4-(4-Fluoro-benzenesulfonyl)-tetrahydro-pyran-4-carboxylic acid | 226398-02-3

• 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-Fluoro-benzenesulfonyl)-tetrahydro-pyran-4-carboxylic acid
• 英文别名: 4-(4-Fluorophenyl)sulfonyloxane-4-carboxylic acid
• CAS: 226398-02-3
• 化学式: C₁₂H₁₃FO₅S
• mdl: MFCD12678437
• 分子量: 288.297
• InChiKey: DMNSXTDSIMPZKT-UHFFFAOYSA-N

物化性质

• 沸点：
  514.5±50.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-Fluoro-benzenesulfonyl)-tetrahydro-pyran-4-carboxylic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 caesium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 4-[4-(4-chlorophenoxy)phenyl]sulfonyl-N-(oxan-2-yloxy)oxane-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
• 作为产物：
  描述：

  Methyl 4-(4-fluorophenyl)sulfonyloxane-4-carboxylate 在 potassium trimethylsilonate 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以76%的产率得到4-(4-Fluoro-benzenesulfonyl)-tetrahydro-pyran-4-carboxylic acid
  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：Freskos N. John

  公开号：US20050101641A1

  公开（公告）日：2005-05-12

  This invention is directed to aromatic sulfone hydroxamic acids (including hydroxamates) 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.

  该发明涉及芳香磺酰羟肟酸（包括羟肟酸盐）及其盐，其可以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。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（或倾向于患有）与MMP和/或聚集素酶活性相关的病理状况的哺乳动物中，以MMP抑制和/或聚集素酶抑制有效剂量的该化合物或盐的给药。
• Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective α-sulfone hydroxamates
  作者：Stephen A. Kolodziej、Susan L. Hockerman、Terri L. Boehm、Jeffery N. Carroll、Gary A. DeCrescenzo、Joseph J. McDonald、Debbie A. Mischke、Grace E. Munie、Theresa R. Fletcher、Joseph G. Rico、Nathan W. Stehle、Craig Swearingen、Daniel P. Becker

  DOI：10.1016/j.bmcl.2010.04.130

  日期：2010.6

  A series of phenyl piperidine alpha-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats. (C) 2010 Elsevier Ltd. All rights reserved.
• MMP-13 selective isonipecotamide α-sulfone hydroxamates
  作者：Stephen A. Kolodziej、Susan L. Hockerman、Gary A. DeCrescenzo、Joseph J. McDonald、Debbie A. Mischke、Grace E. Munie、Theresa R. Fletcher、Nathan Stehle、Craig Swearingen、Daniel P. Becker

  DOI：10.1016/j.bmcl.2010.04.111

  日期：2010.6

  A series of N-aryl isonipecotamide alpha-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13. (C) 2010 Elsevier Ltd. All rights reserved.
• EP1385836A2
  申请人：——

  公开号：EP1385836A2

  公开（公告）日：2004-02-04