2-(4-methoxy-benzenesulfonyl)-octanoic acid ethyl ester | 212769-55-6

• 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-(4-methoxy-benzenesulfonyl)-octanoic acid ethyl ester
• 英文别名: 2-(4-methoxy-phenylsulfonyl)-octanoic acid ethyl ester；Ethyl 2-(4-methoxyphenyl)sulfonyloctanoate
• CAS: 212769-55-6
• 化学式: C₁₇H₂₆O₅S
• 分子量: 342.456
• InChiKey: RYUMOQZQWYMLME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-methoxy-benzenesulfonyl)-octanoic acid ethyl ester 在 sodium hydroxide 、 草酰氯 、 盐酸羟胺 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 2-(4-Methoxy-benzenesulfonyl)-octanoic acid hydroxyamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors

  摘要：

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.

  DOI：

  10.1021/jm040086x
• 作为产物：
  描述：

  2-溴辛酸乙酯 在 Oxone 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 6.0h， 生成 2-(4-methoxy-benzenesulfonyl)-octanoic acid ethyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors

  摘要：

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.

  DOI：

  10.1021/jm040086x

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。
• N-hdroxy-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：US06197791B1

  公开（公告）日：2001-03-06

  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 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.

  基质金属蛋白酶（MMPs）是一组酶，已被指责参与病理性破坏结缔组织和基底膜。这些含锌的内肽酶包括几种酶亚型，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，催化将膜结合的TNF-α前体蛋白转化为TNF-α。预计MMPs和TACE的小分子抑制剂有望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、非肽类抑制剂，用于治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周疾病、骨病、糖尿病（胰岛素抵抗）和HIV感染，其化学式为R2和R3形成杂环环，A为S、S(O)或S(O)2，R1和R4在此处定义。
• [EN] N-HYDROXY-2-(ALKYL, ARYL, OR HETEROARYL SULFANYL, SULFINYL OR SULFONYL)-3-SUBSTITUTED-ALKYL, ARYL OR HETEROARYLAMIDES AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] 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。