2-[(2-Hydroxy-ethyl)-(3,4-dichloro-benzyl)-amino]-ethanol | 60876-94-0

• 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: 2-[(2-Hydroxy-ethyl)-(3,4-dichloro-benzyl)-amino]-ethanol
• 英文别名: 2-[(2-hydroxyethyl)(3,4-dichlorobenzyl)amino]ethanol；2,2'-(3,4-dichlorobenzylazanediyl)diethanol；3,4-dichlorobenzyl diethanolamine；2-[(2-hydroxy-ethyl)-(3,4-dichlor-benzyl)-amino]-ethanol；2-[(2-hydroxyethyl)-(3,4-dichlorobenzyl)amino]ethanol；2-[(3,4-Dichlorophenyl)methyl-(2-hydroxyethyl)amino]ethanol
• CAS: 60876-94-0
• 化学式: C₁₁H₁₅Cl₂NO₂
• mdl: MFCD00979647
• 分子量: 264.152
• InChiKey: YXYOXGSDQLJFDP-UHFFFAOYSA-N

物化性质

• 沸点：
  190-192 °C(Press: 1 Torr)
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(2-Hydroxy-ethyl)-(3,4-dichloro-benzyl)-amino]-ethanol 在 三溴化磷 、 potassium carbonate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.0h， 生成 N-(3,4-dichlorobenzyl)-N-(2-(5-nitro-1H-imidazol-1-yl)ethyl)-2-(2-berberinoxyethoxy)ethanamine
  参考文献：
  名称：

  Synthesis and bioactive evaluation of novel hybrids of metronidazole and berberine as new type of antimicrobial agents and their transportation behavior by human serum albumin

  摘要：

  A series of novel hybrids of metronidazole and berberine as new type of antimicrobial agents were synthesized and characterized by H-1 NMR, C-13 NMR, IR, MS and FIRMS spectra. Bioactive assay manifested that most of the prepared compounds exhibited effective antibacterial and antifungal activities and some showed comparable or superior potency against Methicillin-resistant Staphylococcus aureus to reference drugs Norfloxacin, Chloromycin and Berberine. The transportation behavior of human serum albumin (HSA) to the highly active compound 5g was evaluated and revealed that the association of imidazole derivative 5g with HSA was spontaneous and the electrostatic interactions played important roles in the transportation of HSA to 5g. The calculated parameters indicated that compound 5g could be effectively stored and carried by HSA. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.007
• 作为产物：
  描述：

  3,4-二氯氯苄 、 二乙醇胺 以 乙腈 为溶剂， 生成 2-[(2-Hydroxy-ethyl)-(3,4-dichloro-benzyl)-amino]-ethanol
  参考文献：
  名称：

  新型胺衍生双唑类化合物的合成及其生物活性

  摘要：

  通过对氟康唑的系统结构修饰，设计了一系列新颖的胺衍生双唑化合物，并通过便捷有效的方法进行了合成，并在体外评估了所有制备的化合物对六种代表性细菌菌株和两种真菌菌株的抗菌活性。。生物活性结果表明，与参考药物相比，某些合成的化合物表现出中等甚至更好的活性。特别是，双咪唑5b及其盐类对包括MRSA在内的所有测试细菌菌株均具有显着的抗菌作用，而双三唑4b – c及其相应的盐类对白色念珠菌具有更好的活性。，变形杆菌比标准药物氟康唑和诺氟沙星分别高。出乎意料的是，双溴化物3a – f对所有测试的微生物菌株均表现出出色的活性。

  DOI：

  10.1016/j.ejmech.2010.06.012

文献信息

• N-hydroxy-2-(Alkyl,Aryl or Heteroaryl sulfanyl, sulfinyl or sulfonyl) 3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors
  申请人：American Cyanamid Company

  公开号：US06342508B1

  公开（公告）日：2002-01-29

  Matrix metalloproteinases (MMps) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by the formula where R1, R2, R3 and R4 are described herein.

  翻译结果如下： 基质金属蛋白酶（MMps）是一组与连接组织和基底膜病理破坏有关的酶。这些含有锌的内切肽酶包括几个酶亚组，如胶原酶、溶素和明胶酶。肿瘤坏死因子-α转化酶（TACE），一种促炎症细胞因子，催化膜结合的肿瘤坏死因子-α前体蛋白形成肿瘤坏死因子-α。因此，人们预期基质金属蛋白酶（MMPs）和TACE的小分子抑制剂可能具有治疗多种疾病状态的前景。本发明提供了低分子量、非肽类的基质金属蛋白酶（MMPs）和肿瘤坏死因子-α转化酶（TACE）的抑制剂，用于治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周病、骨病、糖尿病（胰岛素抵抗）和HIV感染。本发明中的化合物由以下公式表示： 其中R1、R2、R3和R4在本说明书中有所描述。
• Berberine azoles as antimicrobial agents: synthesis, biological evaluation and their interactions with human serum albumin
  作者：Shao-Lin Zhang、Juan-Juan Chang、Guri L. V. Damu、Rong-Xia Geng、Cheng-He Zhou

  DOI：10.1039/c3md00032j

  日期：——

  A series of berberine azoles was synthesized and characterized by NMR, IR, MS and HRMS spectroscopy. All the newly prepared compounds were screened for their antimicrobial activities. Bioactivity assays manifested that most of the berberine azoles exhibited good antimicrobial activities. Especially compound 7a displayed remarkable anti-Proteus vulgaris and anti-Candida mycoderma efficacies, which were comparable to or even better than for the reference drugs. The binding behavior of compound 7a to human serum albumin (HSA) revealed that hydrophobic interactions and hydrogen bonds play important roles in the association of compound 7a with HSA. Molecular docking experiments showed that compound 7a has moderate affinity to HSA, and the theoretical calculations were in accordance with the experimental results.

  合成并表征了一系列小檗碱噁唑化合物，采用了核磁共振（NMR）、红外光谱（IR）、质谱（MS）和高分辨率质谱（HRMS）等技术。对所有新制备的化合物进行了抗菌活性筛选。生物活性实验表明，大多数小檗碱噁唑化合物表现出良好的抗菌活性。特别是化合物7a在抑制变形杆菌和抗念珠菌微球菌方面显示出显著效果，其活性与参考药物相当甚至更好。化合物7a与人血清白蛋白（HSA）的结合行为表明，疏水作用和氢键在化合物7a与HSA的结合中起着重要作用。分子对接实验表明，化合物7a对HSA具有适度亲和力，而且理论计算结果与实验结果一致。
• [EN] N-HYDROXY-2-(ALKYL, ARYL, OR HETEROARYL SULFANYL, SULFINYL OR SULFONYL)-3-SUBSTITUTED-ALKYL, ARYL OR HETEROARYLAMIDES AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] ALKYLE, ARYLE OU HETEROARYLAMIDES N-HYDROXY-2-(ALKYL, ARYL OU HETEROARYL SULFANYL, SULFINYL OU SULFONYL)-3-SUBSTITUES EN TANT QU'INHIBITEURS DE LA METALLOPROTEINASE MATRICIELLE
  申请人：AMERICAN CYANAMID COMPANY

  公开号：WO1999042436A1

  公开（公告）日：1999-08-26

  (EN) Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-$g(a) converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-$g(a) from membrane bound TNF-$g(a) precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-$g(a) converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection having formula (I), wherein R2 and R3 form a heterocyclic ring and A is S, S(O), or S(O)2 and R1 and R4 are defined herein.(FR) L'invention concerne les métalloprotéinases matricielles (MMP) qui sont un groupe d'enzymes impliquées dans la destruction pathologique d'un tissu conjonctif et d'une membrane basale. Ces endopeptidases contenant du zinc sont formée de différents sous-ensembles d'enzymes comprenant des collagénases, des stomélysines et des gélatinases. L'enzyme de conversion TNF-$g(a) (TACE), une cytokine pro-inflammatoire, catalyse la formation de TNF-$g(a) à partir d'une membrane liée à la protéine précurseur TNF-$g(a). On pense que de petits inhibiteurs de molécules de MMP et TACE sont en mesure de traiter un certain nombre de pathologies. L'invention concerne en outre des inhibiteurs non peptidiques à faible poids moléculaire de métalloprotéinases matricielles (MMP) et d'une enzyme de conversion TNF-$g(a) (TACE) pour le traitement de l'arthrite, de métastases tumorales, d'ulcération tissulaire, de subérification d'une blessure anormale, de parodontopathie, de maladies osseuses, du diabète (résistance insulinique) de l'infection par VIH de formule (I), dans laquelle R2 et R3 désignent un noyau hétérocyclique et A désigne S, S(O) ou S(O)2 et R1 et R4 sont tels que définis.

  基质金属蛋白酶（MMPs）是一组酶，已被认为参与了结缔组织和基底膜的病理性破坏。这些含锌的内切酶包括几个亚组酶，包括胶原酶、基质金属蛋白酶和明胶酶。TNF-$g(a)转化酶（TACE）是一种促炎细胞因子，催化膜结合型TNF-$g(a)前体蛋白形成TNF-$g(a)。因此，MMPs和TACE的小分子抑制剂具有治疗多种疾病的潜力。本发明提供了低分子量、非肽类基质金属蛋白酶（MMPs）和TNF-$g(a)转化酶（TACE）的抑制剂，用于治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周病、骨病、糖尿病（胰岛素抵抗）和HIV感染，其化学式为（I），其中R2和R3形成杂环环，A为S、S（O）或S（O）2，R1和R4如本文所定义。
• [EN] N-HYDROXY-2-(ALKYL, ARYL, OR HETEROARYL SULFANYL, SULFINYL OR SULFONYL)-3-SUBSTITUTED ALKYL, ARYL OR HETEROARYLAMIDES AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] N-HYDROXY-2-(ALKYL,ARYL OU HETEROARYL SULFANYL, SULFINYL OU SULFONYL)-ALKYL, ARYL OU HETEROARYLAMIDES SUBSTITUES EN POSITION 3, UTILISES COMME INHIBITEURS DES METALLOPROTEINASE MATRICIELLE
  申请人：AMERICAN CYANAMID COMPANY

  公开号：WO1998038163A1

  公开（公告）日：1998-09-03

  (EN) Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-$g(a) converting enzymes (TACE), a pro-inflammatory cytokine, catalyze the formation of TNF-$g(a) from membrane-bound TNF-$g(a) precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-$g(a) converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by formula (I), where R1, R2, R3 and R4 are described herein.(FR) Les métalloprotéinases matricielles (MMP) sont un groupe d'enzymes ayant été impliquées dans la destruction pathologique de la membrane basale et du tissu conjonctif. Ces endopeptidases contenant du zinc consistent en plusieurs sous-ensembles d'enzymes comprenant des collagénases, des stromélysines et des gélatinases. L'enzyme de conversion de TNF-$g(a) (TACE), une cytokine pro-inflammatoire, catalyse la formation de TNF-$g(a) à partir de la protéine précurseur de TNF-$g(a) liée à la membrane. On suppose que les inhibiteurs à petites molécules de MMP et TACE ont donc la capacité de traiter plusieurs états pathologiques. L'invention se rapporte à des inhibiteurs de non peptides, à faible poids moléculaire, des métalloprotéinases matricielles (MMP) et à l'enzyme de conversion TNF-$g(a) (TACE) pour le traitement de l'arthrite, de métastases tumorales, de l'ulcération de tissu, de cicatrisation anormale, de la parodontopathie, les maladies osseuses, de diabètes (résistance à l'insuline) et de l'infection au VIH. Les composés de l'invention sont représentés par la formule (I), R1, R2, R3 et R4 étant décrits.

  基质金属蛋白酶（MMP）是一组酶，已被认为参与了结缔组织和基底膜的病理性破坏。这些含锌的内切酶由几个亚组成，包括胶原酶、基质金属蛋白酶和明胶酶。TNF-$g(a)转化酶（TACE）是一种促炎细胞因子，可催化膜结合型TNF-$g(a)前体蛋白形成TNF-$g(a)。因此，MMP和TACE的小分子抑制剂有望治疗多种疾病。本发明提供了用于治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周病、骨病、糖尿病（胰岛素抵抗）和HIV感染的基质金属蛋白酶（MMP）和TNF-$g(a)转化酶（TACE）的低分子量非肽抑制剂。本发明的化合物由公式（I）表示，其中R1、R2、R3和R4如本文所述。
• N-hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl, or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors
  申请人：American Cyanamid Company

  公开号：US20020188120A1

  公开（公告）日：2002-12-12

  Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection having the formula 1 wherein R 2 and R 3 form a heterocyclic ring and A is S, S(O), or S(O)2, and R 1 and R 4 are defined herein.

  基质金属蛋白酶（MMPs）是一组酶，已被认为与结缔组织和基底膜的病理性破坏有关。这些含锌内切酶包括几个酶亚组，包括胶原酶、基质金属蛋白酶和明胶酶。TNF-α转化酶（TACE）是一种促炎细胞因子，催化膜结合的TNF-α前体蛋白形成TNF-α。因此，MMPs和TACE的小分子抑制剂有潜力用于治疗多种疾病状态。本发明提供了基质金属蛋白酶（MMPs）和TNF-α转化酶（TACE）的低分子量、非肽抑制剂，用于治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周病、骨病、糖尿病（胰岛素抵抗）和HIV感染，其化学式为1，其中R2和R3形成杂环环，A为S、S（O）或S（O）2，R1和R4如本文所定义。