2-[3-(Oxan-2-yloxy)propyl]-5-[4-(trifluoromethoxy)phenyl]tetrazole | 476194-11-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[3-(Oxan-2-yloxy)propyl]-5-[4-(trifluoromethoxy)phenyl]tetrazole
• CAS: 476194-11-3
• 化学式: C₁₆H₁₉F₃N₄O₃
• 分子量: 372.347
• InChiKey: MPHNDTNWAQDKBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[3-(Oxan-2-yloxy)propyl]-5-[4-(trifluoromethoxy)phenyl]tetrazole 在 sodium hydride 、 乙酰氯 作用下， 以 N-甲基吡咯烷酮 、 甲醇 为溶剂， 反应 1.0h， 生成 C₂₈H₃₄F₃N₅O₇S
  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
• 作为产物：
  描述：

  2-(3-氯丙氧基)四氢-2H-吡喃 、 5-[4-(trifluoromethoxy)phenyl]-1H-tetrazole 在 sodium hydride 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 21.0h， 以45%的产率得到2-[3-(Oxan-2-yloxy)propyl]-5-[4-(trifluoromethoxy)phenyl]tetrazole
  参考文献：
  名称：

  Aromatic sulfone hydroxamates and their use as protease inhibitors

  摘要：

  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。

  公开号：

  US20040010019A1

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。
• [EN] AROMATIC SULFONE HYDROXAMIC ACIDS AND THEIR USE AS PROTEASE INHIBITORS<br/>[FR] ACIDES HYDROXAMIQUES SULFONIQUES AROMATIQUES ET LEUR UTILISATION COMME INHIBITEURS DE LA PROTEASE
  申请人：PHARMACIA CORP

  公开号：WO2004043943A1

  公开（公告）日：2004-05-27

  This invention is directed to aromatic sulfone hydroxamic acids (including aromatic sulfone 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.
• MMP-13 selective α-sulfone hydroxamates: A survey of P1′ heterocyclic amide isosteres
  作者：Thomas E. Barta、Daniel P. Becker、Louis J. Bedell、Alan M. Easton、Susan L. Hockerman、James Kiefer、Grace E. Munie、Karl J. Mathis、Madeleine H. Li、Joseph G. Rico、Clara I. Villamil、Jennifer M. Williams

  DOI：10.1016/j.bmcl.2011.03.099

  日期：2011.5

  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.