N-hydroxy-1-(1-methylethyl)-4-[[4-[4-(trifluoromethyl)-phenoxy]phenyl]sulfonyl]-4-piperidinecarboxamide, monohydrochloride | 226396-04-9

• 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: N-hydroxy-1-(1-methylethyl)-4-[[4-[4-(trifluoromethyl)-phenoxy]phenyl]sulfonyl]-4-piperidinecarboxamide, monohydrochloride
• 英文别名: N-hydroxy-1-propan-2-yl-4-[4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide;hydrochloride
• CAS: 226396-04-9
• 化学式: C₂₂H₂₅F₃N₂O₅S*ClH
• 分子量: 522.973
• InChiKey: NDAZVZYHYGUPBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-(oxan-2-yloxy)-1-propan-2-yl-4-[4-[4-(trifluoromethyl)phenoxy]phenyl]sulfonylpiperidine-4-carboxamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以84%的产率得到N-hydroxy-1-(1-methylethyl)-4-[[4-[4-(trifluoromethyl)-phenoxy]phenyl]sulfonyl]-4-piperidinecarboxamide, monohydrochloride
  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

• Aromatic sulfone hydroxamic acid metalloprotease inhibitor
  申请人：Barta Thomas E.

  公开号：US06890937B2

  公开（公告）日：2005-05-10

  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. The administered enzyme inhibitor corresponds in structure to formula (I), below, or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are both hydrido or R 1 and R 2 together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two, or three heteroatoms in the ring that are oxygen, sulfur, or nitrogen. R 3 in formula (I) is an optionally substituted aryl or optionally substituted heteroaryl radical. 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，其中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具有出色的抑制活性的芳香基磺酰羟肟酸，该抑制活性针对一种或多种基质金属蛋白酶（MMP）酶，例如MMP-2、MMP-9和MMP-13，同时在至少MMP-1方面表现出明显较少的抑制作用。所施用的酶抑制剂在结构上与下式（I）或其药学上可接受的盐相对应，其中R1和R2均为氢基或R1和R2与它们键合的原子形成一个含有一个、两个或三个杂原子（氧、硫或氮）的5-8元环。式（I）中的R3是一个可选的取代芳基或可选的取代杂原芳基基团。此外，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药物组合物。