3-甲基-5-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吡唑 | 1888441-67-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-甲基-5-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吡唑
• 英文名称: 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
• CAS: 1888441-67-5
• 化学式: C₁₀H₁₇BN₂O₂
• mdl: MFCD18250640
• 分子量: 208.068
• InChiKey: YJFDJTNGFPHWAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.02
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine 、 3-甲基-5-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-1H-吡唑 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 60.0h， 以63.4%的产率得到1-isopropyl-3-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3.4-d]pyrimidin-4-amine
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRAZOLO[3,4-d]PYRIMIDINE COMPOUNDS AS RET KINASE INHIBITORS
  [FR] COMPOSÉS DE PYRAZOLO[3,4-D]PYRIMIDINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE RET

  摘要：

  本文提供的是Formula I的化合物，以及其互变异构体和药学上可接受的盐和溶剂化合物，其中R1和R2具有规范中给定的含义，它们是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，包括与RET相关的疾病和疾病。

  公开号：

  WO2019143991A1

文献信息

• SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20150152108A1

  公开（公告）日：2015-06-04

  The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

  本发明涉及新型取代桥式脲化合物，相应的相关类似物，药物组合物以及其使用方法。本发明的抑制素调节化合物可用于延长细胞寿命，并治疗和/或预防各种疾病和疾病，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块疾病、炎症、癌症和/或潮红有关的疾病或疾病，以及那些会受益于增加线粒体活性的疾病或疾病。本发明还涉及包含抑制素调节化合物与另一治疗剂组合的组合物。
• [EN] SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS<br/>[FR] ANALOGUES D'URÉE PONTÉS SUBSTITUÉS EN TANT QUE MODULATEURS DE SIRTUINE
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2016079709A1

  公开（公告）日：2016-05-26

  The present invention relates to novel substituted bridged urea analog compounds of Formula (I) or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, processes for making and use of such compounds, alone or in combination with other therapeutic agents, as Sirtuin Modulators useful for increasing lifespan of a cell, and for use in treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.

  本发明涉及一种新型的取代桥式脲类似物化合物，其化学式为（I）或其药学上可接受的盐，相应的药物组合物，制备这种化合物的方法以及单独使用或与其他治疗剂联合使用的这些化合物作为Sirtuin调节剂，可用于增加细胞寿命，并用于治疗和/或预防各种疾病和紊乱，包括但不限于与衰老或压力、糖尿病、肥胖、神经退行性疾病、心血管疾病、血液凝块紊乱、炎症、癌症和/或潮红有关的疾病或紊乱，以及那些会受益于增加线粒体活性的疾病或紊乱。
• Discovery of (<i>S</i>)-3-(3-(3,5-Dimethyl-1<i>H</i>-pyrazol-1-yl)phenyl)-4-((<i>R</i>)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic α_vβ₆ Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis
  作者：Panayiotis A. Procopiou、Niall A. Anderson、John Barrett、Tim N. Barrett、Matthew H. J. Crawford、Brendan J. Fallon、Ashley P. Hancock、Joelle Le、Seble Lemma、Richard P. Marshall、Josie Morrell、John M. Pritchard、James E. Rowedder、Paula Saklatvala、Robert J. Slack、Steven L. Sollis、Colin J. Suckling、Lee R. Thorp、Giovanni Vitulli、Simon J. F. Macdonald

  DOI：10.1021/acs.jmedchem.8b00959

  日期：2018.9.27

  the major product. A variety of aryl substituents including morpholine, pyrazole, triazole, imidazole, and cyclic ether were screened in cell adhesion assays for affinity against αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8 integrins. Numerous analogs with high affinity and selectivity for the αvβ6 integrin were identified. The analog (S)-3-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1

  在（R）-BINAP存在下，通过铑催化的芳基硼酸的不对称1,4-加成反应，使用非对映选择性路线合成了一系列3-芳基（吡咯烷-1-基）丁酸主要产品的（S）绝对配置。包括吗啉，吡唑，三唑，咪唑，和环醚的各种芳基取代基中的细胞粘附试验中筛选针对α亲和力v β 1，α v β 3，α v β 5，α v β 6，α v β 8整联蛋白。具有高亲和力和选择性的α众多类似物v β 6整联进行鉴定。类似物（S）-3-（3-（3,5-二甲基-1 H-吡唑-1-基）苯基）-4-（（R）-3-（2-（5,6,7,8 -四氢-1,8-萘啶-2-基）乙基）吡咯烷-1-基）丁酸盐酸盐被发现具有为α非常高的亲和力v β 6整联在放射性配体结合测定（对ķ我= 11），较长的解离半衰期（7 h），在pH 7的盐水中具有很高的溶解度（> 71 mg / mL）和药代动力学特性，与通过雾化吸入给药相当。它被选作进一步的临床研
• [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] SUBSTITUTED PYRAZOLYL[4,3-C]PYRIDINECOMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRAZOLYL[4,3-C]PYRIDINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2019143994A1

  公开（公告）日：2019-07-25

  Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2 and R3 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 RET-associated diseases and disorders.

  提供以下式I的化合物：及其互变异构体和药用可接受的盐和溶剂化物，其中R1、R2和R3具有说明书中给出的含义，它们是RET激酶的抑制剂，可用于治疗和预防可通过RET激酶抑制剂治疗的疾病，包括RET相关疾病和失调。