((R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-hydroxyhexyl)carbamic acid tert-butyl ester | 406233-46-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: ((R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-hydroxyhexyl)carbamic acid tert-butyl ester
• 英文别名: (9H-fluoren-9-yl)methyl ((R)-N⁶-(tert-butoxycarbonyl)-6-amino-1-hydroxyhexan-2-yl)carbamate；tert-butyl N-((5R)-5-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)-6-hydroxyhexyl) carbamate；Tert-butyl n-((5r)-5-(((9h-fluoren-9-ylmethoxy)carbonyl)amino)-6-hydroxyhexyl)carbamate；tert-butyl N-[(5R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-hydroxyhexyl]carbamate
• CAS: 406233-46-3
• 化学式: C₂₆H₃₄N₂O₅
• 分子量: 454.566
• InChiKey: CQPCXWDXTZJRSX-GOSISDBHSA-N

物化性质

• 沸点：
  658.6±55.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  96.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ((R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-hydroxyhexyl)carbamic acid tert-butyl ester 在 三丁基膦 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 30.0h， 生成 ((R)-5-(2-nitro-4-sulfamoylphenylamino)-6-phenylsulfanylhexyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of Antagonists of B-Cell Lymphoma 2 Family Proteins with Chemopotentiation Activity in Vitro and in Vivo

  摘要：

  Development of a rationally designed potentiator of cancer chemotherapy, via inhibition of Bcl-X-L function, is described. Lead compounds generated by NMR screening and directed parallel synthesis displayed sub mu M binding but were strongly deactivated in the presence of serum. The dominant component of serum deactivation was identified as domain III of human serum albumin (HSA); NMR solution structures of inhibitors bound to both Bcl-X-L and HSA domain III indicated two potential optimization sites for separation of affinities. Modifications at both sites resulted in compounds with improved Bcl-X-L binding and greatly increased activity in the presence of human serum, culminating in 73R, which bound to Bcl-X-L with a K-i of 0.8 nM. In a cellular assay 73R reversed the protection afforded by Bcl-X-L overexpression against cytokine deprivation in FL5.12 cells with an EC50 of 0.47 mu M. 73R showed little effect on the viability of the human non small cell lung cancer cell line A549. However, consistent with the proposed mechanism, 73R potentiated the activity of paclitaxel and UV irradiation in vitro and potentiated the antitumor efficacy of paclitaxel in a mouse xenograft model.

  DOI：

  10.1021/jm050754u
• 作为产物：
  描述：

  N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-D-赖氨酸 在 N-甲基吗啉 、 氯甲酸异丁酯 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.5h， 生成 ((R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-hydroxyhexyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Urea based foldamers

  摘要：

  DOI：

  10.1016/bs.mie.2021.04.019

文献信息

• N-acylsulfonamide apoptosis promoters
  申请人：——

  公开号：US20020055631A1

  公开（公告）日：2002-05-09

  N-Benzoyl arylsulfonamides having the formula 1 are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

  N-苯甲酰芳基磺胺酰胺具有以下化学式，是BCL-Xl抑制剂，有助于促进细胞凋亡。还公开了BCL-Xl抑制组合物和在哺乳动物中促进细胞凋亡的方法。
• N-Acylsulfonamide apoptosis promoters
  申请人：——

  公开号：US20020086887A1

  公开（公告）日：2002-07-04

  N-Benzoyl arylsulfonamides having the formula 1 Are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.

  N-苯甲酰芳基磺胺酰胺具有以下化学式，是BCL-X1抑制剂，有助于促进细胞凋亡。还公开了BCL-X1抑制组合物和在哺乳动物中促进细胞凋亡的方法。
• Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles targeting Clostridioides (Clostridium) difficile: Synthesis, antibacterial evaluation and an in vivo C. difficile infection model
  作者：Andrew J. Tague、Papanin Putsathit、Melanie L. Hutton、Katherine A. Hammer、Steven M. Wales、Daniel R. Knight、Thomas V. Riley、Dena Lyras、Paul A. Keller、Stephen G. Pyne

  DOI：10.1016/j.ejmech.2019.02.068

  日期：2019.5

  treatments for C. difficile infection with improved efficacy are urgently needed. A streamlined synthetic pathway was developed to allow access to 38 novel mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics with increased synthetic efficiency, aqueous solubility and enhanced antibacterial efficacy. The monocationic arginine derivative 28 was identified as a potent, Gram-positive selective antibacterial

  Clostridioides（原梭菌）艰难是革兰氏阳性厌氧细菌病原体引起严重的胃肠道感染人类。当前的化学治疗方案非常不足，昂贵且有限。这导致了巨大的医疗和财务负担。迫切需要新的，廉价的，对艰难梭菌感染进行化学治疗的方法，以提高疗效。开发了一种简化的合成途径，以允许获得38种新颖的单和双阳离子联芳基1,2,3-三唑基肽模拟物，具有提高的合成效率，水溶性和增强的抗菌功效。单阳离子精氨酸衍生物28被鉴定为有效的革兰氏阳性选择性抗菌剂，对耐甲氧西林的金黄色葡萄球菌的MIC值为4μg/ mL，对艰难梭菌的MIC值为8μg/ mL 。此外，发现双效三唑类似物50具有广谱活性，并且对鲍曼不动杆菌（8μg/ mL），铜绿假单胞菌（8μg/ mL）和肺炎克雷伯菌（16μg/ mL）具有显着的革兰氏阴性功效。; 此外，化合物50在体外的溶血活性降低（<13％）溶血分析。在选定的衍生物上进行膜破坏试验，以确认合
• Positional Isomers of Biphenyl Antimicrobial Peptidomimetic Amphiphiles
  作者：Andrew J. Tague、Papanin Putsathit、Thomas V. Riley、Paul A. Keller、Stephen G. Pyne

  DOI：10.1021/acsmedchemlett.0c00611

  日期：2021.3.11

  efficacy and selectivity, positional isomers of the lead biphenyl antimicrobial peptidomimetic compound 1 were synthesized and subjected to microbial growth inhibition and mammalian toxicity assays. Positional isomer 4 exhibited 4–8× increased efficacy against the pathogenic Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli (MIC = 2 μg/mL), while isomers 2, 3, and 7 exhibited a 4×

  小分子抗菌拟肽两亲物代表了一类有前途的新型抗菌药物，具有广泛治疗应用的潜力。为了研究关键疏水基团和亲水基团的空间定位对抗菌功效和选择性的作用，合成了先导联苯抗菌拟肽化合物1的位置异构体，并进行了微生物生长抑制和哺乳动物毒性测定。位置异构体4对致病性革兰氏阴性菌铜绿假单胞菌和大肠杆菌(MIC = 2 μg/mL)的功效提高了 4-8 倍，而异构体2、3和7对鲍曼不动杆菌的活性提高了 4 倍（ MIC = 4 微克/毫升）。分子形状的变化对革兰氏阴性细菌的抗菌功效和由此产生的活性谱有显着影响，而所有结构异构体对革兰氏阳性细菌病原体（例如耐甲氧西林细菌）均表现出显着的功效（MIC = 0.25–8μg/mL）金黄色葡萄球菌、肺炎链球菌和粪肠球菌）。
• N-ACYLSULFONAMIDE APOPTOSIS PROMOTERS
  申请人：Augeri David J.

  公开号：US20090137585A1

  公开（公告）日：2009-05-28

  N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

  具有以下式子的N-苯甲酰基芳基磺酰胺是BCL-Xl抑制剂，有助于促进细胞凋亡。本文还披露了BCL-Xl抑制剂组合物和在哺乳动物中促进细胞凋亡的方法。