tert-butyl 6-((tert-butyldiphenylsilyl)oxy)-3-iodo-1H-indazole-1-carboxylate | 1204772-92-8

• 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: tert-butyl 6-((tert-butyldiphenylsilyl)oxy)-3-iodo-1H-indazole-1-carboxylate
• 英文别名: Tert-butyl 6-(tert-butyldiphenylsilyloxy)-3-iodoindazole-1-carboxylate；t-butyl 6-(t-butyldiphenylsiloxy)-3-iodo-1H-indazole-1-carboxylate；Tert-butyl 6-[tert-butyl(diphenyl)silyl]oxy-3-iodoindazole-1-carboxylate
• CAS: 1204772-92-8
• 化学式: C₂₈H₃₁IN₂O₃Si
• 分子量: 598.556
• InChiKey: BATPCTVMGVIELN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.36
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-((tert-butyldiphenylsilyl)oxy)-3-iodo-1H-indazole-1-carboxylate 在 盐酸 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 偶氮二甲酰胺 、 水 、 三苯基膦 、 三(邻甲基苯基)磷 作用下， 以 1,4-二氧六环 、 甲基叔丁基醚 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 N-(3-((1R)-1-hydroxy-2-(2-((3-phenyl-1H-indazol-6-yl)oxy)ethylamino)ethyl)phenyl)methanesulfonamide dihydrochloride
  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：

  6-氟(1H)吲唑 在 咪唑 、 4-二甲氨基吡啶 、 potassium tert-butylate 、 水 、 碘 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.67h， 生成 tert-butyl 6-((tert-butyldiphenylsilyl)oxy)-3-iodo-1H-indazole-1-carboxylate
  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

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。
• BICYCLIC NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS
  申请人：Atobe Masakazu

  公开号：US20100029733A1

  公开（公告）日：2010-02-04

  A nitrogen-containing bicyclic heterocyclic compound represented by the following formula (1) is provided. When the compound or a salt thereof is administered to a human being or an animal, the compound has a strong antagonistic action against EP1 receptors, and is useful, for example, as an active ingredient of a medicine for the prevention and/or treatment of overactive bladder. The compound is also useful as an active ingredient of a medicine for the prevention and/or treatment of symptoms such as frequency urinary, urinary urgency, or urinary incontinence.

  提供一种由以下式（1）表示的含氮双环杂环化合物。当该化合物或其盐被用于人类或动物时，该化合物对EP1受体具有强烈的拮抗作用，并且可用作预防和/或治疗膀胱过度活跃的药物的活性成分。该化合物还可用作预防和/或治疗频繁排尿、尿急或尿失禁等症状的药物的活性成分。