methyl 3-<2-<(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)oxy>phenyl>phenylacetate | 173204-11-0

• 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: methyl 3-<2-<(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)oxy>phenyl>phenylacetate
• 英文别名: methyl {3-[2-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxy)phenyl]phenyl}acetate；Methyl 3-(2-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyloxy)phenyl)phenylacetate；methyl 2-[3-[2-[(2R,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyphenyl]phenyl]acetate
• CAS: 173204-11-0
• 化学式: C₂₉H₃₂O₁₂
• 分子量: 572.566
• InChiKey: WKIFREHXFVQZOT-OOLDPQGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  150
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  methyl 3-<2-<(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)oxy>phenyl>phenylacetate 在 三氯化铝 、 硼烷四氢呋喃络合物 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 methyl {3-[5-(3-bromopropyl)-2-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxy)phenyl]phenyl}acetate
  参考文献：
  名称：

  与 DTPA 共轭的唾液酸 LewisX 模拟物的合成，DTPA 是用于医学成像的新型造影剂的潜在配体

  摘要：

  唾液酸基 LewisX 模拟物的结构，即 3-[2-(α-D-吡喃甘露糖氧基)苯基]苯乙酸，通过灵活的烷基间隔基和酰胺键与二亚乙基三胺五乙酸 (DTPA) 偶联。从 3-溴苯乙酸开始的 11 步合成的总产率为 4-8%。这种新配体有望通过与选择素的特异性相互作用来靶向炎症部位，选择素是病理条件下血管内皮上表达的粘附分子。特别是，DTPA 部分与钆或放射性核素的络合可以产生用于医学成像的造影剂。(© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

  DOI：

  10.1002/1099-0690(200212)2002:23<3966::aid-ejoc3966>3.0.co;2-p
• 作为产物：
  描述：

  3-溴苯乙酸 在 四(三苯基膦)钯 、 硫酸 、 三氟化硼乙醚 三溴化硼 、 sodium carbonate 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 50.0h， 生成 methyl 3-<2-<(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)oxy>phenyl>phenylacetate
  参考文献：
  名称：

  与 DTPA 共轭的唾液酸 LewisX 模拟物的合成，DTPA 是用于医学成像的新型造影剂的潜在配体

  摘要：

  唾液酸基 LewisX 模拟物的结构，即 3-[2-(α-D-吡喃甘露糖氧基)苯基]苯乙酸，通过灵活的烷基间隔基和酰胺键与二亚乙基三胺五乙酸 (DTPA) 偶联。从 3-溴苯乙酸开始的 11 步合成的总产率为 4-8%。这种新配体有望通过与选择素的特异性相互作用来靶向炎症部位，选择素是病理条件下血管内皮上表达的粘附分子。特别是，DTPA 部分与钆或放射性核素的络合可以产生用于医学成像的造影剂。(© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

  DOI：

  10.1002/1099-0690(200212)2002:23<3966::aid-ejoc3966>3.0.co;2-p

文献信息

• Binding of E-selectin or P-selectin to sialyl Lewis.sup.x or
  申请人：Texas Biotechnology Corporation

  公开号：US05444050A1

  公开（公告）日：1995-08-22

  This invention relates to compounds that inhibit the binding of E-selectin and/or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface having the general structure ##STR1## wherein X is selected from the group consisting of --(CH.sub.2).sub.n CO.sub.2 H, --O(CH.sub.2).sub.m CO.sub.2 H, --(CH.sub.2).sub.n O(CH.sub.2).sub.m CO.sub.2 H, --CONH(CH.sub.2).sub.m CO.sub.2 H, --CH(OZ)(CO.sub.2 H), --CH(Z)(CO.sub.2 H), --(CH.sub.2).sub.n SO.sub.3 H, --(CH.sub.2).sub.n PO.sub.3 D.sub.1 D.sub.2, --NH(CH.sub.2).sub.m CO.sub.2 H, --CONH(CHR.sub.6)CO.sub.2 H, (1-H-tetrazolyl-5-alkyl-), and --OH; R.sub.1 and R.sub.2 are independently selected from the group consisting of hydrogen, alkyl, halogen, --OZ, --NO.sub.2, --NH.sub.2 and --NHZ; R.sub.3 is selected from the group consisting of hydrogen, halogen, alkyl, --OZ and --NHZ; R.sub.4 is selected from the group consisting of hydrogen, halogen, alkyl, hydroxyl, hydroxyl-O-sulfate and --OZ; R.sub.5 is selected from the group consisting of hydroxyl, --CN, --N.sub.3, --NH.sub.2, --NHNH.sub.2, --NE.sub.1 E.sub.2, --NHE.sub.1, --NHCO(CH.sub.2).sub.n CO.sub.2 H, --S(CH.sub.2).sub.m CO.sub.2 H and --NHCHNHNH.sub.2 ; R.sub.6 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, alkyl carboxylic acid and alkyl carboxamide; wherein n is 0 to 6, m is 1 to 6, p is 0 to 6, b is 0 to 2, Z is alkyl, aryl or aralkyl, D.sub.1 and D.sub.2 are independantly hydrogen or alkyl, E.sub.1 is alkyl or --(CH.sub.2).sub.8 CO.sub.2 H, and E.sub.2 is alkyl, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof. This invention also relates to methods of inhibiting the binding of E-selectin and/or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface using said compounds and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis.sup.x and to methods of treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occur following heart attacks, strokes and organ transplants.

  本发明涉及抑制E-选择素和/或P-选择素与细胞表面呈现的唾液酸-Lewis.sup.x或唾液酸-Lewis.sup.a的结合的化合物，其具有一般结构##STR1##其中X从以下组中选择：--（CH.sub.2）.sub.n CO.sub.2 H，--O（CH.sub.2）.sub.m CO.sub.2 H，--（CH.sub.2）.sub.n O（CH.sub.2）.sub.m CO.sub.2 H，--CONH（CH.sub.2）.sub.m CO.sub.2 H，--CH（OZ）（CO.sub.2 H），--CH（Z）（CO.sub.2 H），--（CH.sub.2）.sub.n SO.sub.3 H，--（CH.sub.2）.sub.n PO.sub.3 D.sub.1 D.sub.2，--NH（CH.sub.2）.sub.m CO.sub.2 H，--CONH（CHR.sub.6）CO.sub.2 H，（1-H-四唑基-5-烷基-），和--OH；R.sub.1和R.sub.2各自独立地从以下组中选择：氢，烷基，卤素，--OZ，--NO.sub.2，--NH.sub.2和--NHZ；R.sub.3从以下组中选择：氢，卤素，烷基，--OZ和--NHZ；R.sub.4从以下组中选择：氢，卤素，烷基，羟基，羟基-O-硫酸酯和--OZ；R.sub.5从以下组中选择：羟基，--CN，--N.sub.3，--NH.sub.2，--NHNH.sub.2，--NE.sub.1 E.sub.2，--NHE.sub.1，--NHCO（CH.sub.2）.sub.n CO.sub.2 H，--S（CH.sub.2）.sub.m CO.sub.2 H和--NHCHNHNH.sub.2；R.sub.6从以下组中选择：氢，烷基，芳基烷基，羟基烷基，氨基烷基，烷基羧酸和烷基羧酰胺；其中n为0至6，m为1至6，p为0至6，b为0至2，Z为烷基，芳基或芳基烷基，D.sub.1和D.sub.2各自独立地为氢或烷基，E.sub.1为烷基或--（CH.sub.2）.sub.8 CO.sub.2 H，E.sub.2为烷基，以及其药学上可接受的盐，酯，酰胺和前药。本发明还涉及使用上述化合物抑制E-选择素和/或P-选择素与细胞表面呈现的唾液酸-Lewis.sup.x或唾液酸-Lewis.sup.a的结合的方法，以及包含抑制E-选择素与唾液酸-Lewis.sup.x结合的化合物的药学活性组合物，以及治疗败血症休克、ARDS、克罗恩病、慢性炎症性疾病（如银屑病和类风湿性关节炎）以及心脏病发作、中风和器官移植后的再灌注损伤的治疗方法。
• 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.
• US5444050A
  申请人：——

  公开号：US5444050A

  公开（公告）日：1995-08-22