(2R,4S)-1-(4-Benzyloxy-benzenesulfonyl)-4-hydroxy-piperidine-2-carboxylic acid hydroxyamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,4S)-1-(4-Benzyloxy-benzenesulfonyl)-4-hydroxy-piperidine-2-carboxylic acid hydroxyamide
• 英文别名: (2R,4S)-N,4-dihydroxy-1-(4-phenylmethoxyphenyl)sulfonylpiperidine-2-carboxamide
• 化学式: C₁₉H₂₂N₂O₆S
• 分子量: 406.459
• InChiKey: ACEUKQZDNBIUHG-MAUKXSAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(苄氧基)苯-1-磺酰氯 在 羟胺 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,4S)-1-(4-Benzyloxy-benzenesulfonyl)-4-hydroxy-piperidine-2-carboxylic acid hydroxyamide
  参考文献：
  名称：

  Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors

  摘要：

  A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme, Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with > 100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00183-x

文献信息

• Hydroxy pipecolate hydroxamic acid derivatives
  申请人：——

  公开号：US20030008901A1

  公开（公告）日：2003-01-09

  A compound of the formula 1 wherein R 1 , R 2 R 3 , R 4 R 5 , R 6 , R 7 , R 8 , R 9 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.

  公式1的化合物，其中R1、R2R3、R4R5、R6、R7、R8、R9和Ar的定义如上所述，可用于治疗选自关节炎、癌症和其他以基质金属蛋白酶或哺乳动物重组蛋白酶活性为特征的疾病。此外，本发明的化合物可以与标准非甾体抗炎药（NSAID'S）、COX-2抑制剂和镇痛剂联合治疗，并与顺铂、多柔比星、顺铂、依托泊苷、紫杉醇、紫杉二酸和其他生物碱（如长春碱）等细胞毒性药物联合使用，用于治疗癌症。
• 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
• US6329397B1
  申请人：——

  公开号：US6329397B1

  公开（公告）日：2001-12-11
• [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.
• Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors
  作者：Michael A. Letavic、Matt Z. Axt、John T. Barberia、Thomas J. Carty、Dennis E. Danley、Kieran F. Geoghegan、Nadia S. Halim、Lise R. Hoth、Ajith V. Kamath、Ellen R. Laird、Lori L. Lopresti-Morrow、Kim F. McClure、Peter G. Mitchell、Vijayalakshmi Natarajan、Mark C. Noe、Jayvardhan Pandit、Lisa Reeves、Gayle K. Schulte、Sheri L. Snow、Francis J. Sweeney、Douglas H. Tan、Chul H. Yu

  DOI：10.1016/s0960-894x(02)00183-x

  日期：2002.5

  A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme, Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with > 100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood. (C) 2002 Elsevier Science Ltd. All rights reserved.