4-[(4-fluorophenyl)sulfonyl]tetrahydro-N-[(tetrahydro-2H-pyran-2-yl)oxy]-2H-pyran-4-carboxamide | 226389-21-5

• 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: 4-[(4-fluorophenyl)sulfonyl]tetrahydro-N-[(tetrahydro-2H-pyran-2-yl)oxy]-2H-pyran-4-carboxamide
• 英文别名: 4-(4-fluorophenyl)sulfonyl-N-(oxan-2-yloxy)oxane-4-carboxamide
• CAS: 226389-21-5
• 化学式: C₁₇H₂₂FNO₆S
• 分子量: 387.429
• InChiKey: IIZMZVONZKXFHC-UHFFFAOYSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(4-fluorophenyl)sulfonyl]tetrahydro-N-[(tetrahydro-2H-pyran-2-yl)oxy]-2H-pyran-4-carboxamide 在 盐酸 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 alpha-Sulfone 21
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

  摘要：

  alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Tiperidine-alpha-sulfone, hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.

  DOI：

  10.1021/jm0500875
• 作为产物：
  描述：

  Methyl 4-(4-fluorophenyl)sulfonyloxane-4-carboxylate 在 N-甲基吗啉 、 potassium trimethylsilonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 4-[(4-fluorophenyl)sulfonyl]tetrahydro-N-[(tetrahydro-2H-pyran-2-yl)oxy]-2H-pyran-4-carboxamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

  摘要：

  alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Tiperidine-alpha-sulfone, hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.

  DOI：

  10.1021/jm0500875

文献信息

• Aromatic sulfone hydroxamates and their use as protease inhibitors
  申请人：——

  公开号：US20040010019A1

  公开（公告）日：2004-01-15

  This invention is directed to aromatic sulfone hydroxamates (also known as “aromatic sulfone hydroxamic acids”) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

  这项发明涉及芳香砜羟肟酸酯（也称为“芳香砜羟肟酸”）及其盐，该化合物在抑制基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP”）活性和/或聚集素酶活性方面具有作用。该发明还涉及一种预防或治疗方法，包括向动物，特别是患有（或易患）与MMP和/或聚集素酶活性相关的病理状况的哺乳动物，施用此类化合物或盐以达到抑制MMP和/或聚集素酶的有效量。
• Aromatic sulfone hydroxamic acids and their use as protease inhibitors
  申请人：——

  公开号：US20030073718A1

  公开（公告）日：2003-04-17

  This invention is directed to aromatic sulfone hydroxamates (also known as aromatic sulfone hydroxamic acids) and salts thereof that, inter alia, tend to inhibit matrix metalloproteinase (also known as matrix metalloprotease or MMP) activity and/or aggrecanase activity. This invention also is directed to a treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP activity and/or aggrecanase activity.

  本发明涉及芳香基磺酮羟肟酸（也称为芳香基磺酮羟肟酸）及其盐，该化合物在抑制基质金属蛋白酶（也称为基质金属蛋白酶或MMP）活性和/或聚集素酶（aggrecanase）活性方面具有倾向性。本发明还涉及一种治疗方法，其包括向动物，特别是患有（或有病理条件与MMP活性和/或聚集素酶活性相关的）哺乳动物中，以MMP抑制剂和/或聚集素酶抑制剂有效量的该化合物或盐进行治疗。
• [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：US20040235818A1

  公开（公告）日：2004-11-25

  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. A contemplated compound corresponds in structure to formula B, below, 1

  本发明揭示了一种治疗过程，其中包括向患有与病理基质金属蛋白酶活性相关的病情的宿主施用一种有效量的芳香磺酰羟肟酸，该肟酸表现出对一种或多种基质金属蛋白酶（MMP）酶的出色抑制活性，例如MMP-2、MMP-9和MMP-13，同时对至少MMP-1的抑制作用明显较少。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，制造这种化合物的过程以及使用抑制剂的制药组合物。考虑的化合物与下面的B式结构相对应，1。