[3-(S)-benyloxycarbamoyl-4-(S)-(4-phenyl-piperazine-1-carbonyl)-cyclohexyl]-acetic acid methyl ester | 851001-19-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: [3-(S)-benyloxycarbamoyl-4-(S)-(4-phenyl-piperazine-1-carbonyl)-cyclohexyl]-acetic acid methyl ester
• 英文别名: methyl 2-[(3S,4S)-3-(phenylmethoxycarbamoyl)-4-(4-phenylpiperazine-1-carbonyl)cyclohexyl]acetate
• CAS: 851001-19-9
• 化学式: C₂₈H₃₅N₃O₅
• 分子量: 493.603
• InChiKey: HHSVUXCOJOALBU-GARJWBAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [3-(S)-benyloxycarbamoyl-4-(S)-(4-phenyl-piperazine-1-carbonyl)-cyclohexyl]-acetic acid methyl ester 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 [3-(S)-benzyloxyaminoformyl-4-(S)-(4-phenyl-piperazine-1-carbonyl)-cyclohexyl]-ethanoic acid
  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
• 作为产物：
  描述：

  (1S,2S)-5-(2-methoxy-2-oxoethyl)-2-(4-phenylpiperazine-1-carbonyl)cyclohexane-1-carboxylic acid 、 苄氧基胺盐酸盐 在 N-甲基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以88%的产率得到[3-(S)-benyloxycarbamoyl-4-(S)-(4-phenyl-piperazine-1-carbonyl)-cyclohexyl]-acetic acid methyl ester
  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 lnhibitors of matrix metalloproteinases
  申请人：Li Yun Long

  公开号：US20080167288A1

  公开（公告）日：2008-07-10

  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.

  本发明提供了公式的化合物：其对映异构体、非对映异构体、混合物、前药、晶体形式、非晶体形式、无定形形式、溶剂化物、代谢物和药学上可接受的盐，其中环A的取代基在下面的披露中被完全定义。公式化合物是金属蛋白酶抑制剂，如基质金属蛋白酶和脱落酶，可用于治疗风湿性关节炎、银屑病、肿瘤性疾病、过敏和所有需要抑制MMP的疾病。
• 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。
• Substituted cyclic hydroxamates as inhibitors of matrix metalloproteinases
  申请人：Li Yun-Long

  公开号：US08853243B2

  公开（公告）日：2014-10-07

  The present invention provides compounds of the formula I: 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 I 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.

  本发明提供了公式I的化合物：其对映体、二对映异构体、混合物、前药、晶体形式、非晶体形式、无定形形式、溶剂化物、代谢物和药学上可接受的盐，其中环A取代基在以下披露中得到充分定义。公式I的化合物是金属蛋白酶抑制剂，如基质金属蛋白酶和剪切酶，并且在治疗风湿性关节炎、银屑病、肿瘤性疾病、过敏和所有需要抑制MMPs的疾病中有用。
• US7973041B2
  申请人：——

  公开号：US7973041B2

  公开（公告）日：2011-07-05
• US8853243B2
  申请人：——

  公开号：US8853243B2

  公开（公告）日：2014-10-07