Tert-butyl (2s,3s)-5-{2-[(5-{[(benzyloxy)carbonyl]amino}pentyl)amino]-2-oxoethyl}-2-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidine-3-carboxylate | 851001-10-0

• 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: Tert-butyl (2s,3s)-5-{2-[(5-{[(benzyloxy)carbonyl]amino}pentyl)amino]-2-oxoethyl}-2-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidine-3-carboxylate
• 英文别名: tert-butyl (2S,3S)-5-[2-oxo-2-[5-(phenylmethoxycarbonylamino)pentylamino]ethyl]-2-(3-phenylpyrrolidine-1-carbonyl)piperidine-3-carboxylate
• CAS: 851001-10-0
• 化学式: C₃₆H₅₀N₄O₆
• 分子量: 634.816
• InChiKey: OIWCRGFZNXQBMP-DCOOZXFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  46
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Tert-butyl (2s,3s)-5-{2-[(5-{[(benzyloxy)carbonyl]amino}pentyl)amino]-2-oxoethyl}-2-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidine-3-carboxylate 、 水 、 三氟乙酸 在 苯 、 正庚烷 、 crude product 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 (2S,3S)-5-{2-[(5-{[(benzyloxy)carbonyl]amino}pentyl)amino]-2-oxoethyl}-2-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidine-3-carboxylic acid
  参考文献：
  名称：

  SUBSTITUTED CYCLIC HYDROXAMATES AS INHIBITORS OF MATRIX METALLOPROTEINASES

  摘要：

  本发明提供了I式化合物：其对映异构体，对映体混合物，前药，结晶形式，非晶形式，无定形形式，其溶剂化物，其代谢物和药学上可接受的盐，其中环A取代基团在以下披露中得到充分定义。I式化合物是金属蛋白酶抑制剂，如基质金属蛋白酶和剪切酶的抑制剂，并且在治疗风湿性关节炎，牛皮癣，肿瘤性疾病，过敏和所有需要抑制MMP的疾病中有用。

  公开号：

  US20150025056A1
• 作为产物：
  描述：

  {(5s,6s)-5-(Tert-butoxycarbonyl)-6-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidin-3-yl}acetic acid 、 5-氨基戊基氨基甲酸苄酯 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66%的产率得到Tert-butyl (2s,3s)-5-{2-[(5-{[(benzyloxy)carbonyl]amino}pentyl)amino]-2-oxoethyl}-2-[(3-phenylpyrrolidin-1-yl)carbonyl]piperidine-3-carboxylate
  参考文献：
  名称：

  Compelling P1 substituent affect on metalloprotease binding profile enables the design of a novel cyclohexyl core scaffold with excellent MMP selectivity and HER-2 sheddase inhibition

  摘要：

  A serendipitous discovery that the metalloprotease binding pro. le of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modi. cation of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core that exhibited excellent HER-2 potency and unprecedented MMP-selectivity that we believe would not have been possible via conventional P1' perturbations. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.143

文献信息

• SUBSTITUTED CYCLIC HYDROXAMATES AS INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：Li Yun-Long

  公开号：US20110224189A1

  公开（公告）日：2011-09-15

  The present invention provides compounds of the formula: its enantiomers, diastereomers, racemic mixtures thereof, prodrugs, crystalline forms, non-crystalline forms, amorphous forms thereof, solvates thereof, metabolites thereof, and pharmaceutically acceptable salts, wherein the ring A substituent groups are fully defined in the following disclosure. The compounds of formula are inhibitors of metalloproteases such as matrix metalloproteases and sheddases, and are useful in treating diseases such as rheumatoid arthritis, psoriasis, neoplastic diseases, allergies and all those diseases wherein inhibition of MMPs is desirable.

  本发明提供了化合物的公式：其对映异构体，对映体混合物，前药，晶体形式，非晶体形式，无定形形式，其溶剂化物，代谢产物以及药学上可接受的盐，其中环A的取代基在以下披露中完全定义。公式化合物是金属蛋白酶抑制剂，例如基质金属蛋白酶和剪切酶，并且在治疗风湿性关节炎，牛皮癣，肿瘤性疾病，过敏和所有需要抑制MMP的疾病中有用。
• US7491724B2
  申请人：——

  公开号：US7491724B2

  公开（公告）日：2009-02-17
• US7973041B2
  申请人：——

  公开号：US7973041B2

  公开（公告）日：2011-07-05
• US9440958B2
  申请人：——

  公开号：US9440958B2

  公开（公告）日：2016-09-13
• Compelling P1 substituent affect on metalloprotease binding profile enables the design of a novel cyclohexyl core scaffold with excellent MMP selectivity and HER-2 sheddase inhibition
  作者：David M. Burns、Yun-Long Li、Eric Shi、Chunhong He、Meizhong Xu、Jincong Zhuo、Colin Zhang、Ding-Quan Qian、Yanlong Li、Richard Wynn、Maryanne B. Covington、Kamna Katiyar、Cindy A. Marando、Jordan S. Fridman、Peggy Scherle、Steve Friedman、Brian Metcalf、Wenqing Yao

  DOI：10.1016/j.bmcl.2009.04.143

  日期：2009.7

  A serendipitous discovery that the metalloprotease binding pro. le of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modi. cation of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core that exhibited excellent HER-2 potency and unprecedented MMP-selectivity that we believe would not have been possible via conventional P1' perturbations. (C) 2009 Elsevier Ltd. All rights reserved.