6-乙氧基烟酸乙酯 | 24903-80-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 6-乙氧基烟酸乙酯
• 英文名称: ethyl 6-ethoxynicotinate
• 英文别名: 6-ethoxy-nicotinic acid ethyl ester；2-Ethoxy-5-carbethoxypyridin；ethyl 6-ethoxypyridine-3-carboxylate
• CAS: 24903-80-8
• 化学式: C₁₀H₁₃NO₃
• 分子量: 195.218
• InChiKey: FBQJIRFPCZOBRI-UHFFFAOYSA-N

物化性质

• 沸点：
  272.7±20.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-乙氧基烟酸乙酯 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 以91%的产率得到6-ethoxy-3-hydroxymethylpyridine
  参考文献：
  名称：

  Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors

  摘要：

  Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a Ki value of 0.049 nM. It stops the spread of the HIVIIIb-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

  DOI：

  10.1021/jm9903848
• 作为产物：
  描述：

  sodium ethanolate 、 6-氯烟酸乙酯 在 乙醇 作用下， 反应 16.0h， 以77%的产率得到6-乙氧基烟酸乙酯
  参考文献：
  名称：

  Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors

  摘要：

  Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a Ki value of 0.049 nM. It stops the spread of the HIVIIIb-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

  DOI：

  10.1021/jm9903848

文献信息

• First, Second, and Third Generation Scalable Syntheses of Two Potent H₃ Antagonists
  作者：Daniel J. Pippel、John E. Mills、Chennagiri R. Pandit、Lana K. Young、Hua M. Zhong、Frank J. Villani、Neelakandha S. Mani

  DOI：10.1021/op200005e

  日期：2011.5.20

  Our teams have recently completed scale-up campaigns for two structurally similar H-3 receptor antagonists. The first and second generation processes were developed for the synthesis of 107 and 125 g batches of (4-cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone center dot HCl (1 center dot HCl). A third generation process was utilized for production of 104 g of 3-((5-(4-cyclobutyl-1,4-diazepane-1-carbonyl)pyridin-2-yl)oxy)benzonitrile center dot HCl (2 center dot HCl). The evolution from first to second generation process was driven by a desire to minimize cost of goods through employment of symmetrical homopiperazine rather than a more expensive monoprotected variant. Project demands for a late stage intermediate that could provide 1 or 2 led to additional route scouting and the ultimate determination of a third scalable synthesis for these types of molecules. The use of a lithium alkoxide for Lewis base catalysis of an ester to amide transformation represents a key improvement for the third generation synthesis.
• Pyrolysis of alkyl 2- or 6-alkoxynicotinates. An unexpected decarbalkoxylation reaction
  作者：George R. Newkome、Dalip K. Kohli、Toshio Kawato

  DOI：10.1021/jo01310a052

  日期：1980.10
• NEWKOME G. R.; KOHLI D. K.; KAWATO TOSHIO, J. ORG. CHEM., 1980, 45, NO 22, 4508-4511
  作者：NEWKOME G. R.、 KOHLI D. K.、 KAWATO TOSHIO

  DOI：——

  日期：——