1-(4-bromobenzyl)-4-[4-(4-morpholin-4-ylbut-2-ynyloxy)benzenesulfonyl]piperidine-4-carboxylic acid ethyl ester | 287201-92-7

• 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: 1-(4-bromobenzyl)-4-[4-(4-morpholin-4-ylbut-2-ynyloxy)benzenesulfonyl]piperidine-4-carboxylic acid ethyl ester
• 英文别名: 1-(4-bromo-benzyl)-4-[4-(4-morpholin-4-yl-but-2-ynyloxy)-benzenesulfonyl]-piperidine-4-carboxylic acid ethyl ester；ethyl 1-[(4-bromophenyl)methyl]-4-[4-(4-morpholin-4-ylbut-2-ynoxy)phenyl]sulfonylpiperidine-4-carboxylate
• CAS: 287201-92-7
• 化学式: C₂₉H₃₅BrN₂O₆S
• 分子量: 619.577
• InChiKey: IVRMUZYEBPFGFP-UHFFFAOYSA-N

物化性质

• 沸点：
  726.0±60.0 °C(Predicted)
• 密度：
  1.367±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  93.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(4-bromobenzyl)-4-[4-(4-morpholin-4-ylbut-2-ynyloxy)benzenesulfonyl]piperidine-4-carboxylic 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 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 1-(4-bromobenzyl)-4-[4-(4-morpholin-4-ylbut-2-ynyloxy)benzenesulfonyl]piperidine-4-carboxylic acid hydroxamide hydrochloride
  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：

  (4-bromo-benzyl)-bis-(2-chloro-ethyl)-amine 在 18-冠醚-6 、 四丁基溴化铵 、 potassium carbonate 、 溶剂黄146 、 copper(l) chloride 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 反应 25.0h， 生成 1-(4-bromobenzyl)-4-[4-(4-morpholin-4-ylbut-2-ynyloxy)benzenesulfonyl]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 compounds as matrix metalloproteinase/TACE inhibitors
  申请人：WYETH

  公开号：US20040229924A1

  公开（公告）日：2004-11-18

  Compounds of the formula: 1 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。
• 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