tetrahydro-N-hydroxy-4-[[4-[3-[3[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]propoxy]phenyl]sulfonyl]-2H-pyran-4-carboxamide | 476185-58-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tetrahydro-N-hydroxy-4-[[4-[3-[3[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]propoxy]phenyl]sulfonyl]-2H-pyran-4-carboxamide
• 英文别名: N-hydroxy-4-(4-(3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)propoxy)phenylsulfonyl)tetrahydro-2H-pyran-4-carboxamide；N-hydroxy-4-[4-[3-[3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]propoxy]phenyl]sulfonyloxane-4-carboxamide
• CAS: 476185-58-7
• 化学式: C₂₄H₂₄F₃N₃O₈S
• 分子量: 571.531
• InChiKey: VCIBNYPUVKINDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  4-[[4-(3-carboxypropoxy)phenyl] sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid 1,1-dimethylethyl ester 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 乙酰氯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 72.0h， 生成 tetrahydro-N-hydroxy-4-[[4-[3-[3[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]propoxy]phenyl]sulfonyl]-2H-pyran-4-carboxamide
  参考文献：
  名称：

  MMP-13 selective α-sulfone hydroxamates: A survey of P1′ heterocyclic amide isosteres

  摘要：

  Seeking compounds preferentially potent and selective for MMP-13, we reported in the preceding Letter on a series of hydroxamic acids with a flexible benzamide tail groups. (1a) Here, we replace the amide moiety with non-hydrolyzable heterocycles in an effort to improve half-life. We identify a hydroxamate tetrazole 4e that spares MMP-1 and -14, shows >400-fold selectivity versus MMP-8 and >600-fold selectivity versus MMP-2, and has a 4.8 h half-life in rats. X-ray data (1.9 angstrom) for tetrazole 4c is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.099

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。
• AROMATIC SULFONE HYDROXAMIC ACIDS AND THEIR USE AS PROTEASE INHIBITORS
  申请人：Pharmacia Corporation

  公开号：EP1562928A1

  公开（公告）日：2005-08-17
• US6689794B2
  申请人：——

  公开号：US6689794B2

  公开（公告）日：2004-02-10
• US6890928B2
  申请人：——

  公开号：US6890928B2

  公开（公告）日：2005-05-10