N-(2-Cyanoethyl)-6-pentafluoroethyl-2,2-bis(fluoromethyl)-2H-1-benzopyran-4-carboxamide | 152661-26-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-(2-Cyanoethyl)-6-pentafluoroethyl-2,2-bis(fluoromethyl)-2H-1-benzopyran-4-carboxamide
• 英文别名: N-(2-cyanoethyl)-6-pentafluoroethyl-2,2-bisfluoromethyl-2H-1-benzopyran-4-carbamide；N-(2-cyanoethyl)-2,2-bis(fluoromethyl)-6-(1,1,2,2,2-pentafluoroethyl)chromene-4-carboxamide
• CAS: 152661-26-2
• 化学式: C₁₇H₁₃F₇N₂O₂
• 分子量: 410.291
• InChiKey: KJRASUCTGRMLNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-(2-Cyanoethyl)-6-pentafluoroethyl-2,2-bis(fluoromethyl)-2H-1-benzopyran-4-carboxamide 在 劳森试剂 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 1.0h， 以62%的产率得到N-(2-cyanoethyl)-6-pentafluoroethyl-2,2-bis-fluoromethyl-2H-1-benzopyran-4-carbothioamide
  参考文献：
  名称：

  6-Substituted 2,2-Bis(fluoromethyl)-benzopyran-4-carboxamide K + channel openers

  摘要：

  In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N-(2-cyanoethyl)-2,2 bis(fluoromethyl)-6-pentafluoroethyl-2H-1-benzopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 (13f) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00064-x
• 作为产物：
  描述：

  2,2-bis(fluoromethyl)-6-iodo-2H-1-benzopyran-4-carboxylic acid ethyl ester 在 氢氧化钾 、 copper(l) iodide 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 13.0h， 生成 N-(2-Cyanoethyl)-6-pentafluoroethyl-2,2-bis(fluoromethyl)-2H-1-benzopyran-4-carboxamide
  参考文献：
  名称：

  6-Substituted 2,2-Bis(fluoromethyl)-benzopyran-4-carboxamide K + channel openers

  摘要：

  In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N-(2-cyanoethyl)-2,2 bis(fluoromethyl)-6-pentafluoroethyl-2H-1-benzopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 (13f) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00064-x

文献信息

• Remedies for peripheral circulation disturbances
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US06248777B1

  公开（公告）日：2001-06-19

  It is an object of the present invention to provide novel therapeutic agents for peripheral vascular disease. The present invention provides pharmaceutical compositions comprising a benzopyran or benzoxazine derivative of the general formula (1): wherein; R1 represents a hydrogen atom, a lower alkyl group or an aryl group, or R1 directly couples with Q or R11 to form a single bond; R2represents a substituted or unsubstituted amino group, a saturated or unsaturated heterocyclic group, A—O—or —C(═X)Y; Q represents ═N—, N+—O−or C(R11)R12; R3 and R4 each represent a hydrogen atom, a lower alkyl group or a substituted lower alkyl group having a halogen atom or a lower alkoxy group as a substituent or the like; and R5 and R6 each represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group or the like; and a pharmaceutically acceptable carrier.

  本发明的目的是为外周血管疾病提供新型治疗药物。 本发明提供了包含一种通式（1）的苯并吡喃或苯并噁嗪衍生物的药物组合物： 其中； R1代表氢原子、较低的烷基或芳基，或R1直接与Q或R11结合形成单键； R2代表取代或未取代的氨基、饱和或不饱和的杂环基、A—O—或—C(═X)Y； Q代表═N—、N+—O−或C(R11)R12； R3和R4各自代表氢原子、较低的烷基或具有卤原子或较低的烷氧基等取代基的取代的较低烷基，R5和R6各自代表氢原子、卤原子、较低的烷基、较低的卤代烷基或类似物；以及一种药学上可接受的载体。
• Processes for the preparation of 4-substituted benzopyran derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US06455708B1

  公开（公告）日：2002-09-24

  Starting, for example, from 1-fluoro-2-fluoromethyl-3-butyn-2-yl 4-trifluoromethylphenyl; ether, N-(2-cyanoethyl)-5-fluoro-4-fluoromethyl-4-(4-trifluoromethylphenoxy)-2-pentynamide is produced and then cyclized to synthesize 2,2-bis(fluoromethyl)-N-(2-cyanoethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxamide. The invention processes for producing 4-substituted benzopyran derivatives involve fewer steps, feature greater safety and allow for easier purification than the prior art processes.

  例如，从1-氟-2-氟甲基-3-丁炔-2-基-4-三氟甲基苯基醚开始；产生N-(2-氰乙基)-5-氟-4-氟甲基-4-(4-三氟甲基苯氧基)-2-戊炔酰胺，然后环化合成2,2-双(氟甲基)-N-(2-氰乙基)-6-三氟甲基-2H-1-苯并吡喃-4-甲酰胺。本发明的生产4-取代苯并吡喃衍生物的工艺步骤比现有技术的工艺步骤更少，具有更高的安全性，并且比以往更容易纯化。
• Processes for producing 4-substituted benzopyran derivatives
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US20030065189A1

  公开（公告）日：2003-04-03

  Starting, for example, from 1-fluoro-2-fluoromethyl-3-butyn-2-yl 4-trifluoromethylphenyl ether, N-(2-cyanoethyl)-5-fluoro-4-fluoromethyl-4-(4-trifluoromethylphenoxy)-2-pentynamide is produced and then cyclized to synthesize 2,2-bis(fluoromethyl)-N-(2-cyanoethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxamide. The invention processes for producing 4-substituted benzopyran derivatives involve fewer steps, feature greater safety and allow for easier purification than the prior art processes.

  以1-氟-2-氟甲基-3-丁炔-2-基-4-三氟甲基苯醚为起始物，生产N-(2-氰基乙基)-5-氟-4-氟甲基-4-(4-三氟甲基苯氧基)-2-戊炔酰胺，然后环化合成2,2-双(氟甲基)-N-(2-氰基乙基)-6-三氟甲基-2H-1-苯并吡喃-4-羧酰胺。该发明生产4-取代苯并吡喃衍生物的工艺步骤较少，更安全，并且易于纯化，比现有技术工艺更具优势。
• NOVEL BENZOPYRAN DERIVATIVE
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0632033A1

  公开（公告）日：1995-01-04

  A benzopyran derivative represented by general formula (I), which has a K⁺ channel activating function and thus can be widely applied as antiasthmatic, antiepileptic, and so forth. In formula (I), R₁ represents hydrogen or hydroxy; R₂ and R₃ represent each lower alkyl, etc.; R₄ and R₅ represent each hydrogen, lower haloalkyl, halogeno, nitro, etc.; X represents =O, =S, = N-CN, etc.; and Y represents hydroxy, substituted amino, etc.

  一种由通式(I)代表的苯并吡喃衍生物，它具有激活 K⁺通道的功能，因此可广泛应用于抗哮喘、抗癫痫等方面。在式（I）中，R₁ 代表氢或羟基；R₂ 和 R₃ 分别代表低级烷基等；R₄ 和 R₅ 分别代表氢、低级卤代烷基、卤代、硝基等；X 代表＝O、＝S、＝N-CN 等；Y 代表羟基、取代氨基等。
• BENZOPYRAN DERIVATIVE
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP0702952A1

  公开（公告）日：1996-03-27

  A benzopyran derivative represented by general formula (I) and a pharmaceutically acceptable salt thereof, whrein R, X and Y represent together any of the combinations represented by (A). These compounds are excellent in the potassium channel activity and also in safety.

  通式（I）代表的苯并吡喃衍生物及其药学上可接受的盐，其中 R、X 和 Y 共同代表（A）所代表的任何组合。这些化合物具有优异的钾通道活性和安全性。