Fmoc-Dap(Dde)-OH | 247127-51-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Dap(Dde)-OH
• 英文别名: (2S)-3-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethylamino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 247127-51-1
• 化学式: C₂₈H₃₀N₂O₆
• 分子量: 490.556
• InChiKey: IGNPBNCBFYUHTM-QFIPXVFZSA-N

物化性质

• 沸点：
  719.2±60.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  121.8
• 氢给体数：
  3.0
• 氢受体数：
  6.0

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H317,H319

反应信息

• 作为反应物：
  描述：

  Fmoc-Dap(Dde)-OH 在 N-甲基吗啉 、 氯甲酸异丁酯 、 ammonium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 1.83h， 生成 Dap(Dde)-NH₂
  参考文献：
  名称：

  Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo

  摘要：

  Somatostatin receptor 2 (SSTR2) is frequently overexpressed on several types of solid tumors, including neuroendocrine tumors and small-cell lung cancer. Peptide agonists of SSTR2 are rapidly internalized upon binding to the receptor and linking a toxic payload to an SSTR2 agonist is a potential method to kill SSTR2-expressing tumor cells. Herein, we describe our efforts towards an efficacious SSTR2-targeting cytotoxic conjugate; examination of different SSTR2-targeting ligands, conjugation sites, and payloads led to the discovery of 22 (PEN-221), a conjugate consisting of microtubule-targeting agent DM1 linked to the C-terminal side chain of Tyr(3)-octreotate. PEN-221 demonstrates in vitro activity which is both potent (IC50 = 10 nM) and receptor-dependent (IC50 shifts 90-fold upon receptor blockade). PEN-221 targets high levels of DM1 to SSTR2-expressing xenograft tumors, which has led to tumor regressions in several SSTR2-expressing xenograft mouse models. The safety and efficacy of PEN-221 is currently under evaluation in human clinical trials.

  DOI：

  10.1021/acs.jmedchem.8b02036
• 作为产物：
  描述：

  5,5-二甲基-1,3-环己二酮 在 吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 Fmoc-Dap(Dde)-OH
  参考文献：
  名称：

  玻连蛋白受体（alphavbeta3）抑制剂的并行固相合成。

  摘要：

  通过固相合成完成了用于快速优化玻连蛋白受体（alphavbeta3）抑制剂前导的组合方法。正交双保护的2，3-二氨基丙酸用于固定分子的C末端。选择性脱保护和功能化的α-氨基，然后酰基间苯二酚支架附着和N末端多样化被用来探讨结构活性关系（SAR）。

  DOI：

  10.1016/s0960-894x(00)00319-x

文献信息

• On‐Resin Preparation of Allenamidyl Peptides: A Versatile Chemoselective Conjugation and Intramolecular Cyclisation Tool
  作者：Alan J. Cameron、Paul W. R. Harris、Margaret A. Brimble

  DOI：10.1002/anie.202004656

  日期：2020.10.5

  “click” approach, a model peptide was successfully modified with a diverse range of alkyl and aryl thiols. Furthermore, this technique was demonstrated as a valuable tool to induce spontaneous intramolecular cyclisation by preparation of an oxytocin analogue, in which the native disulfide bridge was replaced with a vinyl sulfide moiety formed by thia‐Michael addition of a cysteine thiol to the allenamide

  在医学化学中，化学选择性修饰肽和蛋白质的能力一直受到关注，在现代肽化学的最前沿，肽的缀合，脂化，装订和二硫键工程化。本文中，我们报告了一种树脂上制备烯丙酰胺修饰的肽的可靠方法，该肽的未开发功能为硫醇的化学选择性分子间或分子内桥连反应提供了一种通用的化学工具。桥接反应具有生物相容性，在无催化剂的水性介质中于pH 7.4时自发发生。通过这种“点击”方法，模型肽成功地被各种烷基和芳基硫醇修饰。此外，该技术被证明是通过制备催产素类似物来诱导自发分子内环化的有价值的工具，
• Cell adhesion inhibitors
  申请人：Biogen Idec MA, Inc.

  公开号：EP1741428A2

  公开（公告）日：2007-01-10

  A cell adhesion inhibitor of the general formula: R3-L-L'-R1 is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.

  本发明公开了一种通式为R3-L-L'-R1 的细胞粘附抑制剂。本发明的抑制剂与 VLA-4 分子相互作用，抑制依赖 VLA-4 的细胞粘附。还公开了制备和使用这种细胞粘附抑制剂的方法，以及含有这种抑制剂的药物组合物。
• WO2022/96394
  申请人：——

  公开号：——

  公开（公告）日：——
• Parallel solid-phase synthesis of vitronectin receptor (αvβ3) inhibitors
  作者：Ariamala Gopalsamy、Hui Yang、John W Ellingboe、Kenneth L Kees、Jeanne Yoon、Richard Murrills

  DOI：10.1016/s0960-894x(00)00319-x

  日期：2000.8

  A combinatorial approach for rapid optimization of a vitronectin receptor (alphavbeta3) inhibitor lead was accomplished by solid-phase synthesis. Orthogonally bis protected 2,3-diaminopropionic acid was used to immobilize the C-terminus of the molecule. Selective deprotection and functionalization of the alpha-amino group followed by acyl resorcinol scaffold attachment and N-terminus diversification

  通过固相合成完成了用于快速优化玻连蛋白受体（alphavbeta3）抑制剂前导的组合方法。正交双保护的2，3-二氨基丙酸用于固定分子的C末端。选择性脱保护和功能化的α-氨基，然后酰基间苯二酚支架附着和N末端多样化被用来探讨结构活性关系（SAR）。
• Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo
  作者：Brian H. White、Kerry Whalen、Kristina Kriksciukaite、Rossitza Alargova、Tsun Au Yeung、Patrick Bazinet、Adam Brockman、Michelle DuPont、Haley Oller、Charles-Andre Lemelin、Patrick Lim Soo、Benoît Moreau、Samantha Perino、James M. Quinn、Gitanjali Sharma、Rajesh Shinde、Beata Sweryda-Krawiec、Richard Wooster、Mark T. Bilodeau

  DOI：10.1021/acs.jmedchem.8b02036

  日期：2019.3.14

  Somatostatin receptor 2 (SSTR2) is frequently overexpressed on several types of solid tumors, including neuroendocrine tumors and small-cell lung cancer. Peptide agonists of SSTR2 are rapidly internalized upon binding to the receptor and linking a toxic payload to an SSTR2 agonist is a potential method to kill SSTR2-expressing tumor cells. Herein, we describe our efforts towards an efficacious SSTR2-targeting cytotoxic conjugate; examination of different SSTR2-targeting ligands, conjugation sites, and payloads led to the discovery of 22 (PEN-221), a conjugate consisting of microtubule-targeting agent DM1 linked to the C-terminal side chain of Tyr(3)-octreotate. PEN-221 demonstrates in vitro activity which is both potent (IC50 = 10 nM) and receptor-dependent (IC50 shifts 90-fold upon receptor blockade). PEN-221 targets high levels of DM1 to SSTR2-expressing xenograft tumors, which has led to tumor regressions in several SSTR2-expressing xenograft mouse models. The safety and efficacy of PEN-221 is currently under evaluation in human clinical trials.