4-<2-<(2,3:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>benzoic acid | 171905-66-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-<2-<(2,3:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>benzoic acid
• 英文别名: 4-[2-[[(1R,2S,6S,7R,9R)-4,4,12,12-tetramethyl-3,5,8,11,13-pentaoxatricyclo[7.4.0.02,6]tridecan-7-yl]oxy]phenyl]benzoic acid
• CAS: 171905-66-1
• 化学式: C₂₅H₂₈O₈
• 分子量: 456.493
• InChiKey: CMVBULBBEQGXKO-RBRWEJTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-<2-<(2,3:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>benzoic acid 在 盐酸 、 sodium hydroxide 、 N-羟基丁二酰亚胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 (2S)-6-amino-2-[[4-[2-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]benzoyl]amino]hexanoic acid
  参考文献：
  名称：

  Rational Design and Synthesis of Small Molecule, Non-oligosaccharide Selectin Inhibitors: (.alpha.-D-Mannopyranosyloxy)biphenyl-Substituted Carboxylic Acids

  摘要：

  The calcium dependent E-selectin/sialyl Lewis(x) (sLe(x)) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLe(x) binding, along with previously reported structure-activity relationships of sLe(x)-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLe(x) expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLe(x) tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.

  DOI：

  10.1021/jm00026a004
• 作为产物：
  描述：

  2-羟基-[1,1-联苯]-4-羧酸甲酯 在 lithium hydroxide 、 三氟化硼乙醚 、 对甲苯磺酸 、 丙酮 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 0.75h， 生成 4-<2-<(2,3:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>benzoic acid
  参考文献：
  名称：

  Rational Design and Synthesis of Small Molecule, Non-oligosaccharide Selectin Inhibitors: (.alpha.-D-Mannopyranosyloxy)biphenyl-Substituted Carboxylic Acids

  摘要：

  The calcium dependent E-selectin/sialyl Lewis(x) (sLe(x)) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLe(x) binding, along with previously reported structure-activity relationships of sLe(x)-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLe(x) expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLe(x) tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.

  DOI：

  10.1021/jm00026a004

文献信息

• BINDING OF E-SELECTIN, P-SELECTIN OR L-SELECTIN TO SIALYL-LEWISx OR SIALYL-LEWISa
  申请人：TEXAS BIOTECHNOLOGY CORPORATION

  公开号：EP0758243B1

  公开（公告）日：2003-03-12
• US5444050A
  申请人：——

  公开号：US5444050A

  公开（公告）日：1995-08-22
• Rational Design and Synthesis of Small Molecule, Non-oligosaccharide Selectin Inhibitors: (.alpha.-D-Mannopyranosyloxy)biphenyl-Substituted Carboxylic Acids
  作者：Timothy P. Kogan、Brian Dupre、Karin M. Keller、Ian L. Scott、Huong Bui、Robert V. Market、Pamela J. Beck、Jennifer A. Voytus、B. Mitch Revelle、Delores Scott

  DOI：10.1021/jm00026a004

  日期：1995.12

  The calcium dependent E-selectin/sialyl Lewis(x) (sLe(x)) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLe(x) binding, along with previously reported structure-activity relationships of sLe(x)-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLe(x) expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLe(x) tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.