3-Methyl-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 3-Methyl-6-trifluoromethyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide
• 英文别名: 3-methyl-1,1-dioxo-6-(trifluoromethyl)-4H-1λ6,4-benzothiazine-2-carbonitrile
• 化学式: C₁₁H₇F₃N₂O₂S
• 分子量: 288.25
• InChiKey: YVKITSHTGKQBEK-UHFFFAOYSA-N

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：
  0.18
• 拓扑面积：
  78.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 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 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Methyl-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

文献信息

• Fused 1,4-thiazine-2-carbonitrile derivatives, their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US06232310B1

  公开（公告）日：2001-05-15

  The present invention relates to fused 1,4-thiazine-2-carbonitrile derivatives, compositions thereof and methods for preparing the compounds. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

  本发明涉及融合的1,4-噻嗪-2-碳腈衍生物、其组合物以及制备这些化合物的方法。这些化合物在治疗中枢神经系统、心血管系统、肺系统、胃肠系统和内分泌系统的疾病方面具有用途。
• Intranasal administration of modulators of hypothalamic ATP-sensitive potassium channels
  申请人：Herlands Louis

  公开号：US20070026079A1

  公开（公告）日：2007-02-01

  Provided are methods of increasing K ATP channel activity in the hypothalamus of a mammal, methods of reducing glucose production in a mammal, methods of reducing peripheral glucose levels in a mammal, methods of reducing triglyceride levels in a mammal, methods of reducing very low density lipoprotein (VLDL) levels in a mammal, methods of methods of reducing gluconeogenesis in the liver of a mammal, methods of treating metabolic disorders such as diabetes, hyperglycemia, insulin resistance, glucose intolerance, metabolic syndrome and/or obesity, and methods of increasing glucose production and peripheral glucose levels in a mammal. Also provided are methods of treating heart failure, ischemia, coronary heart disease, familial lipoprotein lipase deficiency, hypopituitarism, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, atherosclerosis, hypercholesterolemia, hypertension, polycystic ovary syndrome, gonadotropin deficiency and/or amenorrhea.
• Modulation of Hypothalamic Atp-Sensitive Potassium Channels
  申请人：Rossetti Luciano

  公开号：US20090012067A1

  公开（公告）日：2009-01-08

  Provided are methods of increasing K ATP activity in the hypothalamus of a mammal, methods of reducing glucose production and peripheral blood glucose levels in a mammal, methods of inhibiting gluconeogenesis in the liver of a mammal, and methods of increasing glucose production and peripheral blood glucose levels in a mammal.
• US6232310B1
  申请人：——

  公开号：US6232310B1

  公开（公告）日：2001-05-15
• 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
  作者：Søren C. Schou、Holger C. Hansen、Tina M. Tagmose、Harrie C.M. Boonen、Anne Worsaae、Michael Drabowski、Philip Wahl、Per O.G. Arkhammar、Thora Bodvarsdottir、Marie-Hélène Antoine、Philippe Lebrun、John Bondo Hansen

  DOI：10.1016/j.bmc.2004.09.051

  日期：2005.1

  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.