Phosphoric acid di-tert-butyl ester (R)-3-(4-hydroxy-phenyl)-2-((Z)-octadec-9-enoylamino)-propyl ester | 870862-63-8

• 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: Phosphoric acid di-tert-butyl ester (R)-3-(4-hydroxy-phenyl)-2-((Z)-octadec-9-enoylamino)-propyl ester
• CAS: 870862-63-8
• 化学式: C₃₅H₆₂NO₆P
• 分子量: 623.854
• InChiKey: CXKMDUCHLFIQBT-AHVPQQLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.21
• 重原子数：
  43.0
• 可旋转键数：
  23.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  94.09
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Phosphoric acid di-tert-butyl ester (R)-3-(4-hydroxy-phenyl)-2-((Z)-octadec-9-enoylamino)-propyl ester 在 palladium dihydroxide 偶氮二甲酸二异丙酯 、 氢气 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 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：

  (Z)-Octadec-9-enoic acid {(R)-2-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-1-hydroxymethyl-ethyl}-amide 在 四氮唑 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 Phosphoric acid di-tert-butyl ester (R)-3-(4-hydroxy-phenyl)-2-((Z)-octadec-9-enoylamino)-propyl ester
  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

• [EN] NOVEL LYSOPHOSPHATIDIC ACID RECEPTOR SELECTIVE ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES SELECTIFS DU RECEPTEUR DE L'ACIDE LYSOPHOSPHATIDIQUE
  申请人：UNIV VIRGINIA

  公开号：WO2005115150A3

  公开（公告）日：2006-05-04
• A novel series of 2-pyridyl-containing compounds as lysophosphatidic acid receptor antagonists: development of a nonhydrolyzable LPA3 receptor-selective antagonist
  作者：Brian H Heasley、Renata Jarosz、Karen M Carter、S Jenny Van、Kevin R Lynch、Timothy L Macdonald

  DOI：10.1016/j.bmcl.2004.05.023

  日期：2004.8

  A recently reported dual LPA(1)/LPA(3) receptor antagonist (1) has been modified so as to modulate the basicity, sterics, and dipole moment of the 2-pyridyl moiety. Additionally, the implications of installing nonhydrolyzable phosphate head group isosteres with regard to antagonist potency and selectivity at LPA receptors is described. This study has resulted in the development of the first nonhydrolyzable and presumably phosphatase-resistant LPA(3)-selective antagonist reported to date. (C) 2004 Elsevier Ltd. All rights reserved.