2,2-difluorocyclopropyl 4-methylbenzenesulfonate | 1536473-24-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,2-difluorocyclopropyl 4-methylbenzenesulfonate
• 英文别名: (2,2-difluorocyclopropyl) 4-methylbenzenesulfonate
• CAS: 1536473-24-1
• 化学式: C₁₀H₁₀F₂O₃S
• 分子量: 248.25
• InChiKey: QDOUPYWOXVTNIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.11
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  T406石油添加剂 、 2,2-difluorocyclopropyl 4-methylbenzenesulfonate 在 sodium hydride 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 1.0h， 以60%的产率得到1-(2,2-difluorocyclopropyl)benzotriazole
  参考文献：
  名称：

  Direct N-gem-difluorocyclopropylation of nitro-heterocycles by utilizing gem-difluorocyclopropyl tosylate

  摘要：

  We have developed an efficient method to achieve N-gem-difluorocyclopropylation of N-heterocycles with the use of gem-difluorocyclopropyl tosylate as a building block under mild conditions. gem-Difluorocyclopropyl tosylates could be easily prepared on a large scale and exhibit great stability. (C) 2013 Ji-Chang Xiao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2013.11.027
• 作为产物：
  描述：

  对甲苯磺酰氯 在 正丁基锂 、 sodium fluoride 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 正己烷 为溶剂， 反应 19.0h， 生成 2,2-difluorocyclopropyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  TYK2 INHIBITORS AND USES THEREOF

  摘要：

  本发明提供了化合物、其组合物以及使用它们来抑制TYK2并治疗TYK2介导的疾病的方法。

  公开号：

  US20200131201A1

文献信息

• [EN] INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR KINASES<br/>[FR] INHIBITEURS DES KINASES RÉCEPTRICES DU FACTEUR DE CROISSANCE DES FIBROBLASTES
  申请人：KINNATE BIOPHARMA INC

  公开号：WO2021247969A1

  公开（公告）日：2021-12-09

  Provided herein are heteroaryl inhibitors of fibroblast growth factor receptor kinases, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

  提供了一种杂芳基的成纤维细胞生长因子受体激酶抑制剂，包括所述化合物的药物组合物，以及使用所述化合物治疗疾病的方法。
• [EN] ISOQUINOLINE DERIVATIVES AS PERK INHIBITORS<br/>[FR] DÉRIVÉS D'ISOQUINOLÉINE UTILISÉS COMME INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018015879A1

  公开（公告）日：2018-01-25

  The invention is directed to substituted isoquinoline derivatives and uses thereof. Specifically, the invention is directed to compounds according to Formula I and the use of compounds of Formula (I) in treating disease states: (I) wherein R1, R2, R3, R4, R5, R6, R7 and X are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, ather osclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及取代异喹啉衍生物及其用途。具体而言，该发明涉及符合以下式(I)的化合物以及在治疗疾病状态中使用式(I)化合物：(I)其中R1、R2、R3、R4、R5、R6、R7和X如本文所定义。该发明的化合物是PERK的抑制剂，可用于治疗癌症、癌前综合征以及与激活的未折叠蛋白应答途径相关的疾病，如阿尔茨海默病、脊髓损伤、创伤性脑损伤、缺血性中风、中风、帕金森病、糖尿病、代谢综合征、代谢紊乱、亨廷顿病、克雅氏病、致命性家族性失眠、格斯曼-施特劳斯勒-谢因克症候群以及相关朊蛋白病、肌萎缩侧索硬化、进行性核上性麻痹、心肌梗死、心血管疾病、炎症、器官纤维化、肝脏慢性和急性疾病、脂肪肝病、肝脂肪变性、肝纤维化、肺部慢性和急性疾病、肺纤维化、肾脏慢性和急性疾病、肾脏纤维化、慢性创伤性脑病（CTE）、神经退行性疾病、痴呆症、额颞叶痴呆症、tau蛋白病、皮克氏病、尼曼-皮克氏病、淀粉样变性、认知障碍、动脉粥样硬化、眼部疾病、心律失常、器官移植以及器官移植用途中的运输。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制PERK活性和治疗相关疾病的方法。
• BICYCLIC SULFONES AND SULFOXIDES AND METHODS OF USE THEREOF
  申请人：Genentech, Inc.

  公开号：US20190127382A1

  公开（公告）日：2019-05-02

  The invention provides novel compounds having the general formula I: wherein R 1 , R B1 , R B2 , n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

  该发明提供了具有一般式I的新化合物：其中R1、RB1、RB2、n、p、q、A环和B环如本文所述，包括这些化合物的药物组合物，以及使用这些化合物的方法。
• Targeting the Tyrosine Kinase 2 (TYK2) Pseudokinase Domain: Discovery of the Selective TYK2 Inhibitor ABBV-712
  作者：Eric Breinlinger、Stacy Van Epps、Michael Friedman、Maria Argiriadi、Ellen Chien、Gekleng Chhor、Marlon Cowart、Theresa Dunstan、Candace Graff、David Hardee、J. Martin Herold、Andrew Little、Richard McCarthy、Julie Parmentier、Matthew Perham、Wei Qiu、Michael Schrimpf、Thomas Vargo、Matthew P. Webster、Fei Wu、Dawn Bennett、Jeremy Edmunds

  DOI：10.1021/acs.jmedchem.3c01373

  日期：2023.10.26

  family members has been difficult to achieve with small molecules that inhibit the catalytically active kinase domain. Successful targeting of the TYK2 pseudokinase domain as a strategy to achieve isoform selectivity was recently exemplified with deucravacitinib. Described herein is the optimization of selective TYK2 inhibitors targeting the pseudokinase domain, resulting in the discovery of the clinical

  酪氨酸激酶 2 (TYK2) 是一种非受体酪氨酸激酶，属于 JAK 家族，还包括 JAK1、JAK2 和 JAK3。TYK2 是多种自身免疫性疾病的有吸引力的靶点，因为它调节 IL-23 和 IL-12 受体下游的信号转导。与目前批准的 JAK 抑制剂相比，选择性 TYK2 抑制提供了差异化的临床特征。然而，使用抑制催化活性激酶结构域的小分子很难实现 TYK2 相对于其他 JAK 家族成员的选择性。最近，deucravacitinib 成功地靶向 TYK2 假激酶结构域作为实现异构体选择性的策略。本文描述的是针对假激酶结构域的选择性 TYK2 抑制剂的优化，从而发现了临床候选药物 ABBV-712 ( 21 )。
• INHIBITORS OF TYROSINE KINASE 2 MEDIATED SIGNALING
  申请人：AbbVie Inc.

  公开号：EP3539966A1

  公开（公告）日：2019-09-18

  Disclosed herein are compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4a, R4b, X1, X2, X3, X4, X5, and n are as defined herein, pharmaceutical compositions comprising same, and methods of preparation and use.

  本文公开了式 (I) 化合物及其药学上可接受的盐（其中 R1、R2、R3、R4a、R4b、X1、X2、X3、X4、X5 和 n 如本文所定义）、包含这些化合物的药物组合物以及制备和使用方法。