(R)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol | 1282530-87-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硼酸衍生物
• 英文名称: (R)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol
• 英文别名: (R)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-pyrazol-1-yl)propan-2-ol；(2R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]propan-2-ol
• CAS: 1282530-87-3
• 化学式: C₁₂H₂₁BN₂O₃
• 分子量: 252.121
• InChiKey: NMQGFBNAKPAMKE-SECBINFHSA-N

物化性质

• 沸点：
  386.0±22.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.56
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  56.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 水 、 异丙醇 为溶剂， 反应 16.0h， 生成 (R)-3-fluoro-4-((4-(1-(2-hydroxypropyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzenesulfonamide
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIMIDINYL-PYRAZOLES AS CDK2 INHIBITORS
  [FR] PYRIMIDINYL-PYRAZOLES SUBSTITUÉS UTILES EN TANT QU'INHIBITEURS DE CDK2

  摘要：

  The present disclosure provides a compound represented by structural formula (I): (I), or a pharmaceutically acceptable salt thereof useful for treating a cancer.

  公开号：

  WO2022266190A1
• 作为产物：
  描述：

  4-吡唑硼酸频哪醇酯 、 (R)-(+)-环氧丙烷 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以78.9%的产率得到(R)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR TREATING KIT-AND PDGFRA-MEDIATED DISEASES
  [FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE MALADIES À MÉDIATION PAR KIT ET PDGFRA

  摘要：

  本公开提供式（I-0）的化合物，其医药盐和/或任何前述的溶剂，对于治疗与突变型KIT和PDGFRα相关的疾病和病况具有有利的非脑穿透特性，本公开还提供了治疗胃肠间质瘤和系统性肥大细胞症的方法。

  公开号：

  WO2022081627A1

文献信息

• [EN] SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS SUBSTITUÉS DE PYRAZOLO[1,5-A]PYRIDINES COMME INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2017011776A1

  公开（公告）日：2017-01-19

  Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供了一般式I的化合物及其立体异构体和药用可接受的盐或溶剂，其中A、B、D、E、X1、X2、X3和X4的含义如规范中所述，这些化合物是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括由RET激酶介导的疾病或紊乱。
• [EN] INDAZOLE COMPOUNDS AS IRAK4 INHIBITORS<br/>[FR] COMPOSÉS D'IMIDAZOLE UTILISABLES EN TANT QU'INHIBITEURS DE L'IRAK4
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2015104662A1

  公开（公告）日：2015-07-16

  The present invention provides indazole compound of formula (I), which are therapeutically useful as kinase inhibitor, particularly IRAK4 inhibitors. wherein Z1, Z2, R1, R2, R3, 'm' and 'n' have the meanings given in the specification, and pharmaceutically acceptable salts or stereoisomers thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了式（I）的吲唑化合物，其在治疗中具有潜在的激酶抑制作用，特别是IRAK4抑制剂。其中Z1、Z2、R1、R2、R3、'm'和'n'的含义如规范中所述，并且其药学上可接受的盐或立体异构体在治疗和预防疾病或紊乱方面具有用处，特别是在由激酶酶介导的疾病或紊乱中的应用，特别是IRAK4酶。本发明还提供了包括至少一种式（I）化合物的药物组合物，以及药学上可接受的载体、稀释剂或赋形剂。
• Indazole Compounds as IRAK4 Inhibitors
  申请人：AURIGENE DISCOVERY TECHNOLOGIES LIMITED

  公开号：US20160326151A1

  公开（公告）日：2016-11-10

  The present invention provides indazole compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors, wherein Z 1 , Z 2 , R 1 , R 2 , R 3 , ‘m’ and ‘n’ have the meanings given in the specification, and pharmaceutically acceptable salts or stereoisomers thereof that are useful in the treatment and prevention of diseases or disorders, in particular their use in diseases or disorders mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical compositions comprising at least one of the compounds of the compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient.

  本发明提供了式（I）的吲唑化合物，作为激酶抑制剂在治疗上具有疗效，特别是IRAK4抑制剂，其中Z1、Z2、R1、R2、R3、'm'和'n'在规范中给出了含义，并且其药学上可接受的盐或立体异构体在治疗和预防疾病或疾病中有用，特别是它们在由激酶酶介导的疾病或疾病中的使用，特别是IRAK4酶。本发明还提供了包括至少一种式（I）化合物的药物组合物，以及药学上可接受的载体、稀释剂或赋形剂。
• Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families
  作者：Michael L. Curtin、Robin R. Frey、H. Robin Heyman、Niru B. Soni、Patrick A. Marcotte、Lori J. Pease、Keith B. Glaser、Terrance J. Magoc、Paul Tapang、Daniel H. Albert、Donald J. Osterling、Amanda M. Olson、Jennifer J. Bouska、Zhiwen Guan、Lee C. Preusser、James S. Polakowski、Kent D. Stewart、Chris Tse、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1016/j.bmcl.2012.03.035

  日期：2012.5

  effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles

  为了鉴定具有新型激酶活性谱的多靶点激酶抑制剂，我们对 Abbott 专有的 KDR 抑制剂针对多种激酶进行了筛选，结果发现一系列噻吩并吡啶脲对 Aurora 激酶具有良好的活性。这些化合物的二苯基脲和 C7 部分的修饰提供了具有良好药代动力学特征的有效抑制剂，口服给药后在小鼠肿瘤模型中有效。该系列化合物 (ABT-348) 目前正在实体癌和血液癌人群中进行 I 期临床试验。
• Benzoxepin PI3K inhibitor compounds and methods of use
  申请人：F. Hoffman-La Roche AG

  公开号：US08263633B2

  公开（公告）日：2012-09-11

  Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and where (i) X1 is N and X2 is S, (ii) X1 is S and X2 is N, (iii) X1 is CR7 and X2 is S, (iv) X1 is S and X2 is CR7; (v) X1 is NR8 and X2 is N, (vi) X1 is N and X2 is NR8, (vii) X1 is CR7 and X2 is O, (viii) X1 is O and X2 is CR7, (ix) X1 is CR7 and X2 is C(R7)2, (x) X1 is C(R7)2 and X2 is CR7; (xi) X1 is N and X2 is O, or (xii) X1 is O and X2 is N, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I中的苯并噁唑化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，其中：Z1为CR1或N；Z2为CR2或N；Z3为CR3或N；Z4为CR4或N；其中（i）X1为N且X2为S，（ii）X1为S且X2为N，（iii）X1为CR7且X2为S，（iv）X1为S且X2为CR7；（v）X1为NR8且X2为N，（vi）X1为N且X2为NR8，（vii）X1为CR7且X2为O，（viii）X1为O且X2为CR7，（ix）X1为CR7且X2为C（R7）2，（x）X1为C（R7）2且X2为CR7；（xi）X1为N且X2为O，或（xii）X1为O且X2为N，对于抑制脂质激酶包括p110α和其他PI3K的亚型，并用于治疗由脂质激酶介导的癌症等疾病是有用的。公式I化合物的使用方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗此类疾病，或相关的病理条件。