tert-butyl 3-carbamoyl-2-(4-phenoxybenzamido)-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate | 1585244-86-5

• 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: tert-butyl 3-carbamoyl-2-(4-phenoxybenzamido)-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate
• 英文别名: tert-butyl 3-carbamoyl-2-[(4-phenoxybenzoyl)amino]-5,7-dihydro-4H-thieno[2,3-c]pyridine-6-carboxylate
• CAS: 1585244-86-5
• 化学式: C₂₆H₂₇N₃O₅S
• 分子量: 493.583
• InChiKey: LWHZVKUOTVFAEX-UHFFFAOYSA-N

物化性质

• 沸点：
  566.8±50.0 °C(predicted)
• 密度：
  1.326±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-carbamoyl-2-(4-phenoxybenzamido)-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 6-methyl-2-(4-phenoxybenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
  参考文献：
  名称：

  Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3-carboxamides and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from known antimycobacterial lead

  摘要：

  Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide and ten of 2-substituted 4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide were synthesized by molecular modification of a known antimycobacterial molecule. Compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most active compound against MTB with MIC of 3.70 mu M and was more potent than Ethambutol (MIC of 7.64 mu M), Ciprofloxacin (MIC of 9.41 mu M) and standard lead compound SID 92097880 (MIC of 9.15 mu M). Compound 12f also showed MTB MIC of 1.23 mu M in the presence of an efflux pump inhibitor verapamil, and showed no cytotoxicity at 50 mu M. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.02.028
• 作为产物：
  描述：

  4-苯氧基苯甲酸 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.33h， 生成 tert-butyl 3-carbamoyl-2-(4-phenoxybenzamido)-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate
  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

• Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3-carboxamides and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from known antimycobacterial lead
  作者：Radhika Nallangi、Ganesh Samala、Jonnalagadda Padma Sridevi、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.ejmech.2014.02.028

  日期：2014.4

  Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide and ten of 2-substituted 4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide were synthesized by molecular modification of a known antimycobacterial molecule. Compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most active compound against MTB with MIC of 3.70 mu M and was more potent than Ethambutol (MIC of 7.64 mu M), Ciprofloxacin (MIC of 9.41 mu M) and standard lead compound SID 92097880 (MIC of 9.15 mu M). Compound 12f also showed MTB MIC of 1.23 mu M in the presence of an efflux pump inhibitor verapamil, and showed no cytotoxicity at 50 mu M. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 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.