methyl 4-methyl-3-((trimethylsilyl)ethynyl)benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-methyl-3-((trimethylsilyl)ethynyl)benzoate
• 英文别名: methyl 4-methyl-3-(2-trimethylsilylethynyl)benzoate
• 化学式: C₁₄H₁₈O₂Si
• 分子量: 246.381
• InChiKey: QXMYBKYVOMIHGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 4-methyl-3-((trimethylsilyl)ethynyl)benzoate 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.08h， 生成 4-methyl-N-phenyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide
  参考文献：
  名称：

  Discovery and Optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors

  摘要：

  Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)-benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a K-d value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.

  DOI：

  10.1021/jm301824k
• 作为产物：
  描述：

  3-氨基-4-甲基苯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 硫酸 、 三乙胺 、 sodium nitrite 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 生成 methyl 4-methyl-3-((trimethylsilyl)ethynyl)benzoate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2

  摘要：

  Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, Sn, tightly bound to DDR1 and DDR2 proteins with K-d values of 7.9 and 8.0 nM; potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, respectively; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 mu M. DDR1- and DDR2-kinase inhibition by 5n was validated by Western-blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery.

  DOI：

  10.1021/acs.jmedchem.8b01045

文献信息

• [EN] RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF<br/>[FR] INHIBITEURS DE RET, COMPOSITIONS PHARMACEUTIQUES ET UTILISATIONS ASSOCIÉES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2020114494A1

  公开（公告）日：2020-06-11

  Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.

  本文提供了一种RET抑制剂，其药物组合物及用途。具体而言，提供了具有化学式（I）或其立体异构体、几何异构体、互变异构体、N-氧化物、溶剂合物、代谢物、药用可接受的盐或其前药的化合物。提供了包含该化合物的药物组合物，并提供了该化合物及其药物组合物的用途，用于制备药物，特别是用于治疗和预防与RET相关的疾病和症状，包括癌症、肠易激综合征以及与肠易激综合征相关的疼痛。
• [EN] NEW COMPOUNDS AND METHODS<br/>[FR] NOUVEAUX COMPOSÉS ET PROCÉDÉS
  申请人：BENEVOLENTAI BIO LTD

  公开号：WO2020260871A1

  公开（公告）日：2020-12-30

  The present invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, optical isomer, N-oxide, and/or prodrug thereof. The present invention also relates to pharmaceutical compositions comprising the compounds of the invention, and to their use in the treatment or prevention of medical conditions in which inhibition of c-ABL is beneficial. (I)

  本发明涉及式(I)的化合物或其药用可接受的盐、溶剂化合物、水合物、互变异构体、光学异构体、N-氧化物和/或前药。本发明还涉及包括本发明化合物的药物组合物，以及它们在治疗或预防抑制c-ABL有益的医疗状况中的使用。
• 3-ACETYLENYL-PYRAZOLE-PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND USES THEREOF
  申请人：Si Chuan University

  公开号：US20170305920A1

  公开（公告）日：2017-10-26

  The present invention relates to the field of chemical and medicine, more particularly, 3-ethynylpyrazolopyrimidine derivatives and their preparation methods and uses. The invention provides a 3-ethynylpyrazolopyrimidine derivative, and the structure is shown in formula I. The present invention also provides preparation methods and use of 3-ethynylpyrazolopyrimidine derivatives, comprising the compounds and derivatives, and their pharmaceutical compositions for the use of the treatment and prevention of tumors.

  本发明涉及化学和药物领域，更具体地涉及3-乙炔吡唑吡嘧啶衍生物及其制备方法和用途。该发明提供了一种3-乙炔吡唑吡嘧啶衍生物，其结构如公式I所示。本发明还提供了3-乙炔吡唑吡嘧啶衍生物的制备方法和用途，包括该化合物和衍生物，以及它们的药物组合物，用于治疗和预防肿瘤。
• Design, Synthesis, and <i>in vitro</i> Evaluation of P2X7 Antagonists
  作者：Dimitra T. Pournara、Anna Durner、Eftichia Kritsi、Alexios Papakostas、Panagiotis Zoumpoulakis、Annette Nicke、Maria Koufaki

  DOI：10.1002/cmdc.202000303

  日期：2020.12.15

  is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan‐1‐yl)methylbenzamides able to inhibit the receptor

  由于 P2X7 受体在炎症和免疫细胞信号传导中的重要作用，它是治疗各种疾病的有希望的靶点。这项工作描述了一系列带有多种支架的新型衍生物作为有效的 P2X7 拮抗剂的设计、合成和体外评估。我们的方法基于已报道的（金刚烷-1-基）甲基苯甲酰胺的结构修饰，能够抑制受体激活。金刚烷部分和酰胺键被替换，并通过基于配体的药效团模型评估替换。通过双电极电压钳实验评估合成类似物的拮抗效力，使用非洲爪蟾表达人 P2X7 受体的卵母细胞。SAR 研究表明，用芳基-环己基部分取代金刚烷环是对抗 P2X7 阳离子通道激活的最有效拮抗剂，类似物 2-氯-N- [1-(3-(硝基氧基甲基)苯基)环己基)甲基]苯甲酰胺 ( 56 ) 表现出最佳效力，IC 50值为 0.39 μM。
• NEW CHEMICAL COMPOUNDS
  申请人：STEURER Steffen

  公开号：US20080182837A1

  公开（公告）日：2008-07-31

  The present invention encompasses compounds of general formula (1) wherein the groups R 2 to R 4 , L, Q and n are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.

  本发明涵盖了一般式（1）中的化合物，其中基团R2至R4、L、Q和n的定义如权利要求书中所述，适用于治疗以细胞过度或异常增殖为特征的疾病，并且用于制备具有上述特性的药物。