carbonic acid 3-[4-chloro-3-(3,5-dicyano-phenoxy)-2-fluoro-benzyl]-5-methyl-6-oxo-6H-pyridazin-1-ylmethyl ester 2-morpholin-4-yl-ethyl ester hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: carbonic acid 3-[4-chloro-3-(3,5-dicyano-phenoxy)-2-fluoro-benzyl]-5-methyl-6-oxo-6H-pyridazin-1-ylmethyl ester 2-morpholin-4-yl-ethyl ester hydrochloride
• 英文别名: [3-[[4-Chloro-3-(3,5-dicyanophenoxy)-2-fluorophenyl]methyl]-5-methyl-6-oxopyridazin-1-yl]methyl 2-morpholin-4-ylethyl carbonate;hydrochloride
• 化学式: C₂₈H₂₅ClFN₅O₆*ClH
• 分子量: 618.449
• InChiKey: HXAUOYFRYUCRQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-吗啉乙醇 、 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 34.0h， 生成 carbonic acid 3-[4-chloro-3-(3,5-dicyano-phenoxy)-2-fluoro-benzyl]-5-methyl-6-oxo-6H-pyridazin-1-ylmethyl ester 2-morpholin-4-yl-ethyl ester hydrochloride
  参考文献：
  名称：

  Orally bioavailable prodrugs of a BCS class 2 molecule, an inhibitor of HIV-1 reverse transcriptase

  摘要：

  The N-2 position of pyridazinone 1, a potent HIV-1 NNRTI that has limited aqueous solubility, was derivatized into a series of hydroxymethyl esters and carbonates as well as one phosphate. The derivatives served as prodrugs to effectively deliver 1 to rat plasma upon oral treatment at 50 mpk. Increases of 4.3- to 8.6-fold in 24-hour exposure of 1 (over that of parent) were observed while the prodrugs and the hydroxymethyl adduct 2 were undetectable. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.090

文献信息

• Orally bioavailable prodrugs of a BCS class 2 molecule, an inhibitor of HIV-1 reverse transcriptase
  作者：Todd R. Elworthy、James P. Dunn、J. Heather Hogg、Grace Lam、Y. David Saito、Tania M.P.C. Silva、Dimitrios Stefanidis、Witold Woroniecki、Eugenia Zhornisky、Amy S. Zhou、Klaus Klumpp

  DOI：10.1016/j.bmcl.2008.10.090

  日期：2008.12

  The N-2 position of pyridazinone 1, a potent HIV-1 NNRTI that has limited aqueous solubility, was derivatized into a series of hydroxymethyl esters and carbonates as well as one phosphate. The derivatives served as prodrugs to effectively deliver 1 to rat plasma upon oral treatment at 50 mpk. Increases of 4.3- to 8.6-fold in 24-hour exposure of 1 (over that of parent) were observed while the prodrugs and the hydroxymethyl adduct 2 were undetectable. (C) 2008 Elsevier Ltd. All rights reserved.