N-[2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-1,3-thiazinan-3-yl]pyridine-4-carboxamide | 1373257-83-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-[2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-1,3-thiazinan-3-yl]pyridine-4-carboxamide
• 英文别名: N-[2-(4-hydroxy-3-methoxyphenyl)-4-oxo-1,3-thiazinan-3-yl]pyridine-4-carboxamide
• CAS: 1373257-83-0
• 化学式: C₁₇H₁₇N₃O₄S
• 分子量: 359.406
• InChiKey: GTKREXUJDLLNJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  异烟肼 、 香草醛 、 3-巯基丙酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 以75%的产率得到N-[2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-1,3-thiazinan-3-yl]pyridine-4-carboxamide
  参考文献：
  名称：

  Synthesis of highly potent novel anti-tubercular isoniazid analogues with preliminary pharmacokinetic evaluation

  摘要：

  Thirty two novel isoniazid analogues were prepared by one-pot three component condensations of isoniazid (INH), 3-mercaptopropionic acid and various aryl/heteroaryl aldehydes. The synthesized compounds were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37Rv (MTB) and cytotoxicity. Among the compounds, compound N-(2-(4-(benzyloxy) phenyl)-4-oxo-1,3-thiazinan-3-yl) isonicotinamide (17) inhibited MTB with MIC of 0.12 mu M and was three times more potent than INH. The main pharmacokinetic parameters after intravenous administration (10 mg/kg body weight) in male Wistar rats viz. t(1/2), K-el, mean plasma clearance and mean volume of distribution were found to be 1.14 +/- 0.20 h, 0.62 +/- 0.10 h (1), 22.48 +/- 0.16 mL/kg/min and 1.99 +/- 0.49 L, respectively. The systemic absorption was slow after oral administration (50 mg/kg body weight). The peak plasma concentration was found to be 1.31 +/- 0.06 mu g/mL attained in 3 h. The bioavailability was found to be 16.7%. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.091

文献信息

• Synthesis of highly potent novel anti-tubercular isoniazid analogues with preliminary pharmacokinetic evaluation
  作者：Addepalli Venkata Ramani、Arumalla Monika、Vadlamani Lakshmi Indira、Gopisetti Karyavardhi、Jangala Venkatesh、Variam Ullas Jeankumar、Thimmappa H. Manjashetty、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.bmcl.2012.02.091

  日期：2012.4

  Thirty two novel isoniazid analogues were prepared by one-pot three component condensations of isoniazid (INH), 3-mercaptopropionic acid and various aryl/heteroaryl aldehydes. The synthesized compounds were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37Rv (MTB) and cytotoxicity. Among the compounds, compound N-(2-(4-(benzyloxy) phenyl)-4-oxo-1,3-thiazinan-3-yl) isonicotinamide (17) inhibited MTB with MIC of 0.12 mu M and was three times more potent than INH. The main pharmacokinetic parameters after intravenous administration (10 mg/kg body weight) in male Wistar rats viz. t(1/2), K-el, mean plasma clearance and mean volume of distribution were found to be 1.14 +/- 0.20 h, 0.62 +/- 0.10 h (1), 22.48 +/- 0.16 mL/kg/min and 1.99 +/- 0.49 L, respectively. The systemic absorption was slow after oral administration (50 mg/kg body weight). The peak plasma concentration was found to be 1.31 +/- 0.06 mu g/mL attained in 3 h. The bioavailability was found to be 16.7%. (C) 2012 Elsevier Ltd. All rights reserved.