Ethyl 4-(4-fluorophenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxylate | 226396-35-6

• 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: Ethyl 4-(4-fluorophenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxylate
• CAS: 226396-35-6
• 化学式: C₁₇H₂₄FNO₄S
• 分子量: 357.446
• InChiKey: BQUQTKWHNGXHHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-异丙基苯酚 、 Ethyl 4-(4-fluorophenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxylate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 以5.1 g的产率得到Ethyl 1-propan-2-yl-4-[4-(4-propan-2-ylphenoxy)phenyl]sulfonylpiperidine-4-carboxylate
  参考文献：
  名称：

  Orally Active MMP-1 Sparing α-Tetrahydropyranyl and α-Piperidinyl Sulfone Matrix Metalloproteinase (MMP) Inhibitors with Efficacy in Cancer, Arthritis, and Cardiovascular Disease

  摘要：

  alpha-Sulfone-alpha-piperidine and alpha-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. alpha-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while alpha-piperidine and alpha-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9l (SC-77774), respectively, were identified as backup compounds.

  DOI：

  10.1021/jm100669j
• 作为产物：
  描述：

  Ethyl 4-(4-fluorophenyl)sulfonylpiperidine-4-carboxylate;2,2,2-trifluoroacetic acid 、 2-溴丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 Ethyl 4-(4-fluorophenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxylate
  参考文献：
  名称：

  Orally Active MMP-1 Sparing α-Tetrahydropyranyl and α-Piperidinyl Sulfone Matrix Metalloproteinase (MMP) Inhibitors with Efficacy in Cancer, Arthritis, and Cardiovascular Disease

  摘要：

  alpha-Sulfone-alpha-piperidine and alpha-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. alpha-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while alpha-piperidine and alpha-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9l (SC-77774), respectively, were identified as backup compounds.

  DOI：

  10.1021/jm100669j

文献信息

• [EN] AROMATIC SULFONE HYDROXAMIC ACID METALLOPROTEASE INHIBITOR<br/>[FR] INHIBITEUR DE METALLOPROTEASE A BASE D'ACIDE HYDROXAMIQUE AROMATIQUE SULFONÉ
  申请人：SEARLE & CO

  公开号：WO2000050396A1

  公开（公告）日：2000-08-31

  A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.

  本发明公开了一种治疗过程，包括向患有与病理性基质金属蛋白酶活性相关的疾病的宿主施用一种具有出色抑制活性的芳香基磺酮羟肟酸的有效量，例如MMP-2、MMP-9和MMP-13，同时对至少MMP-1的抑制作用明显较小。此外，还公开了具有这些选择性活性的金属蛋白酶抑制剂化合物，制造这种化合物的过程以及使用抑制剂的制药组合物。
• AROMATIC SULFONE HYDROXAMIC ACID METALLOPROTEASE INHIBITOR
  申请人：——

  公开号：US20010014688A1

  公开（公告）日：2001-08-16

  A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.

  本发明涉及一种治疗过程，包括向患有与病理基质金属蛋白酶活性相关的状况的宿主施用有效量的芳香磺酮羟肟酸，该芳香磺酮羟肟酸表现出优异的抑制活性，可抑制一种或多种基质金属蛋白酶(MMP)酶，如MMP-2、MMP-9和MMP-13，同时对MMP-1的抑制显著较少。还揭示了具有这些选择性活性的金属蛋白酶抑制剂化合物、制造这种化合物的工艺以及使用抑制剂的制药组合物。
• Aromatic sulfone hydroxamic acid metalloprotease inhibitor
  申请人：——

  公开号：US20020177588A1

  公开（公告）日：2002-11-28

  A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.

  本发明揭示了一种治疗过程，包括向患有与病理性基质金属蛋白酶活性相关的病症的宿主施用一种有效量的芳香族磺酰羟肟酸，该芳香族磺酰羟肟酸在MMP-2、MMP-9和MMP-13等一种或多种基质金属蛋白酶（MMP）酶活性上表现出优异的抑制活性，同时在至少MMP-1的抑制上表现出明显较少的抑制。还揭示了具有这些选择性活性的金属蛋白酶抑制剂化合物、制造这种化合物的过程以及使用抑制剂的制药组合物。
• AROMATIC SULFONS HYDROXAMIC ACID METALLOPROTEASE INHIBITOR
  申请人：G.D. Searle & Co.

  公开号：EP1230219A1

  公开（公告）日：2002-08-14
• US6541489B1
  申请人：——

  公开号：US6541489B1

  公开（公告）日：2003-04-01