tert-butyl 4-(1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate | 1138327-98-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-(1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[1-[3-(trifluoromethyl)phenyl]sulfonylethyl]piperidine-1-carboxylate
• CAS: 1138327-98-6
• 化学式: C₁₉H₂₆F₃NO₄S
• 分子量: 421.481
• InChiKey: WJRZPPRNXUNDPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate 在 盐酸 、 sodium hexamethyldisilazane 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 生成 (4-(methylsulfonyl)-2-(trifluoromethoxy)phenyl)(4-(2-((3-(trifluoromethyl)phenyl)sulfonyl)propan-2-yl)piperidin-1-yl)methanone
  参考文献：
  名称：

  Improved Ca_v2.2 Channel Inhibitors through a gem-Dimethylsulfone Bioisostere Replacement of a Labile Sulfonamide

  摘要：

  We report the investigation of sulfonamide-derived Ca(v)2.2 inhibitors to address drug-metabolism liabilities with this lead class of analgesics. Modification of the benzamide substituent provided improvements in both potency and selectivity. However, we discovered that formation of the persistent 3-(trifluoromethyl)-benzenesulfonamide metabolite was an endemic problem in the sulfonamide series and that the replacement of the center aminopiperidine scaffold failed to prevent this metabolic pathway. This issue was eventually addressed by application of a bioisostere strategy. The new gem-dimethyl sulfone series retained Ca(v)2.2 potency without the liability of the circulating sulfonamide metabolite.

  DOI：

  10.1021/ml4002612
• 作为产物：
  描述：

  4-(1-羟基乙基)哌啶-1-羧酸叔丁酯 在 Oxone 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.83h， 生成 tert-butyl 4-(1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Improved Ca_v2.2 Channel Inhibitors through a gem-Dimethylsulfone Bioisostere Replacement of a Labile Sulfonamide

  摘要：

  We report the investigation of sulfonamide-derived Ca(v)2.2 inhibitors to address drug-metabolism liabilities with this lead class of analgesics. Modification of the benzamide substituent provided improvements in both potency and selectivity. However, we discovered that formation of the persistent 3-(trifluoromethyl)-benzenesulfonamide metabolite was an endemic problem in the sulfonamide series and that the replacement of the center aminopiperidine scaffold failed to prevent this metabolic pathway. This issue was eventually addressed by application of a bioisostere strategy. The new gem-dimethyl sulfone series retained Ca(v)2.2 potency without the liability of the circulating sulfonamide metabolite.

  DOI：

  10.1021/ml4002612

文献信息

• [EN] SUBSTITUTED ARYL SULFONE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS<br/>[FR] DÉRIVÉ D'ARYLSULFONE SUBSTITUÉE COMME BLOQUEURS DES CANAUX CALCIQUES
  申请人：MERCK & CO INC

  公开号：WO2009045382A1

  公开（公告）日：2009-04-09

  A series of substituted aryl sulfone derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.

  一系列以化学式I表示的取代芳基磺酮衍生物，或其药用盐。药物组合物包括即时化合物的有效量，可以单独使用，也可以与一个或多个其他治疗活性化合物结合使用，并含有药用可接受载体。治疗与或由钙通道活性相关的疾病的方法，包括例如急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经病性疼痛、尿失禁、瘙痒、过敏性皮炎、癫痫、糖尿病神经病、肠易激综合征、抑郁症、焦虑症、多发性硬化、睡眠障碍、躁郁症和中风，包括给予现有化合物的有效量，可以单独使用，也可以与一个或多个其他治疗活性化合物结合使用。
• Substituted Aryl Sulfone Derivatives as Calcium Channel Blockers
  申请人：Chakravarty Prasun K.

  公开号：US20100210620A1

  公开（公告）日：2010-08-19

  A series of substituted aryl sulfone derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.

  一系列以式I表示的取代芳基磺酰衍生物，或其药学上可接受的盐。制药组合物包括即时化合物的有效量，单独使用或与一个或多个其他治疗活性化合物结合，并且药学上可接受的载体。治疗与钙通道活性相关或由其引起的病症的方法，包括例如急性疼痛，慢性疼痛，内脏疼痛，炎症性疼痛，神经病性疼痛，尿失禁，瘙痒，过敏性皮炎，癫痫，糖尿病神经病变，肠易激综合症，抑郁症，焦虑症，多发性硬化，睡眠障碍，躁症和中风，包括单独或与一个或多个其他治疗活性化合物结合的即时化合物的有效量的给药。
• Substituted aryl sulfone derivatives as calcium channel blockers
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08304434B2

  公开（公告）日：2012-11-06

  A series of substituted aryl sulfone derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.

  一系列代表为I式的取代芳基磺酰衍生物，或其药学上可接受的盐。制药组合物包括有效量的此类化合物，单独使用或与一个或多个其他治疗活性化合物结合，并且药学上可接受的载体。治疗与钙通道活性相关或由此引起的病症的方法，包括例如急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经病性疼痛、尿失禁、瘙痒、过敏性皮炎、癫痫、糖尿病神经病变、肠易激综合征、抑郁症、焦虑症、多发性硬化、睡眠障碍、躁郁症和中风，包括单独或与一个或多个其他治疗活性化合物结合的现有化合物的有效量的给药。
• SUBSTITUTED ARYL SULFONE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20130040932A1

  公开（公告）日：2013-02-14

  A series of substituted aryl sulfone derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.

  一系列由式I所代表的取代芳基磺酰衍生物或其药学上可接受的盐。制药组合物包括有效量的该化合物，单独或与一个或多个其他治疗活性化合物结合，并且药学上可接受的载体。治疗与钙通道活性相关或由此引起的疾病的方法，包括但不限于急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经病性疼痛、尿失禁、瘙痒、过敏性皮炎、癫痫、糖尿病神经病变、肠易激综合征、抑郁症、焦虑症、多发性硬化、睡眠障碍、躁郁症和中风，包括单独或与一个或多个其他治疗活性化合物结合，给予有效量的该化合物。
• US8304434B2
  申请人：——

  公开号：US8304434B2

  公开（公告）日：2012-11-06