(9S)-9-dihydro-N-desmethyl-N-isopropylerythromycin A | 916242-28-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (9S)-9-dihydro-N-desmethyl-N-isopropylerythromycin A
• 英文别名: 9-dihydro-N-des-methyl-N-isopropylerythromycin A；3 9-dihydro-N-desmethyl-N-isopropylerythromycin A；(3R,4S,5S,6R,7R,9R,10S,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-6-[(2S,3R,4S,6R)-3-hydroxy-6-methyl-4-[methyl(propan-2-yl)amino]oxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one
• CAS: 916242-28-9
• 化学式: C₃₉H₇₃NO₁₃
• 分子量: 764.008
• InChiKey: RXJCJWPPKSQMAS-IRNFSOKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  53
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  197
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (9S)-9-dihydro-N-desmethyl-N-isopropylerythromycin A 在 碘 、 sodium acetate 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  9-Dihydroerythromycins as non-antibiotic motilin receptor agonists

  摘要：

  A series of 9-dihydroerythromycin A and B analogues with modification of the desosamine nitrogen have been synthesized and screened for motilin agonist activity, antibiotic activity, tachyphylaxis and hERG channel current inhibition. Small alkyl groups resulted in the potency while compounds with a primary or secondary amine resulted in the low motilin agonist potency. Several compounds were identified as non-antibiotic motilin receptor agonists with minimal tachyphylaxis and low hERG interaction. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.030
• 作为产物：
  描述：

  9-dihydro-N-desmethylerythromycin A 在 sodium cyanoborohydride 、 溶剂黄146 、 三乙醇胺 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 5.0h， 生成 (9S)-9-dihydro-N-desmethyl-N-isopropylerythromycin A
  参考文献：
  名称：

  Motilide compounds

  摘要：

  具有如公式（I）所示结构的化合物，其中RA、RB、RC、RD、RE和RF的定义如本文所述，可用作促动力剂。

  公开号：

  US20060270616A1

文献信息

• Motilide polymorphs
  申请人：Licari Peter J.

  公开号：US20080146654A1

  公开（公告）日：2008-06-19

  The invention provides polymorphs of a motilide having a structure represented by formula Ia

  这项发明提供了具有由化学式Ia表示的结构的莫替利德的多型体。
• Structure−Activity Relationships of 9-Substituted-9-Dihydroerythromycin-Based Motilin Agonists: Optimizing for Potency and Safety
  作者：Simon J. Shaw、Yue Chen、Hao Zheng、Hong Fu、Mark A. Burlingame、Saul Marquez、Yong Li、Mark Claypool、Christopher W. Carreras、William Crumb、Dwight J. Hardy、David C. Myles、Yaoquan Liu

  DOI：10.1021/jm901107f

  日期：2009.11.12

  A series of 9-dihydro-9-acetamido-N-desmethyl-N-isopropyl erythromycin A analogues and related derivatives was generated as motilin agonists. The compounds were optimized for potency while showing both minimal antibacterial activity and hERG inhibition. As the substituent on the amide was increased in lipophilicity the potency and hERG inhibition increased, while polar groups lowered potency, without significantly impacting hERG inhibition. The N-methyl acetamide 7a showed the optimal in vitro profile and was probed further by varying the chain length to the macrocycle as well as changing the macrocycle scaffold. 7a remained the compound with the best in vitro properties.
• 9-Dihydroerythromycin ethers as motilin agonists—Developing structure–activity relationships for potency and safety
  作者：Yaoquan Liu、Yong Li、David C. Myles、Mark Claypool、Christopher W. Carreras、Simon J. Shaw

  DOI：10.1016/j.bmc.2010.08.035

  日期：2010.11

  A series of derivatives of the amine of 9-dihydro-9-O-ethylamino-N-desmethyl-N-isopropyl erythromycin A derivatives were synthesized as motilin agonists. The compounds were developed for potency without showing antibacterial activity and inhibition of the hERG potassium channel. The formamide of the amide series was found to show the optimal combination of properties relative to carbamates, ureas, thioureas, and amines. This prompted an investigation of heterocyclic isosteres for the amide. In this series the triazole had the optimal combination of properties. From the study, two compounds met the criteria for detailed pharmacokinetic studies. (C) 2010 Elsevier Ltd. All rights reserved.
• MOTILIDE POLYMORPHS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2104680B1

  公开（公告）日：2013-01-09
• US7582611B2
  申请人：——

  公开号：US7582611B2

  公开（公告）日：2009-09-01