4-nitro-N-(2-(2-(prop-2-ynyloxy)ethoxy)ethyl)aniline | 1245006-66-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-nitro-N-(2-(2-(prop-2-ynyloxy)ethoxy)ethyl)aniline
• 英文别名: 4-nitro-N-[2-(2-prop-2-ynoxyethoxy)ethyl]aniline
• CAS: 1245006-66-9
• 化学式: C₁₃H₁₆N₂O₄
• 分子量: 264.281
• InChiKey: NTFQWQNRXHZGOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-di-tert-butyl 2-(3-((S)-6-azido-1-tert-butoxy-1-oxohexan-2-yl)ureido)pentanedioate 、 4-nitro-N-(2-(2-(prop-2-ynyloxy)ethoxy)ethyl)aniline 在 copper(II) sulfate 、 sodium ascorbate 、 三氟乙酸 作用下， 以 水 、 叔丁醇 、 二氯甲烷 为溶剂， 反应 0.36h， 以27.6%的产率得到(S)-2-(3-((S)-1-carboxy-5-(4-((2-(2-(4-nitrophenylamino)ethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)pentyl)ureido)pentanedioic acid
  参考文献：
  名称：

  A Remote Arene-Binding Site on Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules

  摘要：

  Prostate specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. Our laboratory has recently disclosed a class of small molecules, called ARM-Ps (antibody-recruiting molecule targeting prostate cancer) that are capable of enhancing antibody-mediated immune recognition of prostate cancer cells. Interestingly, during the course of these studies, we found ARM-Ps to exhibit extraordinarily high potencies toward PSMA, compared to previously reported inhibitors. Here, we report in-depth biochemical, crystallographic, and computational investigations which elucidate the origin of the observed affinity enhancement. These studies reveal a previously unreported arene-binding site on PSMA, which we believe participates in an aromatic stacking interaction with ARMs. Although this site is composed of only a few amino acid residues, it drastically enhances small molecule binding affinity. These results provide critical insights into the design of PSMA-targeted small molecules for prostate cancer diagnosis and treatment; more broadly, the presence of similar arene-binding sites throughout the proteome could prove widely enabling in the optimization of small molecule-protein interactions.

  DOI：

  10.1021/ja104591m
• 作为产物：
  描述：

  炔丙基-PEG2-胺 、 对硝基氯苯 在 水 、 二氯甲烷 、 Sodium sulfate-III 、 silica gel 、 乙酸乙酯 作用下， 反应 19.0h， 以30% EtOAc in CH2Cl2 to yield 4-nitro-N-(2-(2-(prop-2-ynyloxy)ethoxy)ethyl)aniline (s-7) as a dark yellow oil (40 mg, 16%)的产率得到4-nitro-N-(2-(2-(prop-2-ynyloxy)ethoxy)ethyl)aniline
  参考文献：
  名称：

  CHIMERIC SMALL MOLECULES FOR THE RECRUITMENT OF ANTIBODIES TO CANCER CELLS

  摘要：

  本发明涉及嵌合化学化合物，用于招募抗体到癌细胞，特别是前列腺癌细胞或转移的前列腺癌细胞。根据本发明的化合物包括通过连接器和可选的连接分子共价结合到细胞结合端（CBT）的抗体结合端（ABT）基团。

  公开号：

  US20120034295A1

文献信息

• CHIMERIC SMALL MOLECULES FOR THE RECRUITMENT OF ANTIBODIES TO CANCER CELLS
  申请人：Spiegel David

  公开号：US20120034295A1

  公开（公告）日：2012-02-09

  The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) through a linker and optionally, a connector molecule.

  本发明涉及嵌合化学化合物，用于招募抗体到癌细胞，特别是前列腺癌细胞或转移的前列腺癌细胞。根据本发明的化合物包括通过连接器和可选的连接分子共价结合到细胞结合端（CBT）的抗体结合端（ABT）基团。
• Chimeric small molecules for the recruitment of antibodies to cancer cells
  申请人：Spiegel David

  公开号：US08852630B2

  公开（公告）日：2014-10-07

  The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) through a linker and optionally, a connector molecule.

  本发明涉及嵌合化学化合物，用于招募抗体至癌细胞，特别是前列腺癌细胞或转移的前列腺癌细胞。根据本发明，所述化合物包括通过连接剂和可选的连接分子共价结合到细胞结合端（CBT）的抗体结合端（ABT）基团。
• US8852630B2
  申请人：——

  公开号：US8852630B2

  公开（公告）日：2014-10-07
• US9296708B2
  申请人：——

  公开号：US9296708B2

  公开（公告）日：2016-03-29
• A Remote Arene-Binding Site on Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules
  作者：Andrew X. Zhang、Ryan P. Murelli、Cyril Barinka、Julien Michel、Alexandra Cocleaza、William L. Jorgensen、Jacek Lubkowski、David A. Spiegel

  DOI：10.1021/ja104591m

  日期：2010.9.15

  Prostate specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. Our laboratory has recently disclosed a class of small molecules, called ARM-Ps (antibody-recruiting molecule targeting prostate cancer) that are capable of enhancing antibody-mediated immune recognition of prostate cancer cells. Interestingly, during the course of these studies, we found ARM-Ps to exhibit extraordinarily high potencies toward PSMA, compared to previously reported inhibitors. Here, we report in-depth biochemical, crystallographic, and computational investigations which elucidate the origin of the observed affinity enhancement. These studies reveal a previously unreported arene-binding site on PSMA, which we believe participates in an aromatic stacking interaction with ARMs. Although this site is composed of only a few amino acid residues, it drastically enhances small molecule binding affinity. These results provide critical insights into the design of PSMA-targeted small molecules for prostate cancer diagnosis and treatment; more broadly, the presence of similar arene-binding sites throughout the proteome could prove widely enabling in the optimization of small molecule-protein interactions.