2-(4-tert-butylbenzyl)-3-[2-(3-bromo-4-hydroxy-5-methoxyphenyl)acetamido]propyl pivalate | 1258845-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(4-tert-butylbenzyl)-3-[2-(3-bromo-4-hydroxy-5-methoxyphenyl)acetamido]propyl pivalate
• 英文别名: [2-[[[2-(3-bromo-4-hydroxy-5-methoxyphenyl)acetyl]amino]methyl]-3-(4-tert-butylphenyl)propyl] 2,2-dimethylpropanoate
• CAS: 1258845-63-4
• 化学式: C₂₈H₃₈BrNO₅
• 分子量: 548.517
• InChiKey: QTGJHORUBMNVER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-tert-butylbenzyl)-3-[2-(3-bromo-4-hydroxy-5-methoxyphenyl)acetamido]propyl pivalate 、 乙酸酐 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 以53%的产率得到2-(4-tert-butylbenzyl)-3-[2-(4-acetoxy-3-bromo-5-methoxyphenyl)acetamido]propyl pivalate
  参考文献：
  名称：

  Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin

  摘要：

  As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3-methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with K-i (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6'-iodononivamide. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.001
• 作为产物：
  描述：

  3-溴-4-羟基-5-甲氧基苯乙酸 、 N-[2-(4-tert-butylbenzyl)-3-pivaloyloxy-propyl]hydroxylamine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以85%的产率得到2-(4-tert-butylbenzyl)-3-[2-(3-bromo-4-hydroxy-5-methoxyphenyl)acetamido]propyl pivalate
  参考文献：
  名称：

  Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin

  摘要：

  As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3-methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with K-i (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6'-iodononivamide. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.001

文献信息

• Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin
  作者：Dong Wook Kang、Yong Soo Kim、Kwang Su Lim、Myeong Seop Kim、Larry V. Pearce、Vladimir A. Pavlyukovets、Andy K. Tao、Krystle A. Lang-Kuhs、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1016/j.bmc.2010.09.001

  日期：2010.11.15

  As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3-methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with K-i (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6'-iodononivamide. (C) 2010 Elsevier Ltd. All rights reserved.