2-chloro-N'-hydroxy-4-(methylsulfonyl)benzenecarboximidamide

• 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-chloro-N'-hydroxy-4-(methylsulfonyl)benzenecarboximidamide
• 英文别名: 2-chloro-N'-hydroxy-4-methylsulfonylbenzenecarboximidamide
• 化学式: C₈H₉ClN₂O₃S
• 分子量: 248.69
• InChiKey: KYJDODYUQPGLEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N'-hydroxy-4-(methylsulfonyl)benzenecarboximidamide 在 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3S)-2-Amino-3-[3-(2-chloro-4-methanesulfonyl-phenyl)-[1,2,4]oxadiazol-5-yl]-1-((S)-3-fluoro-pyrrolidin-1-yl)-butan-1-one; compound with trifluoro-acetic acid
  参考文献：
  名称：

  发现有效的，选择性的和口服生物利用的基于恶二唑的二肽基肽酶IV抑制剂。

  摘要：

  一系列新的基于乙二唑的酰胺已被证明是有效的DPP-4抑制剂。优化的化合物43对多种DPP-4同源物显示出极好的选择性。

  DOI：

  10.1016/j.bmcl.2006.07.061
• 作为产物：
  描述：

  2-氯-4-甲砜基苯甲酸 在 三聚氯氰 、 氨 、 羟胺 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,4-二氧六环 、 DMF (N,N-dimethyl-formamide) 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 34.0h， 生成 2-chloro-N'-hydroxy-4-(methylsulfonyl)benzenecarboximidamide
  参考文献：
  名称：

  [EN] 1,2,4-OXADIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  [FR] DERIVES DE 1,2,4-OXADIAZOLE EN TANT QU'INHIBITEURS DE LA DIPEPTIDYLPEPTIDASE-IV DANS LE TRAITEMENT OU LA PREVENTION DE DIABETES

  摘要：

  本发明涉及一种新颖的1,2,4-噁二唑衍生物，这些衍生物是二肽基肽酶-IV酶（'DP-IV抑制剂'）的抑制剂，并且在治疗或预防涉及二肽基肽酶-IV酶的疾病方面具有用处，例如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病方面的用途。

  公开号：

  WO2005108382A1

文献信息

• 1,2,4-Oxadiazole Derivatives as Dipeptidyl Peptidase-IV Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Xu Jinyou

  公开号：US20080021009A1

  公开（公告）日：2008-01-24

  The present invention is directed to novel 1,2,4-oxadiazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及新型1,2,4-噁二唑衍生物，它们是二肽基肽酶-IV酶（“DP-IV酶”）的抑制剂，可用于治疗或预防涉及DP-IV酶的疾病，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的制药组合物，以及在涉及DP-IV酶的这些疾病的预防或治疗中使用这些化合物和组合物。
• 1,2,4-Oxadiazole derivatives as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07687492B2

  公开（公告）日：2010-03-30

  The present invention is directed to novel 1,2,4-oxadiazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及一种新型1,2,4-噁二唑衍生物，其为二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂，并且对于涉及二肽基肽酶-IV酶的疾病的治疗或预防具有用处，例如糖尿病，特别是2型糖尿病。本发明还涉及包含这些化合物的制药组合物以及在涉及二肽基肽酶-IV酶的这些疾病的预防或治疗中使用这些化合物和组合物。
• Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design
  作者：Gui-Bai Liang、Xiaoxia Qian、Tesfaye Biftu、Suresh Singh、Ying-Duo Gao、Giovanna Scapin、Sangita Patel、Barbara Leiting、Reshma Patel、Joseph Wu、Xiaoping Zhang、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2008.05.061

  日期：2008.7

  Probing with tool molecules, and by modeling and X-ray crystallography the binding modes of two structurally distinct series of DPP-4 inhibitors led to the discovery of a rare aromatic fluorine H-bond and the spatial requirement for better biaryl binding in the DPP-4 enzyme active site. These newly found binding elements were successfully incorporated into novel DPP-4 inhibitors.
• Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors
  作者：Scott D. Edmondson、Lan Wei、Jinyou Xu、Jackie Shang、Shiyao Xu、Jianmei Pang、Ashok Chaudhary、Dennis C. Dean、Huaibing He、Barbara Leiting、Kathryn A. Lyons、Reshma A. Patel、Sangita B. Patel、Giovanna Scapin、Joseph K. Wu、Maria G. Beconi、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2008.02.050

  日期：2008.4

  The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
• 1,2,4-OXADIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  申请人：Merck & Co., Inc.

  公开号：EP1756074A1

  公开（公告）日：2007-02-28