10-(4-Methoxyphenyl)-4-nitro-5-thia-2,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,6-triene-8,12-dione | 1423875-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 10-(4-Methoxyphenyl)-4-nitro-5-thia-2,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,6-triene-8,12-dione
• 英文别名: 10-(4-methoxyphenyl)-4-nitro-5-thia-2,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,6-triene-8,12-dione
• CAS: 1423875-24-4
• 化学式: C₁₅H₁₁N₅O₅S
• 分子量: 373.349
• InChiKey: SCRNPLLQADZIRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  155
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-imino-2-nitro-5H-thiazolo[3,2-a]pyrimidin-7(6H)-one 在 盐酸 、 水 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 10-(4-Methoxyphenyl)-4-nitro-5-thia-2,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,6-triene-8,12-dione
  参考文献：
  名称：

  Discovery of novel inhibitors targeting the Mycobacterium tuberculosis O-acetylserine sulfhydrylase (CysK1) using virtual high-throughput screening

  摘要：

  Cysteine biosynthesis in Mycobacterium tuberculosis (MTB) is crucial for this pathogen to combat oxidative stress and for long term survival in the host. Hence inhibition of this pathway is attractive for developing novel drugs against tuberculosis. In the present study, the crystal structure of the mycobacterial enzyme O-acetylserine sulfhydrylase CysK1 bound to an oligopeptide inhibitor was used as a framework for virtual screening of the BITS-Pilani in-house database to identify new scaffolds as CysK1 inhibitors. Thirty compounds were synthesized and evaluated in vitro for their ability to inhibit CysK1, activity against M. tuberculosis and cytotoxicity as steps towards the derivation of structure-activity relationships (SAR) and lead optimization. Compound 8-nitro-4-(2-(trifluoromethyl) phenyl)-4,4a-dihydro-2H-pyrimido[5,4-e]thiazolo[3,2-a]pyrimidine-2,5(3H)-dione (4n) emerged as the most promising lead with an IC50 of 17.7 mu M for purified CysK1 and MIC of 7.6 mu M for M. tuberculosis, with little or no cytotoxicity (>50 mu M). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.031

文献信息

• Discovery of novel inhibitors targeting the Mycobacterium tuberculosis O-acetylserine sulfhydrylase (CysK1) using virtual high-throughput screening
  作者：Variam Ullas Jean kumar、Ömer Poyraz、Shalini Saxena、Robert Schnell、Perumal Yogeeswari、Gunter Schneider、Dharmarajan Sriram

  DOI：10.1016/j.bmcl.2013.01.031

  日期：2013.3

  Cysteine biosynthesis in Mycobacterium tuberculosis (MTB) is crucial for this pathogen to combat oxidative stress and for long term survival in the host. Hence inhibition of this pathway is attractive for developing novel drugs against tuberculosis. In the present study, the crystal structure of the mycobacterial enzyme O-acetylserine sulfhydrylase CysK1 bound to an oligopeptide inhibitor was used as a framework for virtual screening of the BITS-Pilani in-house database to identify new scaffolds as CysK1 inhibitors. Thirty compounds were synthesized and evaluated in vitro for their ability to inhibit CysK1, activity against M. tuberculosis and cytotoxicity as steps towards the derivation of structure-activity relationships (SAR) and lead optimization. Compound 8-nitro-4-(2-(trifluoromethyl) phenyl)-4,4a-dihydro-2H-pyrimido[5,4-e]thiazolo[3,2-a]pyrimidine-2,5(3H)-dione (4n) emerged as the most promising lead with an IC50 of 17.7 mu M for purified CysK1 and MIC of 7.6 mu M for M. tuberculosis, with little or no cytotoxicity (>50 mu M). (C) 2013 Elsevier Ltd. All rights reserved.