4-iodo-3-(trifluoromethyl)-1-tritylpyrazolo[5,4-b]pyridine | 1160502-31-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-iodo-3-(trifluoromethyl)-1-tritylpyrazolo[5,4-b]pyridine
• 英文别名: 4-iodo-3-(trifluoromethyl)-1-trityl-1H-pyrazolo[3,4-b]pyridine；4-Iodo-3-(trifluoromethyl)-1-trityl-pyrazolo[3,4-b]pyridine；4-iodo-3-(trifluoromethyl)-1-tritylpyrazolo[3,4-b]pyridine
• CAS: 1160502-31-7
• 化学式: C₂₆H₁₇F₃IN₃
• 分子量: 555.341
• InChiKey: BOLCACAGZJWTTA-UHFFFAOYSA-N

物化性质

• 沸点：
  605.5±55.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-iodo-3-(trifluoromethyl)-1-tritylpyrazolo[5,4-b]pyridine 在 丁腈 、 二(三叔丁基膦)钯 、 palladium diacetate 、 叔丁胺 、 N,N-二异丙基乙胺 、 1,4-双(二苯基膦)丁烷 作用下， 以 1,4-二氧六环 、 水 为溶剂， 20.0~130.0 ℃ 、101.33 kPa 条件下， 反应 21.5h， 生成
  参考文献：
  名称：

  Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors

  摘要：

  Extensive phase II metabolism of an advanced PKC epsilon inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PR and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.082
• 作为产物：
  描述：

  2-氟-3-碘吡啶 在 manganese(IV) oxide 、 正丁基锂 、 sodium hydride 、 一水合肼 、 二异丙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.25h， 生成 4-iodo-3-(trifluoromethyl)-1-tritylpyrazolo[5,4-b]pyridine
  参考文献：
  名称：

  Discovery of Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis

  摘要：

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.9b00134

文献信息

• [EN] [1H- PYRAZOLO [3, 4-B] PYRIDINE-4-YL] -PHENYLE OR -PYRIDIN-2-YLE DERIVATIVES AS PROTEIN KINASE C-THETA<br/>[FR] DÉRIVÉS DE [1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL]-PHÉNYLE OU -PYRIDIN-2-YLE EN TANT QU'INHIBITEURS DE LA PROTÉINE KINASE C-THÊTA
  申请人：VERTEX PHARMA

  公开号：WO2009073300A1

  公开（公告）日：2009-06-11

  The present invention relates to compounds of formula (I) and (IA) useful as inhibitors of protein kinase (1a). The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. (a) : in particular protein kinase C theta, wherein A and A' are independently -N- or -C(R+) -. Ring B is five- or six-membered saturated carbocyclic or heterocyclic R1, R2, R3, R4, R5, R6, R7, x and y are as described herein.

  本发明涉及式(I)和(IA)的化合物，可用作蛋白激酶(1a)的抑制剂。该发明还提供包括所述化合物的药学上可接受的组合物，以及使用这些组合物治疗各种疾病、症状或紊乱的方法。该发明还提供制备本发明化合物的方法。(a)：特别是蛋白激酶Cθ，其中A和A'独立地为-N-或-C(R+) -。环B是五元或六元饱和碳环或杂环，R1、R2、R3、R4、R5、R6、R7、x和y如本文所述。
• KINASE INHIBITORS
  申请人：Jimenez Juan-Miguel

  公开号：US20090291937A1

  公开（公告）日：2009-11-26

  The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

  本发明涉及用作蛋白激酶抑制剂的化合物。本发明还提供了包含上述化合物的药学上可接受的组合物以及使用该组合物治疗各种疾病、病况或障碍的方法。本发明还提供了制备本发明化合物的方法。
• Kinase inhibitors
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US08173635B2

  公开（公告）日：2012-05-08

  The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

  本发明涉及用作蛋白激酶抑制剂的化合物。本发明还提供包含所述化合物的药学上可接受的组合物以及使用该组合物治疗各种疾病、病况或疾病的方法。本发明还提供制备本发明化合物的方法。
• [1H- PYRAZOLO [3, 4-B]PYRIDINE-4-YL]-PHENYLE OR -PYRIDIN-2-YLE DERIVATIVES AS PROTEIN KINASE C-THETA
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP2215089B1

  公开（公告）日：2012-06-27
• US8173635B2
  申请人：——

  公开号：US8173635B2

  公开（公告）日：2012-05-08