methyl 3-<2-<(2,3,:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>phenylacetate | 171905-70-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 3-<2-<(2,3,:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>phenylacetate
• 英文别名: methyl 3-(2-(2,3:4,6-di-O-isopropylidene-α-D-mannopyranosyloxy)phenyl)phenylacetate；methyl 2-[3-[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]phenyl]acetate
• CAS: 171905-70-7
• 化学式: C₂₇H₃₂O₈
• 分子量: 484.546
• InChiKey: NPSOYFFHKPUMOP-PLFWLVBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 3-<2-<(2,3,:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>phenylacetate 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 、 双(三甲基硅烷基)氨基钾 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， -78.0~25.0 ℃ 、275.79 kPa 条件下， 反应 3.34h， 生成 diethyl <3-<3-<2-<(2,3,:4,6-di-O-isopropylidene-α-D-mannopyranosyl)oxy>phenyl>phenyl>propyl>phosphonate
  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：EP0758243A1

  公开（公告）日：1997-02-19
• EP0758243A4
  申请人：——

  公开号：EP0758243A4

  公开（公告）日：1997-08-20
• US5444050A
  申请人：——

  公开号：US5444050A

  公开（公告）日：1995-08-22
• [EN] BINDING OF E-SELECTIN, P-SELECTIN OR L-SELECTIN TO SIALYL-LEWIS OR SIALYL-LEWIS<br/>[FR] FIXATION DE LA E-SELECTINE ET/OU DE LA P-SELECTINE SUR LA SIALYL-LEWIS- OU LA SIALYL-LEWIS-
  申请人：TEXAS BIOTECHNOLOGY CORPORATION

  公开号：WO1995029682A1

  公开（公告）日：1995-11-09

  (EN) This invention relates to compounds having general structure (II) that inhibit the binding of E-selectin and/or P-selectin to sialyl-Lewisx or sialyl-Lewisa presented on a cell surface. This invention also relates to methods of inhibiting the binding of E-selectin and/or P-selectin to sialyl-Lewisx or sialyl-Lewisa presented on a cell surface using said compounds, and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewisx. This invention also concerns methods of using said compounds for treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory disease such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occur following heart attacks, strokes and organ transplants.(FR) L'invention porte sur des composés de structure générale (II) inhibant la fixation de la E-sélectine et/ou de la P-sélectine sur la sialyl-Lewis-x ou la sialyl-Lewis-a présente à la surface d'une cellule. Elle porte également sur des méthodes d'inhibition de la fixation de la E-sélectine et/ou de la P-sélectine sur la sialyl-Lewis-x ou la sialyl-Lewis-a présente à la surface d'une cellule à l'aide desdits composés et sur des compositions pharmaceutiques comprenant des composés inhibant la fixation de la E-sélectine sur la sialyl-Lewis-x. Elle porte en outre sur des méthodes d'emploi desdits composés pour le traitement de chocs septiques, de l'ARDS, de la maladie de Crohn, des troubles inflammatoires chroniques tels que le psoriasis ou l'arthrite rhumatoïde, et les traumatismes de reperfusion consécutifs à des arrêts cardiaques, à des attaques ou à des transplantations d'organes.
• 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.