28(R)-2-(4'-methanesulfonylamino)phenylpropionic acid | 946072-69-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 28(R)-2-(4'-methanesulfonylamino)phenylpropionic acid
• 英文别名: 2-(4-methanesulphonylamino-phenyl)-propionic acid；2-(4-methanesulfonylamino-phenyl)-propanoic acid；2-(4-methanesulfonylamino-phenyl)-propionic acid；2-{4-[(Methylsulfonyl)amino]phenyl}propanoic acid；2-[4-(methanesulfonamido)phenyl]propanoic acid
• CAS: 946072-69-1
• 化学式: C₁₀H₁₃NO₄S
• 分子量: 243.284
• InChiKey: RCZRQUYLYPZNQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  28(R)-2-(4'-methanesulfonylamino)phenylpropionic acid 、 4-叔-丁基苄胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以93%的产率得到KMJ-750
  参考文献：
  名称：

  N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure–activity relationships in the A-region

  摘要：

  Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.008
• 作为产物：
  描述：

  Alpha-甲基-4-硝基苯乙酸 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 硫酸 、 氢气 作用下， 以 甲醇 、 乙醇 、 丙酮 为溶剂， 生成 28(R)-2-(4'-methanesulfonylamino)phenylpropionic acid
  参考文献：
  名称：

  设计对CXCR1和CXCR2起作用的非竞争性白介素8抑制剂。

  摘要：

  趋化因子CXCL8和CXCL1在炎症部位中性粒细胞募集中起关键作用。CXCL8结合两个膜受体CXCR1和CXCR2，而CXCL1是CXCR2的选择性激动剂。在过去的十年中，已经研究了CXCL8和CXCL1的生理病理学作用。已鉴定出一类新型的小分子量变构CXCR1抑制剂，第一个候选药物reparixin目前正在临床研究中，以预防器官移植中的缺血/再灌注损伤。研究了Reparixin与CXCR1的结合模式，并将其用于双变构CXCR1和CXCR2抑制剂的计算机辅助设计程序。本文讨论了由模型驱动的SAR研究用于鉴定有效双重抑制剂的结果，并提出了三种新化合物（56、67，

  DOI：

  10.1021/jm061469t

文献信息

• Stereospecific High-affinity TRPV1 Antagonists: Chiral <i>N</i>-(2-Benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide Analogues
  作者：HyungChul Ryu、Mi-Kyoung Jin、Su Yeon Kim、Hyun-Kyung Choi、Sang-Uk Kang、Dong Wook Kang、Jeewoo Lee、Larry V. Pearce、Vladimir A. Pavlyukovets、Matthew A. Morgan、Richard Tran、Attila Toth、Daniel J. Lundberg、Peter M. Blumberg

  DOI：10.1021/jm701049p

  日期：2008.1.1

  Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K-i values of 4.12 and 1.83 nM and potent antagonism with Ki values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1.
• Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists
  作者：Changhoon Kim、Jihyae Ann、Sunho Lee、Wei Sun、Peter M. Blumberg、Robert Frank-Foltyn、Gregor Bahrenberg、Hannelore Stockhausen、Thomas Christoph、Jeewoo Lee

  DOI：10.1016/j.bmcl.2018.05.043

  日期：2018.8

  A series of A-region analogues of 2-(3-fluoro-4-methylsufonamidophenyl)propanamide 1 were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that a fluoro group at the 3-(or/and) 5-position and a methylsulfonamido group at the 4-position were optimal for antagonism of TRPV1 activation by capsaicin. The most potent antagonist 6 not only exhibited potent antagonism of activation of hTRPV1 by capsaicin, low pH and elevated temperature but also displayed highly potent antagonism of activation of rTRPV1 by capsaicin. Further studies demonstrated that antagonist 6 blocked the hypothermic effect of capsaicin in vivo, consistent with its in vitro mechanism, and it showed promising analgesic activity in the formalin animal model.
• US8642657B2
  申请人：——

  公开号：US8642657B2

  公开（公告）日：2014-02-04