2-bromo-1-(2,4-dimethyl-thiazol-5-yl)propan-1-one | 1377582-68-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-bromo-1-(2,4-dimethyl-thiazol-5-yl)propan-1-one
• 英文别名: 2-Bromo-1-(2,4-dimethylthiazol-5-yl)propan-1-one；2-bromo-1-(2,4-dimethyl-1,3-thiazol-5-yl)propan-1-one
• CAS: 1377582-68-7
• 化学式: C₈H₁₀BrNOS
• 分子量: 248.143
• InChiKey: UXTVQZJOQVHLSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-1-(2,4-dimethyl-thiazol-5-yl)propan-1-one 生成 N-(5-fluoro-2-methoxyphenyl)-2',4',5-trimethyl-[4,5'-bithiazol]-2-amine.HBr
  参考文献：
  名称：

  METHODS OF INHIBITING PRO MATRIX METALLOPROTEINASE ACTIVATION

  摘要：

  这项发明涉及预防、治疗或改善由MMP9和/或MMP13介导的综合症、紊乱或疾病的方法，包括向需要的受试者施用本说明书示例部分列出的化合物的有效量，或其形式、组合或药物。治疗和/或预防的疾病包括类风湿关节炎。

  公开号：

  US20120302573A1
• 作为产物：
  描述：

  2,4-二甲基-5-乙酰基噻唑 在 溴 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 73.5h， 生成 2-bromo-1-(2,4-dimethyl-thiazol-5-yl)propan-1-one
  参考文献：
  名称：

  BISTHIAZOLE INHIBITORS OF PRO-MATRIX METALLOPROTEINASE ACTIVATION

  摘要：

  本发明涉及双噻唑I及其治疗和预防用途，其中变量A，R 5 ，R 6 ，和R 7 在说明书中定义。治疗的和/或预防的疾病包括类风湿性关节炎。

  公开号：

  US20120129842A1

文献信息

• OPIOID RECEPTOR MODULATORS AND USE THEREOF
  申请人：National Health Research Institutes

  公开号：US20170056377A1

  公开（公告）日：2017-03-02

  Disclosed is an in vitro screening method for identifying an antagonist-to-agonist allosteric modifier of a mu-opioid receptor and an in vivo method for confirming that a test compound is such a modifier of a mu-opioid receptor. Also disclosed is a method for treating an opioid receptor-associated condition using a compound of Formula (I) and a pharmaceutical composition containing the same.

  揭示了一种体外筛选方法，用于识别μ-阿片受体的拮抗剂-激动剂异位调节剂，并揭示了一种体内方法，用于确认测试化合物是否为μ-阿片受体的这种调节剂。还揭示了一种使用式（I）化合物和含有该化合物的药物组合物治疗阿片受体相关疾病的方法。
• The in vivo antinociceptive and μ-opioid receptor activating effects of the combination of N-phenyl-2′,4′-dimethyl-4,5′-bi-1,3-thiazol-2-amines and naloxone
  作者：Shu-Yu Lin、Yu-Hsien Kuo、Ya-Wen Tien、Yi-Yu Ke、Wan-Ting Chang、Hsiao-Fu Chang、Li-Chin Ou、Ping-Yee Law、Jing-Hua Xi、Pao-Luh Tao、Horace H. Loh、Yu-Sheng Chao、Chuan Shih、Chiung-Tong Chen、Shiu-Hwa Yeh、Shau-Hua Ueng

  DOI：10.1016/j.ejmech.2019.01.063

  日期：2019.4

  Morphine is widely used for the treatment of severe pain. This analgesic effect is mediated principally by the activation of-opioid receptors (MOR). However, prolonged activation of MOR also results in tolerance, dependence, addiction, constipation, nausea, sedation, and respiratory depression. To address this problem, we sought alternative ways to activate MOR - either by use of novel ligands, or via a novel activation mechanism. To this end, a series of compounds were screened using a sensitive CHO-Kl/MOR/G alpha l 5 cell-based FLIPR (R) calcium high-throughput screening (HTS) assay, and the bithiazole compound 5a was identified as being able activate MOR in combination with naloxone. Structural modifications of 5a resulted in the discovery of lead compound 5j, which could effectively activate MOR in combination with the MOR antagonist naloxone or naltrexone. In vivo, naloxone in combination with 100 mg/kg of compound 5j elicited antinociception in a mouse tail-flick model with an ED50 of 17.5 +/- 4 mg/kg. These results strongly suggest that the mechanism by which the 5j/naloxone combination activates MOR is worthy of further study, as its discovery has the potential to yield an entirely novel class of analgesics. (C) 2019 Elsevier Masson SAS. All rights reserved.
• US9827228B2
  申请人：——

  公开号：US9827228B2

  公开（公告）日：2017-11-28
• [EN] BISTHIAZOLE INHIBITORS OF PRO-MATRIX METALLOPROTEINASE ACTIVATION<br/>[FR] INHIBITEURS BISTHIAZOLE DE L'ACTIVATION DE MÉTALLOPROTÉINASES DE MATRICE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2012068209A2

  公开（公告）日：2012-05-24

  This invention relates to bisthiazole I and its therapeutic and prophylactic uses, wherein the variables A, R5, R6, and R7 are defined in the specification. Disorders treated and/or prevented include rheumatoid arthritis.
• [EN] THIAZOL DERIVATIVES AS PRO -MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] DÉRIVÉS DE THIAZOLE EN TANT QU'INHIBITEURS DE PRO-MÉTALLOPROTÉINASES DE MATRICE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2012162468A1

  公开（公告）日：2012-11-29

  This invention relates to methods for preventing, treating or ameliorating an MMP9 and/or MMP13 mediated syndrome, disorder or disease comprising administering to a subject in need thereof an effective amount of a thiazol derivative such as a compound listed in the examples section of this specification, or a form, composition or medicament thereof. Disorders treated and/or prevented include rheumatoid arthritis.