3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: 3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole
• 英文别名: 3-methyl-1-tetrahydropyran-2-yl-pyrazole；3-methyl-1-(oxan-2-yl)pyrazole
• 化学式: C₉H₁₄N₂O
• 分子量: 166.223
• InChiKey: FXJMDBRWLKAALB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole 在 正丁基锂 、 碘 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.33h， 以74%的产率得到5-iodo-3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole
  参考文献：
  名称：

  Discovery of Potent, Selective, and Brain-Penetrant 1H-Pyrazol-5-yl-1H-pyrrolo[2,3-b]pyridines as Anaplastic Lymphoma Kinase (ALK) Inhibitors

  摘要：

  Anaplastic lymphoma kinase (ALK), a member of the receptor tyrosine kinase family, is predominantly expressed in the brain and implicated in neuronal development and cognition. However, the detailed function of ALK in the central nervous system (CNS) is still unclear. To elucidate the role of ALK in the CNS, it was necessary to discover a potent, selective, and brain-penetrant ALK inhibitor. Scaffold hopping and lead optimization of N-(2,4-difluorobenzyl)-3-(1H-pyrazol-5yl)imidazo[1,2-b]pyridazin-6-amine 1 guided by a cocrystal structure of compound 1 bound to ALK resulted in the identification of (6-(1-(5-fluoropyridin-2-yl)ethoxy)-1-(5-methyl-1H-pyrazol-3-yl)-1H-pyrrolo [2,3-b)]pyridin-3-yl) ( (2S)-2-methylmorpholin-4-yl)methanone 13 as a highly potent, selective, and brain-penetrable compound. Intraperitoneal administration of compound 13 significantly decreased the phosphorylated-ALK (p-ALK) levels in the hippocampus and prefrontal cortex in the mouse brain. These results suggest that compound 13 could serve as a useful chemical probe to elucidate the mechanism of ALK-mediated brain functions and the therapeutic potential of ALK inhibition.

  DOI：

  10.1021/acs.jmedchem.8b01630
• 作为产物：
  描述：

  5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole 反应 48.0h， 以77%的产率得到3-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole
  参考文献：
  名称：

  吡唑的绿色保护，四氢吡喃基吡唑的热异构化和去保护作用以及高产率的一锅合成3（5）-烷基吡唑†

  摘要：

  我们报告了一种新的合成方法，该方法通过各种功能（包括烷基，卤素，羟基，氨基，叠氮基，羰基和有机元素（例如B，Si） ，P）组。高效合成14种3（5）-烷基吡唑，包括新型异戊基和正十六烷基衍生物，以及1,6-双（吡唑-3（5）-基）己烷，可以说明这种方法。新方法的价值在于发现对吡唑具有绿色（无溶剂和无催化剂的定量保护）保护，然后在同一罐中进行高产率的锂化/烷基化/脱保护顺序。第一次，对应的N-四氢吡喃-2-基（THP）中间体已被分离和表征。在吡唑化学中，将5-烷基-1-（THP）异构体热异构化为3-烷基-1-（THP）异构体是酸催化顺序保护基转换方法的一种有利的绿色替代方法。1,6-双（吡唑-3（5）-基）己烷和5-正十六烷基-1-（四氢吡喃-2-基）吡唑的X射线晶体结构揭示了超分子结构，以非凡的亲和力发光用于水，并在亚烷基桥联的双吡唑类有机溶剂中具有不可预期的不溶性。通过一锅法从吡唑以高收率获得3（5）-烷基吡唑。

  DOI：

  10.1039/c5ra00837a

文献信息

• [EN] FUSED PYRAZOLE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLE CONDENSÉS UTILISÉS EN TANT QU'INHIBITEURS DE JAK
  申请人：ALMIRALL SA

  公开号：WO2017220431A1

  公开（公告）日：2017-12-28

  Novel fused pyrazole derivatives of Formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  公开了式（I）的新型融合吡唑衍生物；以及它们的制备方法，包含它们的药物组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的用途。
• [EN] COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 1 PROTEINS<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LA DÉGRADATION CIBLÉE DE PROTÉINES DE KINASE 1 ASSOCIÉS AU RÉCEPTEUR DE L'INTERLEUKINE 1
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2021018118A1

  公开（公告）日：2021-02-04

  The present invention relates to compounds comprising an interleukin-1 receptor-associated kinase 1 (IRAK1) protein binding moiety and a Von Hippel-Lindau (VHL) E3 ubiquitin ligase binding moiety, and associated methods of use. The compounds are useful as modulators of targeted ubiquitination, especially with respect to IRAK1, which is degraded by the compounds according to the invention.

  本发明涉及包含白细胞介素-1受体相关激酶1（IRAK1）蛋白结合基团和Von Hippel-Lindau（VHL）E3泛素连接酶结合基团的化合物，以及相关的使用方法。这些化合物可用作靶向泛素化的调节剂，特别是在与根据本发明降解的IRAK1相关的情况下。
• [EN] SMALL MOLECULE MODULATORS OF IL-17<br/>[FR] MODULATEURS À PETITES MOLÉCULES D'IL-17
  申请人：LEO PHARMA AS

  公开号：WO2021250194A1

  公开（公告）日：2021-12-16

  The present invention relates to a compound according to formula (I), (I) and pharmaceutically acceptable salts, hydrates, or solvates thereof. The invention further relates to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases, e.g. dermal diseases, with said compounds, and to the use of said compounds in the manufacture of medicaments.

  本发明涉及一种符合式(I)的化合物，以及其药学上可接受的盐、水合物或溶剂合物。该发明还涉及上述化合物在治疗中的应用，包括包含该化合物的药物组合物，用于使用该化合物制造药物的方法，例如用于治疗皮肤病等疾病的方法。
• COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1
  申请人：DODD Stephanie Kay

  公开号：US20130310395A1

  公开（公告）日：2013-11-21

  The present invention relates to compounds of formula (I): in which Y, Y 1 , R 1 , R 2 , R 3 and R 4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

  本发明涉及式(I)的化合物：其中Y、Y1、R1、R2、R3和R4如发明摘要中所定义；能够抑制BCR-ABL1及其突变体的活性。本发明还提供了一种制备本发明化合物的方法，包括这种化合物的制药制剂以及使用这种化合物治疗癌症的方法。
• [EN] PYRAZOLE DERIVATIVES USEFUL AS 5-LIPOXYGENASE ACTIVATING PROTEIN (FLAP) INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILES EN TANT QU'INHIBITEURS (FLAP) DE PROTÉINE ACTIVANT LA 5-LIPOXYGÉNASE
  申请人：ASTRAZENECA AB

  公开号：WO2016177703A1

  公开（公告）日：2016-11-10

  The present application relates to novel compounds of formula (I) to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.

  本申请涉及到式(I)的新化合物，以及它们在治疗和/或预防心血管疾病（CVD）等临床疾病方面的用途，以及它们的治疗用途方法，含有它们的药物组合物以及制备这些化合物的过程。