2-chloro-6-fluoro-3-methoxybenzoyl chloride | 886499-44-1

• 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: 2-chloro-6-fluoro-3-methoxybenzoyl chloride
• CAS: 886499-44-1
• 化学式: C₈H₅Cl₂FO₂
• 分子量: 223.031
• InChiKey: STGRVLVQFDZTON-UHFFFAOYSA-N

物化性质

• 沸点：
  276.7±35.0 °C(Predicted)
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  2-chloro-6-fluoro-3-methoxybenzoyl chloride 在 吡啶 、 aluminum (III) chloride 、 四(三苯基膦)钯 、 三溴化硼 、 caesium carbonate 作用下， 以 甲醚 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 N-{3-[5-(2-chloro-6-fluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl}benzenesulfonamide
  参考文献：
  名称：

  Targeted Endocrine Therapy: Design, Synthesis, and Proof-of-Principle of 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors in Bone Fracture Healing

  摘要：

  Current therapies of steroid hormone-dependent diseases predominantly alter steroid hormone concentrations (or their actions) in plasma, in target and nontarget tissues alike, rather than in target organs only. Targeted therapy through the inhibition of steroidogenic enzymes may pose an attractive alternative with much less side effects. Here, we describe the design of a nanomolar potent 17 beta-hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) inhibitor (compound 15) and successful targeted intracrine therapy in a mouse bone fracture model. Blockade of 17 beta-HSD2 in bone is thought to increase intracellular estradiol (E2) and testosterone (T), which thereby inhibits bone resorption by osteoclasts and stimulates bone formation by osteoblasts, respectively. Administration of compound 15 in the mouse fracture model strongly increases the mechanical stability of the healing fractured bone because of a larger periosteal callus with newly formed bone without changing the plasma E2 and T concentrations. Steroidogenic 17 beta-HSD2 inhibition thus enables targeted intracrine therapy.

  DOI：

  10.1021/acs.jmedchem.8b01493
• 作为产物：
  描述：

  2-氯-6-氟-3-甲氧基苯甲酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-chloro-6-fluoro-3-methoxybenzoyl chloride
  参考文献：
  名称：

  Discovery of Potent OTUB1/USP8 Dual Inhibitors Targeting Proteostasis in Non-Small-Cell Lung Cancer

  摘要：

  DOI：

  10.1021/acs.jmedchem.2c00408

文献信息

• Inhibitors of 17Beta-Hydroxysteroid Dehydrogenases Type 1 and Type 2
  申请人：ELEXOPHARM GMBH

  公开号：US20160318895A1

  公开（公告）日：2016-11-03

  Provided herein are non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 and type 2 (17β-HSD1 and 17β-HSD2) inhibitors, their production and use, especially for the treatment and for prophylaxis of hormone-related diseases.

  提供的是非甾体的17β-羟基类固醇脱氢酶1型和2型（17β-HSD1和17β-HSD2）抑制剂，它们的生产和应用，尤其是用于治疗和预防激素相关疾病。
• [EN] SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS DE LA 17-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1
  申请人：UNIV SAARLAND

  公开号：WO2012025638A1

  公开（公告）日：2012-03-01

  The invention relates to selective, non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors their production and use, especially for the treatment and/or prophylaxis of hormone-related diseases.

  这项发明涉及选择性的、非类固醇17β-羟基类固醇脱氢酶1型（17β-HSD1）抑制剂的生产和使用，特别用于治疗和/或预防激素相关疾病。
• Development of potential preclinical candidates with promising in vitro ADME profile for the inhibition of type 1 and type 2 17β-Hydroxysteroid dehydrogenases: Design, synthesis, and biological evaluation
  作者：Ahmed S. Abdelsamie、Mohamed Salah、Lorenz Siebenbürger、Mostafa M. Hamed、Carsten Börger、Chris J. van Koppen、Martin Frotscher、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2019.05.084

  日期：2019.9

  humans. Disturbing the balance between E2 and its weakly active oxidized form estrone (E1) leads to diverse types of estrogen-dependent diseases such as endometriosis or osteoporosis. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the biosynthesis of E2 by reduction of E1 while the type 2 enzyme catalyzes the reverse reaction. Thus, 17β-HSD1 and 17β-HSD2 are attractive targets for treatment

  雌激素是主要的女性类固醇激素，雌二醇（E2）是人类中最有效的形式。扰乱E2及其弱活性氧化形式的雌酮（E1）之间的平衡会导致多种类型的雌激素依赖性疾病，例如子宫内膜异位症或骨质疏松症。1型17β-羟基类固醇脱氢酶（17β-HSD1）通过还原E1催化E2的生物合成，而2型酶则催化逆反应。因此，17β-HSD1和17β-HSD2是治疗雌激素依赖性疾病的有吸引力的靶标。最近，我们报道了使用皮下给药在骨折小鼠模型中对17β-HSD2抑制剂进行的首次原理验证研究。在本研究中，我们的目的是改善体外迄今为止描述的最有效的17β-HSD1和17β-HSD2抑制剂的ADME谱。优化的化合物对人的酶及其鼠直系同源物均表现出强烈的选择性抑制作用。此外，与先导化合物相比，它们在人肝微粒体（S9级分）中显示出良好的代谢稳定性，较低的体外细胞毒性以及更好的水溶性和理化性质。这些成就使这些化合物有资格在临床前体内动物模型
• 4-Aryl-2-Amino-Pyrimidnes or 4-Aryl-2-Aminoalkyl-Pyrimidines as Jak-2 Modulators and Methods of Use
  申请人：Mann Grace

  公开号：US20090298830A1

  公开（公告）日：2009-12-03

  This invention relates to certain pyrimidine derivative inhibitors of JAK-2, having Formula (I): wherein D, E, L, Z, R 1 , R 2 , R 25 , and n1 are as defined in the specification, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本发明涉及某些JAK-2的嘧啶衍生物抑制剂，具有公式（I）：其中D、E、L、Z、R1、R2、R25和n1如规范中所定义，其药学上可接受的盐，其制药组合物以及其使用方法。
• Optimization of Hydroxybenzothiazoles as Novel Potent and Selective Inhibitors of 17β-HSD1
  作者：Alessandro Spadaro、Martin Frotscher、Rolf W. Hartmann

  DOI：10.1021/jm201711b

  日期：2012.3.8

  17 beta-HSD1 is a novel target for the treatment of estrogen-dependent diseases, as it catalyzes intracellular estradiol formation. Starting from two recently described compounds, highly active and selective inhibitors were developed. Benzoyl 6 and benzamide 17 are the most selective compounds toward 17 beta-HSD2 described so far. They also showed a promising profile regarding activity in T47-D cells, selectivity toward ER alpha and ER beta inhibition of hepatic CYP enzymes, metabolic stability, and inhibition of marmoset 17 beta-HSD1 and 17 beta-HSD2.