(S)-methyl 3-(4-(benzyloxy)phenyl)-2-palmitamidopropanoate | 935548-16-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-methyl 3-(4-(benzyloxy)phenyl)-2-palmitamidopropanoate
• CAS: 935548-16-6
• 化学式: C₃₃H₄₉NO₄
• 分子量: 523.756
• InChiKey: PLLSGBUWHMNLKZ-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.95
• 重原子数：
  38.0
• 可旋转键数：
  21.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-methyl 3-(4-(benzyloxy)phenyl)-2-palmitamidopropanoate 生成
  参考文献：
  名称：

  Initial structure–activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist

  摘要：

  A recently reported dual LPA(1)/LPA(3) receptor antagonist (VPC12249, 1) has been modified herein so as to optimize potency and selectivity at LPA receptors. Compounds containing variation in the acyl lipid chain and linker region have been synthesized and screened for activity at individual LPA receptors. LPA(1)-selective (14b) and LPA(3)-selective (10g,m) compounds of modest potency have been discovered. Additionally, 2-pyridyl derivative 10t exhibits a K-i value of 18 nM at the LPA(1) receptor and is significantly more potent than 1 at the LPA(3) receptor. This paper describes the synthetic methods, biological evaluation, and structure-activity relationships (SARs) of LPA receptor antagonists. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.076
• 作为产物：
  描述：

  Boc-O-苄基-L-酪氨酸 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 (S)-methyl 3-(4-(benzyloxy)phenyl)-2-palmitamidopropanoate
  参考文献：
  名称：

  Initial structure–activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist

  摘要：

  A recently reported dual LPA(1)/LPA(3) receptor antagonist (VPC12249, 1) has been modified herein so as to optimize potency and selectivity at LPA receptors. Compounds containing variation in the acyl lipid chain and linker region have been synthesized and screened for activity at individual LPA receptors. LPA(1)-selective (14b) and LPA(3)-selective (10g,m) compounds of modest potency have been discovered. Additionally, 2-pyridyl derivative 10t exhibits a K-i value of 18 nM at the LPA(1) receptor and is significantly more potent than 1 at the LPA(3) receptor. This paper describes the synthetic methods, biological evaluation, and structure-activity relationships (SARs) of LPA receptor antagonists. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.076

文献信息

• Synthesis and structure–activity relationships of tyrosine-based inhibitors of autotaxin (ATX)
  作者：James E. East、Andrew J. Kennedy、Jose L. Tomsig、Alexandra R. De Leon、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2010.09.030

  日期：2010.12

  Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA's role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors
  作者：Peng Cui、Jose L. Tomsig、William F. McCalmont、Sangderk Lee、Christopher J. Becker、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2006.12.114

  日期：2007.3

  Autotaxin (ATX) is an autocrine motility factor that promotes cancer cell invasion, cell migration, and angiogenesis. ATX, originally discovered as a nucleotide phosphodiesterase, is known now to be responsible for the lysophospholipid-preferring phospholipase D activity in plasma. As such, it catalyzes the production of lysophosphatidic acid (LPA) from lysophophatidylcholine (LPC). ATX is thus an attractive drug target; small molecular inhibitors might be efficacious in slowing the spread of cancers. With this study we have generated a series of P-keto and P-hydroxy phosphonate derivatives of LPA, some of which are potent ATX inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.