4-(4-but-2-ynyloxybenzenesulfonyl)-1-(4-chlorobenzyl)piperidine-4-carboxylic acid ethyl ester | 287201-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-but-2-ynyloxybenzenesulfonyl)-1-(4-chlorobenzyl)piperidine-4-carboxylic acid ethyl ester
• 英文别名: 4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-chloro-benzyl)-piperidine-4-carboxylic acid ethyl ester；4-(4-but-2-ynyloxy-benzenesulfonyl)-1-(4-chloro-benzyl)-piperdine-4-carboxylic acid ethyl ester；ethyl 4-(4-but-2-ynoxyphenyl)sulfonyl-1-[(4-chlorophenyl)methyl]piperidine-4-carboxylate
• CAS: 287201-57-4
• 化学式: C₂₅H₂₈ClNO₅S
• 分子量: 490.02
• InChiKey: MUXFBJMGSUDRRK-UHFFFAOYSA-N

物化性质

• 熔点：
  91.8 °C(Solv: methanol (67-56-1))
• 沸点：
  631.8±55.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-but-2-ynyloxybenzenesulfonyl)-1-(4-chlorobenzyl)piperidine-4-carboxylic acid ethyl ester 以 tetrahydrofuran methanol 、 sodium hydroxide 为溶剂， 生成 4-(4-but-2-ynyloxybenzenesulfonyl)-1-(4-chlorobenzyl)piperidine-4-carboxylic acid
  参考文献：
  名称：

  Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/TACE inhibitors

  摘要：

  该式的化合物：1在治疗关节炎、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感染方面有用。

  公开号：

  US20040229924A1
• 作为产物：
  描述：

  ethyl 2-((4-hydroxyphenyl)thio)acetate 在 Oxone 、 18-冠醚-6 、 四丁基溴化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 16.0h， 生成 4-(4-but-2-ynyloxybenzenesulfonyl)-1-(4-chlorobenzyl)piperidine-4-carboxylic 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

• Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors
  申请人：American Cyanamid Company

  公开号：US06358980B1

  公开（公告）日：2002-03-19

  Compounds of the formula: useful in the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

  该式化合物有助于治疗关节炎、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。
• ALKYNYL CONTAINING HYDROXAMIC ACID DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MATRIX METALLOPROTEINASE (MMP) INHIBITORS / TNF-ALPHA CONVERTING ENZYME (TACE) INHIBITORS
  申请人：Wyeth Holdings Corporation

  公开号：EP1147085B1

  公开（公告）日：2005-11-16
• US6358980B1
  申请人：——

  公开号：US6358980B1

  公开（公告）日：2002-03-19
• US6753337B2
  申请人：——

  公开号：US6753337B2

  公开（公告）日：2004-06-22
• [EN] ALKYNYL CONTAINING HYDROXAMIC ACID DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MATRIX METALLOPROTEINASE (MMP) INHIBITORS/TNF-ALPHA CONVERTING ENZYME (TACE) INHIBITORS<br/>[FR] DERIVES D'ACIDE HYDROXAMIQUE ALKYNYLES, LEUR ELABORATION ET LEUR UTILISATION COMME INHIBITEURS DES METALLOPROTEINASES MATRICES OU INHIBITEURS DES TACE (ENZYMES DE CONVERSION DU FACTEUR DE NECROSE TUMORALE ALPHA)
  申请人：AMERICAN CYANAMID CO

  公开号：WO2000044723A1

  公开（公告）日：2000-08-03

  Compounds of formula (I) wherein R1 is hydrogen, aryl, heteroaryl, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, or -C4-C8-cycloheteroalkyl; R2 and R3 are hydrogen, alkyl of 1-6 carbon atoms, -CN, or CCH; R8, R9, R10 and R11 are hydrogen, aryl or heteroaryl, cycloalkyl of 3-6 carbon atoms, -C4-C8-cycloheteroalkyl, alkyl of 1-18 carbon atoms, alkenyl of 2-18 carbon atoms, alkynyl of 2-18 carbon atoms; with the proviso that one of the pairs R8 and R9, R9 and R10 or R10 and R11, together with the carbon atom or atoms to which they are attached, form a cycloalkyl ring of 3-6 carbon atoms, or a -C4-C8-cycloheteroalkyl ring; R12 is hydrogen, aryl or heteroaryl, cycloalkyl of 3-6 carbon atoms; -C4-C8-cycloheteroalkyl, or alkyl of 1-6 carbon atoms; A, X are O, S, SO, SO2, NR7, or CH2; Y is aryl or heteroaryl, with the proviso that A and X are not bonded to adjacent atoms of Y; and n is 0-2; or a pharmaceutically acceptable salt thereof; useful in the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.