6,7-dichloro-2-cyclopentyl-5-methoxy-2,3-dihydro-1H-inden-1-one | 54197-02-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 6,7-dichloro-2-cyclopentyl-5-methoxy-2,3-dihydro-1H-inden-1-one
• 英文别名: 2-Cyclopentyl-5-methoxy-6,7-dichlor-1-indanon；6,7-dichloro-2-cyclopentyl-2,3-dihydro-5-methoxy-1H-inden-1-one；6,7-Dichloro-2-cyclopentyl-5-methoxy-2,3-dihydroinden-1-one
• CAS: 54197-02-3
• 化学式: C₁₅H₁₆Cl₂O₂
• 分子量: 299.197
• InChiKey: SPUBKDVUWXVFDX-UHFFFAOYSA-N

物化性质

• 熔点：
  114-116 °C(Solv: benzene (71-43-2); hexane (110-54-3))
• 沸点：
  443.5±45.0 °C(Predicted)
• 密度：
  1.328±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  6,7-dichloro-2-cyclopentyl-5-methoxy-2,3-dihydro-1H-inden-1-one 在 吡啶盐酸盐 、 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 47.5h， 生成
  参考文献：
  名称：

  Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids

  摘要：

  Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

  DOI：

  10.1021/jm00347a017
• 作为产物：
  描述：

  2,3-二氯茴香醚 在 aluminum (III) chloride 、 盐酸二甲胺 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.17h， 生成 6,7-dichloro-2-cyclopentyl-5-methoxy-2,3-dihydro-1H-inden-1-one
  参考文献：
  名称：

  Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes

  摘要：

  2型糖尿病与胰岛素抵抗、胰岛β细胞胰岛素分泌受损和非酒精性脂肪性肝病有关。组织特异性的SWELL1消融影响了脂肪、骨骼肌和内皮细胞中的胰岛素信号传导，影响了β细胞的胰岛素分泌和血糖控制。在这里，我们展示了在小鼠和人类糖尿病中，脂肪和β细胞中的I_Cl,SWELL和SWELL1蛋白质被降低。通过结合冷冻电镜、分子对接、药物化学和功能研究，我们定义了一种结构活性关系，以合理设计SWELL1通道抑制剂（DCPIB/SN-401）的活性衍生物，这些衍生物结合SWELL1六聚体复合物，通过SWELL1依赖机制恢复SWELL1蛋白质、质膜转运、信号传导、血糖控制和胰岛素分泌。在体内，SN-401恢复小鼠糖尿病的血糖控制，减少肝脏脂肪变性/损伤，改善胰岛素敏感性和胰岛素分泌。这些发现表明，SWELL1通道调节剂改善了2型糖尿病中依赖SWELL1的全身代谢，代表了糖尿病和非酒精性脂肪性肝病的首个一类治疗方法。

  DOI：

  10.1038/s41467-022-28435-0

文献信息

• [1-Hydroxy-5-indanyloxy (or thio)]-alkanoic acids
  申请人：Merck & Co., Inc.

  公开号：US04012524A1

  公开（公告）日：1977-03-15

  [1-Hydroxy-5-indanyloxy (or thio)]alkanoic acids and their salts, esters and amides are disclosed. The products display a dual pharmaceutical utility in that they exhibit diuretic, saluretic and hypouricemic activity. The acid products are prepared by several synthetic methods.

  揭示了1-羟基-5-茚氧（或硫）烷酸及其盐、酯和酰胺。这些产品在药用上具有双重作用，表现出利尿、排钠和降尿酸活性。这些酸产品可以通过几种合成方法制备。
• [1-Hydroximino-2,2-disubstituted-5-indanyloxy-(or thio)]alkanoic acids
  申请人：Merck & Co., Inc.

  公开号：US03974212A1

  公开（公告）日：1976-08-10

  [1-Hydroximino-2,2-disubstituted-5-indanyloxy-(or thio)]alkanoic acids and their salt, ester, anhydride, amide and 5-tetrazolyl derivatives are disclosed. The products display a dual pharmaceutical utility in that they exhibit diuretic, saluretic and uricosuric activity. The acid products are prepared by treating a 1-oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids or derivatives thereof with hydroxylamine in the presence of a base.

  1-羟基亚胺基-2,2-二取代-5-茚氧基（或硫代）烷酸及其盐、酯、酐、酰胺和5-四唑基衍生物已被披露。这些产品具有双重药用功能，因为它们表现出利尿、排盐和尿酸排泄活性。酸性产物是通过将1-氧代-2,2-二取代-5-茚氧（或硫代）烷酸或其衍生物与羟胺在碱的存在下处理而制备的。
• Treatment of gray matter edema
  申请人：Merck & Co., Inc.

  公开号：US04463208A1

  公开（公告）日：1984-07-31

  The invention relates to the treatment of gray matter edema in the brain or spinal cord by the administration of (indanyloxy)acetic acids, and analogs and salts thereof.

  该发明涉及通过给予（茚氧基）乙酸及其类似物和盐来治疗大脑或脊髓中的灰质水肿。
• [EN] SWELL1-LRRC8 COMPLEX MODULATORS<br/>[FR] MODULATEURS DU COMPLEXE SWELL1-LRRC8
  申请人：UNIV WASHINGTON

  公开号：WO2020252041A1

  公开（公告）日：2020-12-17

  The present invention is directed to various polycyclic compounds and methods of using these compounds to treat a variety of diseases including metabolic diseases such as obesity, diabetes, nonalcoholic fatty liver disease; cardiovascular diseases such as hypertension and stroke; neurological diseases, male infertility, muscular disorders, and immune disorders.

  本发明涉及各种多环化合物，以及利用这些化合物治疗各种疾病的方法，包括代谢性疾病，如肥胖、糖尿病、非酒精性脂肪肝病；心血管疾病，如高血压和中风；神经系统疾病、男性不育、肌肉疾病和免疫系统疾病。
• Treatment of brain injury due to gray matter edema with (indanyloxy)
  申请人：Merck & Co., Inc.

  公开号：US04465850A1

  公开（公告）日：1984-08-14

  The invention relates to the treatment and prevention of injury to the gray matter of the brain and to the spinal chord due to accidents, ischemic stroke, cardiac arrest, arrested breathing, Reye's syndrome and hydrocephalus by the administration of (indanyloxy)butanoic acids, their derivatives, analogs and salts thereof.

  本发明涉及通过给予（indanyloxy）丁酸、其衍生物、类似物及其盐的治疗和预防因意外事故、缺血性中风、心脏骤停、呼吸停止、Reye综合症和脑积水导致的脑灰质和脊髓损伤。