(R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride | 1010396-30-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride
• 英文别名: (2R)-3-bromo-2-hydroxy-2-methyIpropanoyl chloride；(2R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride
• CAS: 1010396-30-1
• 化学式: C₄H₆BrClO₂
• 分子量: 201.447
• InChiKey: DEXFBFYVUNWNKF-BYPYZUCNSA-N

物化性质

• 沸点：
  224.9±30.0 °C(Predicted)
• 密度：
  1.770±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氟-3-三氟甲基苯胺 、 (R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride 以 N,N-二甲基乙酰胺 为溶剂， 反应 16.0h， 以56%的产率得到(R)-3-bromo-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide
  参考文献：
  名称：

  Prostate cancer PET bioprobes: Synthesis of [18F]-radiolabeled hydroxyflutamide derivatives

  摘要：

  Approximately 80-90% of prostate cancers are androgen dependent at initial diagnosis. The androgen receptor (AR) is present in most advanced prostate cancer specimens and is believed to have a critical role in its development. Today, treatment of prostate cancer is done by inhibition of AR using antiandrogens such as flutamide (pro-drug of hydroxyflutamide), nilutamide, and bicalutamide. However, there is currently no noninvasive imaging modalities to detect, guide, and monitor specific treatment of AR-positive prostate cancer. (R)-3-Bromo-N-(4-fluoro-3-(trifluoromethy, phenyl)-2-hydroxy-2-methyl-propanamide [F-18]-1 and N-(4fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide [F-18]-2, derivatives of hydroxyflutamide, were synthesized as a fluorine-containing imaging agent candidates. A three-step fluorine-18 radiosynthesis route was developed, and the compounds were successfully labeled with a 10 +/- 3% decay corrected radiochemical yield, 95% radiochemical purity, and a specific activity of 1500 +/- 200 Ci/mmol end of bombardment (n = 10). These labeled biprobes not only may enable for the future quantitative molecular imaging of AR-positive prostate cancer using positron emission tomography but may also allow for image-guided treatment of prostate cancer. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.033
• 作为产物：
  描述：

  (2R)-3-溴-2-羟基-2-甲基丙酸 在 氯化亚砜 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 生成 (R)-3-bromo-2-hydroxy-2-methylpropanoyl chloride
  参考文献：
  名称：

  设计和合成新型比卡鲁胺和恩杂鲁胺衍生物作为抗增殖药，用于治疗前列腺癌

  摘要：

  前列腺癌（PC）是世界范围内男性死亡的主要原因之一，不断开发新的和更有效的抗PC化合物一直是必需的。在当前的治疗方法中，（R）-比卡鲁胺和恩杂鲁胺是在去势抵抗形式的情况下也被批准的非甾体雄激素受体拮抗剂药物。这两种药物均表现出中等的抗增殖活性，并且由于其生物学靶标的抗性突变体的发展，其使用受到限制。 在生物活性化合物中插入氟化和全氟化基团是药物化学的当前趋势，用于改善其功效和稳定性。为了获得这种效果，在比卡鲁胺和恩杂鲁胺结构上合理设计了全氟基团的不同修饰，从而合成了一系列新的抗增殖化合物。几种新的类似物显示出对四种不同前列腺癌细胞系的体外活性得到改善，同时保持了完全的AR拮抗作用，因此代表了进一步开发的有希望的线索。 此外，对AR拮抗剂的构象进行了一系列分子建模研究，为潜在的蛋白质-配体相互作用提供了有用的见解。

  DOI：

  10.1016/j.ejmech.2016.04.052

文献信息

• Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer
  作者：Marcella Bassetto、Salvatore Ferla、Fabrizio Pertusati、Sahar Kandil、Andrew D. Westwell、Andrea Brancale、Christopher McGuigan

  DOI：10.1016/j.ejmech.2016.04.052

  日期：2016.8

  anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the case of castration-resistant forms. Both these drugs present a moderate antiproliferative activity and their use is limited due to the development of resistant mutants of their biological target. Insertion of fluorinated

  前列腺癌（PC）是世界范围内男性死亡的主要原因之一，不断开发新的和更有效的抗PC化合物一直是必需的。在当前的治疗方法中，（R）-比卡鲁胺和恩杂鲁胺是在去势抵抗形式的情况下也被批准的非甾体雄激素受体拮抗剂药物。这两种药物均表现出中等的抗增殖活性，并且由于其生物学靶标的抗性突变体的发展，其使用受到限制。 在生物活性化合物中插入氟化和全氟化基团是药物化学的当前趋势，用于改善其功效和稳定性。为了获得这种效果，在比卡鲁胺和恩杂鲁胺结构上合理设计了全氟基团的不同修饰，从而合成了一系列新的抗增殖化合物。几种新的类似物显示出对四种不同前列腺癌细胞系的体外活性得到改善，同时保持了完全的AR拮抗作用，因此代表了进一步开发的有希望的线索。 此外，对AR拮抗剂的构象进行了一系列分子建模研究，为潜在的蛋白质-配体相互作用提供了有用的见解。
• Prodrugs of selective androgen receptor modulators and methods of use thereof
  申请人：Miller D. Duane

  公开号：US20060009488A1

  公开（公告）日：2006-01-12

  The present invention provides prodrugs of selective androgen receptor modulators (SARMs), and their use in treating or reducing the incidence of osteoporosis, a variety of hormone-related conditions, conditions associated with Androgen Decline in Aging Male (ADAM); conditions associated with Androgen Decline in Female (ADIF), and muscular wasting conditions, obesity, dry eye conditions, and prostate cancer. The prodrugs are also useful in oral androgen replacement therapy and male contraception.

  本发明提供了选择性雄激素受体调节剂（SARMs）的前药，以及它们在治疗或减少骨质疏松症、各种与激素相关的疾病、与男性衰老期间雄激素下降相关的疾病、与女性雄激素下降相关的疾病、肌肉消耗疾病、肥胖、干眼症和前列腺癌的发病率中的应用。这些前药还可用于口服雄激素替代疗法和男性避孕。
• [EN] METABOLITES OF SELECTIVE ANDROGEN RECEPTOR MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MÉTABOLITES DE MODULATEURS DE RÉCEPTEUR ANDROGÈNE SÉLECTIFS ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：GTX INC

  公开号：WO2009155481A1

  公开（公告）日：2009-12-23

  This invention provides metabolites of SARM compounds including inter alia glucuronidated metabolites and uses thereof in treating a variety of diseases or conditions in a subject, including, inter alia, muscle wasting disease and/or disorder, a bone related disease and/or disorder, metabolic syndrome, diabetes and associated diseases, and others.

  这项发明提供了SARM化合物的代谢产物，包括葡萄糖醛酸酯化合物等，并利用它们在治疗受试者中的多种疾病或症状，包括但不限于肌肉消耗疾病和/或紊乱、与骨相关的疾病和/或紊乱、代谢综合征、糖尿病及相关疾病等。
• [EN] PHARMACEUTICAL COMPOSITIONS OF SELECTIVE ANDROGEN RECEPTOR MODULATORS AND METHODS OF USE THEREOF<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DE MODULATEURS SÉLECTIFS DES RÉCEPTEURS DES ANDROGÈNES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GTX INC

  公开号：WO2013067170A1

  公开（公告）日：2013-05-10

  This invention provides a pharmaceutical composition comprising Compound I-V, including inter alia solid dosage forms of powder-filled capsule formulations, liquid-filled softgel capsules (softgels), tablets, and sustained release dosage forms, and uses thereof in treating a variety of diseases or conditions in a subject, for example, treating a muscle wasting disease and/or disorder, a bone related disease and/or disorder, metabolic syndrome, diabetes and associated diseases, and others.

  这项发明提供了一种包含化合物I-V的药物组合物，包括固体剂型的填粉胶囊制剂、液体填充软胶囊（软胶囊）、片剂和缓释剂型，以及在治疗受试者中各种疾病或症状中的用途，例如治疗肌肉消耗疾病和/或紊乱、骨相关疾病和/或紊乱、代谢综合征、糖尿病及相关疾病等。
• Selective androgen receptor modulators and methods of use thereof
  申请人：——

  公开号：US20030225040A1

  公开（公告）日：2003-12-04

  This invention provides a class of androgen receptor targeting agents (ARTA). The agents define a new subclass of compounds, which are selective androgen receptor modulators (SARM). Several of the SARM compounds have been found to have an unexpected androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. Other SARM compounds have been found to have an unexpected antiandrogenic activity of a nonsteroidal ligand for the androgen receptor. The SARM compounds, either alone or as a composition, are useful for a) male contraception; b) treatment of a variety of hormone-related conditions, for example conditions associated with Androgen Decline in Aging Male (ADAM), such as fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, osteoporosis, benign prostate hyperplasia, alterations in mood and cognition and prostate cancer; c) treatment of conditions associated with Androgen Decline in Female (ADIF), such as sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, depression, anemia, hair loss, obesity, endometriosis, breast cancer, uterine cancer and ovarian cancer; d) treatment and/or prevention of acute and/or chronic muscular wasting conditions; e) preventing and/or treating dry eye conditions; f) oral androgen replacement therapy; and/or g) decreasing the incidence of, halting or causing a regression of prostate cancer.

  本发明提供了一类雄激素受体靶向剂（ARTA）。这些剂定义了一类新的化合物亚类，即选择性雄激素受体调节剂（SARM）。其中几种SARM化合物被发现具有非甾体配体的意外雄激素和肌肉增长活性。其他SARM化合物被发现具有非甾体配体的意外抗雄激素活性。这些SARM化合物，无论是单独使用还是作为组合物，都可用于：a）男性避孕；b）治疗各种激素相关疾病，例如与老年男性雄激素下降相关的疾病，如疲劳，抑郁，性欲降低，性功能障碍，勃起功能障碍，睾丸功能减退，骨质疏松症，脱发，贫血，肥胖症，肌肉萎缩症，骨质疏松症，良性前列腺增生，情绪和认知的改变以及前列腺癌；c）治疗与女性雄激素下降相关的疾病，如性功能障碍，性欲降低，睾丸功能减退，肌肉萎缩症，骨质疏松症，认知和情绪的改变，抑郁，贫血，脱发，肥胖症，子宫内膜异位症，乳腺癌，子宫癌和卵巢癌；d）预防和/或治疗急性和/或慢性肌肉消耗疾病；e）预防和/或治疗干眼症；f）口服雄激素替代疗法；和/或g）降低前列腺癌的发病率，阻止或引起其退化。