4-iodo-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine | 1160502-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-iodo-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine
• 英文别名: 4-iodo-3-(trifluoromethyl)-2H-pyrazolo[3,4-b]pyridine
• CAS: 1160502-30-6
• 化学式: C₇H₃F₃IN₃
• 分子量: 313.021
• InChiKey: UAADNKJTABJUQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  196.8±50.0 °C(Predicted)
• 密度：
  2.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-iodo-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine 在 丁腈 、 二(三叔丁基膦)钯 、 palladium diacetate 、 sodium hydride 、 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 、 N,N-二甲基甲酰胺 为溶剂， 130.0 ℃ 、101.33 kPa 条件下， 反应 23.83h， 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-醛基-4-碘吡啶 在 manganese(IV) oxide 、 四丁基氟化铵 、 一水合肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 反应 3.75h， 生成 4-iodo-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine
  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

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。
• AZABICYCLO COMPOUND AND SALT THEREOF
  申请人：Kitade Makoto

  公开号：US20120108589A1

  公开（公告）日：2012-05-03

  It is intended to provide a novel azabicyclo compound which exhibits both HSP90 inhibitory activity and cell proliferation inhibitory effect. Specifically disclosed is a compound represented by the following general formula (I) or a salt thereof: wherein X 1 represents CH or N; any one of X 2 , X 3 and X 4 represents N, and the others represent CH; any one or two of Y 1 , Y 2 , Y 3 and Y 4 represent C—R 4 , and the others are the same or different and represent CH or N; R 1 represents an optionally substituted monocyclic or bicyclic unsaturated heterocyclic group having 1 to 4 heteroatoms selected from N, S and O; R 2 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R 3 and R 4 represent —CO—R 5 or the like.

  本发明旨在提供一种新型的azabicyclo化合物，其具有HSP90抑制活性和细胞增殖抑制作用。具体公开的是以下一般式(I)或其盐所代表的化合物：其中X1代表CH或N；X2、X3和X4中的任意一个代表N，其他代表CH；Y1、Y2、Y3和Y4中的一个或两个代表C—R4，其他者相同或不同，代表CH或N；R1代表1至4个异原子（N、S和O）的单环或双环不饱和杂环基，可选地取代；R2代表具有1至6个碳原子的烷基基团等；R3和R4代表—CO—R5或类似物。
• 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。
• Azabicyclo compound and salt thereof
  申请人：Kitade Makoto

  公开号：US08779142B2

  公开（公告）日：2014-07-15

  It is intended to provide a novel azabicyclo compound which exhibits both HSP90 inhibitory activity and cell proliferation inhibitory effect. Specifically disclosed is a compound represented by the following general formula (I) or a salt thereof: wherein X1 represents CH or N; any one of X2, X3 and X4 represents N, and the others represent CH; any one or two of Y1, Y2, Y3 and Y4 represent C—R4, and the others are the same or different and represent CH or N; R1 represents an optionally substituted monocyclic or bicyclic unsaturated heterocyclic group having 1 to 4 heteroatoms selected from N, S and O; R2 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R3 and R4 represent —CO—R5 or the like.

  本发明旨在提供一种新型的azabicyclo化合物，该化合物既具有HSP90抑制活性，又具有细胞增殖抑制作用。具体披露了以下通式（I）或其盐的化合物：其中X1代表CH或N；X2、X3和X4中的任意一个代表N，其余代表CH；Y1、Y2、Y3和Y4中的任意一个或两个代表C-R4，其余相同或不同，代表CH或N；R1代表具有1至4个N、S和O杂原子的单环或双环不饱和杂环基，可以是取代的；R2代表具有1至6个碳原子的烷基基团或类似物；R3和R4代表-CO-R5或类似物。