3-hydroxy-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide | 821806-28-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3-hydroxy-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide
• 英文别名: 3-hydroxy-1,1-dioxo-6-(trifluoromethyl)-4H-1lambda6,4-benzothiazine-2-carbonitrile；3-hydroxy-1,1-dioxo-6-(trifluoromethyl)-4H-1λ6,4-benzothiazine-2-carbonitrile
• CAS: 821806-28-4
• 化学式: C₁₀H₅F₃N₂O₃S
• 分子量: 290.223
• InChiKey: UUFIQJIOWVZKMF-UHFFFAOYSA-N

物化性质

• 熔点：
  222-224 °C(Solv: acetic acid (64-19-7))
• 沸点：
  379.8±42.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  98.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-hydroxy-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide 在 磷酸 、 吡啶盐酸盐 、 三氯氧磷 作用下， 以93%的产率得到3-chloro-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2-cyanomethylsulfonylphenyl)acylamide derivatives as potential activators of ATP sensitive potassium channels

  摘要：

  1, 2,4-Thiadiazine derivatives, like 3-methyl-7-chlorobenzo-4H-1,2,4-thiadiazine 1,1-dioxide, diazoxide and 7-chloro-3-isopropylamino-4H-benzo-1,2,4-thiadiazine 1,1-dioxide, BPDZ 73, are potent openers of Kir6.2/SUR1 K-ATP channels. To explore the structure-activity relationship of this series of K-ATP openers, 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2-cyano-methylsulfonylphenyl)acylamide derivatives were synthesized from 2-acetylamino-5-chloro-benzenesulfonic acid pyridinium salt or 2-aminobenzenethiols. The 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide derivatives (e.g., 7-chloro-3-isopropylamino-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide, 3f) were found to activate K-ATP channels as indicated by their ability to hyperpolarize beta cell membrane potential, to inhibit glucose-stimulated insulin release in vitro and to increase ion currents through Kir6.2/SUR1 channel as measured by patch clamp. The potency and efficacy of, for example, 3f is however significantly reduced compared to the corresponding 4H-1,2,4-benzothiadiazine 1,1-dioxide derivatives. Opening of the 4H-1,2,4-thiadiazine ring to get (e.g., 2-cyanomethylsulfonyl-4-fluorophenyl) carbamic acid isopropyl ester (4c) gives rise to compounds, which are able to open K-ATP channels but with considerable reduced potency compared to, for example, diazoxide. Compound 3a, 7-chloro-3-methyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide, which inhibits insulin release in vitro from beta cells and rat islets, reduces plasma insulin levels and blood pressure in anaesthetized rats upon intravenous administration. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.09.051
• 作为产物：
  描述：

  2-氨基-4-(三氟甲基)苯硫酚盐酸盐 在 sodium hydroxide 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-hydroxy-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2-cyanomethylsulfonylphenyl)acylamide derivatives as potential activators of ATP sensitive potassium channels

  摘要：

  1, 2,4-Thiadiazine derivatives, like 3-methyl-7-chlorobenzo-4H-1,2,4-thiadiazine 1,1-dioxide, diazoxide and 7-chloro-3-isopropylamino-4H-benzo-1,2,4-thiadiazine 1,1-dioxide, BPDZ 73, are potent openers of Kir6.2/SUR1 K-ATP channels. To explore the structure-activity relationship of this series of K-ATP openers, 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2-cyano-methylsulfonylphenyl)acylamide derivatives were synthesized from 2-acetylamino-5-chloro-benzenesulfonic acid pyridinium salt or 2-aminobenzenethiols. The 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide derivatives (e.g., 7-chloro-3-isopropylamino-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide, 3f) were found to activate K-ATP channels as indicated by their ability to hyperpolarize beta cell membrane potential, to inhibit glucose-stimulated insulin release in vitro and to increase ion currents through Kir6.2/SUR1 channel as measured by patch clamp. The potency and efficacy of, for example, 3f is however significantly reduced compared to the corresponding 4H-1,2,4-benzothiadiazine 1,1-dioxide derivatives. Opening of the 4H-1,2,4-thiadiazine ring to get (e.g., 2-cyanomethylsulfonyl-4-fluorophenyl) carbamic acid isopropyl ester (4c) gives rise to compounds, which are able to open K-ATP channels but with considerable reduced potency compared to, for example, diazoxide. Compound 3a, 7-chloro-3-methyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide, which inhibits insulin release in vitro from beta cells and rat islets, reduces plasma insulin levels and blood pressure in anaesthetized rats upon intravenous administration. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.09.051