6-benzoyl-2-(4-phenoxybenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

• 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: 6-benzoyl-2-(4-phenoxybenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
• 英文别名: 6-benzoyl-2-[(4-phenoxybenzoyl)amino]-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxamide
• 化学式: C₂₈H₂₃N₃O₄S
• 分子量: 497.574
• InChiKey: XVGGFTHIZGWSFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苯氧基苯甲酸 在 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.33h， 生成 6-benzoyl-2-(4-phenoxybenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
  参考文献：
  名称：

  Design and development of novel Mycobacterium tuberculosis l-alanine dehydrogenase inhibitors

  摘要：

  In the present study, we used crystal structure of MTB L-AlaDH protein complex with N-6-methyl adenosine for structure based virtual screening of in house database to identify new small molecule inhibitors for MTB-L-AlaDH. Two molecules identified as better leads and were modified synthetically to obtain thirty novel analogues belonging to 2-iminothiazolidine-4-ones and 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamides. Among the screened compounds four (4n, 40,12 and 14) emerged as potent inhibitors displaying IC50 values ranging from 0.58 +/- 0.02 to 1.74 +/- 0.03 mu M against MTB-L-AlaDH and were non-cytotoxic at 50 mu M. Some of these synthesized compounds also exhibited good activity against nutrient starved dormant MTB cells. The most potent inhibitors were found to stabilize the protein which was confirmed biophysically through differential scanning fluorimetry. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.046

文献信息

• Design and development of novel Mycobacterium tuberculosis l-alanine dehydrogenase inhibitors
  作者：Shalini Saxena、Ganesh Samala、Jonnalagadda Padma Sridevi、Parthiban Brindha Devi、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.ejmech.2014.12.046

  日期：2015.3

  In the present study, we used crystal structure of MTB L-AlaDH protein complex with N-6-methyl adenosine for structure based virtual screening of in house database to identify new small molecule inhibitors for MTB-L-AlaDH. Two molecules identified as better leads and were modified synthetically to obtain thirty novel analogues belonging to 2-iminothiazolidine-4-ones and 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamides. Among the screened compounds four (4n, 40,12 and 14) emerged as potent inhibitors displaying IC50 values ranging from 0.58 +/- 0.02 to 1.74 +/- 0.03 mu M against MTB-L-AlaDH and were non-cytotoxic at 50 mu M. Some of these synthesized compounds also exhibited good activity against nutrient starved dormant MTB cells. The most potent inhibitors were found to stabilize the protein which was confirmed biophysically through differential scanning fluorimetry. (C) 2015 Elsevier Masson SAS. All rights reserved.