2,2-Dimethyl-propionic acid 4-(3,4-dimethyl-phenyl)-2-[3-(4-methanesulfonylamino-benzyl)-thioureido]-butyl ester | 735331-54-1

• 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: 2,2-Dimethyl-propionic acid 4-(3,4-dimethyl-phenyl)-2-[3-(4-methanesulfonylamino-benzyl)-thioureido]-butyl ester
• 英文别名: [4-(3,4-Dimethylphenyl)-2-[[4-(methanesulfonamido)phenyl]methylcarbamothioylamino]butyl] 2,2-dimethylpropanoate
• CAS: 735331-54-1
• 化学式: C₂₆H₃₇N₃O₄S₂
• 分子量: 519.729
• InChiKey: DOXBZTLQXVYVLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,2-Dimethyl-propionic acid 2-amino-4-(3,4-dimethyl-phenyl)-butyl ester 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,2-Dimethyl-propionic acid 4-(3,4-dimethyl-phenyl)-2-[3-(4-methanesulfonylamino-benzyl)-thioureido]-butyl ester
  参考文献：
  名称：

  Structure–activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism

  摘要：

  The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino) benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.034

文献信息

• Analysis of structure–activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism
  作者：Jeewoo Lee、Su Yeon Kim、Jiyoun Lee、Myungsim Kang、Min-Jung Kil、Hyun-Kyung Choi、Mi-Kyung Jin、Yun Wang、Attila Toth、Larry V Pearce、Daniel J Lundberg、Richard Tran、Peter M Blumberg

  DOI：10.1016/j.bmc.2004.04.040

  日期：2004.7

  In a continuing effort to elucidate the structure-activity relationships of the lead antagonist N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N'-[4-(methylsulfonylamino)benzyl]thiourea (1), the distances between the proposed four pharmacophores in 1 have been varied by insertion or deletion of one carbon to optimize their fit to the receptor. In addition, the acyloxy group of the C region was replaced with amide and N-hydroxy amide to identify the pharmacophoric importance of the ester group in the C2 region. The results indicated that the pharmacophoric arrangement of 1 was optimal for receptor binding affinity and antagonism, and the ester of the C2 region was significant for receptor binding. Among the derivatives, compound 19 showed distinct behavior with a 2-fold improvement in antagonism but a 13-fold reduction in binding affinity compared to 1. The partial separation of pharmacophoric requirements of these two assays has been noted before and compound 19 is thus selective for the calcium entry-linked receptor population. The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand. (C) 2004 Elsevier Ltd. All rights reserved.
• Structure–activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism
  作者：Rahul S. Bhondwe、Dong Wook Kang、Myeong Seop Kim、Ho Shin Kim、Seul-gi Park、Karam Son、Sun Choi、Krystle A. Lang Kuhs、Vladimir A. Pavlyukovets、Larry V. Pearce、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1016/j.bmcl.2012.04.034

  日期：2012.6

  The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino) benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor. (C) 2012 Elsevier Ltd. All rights reserved.