2'-O-(3-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)carbonyl]amino}propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A | 1236143-22-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-O-(3-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)carbonyl]amino}propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
• 英文别名: 5-chloro-N-[3-[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-azacyclopentadec-11-yl]oxy]-6-methyloxan-3-yl]oxypropyl]-1,3-dimethylpyrazole-4-carboxamide
• CAS: 1236143-22-8
• 化学式: C₄₇H₈₄ClN₅O₁₃
• 分子量: 962.663
• InChiKey: PTUOKVSSERLULH-OHLRHLMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  66
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  216
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  2'-O-(3-aminopropyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A 、 5-氯-1,3-二甲基-1H-吡唑-4-甲酸 在 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以46%的产率得到2'-O-(3-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)carbonyl]amino}propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  大环内酯周围-大环3D结构对亲脂性和细胞积累的影响。

  摘要：

  这项研究的目的是在分子水平上研究合理设计的阿奇霉素和克拉霉素衍生物的亲脂性和细胞蓄积性。使用计算的结构参数以及实验确定的亲脂性，研究了取代位点和取代基性质对所研究化合物的整体物理化学特征和细胞积累的影响。在基于分子3D结构的计算机模型中，研究了构象效应对所研究性质的影响，并基于非经验参数预测了此类分子的亲脂性和细胞蓄积性。在验证和测试集上探索了开发模型的适用性，并与先前开发的经验模型进行了比较。

  DOI：

  10.1016/j.ejmech.2017.03.056

文献信息

• Compounds
  申请人：Alihodzic Sulejman

  公开号：US20110281812A1

  公开（公告）日：2011-11-17

  2′-O-substituted 14- or 15-membered azalide macrolides of Formula (I) wherein R 6 represents (i) —C 1-8 alkyl, unsubstituted or substituted at the terminal carbon atom by a group selected from hydroxy, —C 1-3 alkoxy and —C(O)OC 1-3 alkyl, or when —C 1-8 alkyl is branched, substitution can alternatively be by a hydroxyl group at each of two terminal carbon atoms, (ii) —CH(NH 2 )C 1-4 alkyl, wherein the —C 1-4 alkyl group may be optionally interrupted by a heteroatom selected from O, S and N, (iii) —CH 2 N(R 7 )(R 8 ), wherein R 7 and R 8 each independently represent H or —C 1-3 alkyl provided that R 7 and R 8 cannot both simultaneously represent H, (iv) a 4-6-membered heterocyclic ring containing up to 2 heteroatoms independently selected from O, S and N, wherein the heterocyclic ring is unsubstituted or substituted by —C 1-3 alkyl, (v) 5-6 membered heteroaromatic ring, unsubstituted or substituted by one to three groups independently selected from halo, hydroxyl, —C 1-3 alkyl, —C 1-3 alkoxy, —CF 3 , —OCF 3 and —NH 2 , (vi) —CH(NH 2 )CH 2 -aryl wherein the aryl group may be unsubstituted or substituted by one or two substituents independently selected from —C 1-3 alkyl, —C 1-3 alkoxy and hydroxyl, (vii) —C 3-7 cycloalkyl, or (viii) phenyl unsubstituted or substituted by one or two groups independently selected from halo, hydroxyl, —C 1-3 alkyl, —C 1-3 alkoxy, —CF 3 , —OCF 3 and —NH 2 , or salts thereof, useful in the treatment of neutrophil dominated inflammatory diseases, especially in the treatment of neutrophil dominated inflammatory diseases resulting from neutrophilic infiltration and/or diseases associated with altered cellular functionality of neutrophils, to methods for their preparation, to their use as therapeutic agents, and to salts thereof.
• Around the macrolide – Impact of 3D structure of macrocycles on lipophilicity and cellular accumulation
  作者：Sanja Koštrun、Vesna Munic Kos、Maja Matanović Škugor、Ivana Palej Jakopović、Ivica Malnar、Snježana Dragojević、Jovica Ralić、Sulejman Alihodžić

  DOI：10.1016/j.ejmech.2017.03.056

  日期：2017.6

  the molecular level. The effect of substitution site and substituent properties on a global physico-chemical profile and cellular accumulation of investigated compounds was studied using calculated structural parameters as well as experimentally determined lipophilicity. In silico models based on the 3D structure of molecules were generated to investigate conformational effect on studied properties and

  这项研究的目的是在分子水平上研究合理设计的阿奇霉素和克拉霉素衍生物的亲脂性和细胞蓄积性。使用计算的结构参数以及实验确定的亲脂性，研究了取代位点和取代基性质对所研究化合物的整体物理化学特征和细胞积累的影响。在基于分子3D结构的计算机模型中，研究了构象效应对所研究性质的影响，并基于非经验参数预测了此类分子的亲脂性和细胞蓄积性。在验证和测试集上探索了开发模型的适用性，并与先前开发的经验模型进行了比较。