(2R,3S)-1-[4-(4-Fluoro-benzyloxy)-benzenesulfonyl]-3-hydroxy-3-methyl-piperidine-2-carboxylic acid | 950888-43-4

• 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: (2R,3S)-1-[4-(4-Fluoro-benzyloxy)-benzenesulfonyl]-3-hydroxy-3-methyl-piperidine-2-carboxylic acid
• 英文别名: (2R,3S)-1-[4-[(4-fluorophenyl)methoxy]phenyl]sulfonyl-3-hydroxy-3-methylpiperidine-2-carboxylic acid
• CAS: 950888-43-4
• 化学式: C₂₀H₂₂FNO₆S
• 分子量: 423.462
• InChiKey: USHXRNMEJLDLSD-ICSRJNTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3S)-1-[4-(4-Fluoro-benzyloxy)-benzenesulfonyl]-3-hydroxy-3-methyl-piperidine-2-carboxylic acid 在 四(三苯基膦)钯 、 甲酸 、 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 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 (2R,3S)-1-[4-(4-Fluorobenzyloxy)-benzenesulfonyl]-3-hydroxy-3-methyl-piperidine-2-carboxylic acid hydroxyamide
  参考文献：
  名称：

  Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13

  摘要：

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.037
• 作为产物：
  描述：

  (2R,3S)-3-Hydroxy-1-(4-hydroxy-benzenesulfonyl)-3-methyl-piperidine-2-carboxylic acid tert-butyl ester 在 caesium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3S)-1-[4-(4-Fluoro-benzyloxy)-benzenesulfonyl]-3-hydroxy-3-methyl-piperidine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13

  摘要：

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.037

文献信息

• HYDROXY PIPECOLATE HYDROXAMIC ACID DERIVATIVES AS MMP INHIBITORS
  申请人：Pfizer Products Inc.

  公开号：EP1104403A1

  公开（公告）日：2001-06-06
• [EN] HYDROXY PIPECOLATE HYDROXAMIC ACID DERIVATIVES AS MMP INHIBITORS<br/>[FR] DERIVES D'ACIDE HYDROXAMIQUE DE PIPECOLATE HYDROXY
  申请人：PFIZER PROD INC

  公开号：WO2000009485A1

  公开（公告）日：2000-02-24

  A compound of formula (I) wherein R?1, R2 R3, R4 R5, R6, R7, R8, R9¿ and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, and other diseases characterized by matrix metalloproteinase or mammalian reprolysin activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.
• Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13
  作者：Mark C. Noe、Vijayalakshmi Natarajan、Sheri L. Snow、Lilli A. Wolf-Gouveia、Peter G. Mitchell、Lori Lopresti-Morrow、Lisa M. Reeves、Sue A. Yocum、Ivan Otterness、Marcia A. Bliven、Thomas J. Carty、John T. Barberia、Francis J. Sweeney、Jennifer L. Liras、Marcie Vaughn

  DOI：10.1016/j.bmcl.2005.05.037

  日期：2005.7

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.