(5S)-6-[[1-[2-[2-[2-[[4-[2-[2-[2-[[4-[[(2S)-1-amino-6-[[(2S)-2-amino-3-[1-[[4-[(4-hydroxy-4,4-diphosphonobutyl)carbamoyl]cyclohexyl]methyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoyl]amino]-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylcarbamoyl]cyclohexyl]amino]-5-[[(2S)-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid | 1363159-28-7

• 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: (5S)-6-[[1-[2-[2-[2-[[4-[2-[2-[2-[[4-[[(2S)-1-amino-6-[[(2S)-2-amino-3-[1-[[4-[(4-hydroxy-4,4-diphosphonobutyl)carbamoyl]cyclohexyl]methyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoyl]amino]-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylcarbamoyl]cyclohexyl]amino]-5-[[(2S)-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid
• CAS: 1363159-28-7
• 化学式: C₈₈H₁₃₃N₁₇O₂₈P₂S
• 分子量: 1971.13
• InChiKey: FGRUYPCSKHMJMZ-RHHLPLLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.1
• 重原子数：
  136
• 可旋转键数：
  65
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  715
• 氢给体数：
  21
• 氢受体数：
  31

反应信息

• 作为产物：
  描述：

  、 (5S)-6-[[1-[2-[2-[2-[[4-[2-[2-[2-[[4-[[(2S)-1-amino-6-[[(2S)-2-amino-3-sulfanylpropanoyl]amino]-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylcarbamoyl]cyclohexyl]amino]-5-[[(2S)-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid 以 aq. phosphate buffer 、 水 、 乙腈 为溶剂， 反应 1.0h， 生成 (5S)-6-[[1-[2-[2-[2-[[4-[2-[2-[2-[[4-[[(2S)-1-amino-6-[[(2S)-2-amino-3-[1-[[4-[(4-hydroxy-4,4-diphosphonobutyl)carbamoyl]cyclohexyl]methyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoyl]amino]-1-oxohexan-2-yl]amino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]amino]ethoxy]ethoxy]ethylcarbamoyl]cyclohexyl]amino]-5-[[(2S)-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid
  参考文献：
  名称：

  [EN] LLP2A-BISPHOSPHONATE CONJUGATES FOR OSTEOPOROSIS TREATMENT
  [FR] CONJUGUÉS LLP2A-BISPHOSPHONATE POUR LE TRAITEMENT DE L'OSTÉOPOROSE

  摘要：

  本发明提供了一种肽类模拟配体化合物和制药组合物，例如LLP2A，与双磷酸盐药物，例如阿伦膦酸，结合。本发明的化合物和制药组合物由于对间充质干细胞上的α4β1整合素和骨表面的特异性，对骨质疏松症的治疗和促进骨生长具有用处。

  公开号：

  WO2013032527A1

文献信息

• LLP2A- BISPHOSPHONATE CONJUGATES FOR OSTEOPOROSIS TREATMENT
  申请人：The Regents of the University of California

  公开号：EP3453711A1

  公开（公告）日：2019-03-13

  The present invention provides compounds and pharmaceutical compositions of a peptidomimetic ligand, e.g. LLP2A, conjugated with a bisphosphonate drug, e.g. Alendronate. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the α4β1 integrin on mesenchymal stem cells and for the surface of bone.

  本发明提供了拟肽配体（如LLP2A）与双膦酸盐药物（如阿仑膦酸盐）共轭的化合物和药物组合物。由于本发明的化合物和药物组合物对间充质干细胞上的α4β1整合素和骨表面具有特异性，因此可用于治疗骨质疏松症和促进骨生长。
• LLP2A-BISPHOSPHONATE CONJUGATES FOR OSTEOPOROSIS TREATMENT
  申请人：The Regents of the University of California

  公开号：EP2753626B1

  公开（公告）日：2018-08-08
• METHODS OF TREATING OSTEONECROSIS WITH LLP2A-BISPHOSPHONATE COMPOUNDS
  申请人：The Regents of the University of California

  公开号：US20210205338A1

  公开（公告）日：2021-07-08

  Methods of treating osteonecrosis in a subject are provided. In some embodiments, the method comprises administering to a subject having or suspected of having osteonecrosis a pharmaceutical composition comprising a conjugate of an LLP2A peptidomimetic ligand and a bisphosphonate drug. In some embodiments, the pharmaceutical composition comprises a conjugate of LLP2A and alendronate (LLP2A-Ale). In some embodiments, the method further comprises administering exogenous mesenchymal stem cells.
• US9561256B2
  申请人：——

  公开号：US9561256B2

  公开（公告）日：2017-02-07
• [EN] LLP2A-BISPHOSPHONATE CONJUGATES FOR OSTEOPOROSIS TREATMENT<br/>[FR] CONJUGUÉS LLP2A-BISPHOSPHONATE POUR LE TRAITEMENT DE L'OSTÉOPOROSE
  申请人：UNIV CALIFORNIA

  公开号：WO2013032527A1

  公开（公告）日：2013-03-07

  The present invention provides compounds and pharmaceutical compositions of a peptidomimetic ligand, e.g. LLP2A, conjugated with a bisphosphonate drug, e.g. Alendronate. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the α4β1 integrin on mesenchymal stem cells and for the surface of bone.

  本发明提供了一种肽类模拟配体化合物和制药组合物，例如LLP2A，与双磷酸盐药物，例如阿伦膦酸，结合。本发明的化合物和制药组合物由于对间充质干细胞上的α4β1整合素和骨表面的特异性，对骨质疏松症的治疗和促进骨生长具有用处。