ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate | 1221178-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate
• 英文别名: Ethyl6-tert-butyldiphenylsilyloxyindazole-3-carboxylate；ethyl 6-[tert-butyl(diphenyl)silyl]oxy-1H-indazole-3-carboxylate
• CAS: 1221178-85-3
• 化学式: C₂₆H₂₈N₂O₃Si
• 分子量: 444.605
• InChiKey: RKCKQBIVTCWGEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.68
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate 在 四丁基氟化铵 、 对甲苯磺酸 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 7.0h， 生成
  参考文献：
  名称：

  Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human β₃-Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects

  摘要：

  Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human A-adrenergic receptor (AR) agonists. Although the initial hit compound 5 exhibited significant beta(3)-AR agonistic activity (EC50 = 21 nM), it also exhibited agonistic activity at the alpha(1A)-AR (EC50 = 219 nM, selectivity: alpha(1A)/beta(3) = 10-fold). The major metabolite of 5, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for beta(3)-AR agonistic activity versus au-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound 11 with potent beta(3)-AR agonistic activity (EC50 = 13 nM) and high selectivity (alpha(1A)/beta(3) = >769-fold). Compound 11 was also inactive toward beta(1) and beta(2)-ARs and showed dose dependent beta(3)-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats.

  DOI：

  10.1021/acs.jmedchem.5b00638
• 作为产物：
  描述：

  7-溴-1H-吲唑-3-甲酸 在 咪唑 、 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate
  参考文献：
  名称：

  EP2484668

  摘要：

  公开号：

文献信息

• INDAZOLE COMPOUNDS
  申请人：Nakano Seiji

  公开号：US20100160256A1

  公开（公告）日：2010-06-24

  Provided are compounds represented by the following formula (A-1) and formula (1), or salts thereof. The compounds of formula (A-1) and formula (1) or salts thereof have 133 adrenergic receptor agonist activity, and thus are useful as therapeutic and prophylactic agent for diabetes mellitus, obesity, hyperlipidemia, depression, diseases caused by gallstones or hypermotility of the biliary tract, diseases caused by hyperactivity of the digestive tract, interstitial cystitis, overactive bladder or urinary incontinence, or as therapeutic and prophylactic agents for diseases concomitant with decreased tears.

  提供的是以下公式（A-1）和公式（1）所代表的化合物，或其盐。公式（A-1）和公式（1）的化合物或其盐具有133肾上腺素受体激动剂活性，因此可作为治疗和预防糖尿病、肥胖、高脂血症、抑郁症、胆石症或胆道高动力性疾病、消化系统过度活动引起的疾病、间质性膀胱炎、膀胱过度活动或尿失禁的药物，或作为治疗和预防伴随眼泪减少的疾病的药物。
• INDAZOLE DERIVATIVES
  申请人：NAKANO Seiji

  公开号：US20100152265A1

  公开（公告）日：2010-06-17

  Compounds represented by the Formula (A-1) and the Formula (1) or salt thereof are provided. The compounds represented by the Formula (A-1) and the Formula (1) or salt thereof have a β3 adrenergic receptor agonist activity, and therefore are useful as an agent for the prevention and treatment of diabetes, obesity, hyperlipidemia, depression, biliary stone, a disorder derived from hyperactivity of biliary tract, a disorder derived from hyperactivity of digestive tract, interstitial cystitis, overactive bladder, urinary incontinence or a disorder derived from decreased tear secretion, etc.

  提供由化学式（A-1）和化学式（1）或其盐表示的化合物。由化学式（A-1）和化学式（1）或其盐表示的化合物具有β3肾上腺素能受体激动剂活性，因此可用作预防和治疗糖尿病、肥胖症、高脂血症、抑郁症、胆结石、胆道过度活动引起的疾病、消化道过度活动引起的疾病、间质性膀胱炎、膀胱过度活动、尿失禁或泪液分泌减少引起的疾病等。
• A mild and readily scalable procedure for the N-1-difluoromethylation of ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate and its applications to the N-difluoromethylation of indazole, benzotriazole, imidazole, indole and pyrazole derivatives
  作者：Zhenqiu Hong、Xiaoping Hou、Rulin Zhao、Jianqing Li、Joseph Pawluczyk、Bei Wang、James Kempson、Purnima Khandelwal、Leon M. Smith、Peter Glunz、Arvind Mathur

  DOI：10.1016/j.jfluchem.2020.109514

  日期：2020.6

  N-1-difluoromethylation of ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate (1) with chlorodifluoromethane (CHClF2) on large scale (up to 33 g) is described. An optimized N-1-difluoromethylation of the functionalized indazole 1 was achieved, under an atmosphere of CHClF2 (balloon) in the presence of NaH and catalytic amounts of NaI and 18-crown-6 ether at a moderate temperature (40 °C). This procedure

  一组为温和条件Ñ（（叔丁基二苯基硅烷基）氧基）-1 - -1-二氟甲基乙基6的ħ -吲唑-3-羧酸甲酯（1）与氯二氟甲烷（CHClF 2上大规模（向上）到33克）进行了说明。在CHClF 2气氛下，对官能化的吲唑1进行了优化的N -1-二氟甲基化（气球）在适中的温度（40°C）下存在NaH和催化量的NaI和18-冠6醚。该程序为需要高压和/或在高温下在DMF中使用NaH的现有方法提供了一种安全方便的替代方法，这在大规模操作时会带来安全隐患。该方法扩展到吲哚，苯并三唑，咪唑，吲哚和吡唑衍生物的N-二氟甲基化，所有这些均带有酯基。
• Indazole derivatives
  申请人：Asahi Kasei Pharma Corporation

  公开号：US08304443B2

  公开（公告）日：2012-11-06

  Compounds represented by the Formula (A-1) and the Formula (1) or salt thereof are provided. The compounds represented by the Formula (A-1) and the Formula (1) or salt thereof have a β3 adrenergic receptor agonist activity, and therefore are useful as an agent for the prevention and treatment of diabetes, obesity, hyperlipidemia, depression, biliary stone, a disorder derived from hyperactivity of biliary tract, a disorder derived from hyperactivity of digestive tract, interstitial cystitis, overactive bladder, urinary incontinence or a disorder derived from decreased tear secretion, etc.

  提供由化学式（A-1）和化学式（1）或其盐所表示的化合物。这些由化学式（A-1）和化学式（1）或其盐所表示的化合物具有β3肾上腺素能受体激动剂活性，因此可用作预防和治疗糖尿病、肥胖症、高脂血症、抑郁症、胆石症、胆道高活性疾病、消化道高活性疾病、间质性膀胱炎、膀胱过度活动、尿失禁或泪液分泌减少等疾病的药物。
• INDAZOLE ANALOG
  申请人：Wada Yasuhiro

  公开号：US20120225909A1

  公开（公告）日：2012-09-06

  [Objective] To provide a drug that selectively stimulates the β3-adrenergic receptors, particularly a drug capable of preferentially stimulating the β3-adrenergic receptors over the α1-adrenergic receptors. This drug can be used in the treatment and prevention of diabetes, obesity, hyperlipidemia, depression, cholelithiasis, diseases caused by biliary hyperkinesia, diseases caused by hyperfunction of the gastrointestinal tract, interstitial cystitis, overactive bladder or urinary incontinence, diseases associated with decreased lacrimation, and the like. [Solution] Indazole analogs represented by the general formula (I) or a salt thereof. Drugs that contains these indazole analogs or a salt thereof as the active ingredient.

  【目的】提供一种选择性刺激β3-肾上腺素能受体的药物，特别是一种能够优先刺激β3-肾上腺素能受体而非α1-肾上腺素能受体的药物。该药可以用于糖尿病、肥胖症、高脂血症、抑郁症、胆石症、胆道高动力症引起的疾病、胃肠道高功能引起的疾病、间质性膀胱炎、过度活动的膀胱或尿失禁、伴有泪液减少的疾病等的治疗和预防。 【解决方案】一般式（I）所代表的吲唑类似物或其盐。包含这些吲唑类似物或其盐作为活性成分的药物。