1-methyl-1H-1,2,3-triazole-4-sulfonyl chloride | 1351676-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methyl-1H-1,2,3-triazole-4-sulfonyl chloride
• 英文别名: 1-methyltriazole-4-sulfonyl chloride
• CAS: 1351676-71-5
• 化学式: C₃H₄ClN₃O₂S
• mdl: MFCD28012156
• 分子量: 181.603
• InChiKey: HGSOQZHRNVVEDM-UHFFFAOYSA-N

物化性质

• 沸点：
  326.5±34.0 °C(Predicted)
• 密度：
  1.79±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  73.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 1-(4-fluorophenyl)-4a-(4-(trifluoromethyl)picolinoyl)-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-6(4H)-carboxylate 、 1-methyl-1H-1,2,3-triazole-4-sulfonyl chloride 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 2.16h， 生成 (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-1,2,3-triazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone
  参考文献：
  名称：

  Identification of the Clinical Candidate (R)-(1-(4-Fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134): A Selective Glucocorticoid Receptor (GR) Antagonist

  摘要：

  The nonselective glucocorticoid receptor (GR) antagonist mifepristone has been approved in the U.S. for the treatment of selected patients with Cushing's syndrome. While this drug is highly effective, lack, of selectivity for GR leads to unwanted side effects in Sonic patients. Optimization pf the previously described fused azadecalin series of selective GR antagonists l'ed to the identification of CORT125134, which is currently being eValuateddp a phase 2 clinical study in patients with Cushing's syndrome.

  DOI：

  10.1021/acs.jmedchem.7b00162
• 作为产物：
  描述：

  4-(benzylthio)-1-methyl-1H-1,2,3-triazole 在 N-氯代丁二酰亚胺 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 2.0h， 以810 mg的产率得到1-methyl-1H-1,2,3-triazole-4-sulfonyl chloride
  参考文献：
  名称：

  [EN] HETEROARYL-KETONE FUSED AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  [FR] MODULATEURS DES RÉCEPTEURS DE GLUCOCORTICOÏDES CONSISTANT EN AZADÉCALINES À HÉTÉROARYLE CÉTONE FUSIONNÉ

  摘要：

  公开号：

  WO2013177559A3

文献信息

• 4,5- DIHYDROPYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY
  申请人：ABBVIE DEUTSCHLAND GMBH & CO. KG

  公开号：US20160075691A1

  公开（公告）日：2016-03-17

  The present invention relates to 4,5-dihydropyrazole derivatives of the formula (I) and physiologically tolerated salts thereof which are GlyT1 inhibitors. The invention further relates to pharmaceutical compositions comprising such 4,5-dihydropyrazole derivatives, and the use of such 4,5-dihydropyrazole derivatives for therapeutic purposes.

  本发明涉及式（I）的4,5-二氢吡唑衍生物及其生理耐受盐，其是GlyT1抑制剂。本发明还涉及包含这种4,5-二氢吡唑衍生物的药物组合物，以及使用这种4,5-二氢吡唑衍生物进行治疗目的的用途。
• Synthesis and Biological Evaluation of<i>N</i>-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1
  作者：Christopher L. Cioffi、Shuang Liu、Mark A. Wolf、Peter R. Guzzo、Kashinath Sadalapure、Visweswaran Parthasarathy、David T. J. Loong、Jun-Ho Maeng、Edmund Carulli、Xiao Fang、Kalesh Karunakaran、Lakshman Matta、Sok Hui Choo、Shailijia Panduga、Ronald N. Buckle、Randall N. Davis、Samuel A. Sakwa、Priya Gupta、Bruce J. Sargent、Nicholas A. Moore、Michele M. Luche、Grant J. Carr、Yuri L. Khmelnitsky、Jiffry Ismail、Mark Chung、Mei Bai、Wei Yee Leong、Nidhi Sachdev、Srividya Swaminathan、Andrew J. Mhyre

  DOI：10.1021/acs.jmedchem.6b00914

  日期：2016.9.22

  We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics. Representative analogue (+)-67 exhibited robust in vivo activity in the cerebral spinal fluid glycine biomarker model in both rodents and nonhuman primates. Furthermore, rodent microdialysis experiments also demonstrated that oral administration of (+)-67 significantly elevated extracellular glycine levels within the medial prefrontal cortex (mPFC).
• Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres
  作者：Douglas J. Sheffler、Michael T. Nedelcovych、Richard Williams、Stephen C. Turner、Brittany B. Duerk、Megan R. Robbins、Sataya B. Jadhav、Colleen M. Niswender、Carrie K. Jones、P. Jeffrey Conn、R. Nathan Daniels、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2014.01.011

  日期：2014.2

  This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores. (C) 2014 Elsevier Ltd. All rights reserved.