(3-chloro-4-hydroxy-5-methoxyphenyl)acetic acid | 88516-93-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (3-chloro-4-hydroxy-5-methoxyphenyl)acetic acid
• 英文别名: 2-(3-Chloro-4-hydroxy-5-methoxyphenyl)acetic acid
• CAS: 88516-93-2
• 化学式: C₉H₉ClO₄
• 分子量: 216.621
• InChiKey: KUSQTFMNHGRCGS-UHFFFAOYSA-N

物化性质

• 沸点：
  373.0±37.0 °C(Predicted)
• 密度：
  1.432±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3-chloro-4-hydroxy-5-methoxyphenyl)acetic acid 、 4-叔-丁基苄胺 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81%的产率得到N-(4-tert-butyl-benzyl)-2-(3-chloro-4-hydroxy-5-methoxyphenyl)acetamide
  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：

  (5-chloro-4-hydroxy-3-methoxyphenyl)acetic acid methoxymethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以90%的产率得到(3-chloro-4-hydroxy-5-methoxyphenyl)acetic acid
  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

• Beta-lactam derivatives
  申请人：BEECHAM GROUP PLC

  公开号：EP0091302A1

  公开（公告）日：1983-10-12

  A compound of formula (I) or a pharmaceutically scceptable salt or in vivo hydrolysable ester thereof: wherein R' is hydrogen or C1-6 alkylcarbonyl or C1-6 alkoxycarbonyl; R2 is hydrogen, halogen, hydroxy, C1-6 alkoxy, nitro, amino, C1-6 alkyl, C1-6 haloalkyl, c1-6 alkylcarbonyloxy, C1-6 alkyl sulphonylamino, carboxy, cyano, or C1-6 alkoxycarbonyl; R3 is halogen, hydroxy, C1-6 alkoxy, nitro, amino, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkycarbonyloxy, or C1-6 alkyl sulphonylamino, carboxy, cyano, or C1-6 alkyloxycarbonyl; a process for the preparation of such compounds and pharmaceutical compositions comprising them.

  式 (I) 的化合物或其药学上可接受的盐或体内可水解的酯： 其中 R' 为氢或 C1-6 烷基羰基或 C1-6 烷氧基羰基；R2 为氢、卤素、羟基、C1-6 烷氧基、硝基、氨基、C1-6 烷基、C1-6 卤代烷基、C1-6 烷基羰氧基、C1-6 烷基磺酰基氨基、羧基、氰基或 C1-6 烷氧基羰基；R3 是卤素、羟基、C1-6 烷氧基、硝基、氨基、C1-6 烷基、C1-6 卤代烷基、C1-6 烷基羰氧基或 C1-6 烷基磺酰基氨基、羧基、氰基或 C1-6 烷氧基羰基；制备这类化合物及其药物组合物的工艺。
• 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.