供了式（I）的化合物 其中R 1 ，R 2 ，R 3 和R 4 具有规范中定义的任何值，以及其药学上可接受的盐，这些化合物在治疗由CFTR介导和调节的疾病和症状中是有用的，包括囊性纤维化、Sjögren综合征、胰腺功能不全、慢性阻塞性肺病和慢性阻塞性气道疾病。还提供了由一个或多个式（I）的化合物组成的药物组合物。
• Discovery of novel 3-(1H-pyrazol-4-yl)-1H-indazole derivatives as potent type II TRK inhibitors against acquired resistance
  作者：Qiaohua Qin、Zhiqiang Guo、Shuyu Lu、Xin Wang、Qinglin Fu、Tianxiao Wu、Yixiang Sun、Nian Liu、Haoyu Zhang、Dongmei Zhao、Maosheng Cheng

  DOI：10.1016/j.ejmech.2023.115953

  日期：2024.1

  cancers. The solvent front and xDFG mutations induced by larotrectinib and entrectinib result in acquired resistance in advanced-stage patients. In this study, we report a highly potent and selective type II TRK inhibitor, 40l, developed using a structure-based design strategy. Compound 40l significantly suppressed Km-12, Ba/F3-TRKAG595R, and Ba/F3-TRKAG667C cell proliferation. In biochemical and cellular

  原肌球蛋白受体激酶 (TRK) 是治疗NTRK融合癌症的一个有前景的靶点。 larotrectinib 和 eNTrectinib诱导的溶剂前沿和 xDFG 突变导致晚期患者获得性耐药。在这项研究中，我们报告了一种高效、选择性的 II 型 TRK 抑制剂40l ，它是使用基于结构的设计策略开发的。化合物40l显着抑制Km-12、Ba/F3-TRKA G595R和Ba/F3-TRKA G667C细胞增殖。在生化和细胞测定中， 40l对 TRKA G667C显示出比阳性对照 Selitrectinib 更好的抑制活性。此外，它还以剂量依赖性方式诱导 Ba/F3-TRKA G595R和 Ba/F3-TRKA G667C细胞凋亡。此外， 40l对一组 41 种激酶表现出良好的选择性。体外试验表明40l具有出色的血浆稳定性和中等的肝微粒体稳定性。基于上述结果，化合物40l可以进一步优化以克服溶剂前沿和xDFG
• Asymmetric synthesis of atropisomeric arylpyrazoles via direct arylation of 5-aminopyrazoles with naphthoquinones
  作者：Jiamin Liu、Xingfu Wei、Yue Wang、Jingping Qu、Baomin Wang

  DOI：10.1039/d4ob00514g

  日期：——

  chiral arylpyrazoles using 5-aminopyrazoles and naphthoquinone derivatives. The chiral axis could be formed through a central-to-axial chirality relay step of the chiral phosphoric acid-catalyzed arylation reaction, which features excellent yields and enantioselectivities with a broad substrate scope under mild reaction conditions.

  由于含有五元杂环的联芳基结构的旋转势垒相对较低，轴向手性芳基吡唑的构建是一个有吸引力的挑战。这项工作描述了使用 5-氨基吡唑和萘醌衍生物催化不对称构建轴向手性芳基吡唑。手性轴可以通过手性磷酸催化芳基化反应的中心到轴手性中继步骤形成，该反应在温和的反应条件下具有优异的产率和对映选择性，底物范围广泛。
• Atroposelective Construction of Naphthylpyrazoles by Chiral Phosphoric Acid Catalyzed Enantioselective Cross‐Coupling of Pyrazoles with Naphthoquinone Esters
  作者：Xi Luo、Sen Li、Yuting Tian、Yuqi Tian、Limei Gao、Qiang Wang、Yongsheng Zheng

  DOI：10.1002/ejoc.202400254

  日期：2024.6.17

  The asymmetric reaction of 5-aminopyrazoles with naphthoquinone esters has been established with a chiral phosphoric acid catalyst, providing a wide range of axially chiral naphthylpyrazole derivatives in moderate to excellent yields (up to 99 % yield) with up to 99 % ee. A preliminary mechanistic investigation was conducted.

  使用手性磷酸催化剂建立了 5-氨基吡唑与萘醌酯的不对称反应，提供了多种轴向手性萘基吡唑衍生物，产率中等至优异（产率高达 99%），ee 高达 99% 。进行了初步的机制研究。