KR-66344 | 342384-83-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: KR-66344
• CAS: 342384-83-2
• 化学式: C₂₃H₁₇NO₅S
• 分子量: 419.458
• InChiKey: NXGMFIRHQMZBHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.68
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  91.75
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  三氟甲磺酸酐 、 KR-66344 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以90%的产率得到(3-Benzoyl-1,1-dioxo-2-phenacyl-1lambda6,2-benzothiazin-4-yl) trifluoromethanesulfonate
  参考文献：
  名称：

  发现环磺酰胺衍生物作为11β-羟类固醇脱氢酶1抑制剂

  摘要：

  合成了一系列新的环状磺酰胺衍生物，并评估了它们抑制11β-HSD1的能力。在2-位具有苯基乙酰基取代基的环状磺酰胺显示出纳摩尔抑制活性。其中，化合物4e对人11β-HSD2显示出良好的体外抑制活性和选择性。

  DOI：

  10.1016/j.bmcl.2009.12.035
• 作为产物：
  描述：

  3-[hydroxy(phenyl)methylidene]-1,1-dioxo-1λ⁶,2-benzothiazin-4-one 、 2-溴苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 KR-66344
  参考文献：
  名称：

  发现环磺酰胺衍生物作为11β-羟类固醇脱氢酶1抑制剂

  摘要：

  合成了一系列新的环状磺酰胺衍生物，并评估了它们抑制11β-HSD1的能力。在2-位具有苯基乙酰基取代基的环状磺酰胺显示出纳摩尔抑制活性。其中，化合物4e对人11β-HSD2显示出良好的体外抑制活性和选择性。

  DOI：

  10.1016/j.bmcl.2009.12.035

文献信息

• Methods and compositions for treating alcohol use disorders
  申请人：Sanna Pietro Paolo

  公开号：US10039772B2

  公开（公告）日：2018-08-07

  Disclosed are methods and compositions for treating alcohol dependence by administration to a patient of an inhibitor of 11β-hydroxysteroid dehydrogenases (11β-HSD) to modulate glucocorticoid effects. One such compound is the 11β-HSD inhibitor carbenoxolone (18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively employed in the clinic for the treatment of gastritis and peptic ulcer. Carbenoxolone is active on both 11β-HSD1 and 2 isoforms. Here, carbenoxolone is surprisingly shown to reduce both baseline and excessive drinking in rats and mice. The carbenoxolone diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which the applicants discovered to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors are a new class of candidate alcohol abuse medications and existing 11β-HSD inhibitor drugs may be re-purposed for alcohol abuse treatment.

  本发明公开了通过向患者施用 11β-羟基类固醇脱氢酶（11β-HSD）抑制剂以调节糖皮质激素作用来治疗酒精依赖症的方法和组合物。其中一种化合物是 11β-HSD 抑制剂卡本诺酮（18β-甘草次酸 3β-O-hemisuccinate ），临床上已广泛用于治疗胃炎和消化性溃疡。卡贝诺酮对 11β-HSD1 和 2 同工酶均有活性。令人惊讶的是，羧甲诺龙在大鼠和小鼠体内可减少基线饮酒量和过量饮酒量。申请人发现，羧诺龙的非对映异构体 18α-甘草次酸 3β-O-hemisuccinate (αCBX)对 11β-HSD2 具有选择性，也能有效减少小鼠的饮酒量。因此，11β-HSD 抑制剂是一类新的候选酗酒药物，现有的 11β-HSD 抑制剂药物可重新用于酗酒治疗。
• METHODS AND COMPOSITIONS FOR TREATING ALCOHOL USE DISORDERS
  申请人：SANNA Pietro Paolo

  公开号：US20170232007A1

  公开（公告）日：2017-08-17

  Disclosed are methods and compositions for treating alcohol dependence by administration to a patient of an inhibitor of 11β-hydroxysteroid dehydrogenases (11β-HSD) to modulate glucocorticoid effects. One such compound is the 11β-HSD inhibitor carbenoxolone (18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively employed in the clinic for the treatment of gastritis and peptic ulcer. Carbenoxolone is active on both 11β-HSD1 and 2 isoforms. Here, carbenoxolone is surprisingly shown to reduce both baseline and excessive drinking in rats and mice. The carbenoxolone diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which the applicants discovered to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors are a new class of candidate alcohol abuse medications and existing 11β-HSD inhibitor drugs may be re-purposed for alcohol abuse treatment.
• Discovery of cyclicsulfonamide derivatives as 11β-hydroxysteroid dehydrogenase 1 inhibitors
  作者：Se Hoan Kim、Ravirala Ramu、Sung Wook Kwon、Su-Hee Lee、Chi Hyun Kim、Seung Kyu Kang、Sang Dal Rhee、Myung Ae Bae、Sung Hoon Ahn、Duck Chan Ha、Hyae Gyeong Cheon、Ki Young Kim、Jin Hee Ahn

  DOI：10.1016/j.bmcl.2009.12.035

  日期：2010.2

  A new series of cyclic sulfonamide derivatives was synthesized and evaluated for their ability to inhibit 11β-HSD1. Cyclic sulfonamides with phenylacetyl substituents at the 2-position showed nanomolar inhibitory activities. Among them, compound 4e exhibited a good in vitro inhibitory activity and selectivity toward human 11β-HSD2.

  合成了一系列新的环状磺酰胺衍生物，并评估了它们抑制11β-HSD1的能力。在2-位具有苯基乙酰基取代基的环状磺酰胺显示出纳摩尔抑制活性。其中，化合物4e对人11β-HSD2显示出良好的体外抑制活性和选择性。