5-叠氮-1H-苯并[d]咪唑 | 34594-87-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 5-叠氮-1H-苯并[d]咪唑
• 英文名称: 5-azido-1H-benzo[d]imidazole
• 英文别名: 6-azido-1H-1,3-benzodiazole；6-azido-1H-benzimidazole
• CAS: 34594-87-1
• 化学式: C₇H₅N₅
• mdl: MFCD06240528
• 分子量: 159.15
• InChiKey: FLLNGOREBREUGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43
• 氢给体数：
  1
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  5-氨基苯并咪唑	5-Aminobenzimidazole	934-22-5	C7H7N3	133.153
  6-硝基苯并咪唑	5-Nitrobenzimidazole	94-52-0	C7H5N3O2	163.13

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  (9ci)-N,N-二乙基-1H-苯并咪唑-5-胺	5(6)-diethylaminobenzimidazole	76007-11-9	C11H15N3	189.26

反应信息

• 作为反应物：
  描述：

  5-叠氮-1H-苯并[d]咪唑 在 盐酸 、 次磷酸 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 11.0h， 生成 (9ci)-N,N-二乙基-1H-苯并咪唑-5-胺
  参考文献：
  名称：

  叠氮基-苯并[ b ]噻吩，-苯并噻唑，-苯并咪唑和-吲唑的合成和光解：新型的6,7-二氨基-苯并噻唑，-苯并咪唑和-吲唑和6-二乙基氨基-8 H-噻唑啉[5,4 - ç ]氮杂

  摘要：

  在过量仲胺存在下照射6-叠氮基苯并噻唑（4）-（9）（参见方案），得到相应的6,7-二氨基苯并噻唑（14）-（20），即6-氨基-8 H-噻唑并[5,4- c ]氮杂（21）-（24），两者的混合物或难处理的物质[如叠氮化物（9）的情况]。7-叠氮基-3-甲基苯并[照射b ]在过量的二乙胺的噻吩，得到7-氨基-3-甲基苯并[ b ]噻吩和3,3'-二甲基-7,7'- azobenzo痕量[ b]噻吩。6-叠氮基吲唑生成7-氨基-6-二乙基氨基吲唑（32）和5（6）-叠氮基苯并咪唑生成4（7）-氨基-5（6）-二乙基氨基苯并咪唑（33）和5（6）-氨基-4的混合物（7）-二乙氨基苯并咪唑（34）。将6-叠氮基苯并噻唑或其2-甲基衍生物在甲醇氧化物甲醇-二恶烷混合物中进行光解，分别得到相应的6-甲氧基-8 H-噻唑并[5,4- c ] a庚因，分别为（30）或（31）。

  DOI：

  10.1039/p19800002362
• 作为产物：
  描述：

  在 sodium azide 作用下， 以 乙腈 为溶剂， 生成 5-叠氮-1H-苯并[d]咪唑
  参考文献：
  名称：

  Discovery and structure-activity relationship studies of 1-aryl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as potent dual inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and trytophan 2,3-dioxygenase (TDO)

  摘要：

  Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), which mediate kynurenine pathway of tryptophan degradation, have emerged as potential new targets in immunotherapy for treatment of cancer because of their critical role in immunosuppression in the tumor microenvironment. In this investigation, we report the structural optimization and structure-activity relationship studies of 1-phenyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as a new class of IDO1/TDO dual inhibitors. Among all the obtained dual inhibitors, 1-(3-chloro-4-fluorophenyl)-6-fluoro-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (38) displayed the most potent IDO1 and TDO inhibitory activities with IC₅₀ (half-maximal inhibitory concentration) values of 5 nM for IDO1 and 4 nM for TDO. It turned out that compound 38 was not a PAINS compound. Compound 38 could efficiently inhibit the biofunction of IDO1 and TDO in intact cells. In LL2 (Lewis lung cancer) and Hepa1-6 (hepatic carcinoma) allograft mouse models, this compound also showed considerable in vivo anti-tumor activity and no obvious toxicity was observed. Therefore, 38 could be a good lead compound for cancer immunotherapy and deserving further investigation.

  DOI：

  10.1016/j.ejmech.2020.112703

文献信息

• [EN] DIHYDROTHIENO[3,2-b]PYRIDINE COMPOUNDS<br/>[FR] COMPOSÉS DE DIHYDROTHIÉNO [3,2-B] PYRIDINE
  申请人：IDEAYA BIOSCIENCES INC

  公开号：WO2019067442A1

  公开（公告）日：2019-04-04

  Compounds are provided having Formula (I): wherein R, R1, Cyc and A have the meanings provided herein. The compounds have utility in the treatment of diseases, either alone or in combination with other agents.

  提供具有公式(I)的化合物：其中R、R1、Cyc和A具有本文件中提供的含义。这些化合物可用于治疗疾病，可以单独使用，也可以与其他药剂联合使用。
• [EN] PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINES KINASES
  申请人：ORION CORP

  公开号：WO2014162039A1

  公开（公告）日：2014-10-09

  A compound of formula (I), wherein R1 to R5, A, B, Z, Z1 and Z2 are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.

  公式（I）的化合物，其中R1至R5，A，B，Z，Z1和Z2如权利要求中所定义，并公开其药学上可接受的盐。公式（I）的化合物具有作为FGFR抑制剂的效用，并在需要FGFR激酶抑制的情况下，如癌症治疗中是有用的。
• PROTEIN KINASE INHIBITORS
  申请人：ORION CORPORATION

  公开号：US20160031855A1

  公开（公告）日：2016-02-04

  A compound of formula (I) wherein R 1 to R 5 , A, B, Z, Z 1 and Z 2 are as defined in the claims or a pharmaceutically acceptable salt thereof is disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.

  本文披露了一种化合物，其化学式为(I)，其中R1至R5、A、B、Z、Z1和Z2如权利要求中所定义，或其药学上可接受的盐。化合物(I)具有作为FGFR抑制剂的效用，并可用于治疗需要FGFR激酶抑制的疾病，如癌症。
• GALLAGHER P. T.; IDDON B.; SUSCHITZKY H., J. CHEM. SOC. PERKIN TRANS., PART 1, 1980, NO 11, 2362-2370
  作者：GALLAGHER P. T.、 IDDON B.、 SUSCHITZKY H.

  DOI：——

  日期：——
• Discovery and structure-activity relationship studies of 1-aryl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as potent dual inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and trytophan 2,3-dioxygenase (TDO)
  作者：Shulei Pan、Yangli Zhou、Qiusheng Wang、Yanlin Wang、Chenyu Tian、Tianqi Wang、Luyi Huang、Jinshan Nan、Linli Li、Shengyong Yang

  DOI：10.1016/j.ejmech.2020.112703

  日期：2020.12

  Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), which mediate kynurenine pathway of tryptophan degradation, have emerged as potential new targets in immunotherapy for treatment of cancer because of their critical role in immunosuppression in the tumor microenvironment. In this investigation, we report the structural optimization and structure-activity relationship studies of 1-phenyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as a new class of IDO1/TDO dual inhibitors. Among all the obtained dual inhibitors, 1-(3-chloro-4-fluorophenyl)-6-fluoro-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (38) displayed the most potent IDO1 and TDO inhibitory activities with IC₅₀ (half-maximal inhibitory concentration) values of 5 nM for IDO1 and 4 nM for TDO. It turned out that compound 38 was not a PAINS compound. Compound 38 could efficiently inhibit the biofunction of IDO1 and TDO in intact cells. In LL2 (Lewis lung cancer) and Hepa1-6 (hepatic carcinoma) allograft mouse models, this compound also showed considerable in vivo anti-tumor activity and no obvious toxicity was observed. Therefore, 38 could be a good lead compound for cancer immunotherapy and deserving further investigation.