[4-(4-[1,2,3]Thiadiazol-4-yl-benzylsulfamoyl)-phenoxy]-acetic acid tert-butyl ester | 863977-54-2

• 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: [4-(4-[1,2,3]Thiadiazol-4-yl-benzylsulfamoyl)-phenoxy]-acetic acid tert-butyl ester
• CAS: 863977-54-2
• 化学式: C₂₁H₂₃N₃O₅S₂
• 分子量: 461.563
• InChiKey: YVUAUSSMOXKJDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  107.48
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [4-(4-[1,2,3]Thiadiazol-4-yl-benzylsulfamoyl)-phenoxy]-acetic acid tert-butyl ester 在 三甲基溴硅烷 、 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 {4-[[3-Bromo-4-(difluoro-phosphono-methyl)-benzyl]-(4-[1,2,3]thiadiazol-4-yl-benzyl)-sulfamoyl]-phenoxy}-acetic acid
  参考文献：
  名称：

  Discovery and structure–activity relationships of novel sulfonamides as potent PTP1B inhibitors

  摘要：

  A series of novel sulfonamides containing a single difluoromethylene-phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or K-i values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.061
• 作为产物：
  描述：

  、 [4-(1,2,3-thiadiazol-4-yl)phenyl]methanamine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 [4-(4-[1,2,3]Thiadiazol-4-yl-benzylsulfamoyl)-phenoxy]-acetic acid tert-butyl ester
  参考文献：
  名称：

  Discovery and structure–activity relationships of novel sulfonamides as potent PTP1B inhibitors

  摘要：

  A series of novel sulfonamides containing a single difluoromethylene-phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or K-i values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.061

文献信息

• Discovery of potent, selective and orally bioavailable triaryl-sulfonamide based PTP1B inhibitors
  作者：Dipam Patel、Mukul Jain、Shailesh R. Shah、Rajesh Bahekar、Pradip Jadav、Amit Joharapurkar、Nirav Dhanesha、Mubeen Shaikh、Kalapatapu V.V.M. Sairam、Prashant Kapadnis

  DOI：10.1016/j.bmcl.2011.11.122

  日期：2012.1

  are reported as potent and selective PTP1B inhibitors. Some of the test compounds (5o and 5p) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro). The lead compound 5o showed potent antidiabetic activity (in vivo), along with improved pharmacokinetic profile. These preliminary results confirm discovery of highly potent and selective PTP1B inhibitors for the treatment

  据报道，含有三芳基磺酰胺衍生物（5a – r）的一系列新型p Tyr模拟物是有效的和选择性的PTP1B抑制剂。一些测试化合物（5o和5p）对PTP1B的选择性优于各种PTP，包括TCPTP（体外）。铅化合物5o表现出有效的抗糖尿病活性（体内），并具有改善的药代动力学特征。这些初步结果证实发现了用于治疗T2DM的高效和选择性PTP1B抑制剂。