N6-[叔丁氧羰基]-D-赖氨酸甲酯单盐酸盐 | 66494-53-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 天然氨基酸及其衍生物
• 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
• 中文名称: N6-[叔丁氧羰基]-D-赖氨酸甲酯单盐酸盐
• 中文别名: N'-BOC-D-赖氨酸甲酯盐酸盐
• 英文名称: methyl N6-(tert-butoxycarbonyl)-D-lysinate hydrochloride
• 英文别名: h-d-Lys(boc)-ome.hcl；methyl (2R)-2-amino-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate;hydrochloride
• CAS: 66494-53-9
• 化学式: C₁₂H₂₄N₂O₄*ClH
• 分子量: 296.794
• InChiKey: NANRHOPPXCBHGI-SBSPUUFOSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  90.6
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2924199090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  保存于惰性气体中，2-8°C

反应信息

• 作为反应物：
  描述：

  N6-[叔丁氧羰基]-D-赖氨酸甲酯单盐酸盐 在 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.5h， 生成 (2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-N-[(3-hydroxypyridin-4-yl)methyl]hexanamide
  参考文献：
  名称：

  [EN] KAPPA OPIOID RECEPTOR PEPTIDE AMIDE AGONISTS
  [FR] AGONISTES AMIDES PEPTIDIQUES DU RÉCEPTEUR OPIOÏDE KAPPA

  摘要：

  本发明提供了kappa阿片受体肽激动剂，制备这些化合物的方法，包含这些kappa阿片受体肽激动剂的组合物，以及使用这些kappa阿片受体肽激动剂来治疗疼痛或其他疾病的方法。

  公开号：

  WO2021026492A1
• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-N'-(tert-butyloxycarbonyl)-D-lysine methyl ester 在 重铬酸吡啶 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以96%的产率得到N6-[叔丁氧羰基]-D-赖氨酸甲酯单盐酸盐
  参考文献：
  名称：

  Plasmin-activated prodrugs for cancer chemotherapy. 1. Synthesis and biological activity of peptidylacivicin and peptidylphenylenediamine mustard

  摘要：

  Many tumors contain elevated levels of plasminogen activator and thus produce elevated levels of the protease plasmin in the milieu of the tumor. We have hypothesized, therefore, that it should be possible to prepare peptidyl prodrug derivatives of anticancer drugs that would be locally activated by tumor-associated plasmin. As an initial test of this hypothesis, we synthesized the peptidyl prodrugs of the anticancer drugs (alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin, AT-125) and N,N-bis(2-chloroethyl)-p-phenylenediamine (phenylenediamine mustard) by mixed anhydride coupling of the parent drug with the protected tripeptide, Boc-D-Val-Leu-Lys(Boc)-OH, followed by deprotection with trifluoroacetic acid. The prodrugs showed an increased selective in vitro cytotoxicity for Rous sarcoma virus transformed chicken embryo fibroblasts (which produce elevated levels of plasminogen activator) compared to nontransformed fibroblasts (which produce low levels of plasminogen activator). In the presence of the plasmin inhibitor, p-nitrophenyl p'-guanidinobenzoate at 2 micrograms/mL, the selectivity of the phenylenediamine mustard prodrug was reduced, but there was no effect on the cytotoxicity of the free drug. Furthermore, the prodrug analogue D-valylleucyl-D-lysylphenylenediamine mustard (in which L-Lys has been replaced by D-Lys) was inactive. Finally, the prodrug derivative of acivicin did not display selective toxicity for transformed cells when the cells were cultured in plasminogen-free medium. These results suggest that plasmin hydrolysis is necessary for the activation of the prodrugs. The prodrugs were tested in vivo for antitumor activity. The prodrug of acivicin, like acivicin itself, was inactive against the B16 melanoma, a murine tumor that produces high levels of plasminogen activator. This prodrug was active against the M5076 carcinoma, a tumor that displays only moderate levels of plasminogen activator; however, despite the fact that the prodrug was 2- to 3-fold less toxic on a molar basis than acivicin, there was no evidence of an increased therapeutic index. The prodrug of phenylenediamine mustard was also slightly less toxic than the parent drug, but again there was no evidence for an improved therapeutic index against the B16 tumor.

  DOI：

  10.1021/jm00359a003

文献信息

• [EN] ANTIMICROBIAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIMICROBIENS
  申请人：NEWSOUTH INNOVATIONS PTY LTD

  公开号：WO2018081869A1

  公开（公告）日：2018-05-11

  The present application relates to compounds of Formula (I) and salts thereof. The compounds of Formula (I) have antibacterial and anti-biofilm activities. The present application also relates to compositions comprising the compounds of Formula (I) or salts thereof, methods of treating or preventing bacterial infections using the compounds of Formula (I) or salts thereof, and methods of inhibiting biofilm formation using the compounds of Formula (I) or salts thereof.

  本申请涉及化合物I的盐和化合物。化合物I具有抗菌和抗生物膜活性。本申请还涉及包含化合物I或其盐的组合物，使用化合物I或其盐治疗或预防细菌感染的方法，以及使用化合物I或其盐抑制生物膜形成的方法。
• Amphipathic guanidine-embedded glyoxamide-based peptidomimetics as novel antibacterial agents and biofilm disruptors
  作者：Shashidhar Nizalapur、Onder Kimyon、Eugene Yee、Kitty Ho、Thomas Berry、Mike Manefield、Charles G. Cranfield、Mark Willcox、David StC Black、Naresh Kumar

  DOI：10.1039/c7ob00053g

  日期：——

  Novel antibacterial peptidomimetics that inhibit the growth of planktonic cells and reduce biofilm formation in both Gram-positive and Gram-negative bacteria.

  新型拟肽抗菌剂，可抑制革兰氏阳性和革兰氏阴性细菌的浮游细胞生长并减少生物膜的形成。
• Analogs of Eu3+ DOTAM-Gly-Phe-OH and Tm3+ DOTAM-Gly-Lys-OH: Synthesis and magnetic properties of potential PARACEST MRI contrast agents
  作者：Mojmír Suchý、Alex X. Li、Robert Bartha、Robert H.E. Hudson

  DOI：10.1016/j.bmc.2008.04.038

  日期：2008.6

  PARACEST agents. Two compounds possessed interesting magnetic properties: the Eu(3+) complex of DOTAM-Gly-Phe-OH and the Tm(3+) complex of DOTAM-Gly-Lys-OH. To understand the relationship between the structure of these complexes and their magnetic properties, we have expanded our synthetic methodology and prepared several new complexes. Ligands have been prepared in which the terminal phenylalanine

  已发现螯合的镧系离子，尤其是g，已广泛用作磁共振成像中的造影剂。最近描述了一种用于产生对比度的新范例，称为PARACEST，该范例要求缓慢交换存在于配体骨架中的水或其他可交换质子。在以前的工作中，我们描述了一种制备用作PARACEST试剂的DOTAM二肽共轭物的合成方法。两种化合物具有有趣的磁性：DOTAM-Gly-Phe-OH的Eu（3+）配合物和DOTAM-Gly-Lys-OH的Tm（3+）配合物。为了了解这些配合物的结构与其磁性之间的关系，我们扩展了合成方法，并制备了几种新的配合物。已经制备了配体，其中末端苯丙氨酸部分已被色氨酸或酪氨酸取代，与具有α-取代基的氨基酸残基的距离已改变，或苯丙氨酸和赖氨酸已结合在肽序列中。这些配体的镧系元素（III）配合物的制备已经完成，并确定了它们的PARACEST性质。
• Binaphthyl-Based Dicationic Peptoids with Therapeutic Potential
  作者：John B. Bremner、Paul A. Keller、Stephen G. Pyne、Timothy P. Boyle、Zinka Brkic、Dorothy M. David、Adel Garas、Jody Morgan、Mark Robertson、Kittiya Somphol、Michael H. Miller、Adam S. Howe、Paul Ambrose、Sujata Bhavnani、Thomas R. Fritsche、Douglas J. Biedenbach、Ronald N. Jones、Robert W. Buckheit、Karen M. Watson、Dean Baylis、Jonathan A. Coates、John Deadman、Dharshini Jeevarajah、Andrea McCracken、David I. Rhodes

  DOI：10.1002/anie.200904392

  日期：2010.1.12

  Superbugs stalled! Two newly designed synthetic dicationic peptoids (see one example; red O, blue N, green Cl) show promising in vitro bactericidal activity against a range of Gram‐positive pathogens, including organisms resistant to vancomycin, methicillin, and linezolid, with only slow development of resistance. Moreover their potency is maintained in vivo.

  超级细菌陷入僵局！两种新设计的合成药物类肽（见一个例子；红色O，蓝色N，绿色Cl）显示出对多种革兰氏阳性病原体（包括对万古霉素，甲氧西林和利奈唑胺有抗性的生物）的有希望的体外杀菌活性的抵抗力。此外，它们的效力在体内得以维持。
• [EN] FOLATE CONJUGATES OF ALBUMIN-BINDING ENTITIES<br/>[FR] CONJUGUÉS AVEC DES FOLATES D'ENTITÉS DE LIAISON DE L'ALBUMINE
  申请人：MERCK & CIE

  公开号：WO2013024035A1

  公开（公告）日：2013-02-21

  The present invention is directed towards new trifunctional folate-conjugates comprising a folate, an albumin binder and a radionuclide-based therapeutic or diagnostic moiety as well as pharmaceutical compositions thereof, their method of production and their use in diagnostic and therapeutic medical applications, such as diagnostic nuclear imaging and radionuclide therapy.

  本发明涉及新的三官能叶酸结合物，包括叶酸、白蛋白结合剂和基于放射性核素的治疗或诊断部分，以及其药物组合物、制备方法和在诊断和治疗医学应用中的使用，例如诊断核医学成像和放射性核素治疗。