2-氨基-4-(噻吩-2-基)噻吩-3-甲腈 | 276670-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 双噻吩和低聚噻吩
• 中文名称: 2-氨基-4-(噻吩-2-基)噻吩-3-甲腈
• 英文名称: 5′-amino-[2,3′-bithiophene]-4′-carbonitrile
• 英文别名: 2-amino-4-(thiophene-2-yl)thiophene-3-carbonitrile；2-amino-4-(thiophen-2-yl)thiophene-3-carbonitrile；2-amino-4-(2-thienyl)-3-thiophenecarbonitrile；5'-amino-2,3'-bithiophene-4'-carbonitrile；2-(5-amino-4-cyano-3-thienyl)thiophene；5'-amino-[2,3']bithiophenyl-4'-carbonitrile；2-amino-4-thiophen-2-ylthiophene-3-carbonitrile
• CAS: 276670-60-1
• 化学式: C₉H₆N₂S₂
• mdl: MFCD01105440
• 分子量: 206.292
• InChiKey: OMMDPTFXYBRCBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  13.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.81
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-氨基-4-(噻吩-2-基)噻吩-3-甲腈 在 盐酸 、 亚硝酸特丁酯 、 copper dichloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙腈 为溶剂， 生成 4-chloro-2,5-di(thiophen-2-yl)thieno[2,3-d]pyrimidine
  参考文献：
  名称：

  Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors

  摘要：

  Inactivation of the NF-kappa B signaling pathway by inhibition of IKK beta is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKb inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-alpha, which are well-known inflammatory responses generated by activated NF-kappa B. However, no inhibitory activity against IKK beta was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 mu M. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.058
• 作为产物：
  描述：

  2-乙酰基噻吩 在 哌啶 、 ammonium acetate 、 sulfur 、 溶剂黄146 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 2-氨基-4-(噻吩-2-基)噻吩-3-甲腈
  参考文献：
  名称：

  Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors

  摘要：

  Inactivation of the NF-kappa B signaling pathway by inhibition of IKK beta is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKb inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-alpha, which are well-known inflammatory responses generated by activated NF-kappa B. However, no inhibitory activity against IKK beta was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 mu M. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.058

文献信息

• Synthesis and Antiradiation Activity of Some Sulfur Containing Thiophene Derivatives
  作者：A.Y. Hassan、M.M. Ghorab、O.M. Nassar

  DOI：10.1080/10426509808545453

  日期：1998.2.1

  2-dicyano-1-ethylamino or benzylamino- 1 methylethyl)thiophene (5a,b). Treatment of (2) with elemental sulfur yielded directly the cyclised product 2-(5-amino-4-cyano-3-thienyl)thiophene (6). On the other hand refluxing (2) in pyridine with carbon disulfide gave the pyridine-1,3-dithione derivative (7). Condensation of (2) with phenyl isocyanate and/or phenyl isothiocyanate afforded 6-amino-4-(2-thienyl)-1

  2-(2,2-二氰基-1-甲基乙烯基)噻吩(2)与苯肼缩合得到相应的2-(1-苯肼基乙基)-噻吩(4)。化合物(4)也通过(1)与苯肼的反应获得。(2)与胺的反应得到2-(2,2-二氰基-1-乙氨基或苄氨基-1甲基乙基)噻吩(5a,b)。用元素硫处理(2)直接产生环化产物2-(5-氨基-4-氰基-3-噻吩基)噻吩(6)。另一方面，在吡啶中用二硫化碳回流（2）得到吡啶-1，3-二硫酮衍生物（7）。(2)与异氰酸苯酯和/或异硫氰酸苯酯缩合得到6-氨基-4-(2-噻吩基)-1,2-二氢-2-氧代-1-苯基吡啶-5-甲腈(9)和/或5 -(2-thienyl)-2,7-dithioxo-3,8-N-phenyl-1,2,3,7,8-pentahydropyrido[2,3-d]pyrimidine-4-imine (11)。当与肉桂腈(12)反应时，二氰基衍生物(2)也提供2-(3-氨基-2，4-
• Synthesis of pyridine, pyran and thiazole containing thiophene derivatives and their anti-tumor evaluations
  作者：Rafat M. Mohareb、Rehab A. Ibrahim、Wagnat W. Wardakhan

  DOI：10.1007/s00044-016-1654-3

  日期：2016.10

  ethyl cyanoacetate gave the pyran derivatives 4a–4f and pyridine derivatives 5a–5f. On the other hand, the reaction of the 2-acetylthiophene with elemental sulfur and either malononitrile or ethyl cyanoacetate gave the thiophene derivatives 6a and 6b; respectively. Compounds 6a and 6b underwent a series of heterocyclic reactions to give thiazole and thiophene derivatives. All the products were assessed

  2-乙酰基噻吩与芳族醛，丙二腈或氰基乙酸乙酯的多组分反应得到吡喃衍生物4a - 4f和吡啶衍生物5a - 5f。另一方面，2-乙酰基噻吩与元素硫和丙二腈或氰基乙酸乙酯的反应得到了噻吩衍生物6a和6b。分别。化合物6a和6b进行了一系列杂环反应，得到噻唑和噻吩衍生物。评估了所有产品对人胃癌，胃癌（NUGC和HR），人结肠癌（DLD1），人肝癌（HA22T和HEPG2），人乳腺癌（MCF），鼻咽癌（HONE1）细胞系的抗肿瘤活性。 。化合物4e，4f，5e，5f，7b，8b，10e，10f，11e，11f，14d-f，15d-f，16a，b和18b对癌细胞系表现出最佳的细胞毒性作用，IC 50在nM范围内。此外，7b，10e，14d，15e和16b对虾幼虫没有毒性。最有效的化合物对癌细胞系的抗增殖细胞活性表明，在所测试的化合物中，化合物5f和10e的活性最高。
• New conditions for the synthesis of thiophenes via the Knoevenagel/Gewald reaction sequence. Application to the synthesis of a multitargeted kinase inhibitor
  作者：David M. Barnes、Anthony R. Haight、Thomas Hameury、Maureen A. McLaughlin、Jianzhang Mei、Jason S. Tedrow、Joan Dalla Riva Toma

  DOI：10.1016/j.tet.2006.07.008

  日期：2006.12

  Novel conditions have been developed for the preparation of substituted 2-aminothiophenes employing the Knoevenagel condensation followed by the Gewald reaction. The benefits of these conditions are their mildness, and the ease of product isolation. Thus, the Knoevenagel condensation is run in the presence of hexamethyldisilazane and acetic acid, which combine to perform the roles of desiccant, and catalyst. The Gewald reaction is performed with inorganic base in THF/water, which suppresses byproduct formation. This process has been employed in the total synthesis of a multitargeted kinase inhibitor. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents
  作者：Jee Sun Yang、Chun-Ho Park、Chulho Lee、Hwan Kim、Changmok Oh、Yejoo Choi、Jong Soon Kang、Jieun Yun、Jin-Hyun Jeong、Myung-Hwa Kim、Gyoonhee Han

  DOI：10.1016/j.ejmech.2014.08.001

  日期：2014.10

  The most common mutations in acute myeloid leukemia (AML) are those that cause the activation of FMS-like tyrosine kinase 3 (FLT3). Therefore, FLT3 is regarded as a potential target for the treatment of AML A novel series of thieno[2,3-d]pyrimidine-based analogs was designed and synthesized as FLT3 inhibitors. All synthesized compounds were assayed for the tyrosine kinase activity of FLT3 and growth inhibitory activity in four human leukemia cell lines (THP1, MV4-11, K562, and HL-60). Among these compounds, compound 17a, which possesses relatively short and simple substituents at the C-6 position of thieno[2,3-d]pyrimidine, emerged as the most promising anti-leukemic agent. Compound 17a exhibited potent inhibition of FLT3-positive leukemic cell growth and of the FLT3 D835Y kinase; such inhibition is required for the successful treatment of AML. The data supports the further investigation of this class of compounds as potential anti-leukemic agents. (C) 2014 Elsevier Masson SAS. All rights reserved.
• WO2007/102679
  申请人：——

  公开号：——

  公开（公告）日：——