methyl (2R)-6-{[(tert-butoxy)carbonyl]amino}-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoate | 172846-57-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: methyl (2R)-6-{[(tert-butoxy)carbonyl]amino}-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoate
• 英文别名: methyl (2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
• CAS: 172846-57-0
• 化学式: C₂₇H₃₄N₂O₆
• 分子量: 482.577
• InChiKey: CWFPAKDWGRPOSF-HSZRJFAPSA-N

物化性质

• 沸点：
  653.7±55.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2R)-6-{[(tert-butoxy)carbonyl]amino}-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoate 在 哌啶 、 偶氮二甲酸二异丙酯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 7.5h， 生成 dibenzyl (2R)-7,7'-(1,1'-binaphthyl-2,2'-bisoxy)-2,2'-dibutylamino-3,3'-diaza-4,4'-dioxodiheptanoate dihydrochloride
  参考文献：
  名称：

  Synthesis and antibacterial activity of C2-symmetric binaphthyl scaffolded amino acid derivatives

  摘要：

  The synthesis of eleven novel antibacterial agents is reported. The structures are based on a C-2-symmetric binaphthyl scaffold which holds two identical chains consisting of a short linker, a basic amino acid and a small hydrophobic side chain. Antibacterial activity is revealed for a number of derivatives down to an MIC of 2 mu g/mL (2 mu M) against Staphylococcus aureus - comparable to vancomycin, and an MIC of 31 mu g/mL (31 mu M) against some vancomycin-resistant enterococcal strains. Crown Copyright (C) 2011 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.024
• 作为产物：
  描述：

  N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-D-赖氨酸 、 三甲基硅烷化重氮甲烷 以 甲醇 、 正己烷 为溶剂， 反应 3.0h， 以73%的产率得到methyl (2R)-6-{[(tert-butoxy)carbonyl]amino}-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoate
  参考文献：
  名称：

  反原生动物Barnesin衍生物的模块化固相合成。

  摘要：

  在这里，我们应用并优化了基于固体支持物（SP）的Horner-Wadsworth-Emmons试剂，以制备与SP结合的乙烯基氨基酸。随后的基于SP的肽合成，整体脱保护和化学修饰产生了14种带有乙烯基氨基酸的脂肽，包括天然产物Barnesin A（1）。生物学评估表明，几种合成的衍生物对木瓜蛋白酶样半胱氨酸蛋白酶，人组织蛋白酶L和罗德萨因表现出微摩尔至纳摩尔的抑制活性。

  DOI：

  10.1021/acs.orglett.0c00723

文献信息

• De novo Design of SARS-CoV-2 Main Protease Inhibitors
  作者：Nynke A. Vepřek、Zisis Peitsinis、Yingkai Zhang、Dirk Trauner、Christian Fischer、Klaus-Peter Rühmann、Chao Yang、Jessica N. Spradlin、Dustin Dovala、Daniel K. Nomura

  DOI：10.1055/a-1582-0243

  日期：2022.3

  conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.

  COVID-19 大流行促使许多科学家研究针对 SARS-CoV-2 和未来可能出现的相关病毒的治疗方法。作为病毒的主要蛋白酶 MPro 在冠状病毒中高度保守，因此它已成为开发抑制剂的主要目标。通过结合虚拟筛选和分子建模，我们鉴定了易于获取且可以快速多样化的小分子。生化测定证实一类吡啶酮是病毒主要蛋白酶的低微摩尔非共价抑制剂。
• PEPTOID COMPOUNDS
  申请人：Bremner John

  公开号：US20100167995A1

  公开（公告）日：2010-07-01

  The invention relates to new peptoid compounds of formula (I), as well as their use in the treatment of bacterial infections, such as those caused by vancomycin resistant microorganisms, and to compositions thereof.

  本发明涉及公式（I）的新肽酰胺化合物，以及它们在治疗细菌感染方面的用途，例如由万古霉素耐药微生物引起的感染，以及它们的组成物。
• Peptoid compounds
  申请人：UNIVERSITY OF WOLLONGONG

  公开号：EP2343285A2

  公开（公告）日：2011-07-13

  A compound of the formula (I): wherein A is an aromatic or heteroaromatic ring system or partially or fully reduced derivatives thereof; Q is hydrogen, C1-C12 straight chain, branched or cyclic alkyl substituted with one or more hydroxy groups, or a mono- or di-saccharide moiety; Z is -CR10R11-, -NR12-, -C(O)O-, -C(O)NR12- or -O-, where R10 and R11 are independently selected from hydrogen, hydroxy, C1-C6 alkyl, C6-C10 aryl, C1-C6 alkoxy and -N(R13)2 and where each R13 is independently selected from hydrogen and C1-C6 alkyl, and where R12 is selected from hydrogen and C1-C6 alkyl; R1 is selected from hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, -NR(R13)2 and -N(R12)-COR14; where R12 and R13 are as defined above, and where R14 is selected from hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy and -NR12; R2 is selected from hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, -N(R13)2 and -N(R12)-COCHR2aR2b; where R2a and R2b are selected from hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, -N(R13)2 and -N(R12)-COR14; where R12 , R13 and R14 are as defined above; R3, R4 and R5 are independently selected from hydrogen, C1-C6 alkyl and α side chains of α-amino acids or their enantiomers or their derivatives; R6 is -CO2R15, -CONHR16, -CONHOR16, -CONHNHR16, -SO2N(R16)2, -SO2R17 or -P(O)(OR18)(OR18) where each R15, R16, R17 and R18 is independently selected from hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C6-C10 aryl and C7-C10 arylalkyl; B is an α-amino acid residue, a β-amino acid residue or an α,α-disubstituted amino acid residue, such residue forming amide linkages with the adjacent molecules; W is -O- or CR10R11 where R10 and R11 are as defined above; Y is an optionally substituted amino group, a moiety containing an optionally substituted amino group or a salt thereof: ------ is a single or double bond; R7 and R8a are hydrogen or are absent if ------ is a double bond; and R8b and R9 are hydrogen, and X is selected from (CR10R11)u, -(CR10R11)u-CH=CH-, -NR12(CR10R11)u-, -(CR10R11)uNR12-, -O(CR10R11)u-, -(CR10R11)uO- or -O(CR10R11)CH=CH- where R10, R11 and R12 are as defined above; or R8b and R9 together form a covalent bond between X and the carbon to which R8b is attached, and X is selected from (CR10R11)x, -NR12(CR10R11)x-, -(CR10R11)xNR12-, -O(CR10R11)x- or -(CR10R11)xO-, where R10, R11 and R12 are as defined above; n, m, r and t are independently selected from 0 or 1; s is an integer selected from 0 to 3; p is an integer selected from 0 to 6, provided that when W is -O-, p is at least 1; and u, x and q are independently selected from 0 to 4; and salts and pharmaceutically acceptable derivatives thereof. The compound of formula (I) are useful in the treatment of bacterial infections.

  式 (I) 的化合物： 其中 A 是芳香族或杂芳环系或其部分或全部还原衍生物； Q 是氢、被一个或多个羟基取代的 C1-C12 直链、支链或环状烷基或单糖或二糖分子； Z是-CR10R11-、-NR12-、-C(O)O-、-C(O)NR12-或-O-，其中R10和R11独立选自氢、羟基、C1-C6烷基、C6-C10芳基、C1-C6烷氧基和-N(R13)2，每个R13独立选自氢和C1-C6烷基，R12选自氢和C1-C6烷基；R1 选自氢、羟基、C1-C6 烷基、C1-C6 烷氧基、-NR(R13)2 和-N(R12)-COR14；其中 R12 和 R13 如上定义，R14 选自氢、羟基、C1-C6 烷基、C1-C6 烷氧基和-NR12； R2 选自氢、羟基、C1-C6 烷基、C1-C6 烷氧基、-N(R13)2 和 -N(R12)-COCHR2aR2b；其中 R2a 和 R2b 选自氢、羟基、C1-C6 烷基、C1-C6 烷氧基、-N(R13)2 和 -N(R12)-COR14；其中 R12、R13 和 R14 如上定义； R3、R4 和 R5 独立选自氢、C1-C6 烷基和 α- 氨基酸或其对映体或其衍生物的 α 侧链； R6 是-CO2R15、-CONHR16、-CONHOR16、-CONHNHR16、-SO2N(R16)2、-SO2R17 或-P(O)(OR18)(OR18)，其中每个 R15、R16、R17 和 R18 独立选自氢、C1-C6 烷基、C3-C7 环烷基、C6-C10 芳基和 C7-C10 芳烷基； B 是 α-氨基酸残基、β-氨基酸残基或 α,α-二取代氨基酸残基，此类残基与相邻分子形成酰胺连接； W 是-O-或 CR10R11，其中 R10 和 R11 如上文所定义； Y 是任选取代的氨基、含有任选取代的氨基的分子或其盐： ------ 是单键或双键； R7 和 R8a 是氢，如果 ------ 是双键，则不含 R7 和 R8a；以及 R8b和R9为氢，X选自(CR10R11)u、-(CR10R11)u-CH=CH-、-NR12(CR10R11)u-、-(CR10R11)uNR12-、-O(CR10R11)u-、-(CR10R11)uO-或-O(CR10R11)CH=CH-，其中R10、R11和R12如上定义；或 R8b 和 R9 一起在 X 和 R8b 所连接的碳之间形成共价键，且 X 选自 (CR10R11)x、-NR12(CR10R11)x-、-(CR10R11)xNR12-、-O(CR10R11)x- 或 -(CR10R11)xO-，其中 R10、R11 和 R12 如上文所定义； n、m、r 和 t 分别独立地选自 0 或 1； s 是选自 0 到 3 的整数； p 是选自 0 至 6 的整数，条件是当 W 为-O-时，p 至少为 1；以及 u、x 和 q 独立选自 0 至 4； 及其盐类和药学上可接受的衍生物。 式（I）化合物可用于治疗细菌感染。
• Synthesis and antibacterial activity of C2-symmetric binaphthyl scaffolded amino acid derivatives
  作者：Mark Robertson、John B. Bremner、Jonathan Coates、John Deadman、Paul A. Keller、Stephen G. Pyne、Kittiya Somphol、David I. Rhodes

  DOI：10.1016/j.ejmech.2011.06.024

  日期：2011.9

  The synthesis of eleven novel antibacterial agents is reported. The structures are based on a C-2-symmetric binaphthyl scaffold which holds two identical chains consisting of a short linker, a basic amino acid and a small hydrophobic side chain. Antibacterial activity is revealed for a number of derivatives down to an MIC of 2 mu g/mL (2 mu M) against Staphylococcus aureus - comparable to vancomycin, and an MIC of 31 mu g/mL (31 mu M) against some vancomycin-resistant enterococcal strains. Crown Copyright (C) 2011 Published by Elsevier Masson SAS. All rights reserved.
• Modular Solid-Phase Synthesis of Antiprotozoal Barnesin Derivatives
  作者：Dávid Roman、Luka Raguž、François Keiff、Florian Meyer、Fabian Barthels、Tanja Schirmeister、Florian Kloss、Christine Beemelmanns

  DOI：10.1021/acs.orglett.0c00723

  日期：2020.5.15

  ons reagent to prepare SP-bound vinylogous amino acids. Subsequent SP-based peptide synthesis, global deprotection, and chemical modifications yielded 14 lipodipeptides carrying vinylogous amino acids, including the natural product barnesin A (1). Biological evaluation revealed that several synthesized derivatives show micromolar to nanomolar inhibitory activity against papain-like cysteine proteases

  在这里，我们应用并优化了基于固体支持物（SP）的Horner-Wadsworth-Emmons试剂，以制备与SP结合的乙烯基氨基酸。随后的基于SP的肽合成，整体脱保护和化学修饰产生了14种带有乙烯基氨基酸的脂肽，包括天然产物Barnesin A（1）。生物学评估表明，几种合成的衍生物对木瓜蛋白酶样半胱氨酸蛋白酶，人组织蛋白酶L和罗德萨因表现出微摩尔至纳摩尔的抑制活性。