4-(benzyloxy)-2-(carboxymethyl)-5-methoxybenzoic acid | 1415806-58-4

• 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-(benzyloxy)-2-(carboxymethyl)-5-methoxybenzoic acid
• 英文别名: 2-(Carboxymethyl)-5-methoxy-4-phenylmethoxybenzoic acid；2-(carboxymethyl)-5-methoxy-4-phenylmethoxybenzoic acid
• CAS: 1415806-58-4
• 化学式: C₁₇H₁₆O₆
• 分子量: 316.31
• InChiKey: DQGTWVHFLLTUGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(benzyloxy)-2-(carboxymethyl)-5-methoxybenzoic acid 在 氯化亚砜 、 乙酰氯 、 sodium iodide 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.6h， 生成 15-Hydroxy-16-methoxy-20-(3-morpholin-4-ylpropyl)-5,7-dioxa-20-azapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13,15,17-heptaene-11,19-dione
  参考文献：
  名称：

  Identification, Synthesis, and Biological Evaluation of Metabolites of the Experimental Cancer Treatment Drugs Indotecan (LMP400) and Indimitecan (LMP776) and Investigation of Isomerically Hydroxylated Indenoisoquinoline Analogues as Topoisomerase I Poisons

  摘要：

  Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.

  DOI：

  10.1021/jm300519w
• 作为产物：
  描述：

  (3-苄氧基-4-甲氧基-苯基)乙酸 在 盐酸 、 potassium permanganate 、 水 、 溶剂黄146 、 potassium hydroxide 作用下， 以 水 为溶剂， 反应 90.0h， 生成 4-(benzyloxy)-2-(carboxymethyl)-5-methoxybenzoic acid
  参考文献：
  名称：

  Identification, Synthesis, and Biological Evaluation of Metabolites of the Experimental Cancer Treatment Drugs Indotecan (LMP400) and Indimitecan (LMP776) and Investigation of Isomerically Hydroxylated Indenoisoquinoline Analogues as Topoisomerase I Poisons

  摘要：

  Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.

  DOI：

  10.1021/jm300519w

文献信息

• Isoquinolone derivatives as lysophosphatidic acid receptor 5 (LPA5) antagonists: Investigation of structure-activity relationships, ADME properties and analgesic effects
  作者：Dehui Zhang、Ann M. Decker、Kristen Woodhouse、Rodney Snyder、Purvi Patel、Danni L. Harris、Yuan-Xiang Tao、Jun-Xu Li、Yanan Zhang

  DOI：10.1016/j.ejmech.2022.114741

  日期：2022.12

  lysophosphatidic acid receptor 5 (LPA5) by a recently reported antagonist AS2717638 (2) attenuated inflammatory and neuropathic pains, although it showed moderate in vivo efficacy and its structure-activity relationships and the ADME properties are little studied. We therefore designed and synthesized a series of isoquinolone derivatives and evaluated their potency in LPA5 calcium mobilization and cAMP

  最近报道的拮抗剂 AS2717638 (2) 对溶血磷脂酸受体 5 (LPA5) 的阻断可减轻炎症和神经性疼痛，尽管它显示出中等的体内功效，但其构效关系和 ADME 特性的研究很少。因此，我们设计并合成了一系列异喹诺酮衍生物，并评估了它们在 LPA5 钙动员和 cAMP 测定中的效力。我们的结果表明，取代的苯基或双环芳环（例如苯并噻吩或苯并呋喃）在2位上是可以耐受的，4-取代的哌啶在4位上是有利的，而在6位和7位上的甲氧基对于活动。化合物65和66显示出相当的体外效力、对 LPA1-LPA4 和超过 50 个其他 GPCR 的优异选择性、中等代谢稳定性以及高水溶性和脑通透性。 65和66均在低于2 的剂量下显着减弱伤害性超敏反应，并且在炎性疼痛模型中具有更持久的作用，并且66还可以剂量依赖性地减少慢性压迫性损伤模型中的机械异常性疼痛和阿片类药物引起的痛觉过敏（在没有剂量的情况下）。对大鼠运动的影响。这些结果表明这些作为
• Identification, Synthesis, and Biological Evaluation of Metabolites of the Experimental Cancer Treatment Drugs Indotecan (LMP400) and Indimitecan (LMP776) and Investigation of Isomerically Hydroxylated Indenoisoquinoline Analogues as Topoisomerase I Poisons
  作者：Maris A. Cinelli、P. V. Narasimha Reddy、Peng-Cheng Lv、Jian-Hua Liang、Lian Chen、Keli Agama、Yves Pommier、Richard B. van Breemen、Mark Cushman

  DOI：10.1021/jm300519w

  日期：2012.12.27

  Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.