bis(methoxycarbonylmethyl)aminohex-1-yne

• 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: bis(methoxycarbonylmethyl)aminohex-1-yne
• 英文别名: Dimethyl 2,2'-(hex-5-ynylazanediyl)diacetate；methyl 2-[hex-5-ynyl-(2-methoxy-2-oxoethyl)amino]acetate
• 化学式: C₁₂H₁₉NO₄
• 分子量: 241.287
• InChiKey: OWJPJEPZHKNTCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  bis(methoxycarbonylmethyl)aminohex-1-yne 、 (S)-2-(5-bromo-pyridin-3-yloxymethyl)-azetidine-1-carboxylic acid tert-butyl ester 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 反应 1.0h， 以90%的产率得到5-[bis(methoxycarbonylmethyl)aminohex-1-ynyl]-3-[(S)-1-(tert-butoxycarbonyl)-2-azetidinylmethoxy]pyridine
  参考文献：
  名称：

  Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4

  摘要：

  Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (Tc-99m) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent alpha 4 beta 2-nAChR agonist, we prepared A85380 derivatives labeled with Tc-99m using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a Tc-99m analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at alpha 4 beta 2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 +/- 0.04 nM). Further, Tc-99m-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that Tc-99m-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.

  DOI：

  10.1016/j.bmc.2019.07.053
• 作为产物：
  描述：

  6-氯己炔 、 dimethyl iminodiacetate hydrochloride 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 95.0h， 以45%的产率得到bis(methoxycarbonylmethyl)aminohex-1-yne
  参考文献：
  名称：

  Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4

  摘要：

  Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (Tc-99m) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent alpha 4 beta 2-nAChR agonist, we prepared A85380 derivatives labeled with Tc-99m using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a Tc-99m analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at alpha 4 beta 2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 +/- 0.04 nM). Further, Tc-99m-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that Tc-99m-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.

  DOI：

  10.1016/j.bmc.2019.07.053
• 作为试剂：
  描述：

  5-己炔-1-胺 、 potassium carbonate 、 溴乙酸甲酯 、 氮气 、 四氢呋喃 在 乙酸乙酯 、 silica gel 、 hexanes 、 final product 、 bis(methoxycarbonylmethyl)aminohex-1-yne 作用下， 以 hexanes 为溶剂， 反应 3.0h， 生成 bis(methoxycarbonylmethyl)aminohex-1-yne
  参考文献：
  名称：

  Clickable cross-linker

  摘要：

  一种可点击的交联剂化合物提供了易于扫描的报告离子，以有效和高效地交联和鉴定蛋白质和肽的分子间和分子内相互作用。

  公开号：

  US08778626B2

文献信息

• US8778626B2
  申请人：——

  公开号：US8778626B2

  公开（公告）日：2014-07-15
• [EN] CLICKABLE CROSS-LINKER<br/>[FR] AGENT DE RÉTICULATION POUR CHIMIE CLICK
  申请人：CALIFORNIA INST OF TECHN

  公开号：WO2012006603A2

  公开（公告）日：2012-01-12

  A clickable cross-linker compound provides an easily scanned reporter ion for effective and efficient cross-linking and identification of intermolecular and intramolecular interactions of proteins and peptides.
• Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4
  作者：Daisuke Mori、Hiroyuki Kimura、Hidekazu Kawashima、Yusuke Yagi、Kenji Arimitsu、Masahiro Ono、Hideo Saji

  DOI：10.1016/j.bmc.2019.07.053

  日期：2019.9

  Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (Tc-99m) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent alpha 4 beta 2-nAChR agonist, we prepared A85380 derivatives labeled with Tc-99m using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a Tc-99m analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at alpha 4 beta 2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 +/- 0.04 nM). Further, Tc-99m-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that Tc-99m-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.
• Clickable cross-linker
  申请人：Sohn Chang Ho

  公开号：US20120028285A1

  公开（公告）日：2012-02-02

  A clickable cross-linker compound provides an easily scanned reporter ion for effective and efficient cross-linking and identification of intermolecular and intramolecular interactions of proteins and peptides.

  一种可点击的交联剂化合物提供了一个易于扫描的报告离子，用于有效和高效地交联和鉴定蛋白质和肽的分子间和分子内相互作用。