5-(2-氟苄基)-1,3-噻唑-2-胺 | 876715-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(2-氟苄基)-1,3-噻唑-2-胺
• 中文别名: 5-[(2-氟苯基)甲基]-1,3-噻唑-2-胺
• 英文名称: 5-(2-fluorobenzyl)-2-thiazolamine
• 英文别名: 5-(2-fluorobenzyl)thiazol-2-amine；5-(2-Fluorobenzyl)-1,3-thiazol-2-amine；5-[(2-fluorophenyl)methyl]-1,3-thiazol-2-amine
• CAS: 876715-72-9
• 化学式: C₁₀H₉FN₂S
• mdl: MFCD05863659
• 分子量: 208.259
• InChiKey: MJWGGQHOCHEUHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi

反应信息

• 作为反应物：
  描述：

  5-(2-氟苄基)-1,3-噻唑-2-胺 、 3-环己基丙酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以67%的产率得到3-cyclohexyl-N-[5-(2-fluorobenzyl)thiazol-2-yl]propanamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

  摘要：

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.006
• 作为产物：
  描述：

  2-氟苯甲醛 在 三乙基硅烷 、 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 5-(2-氟苄基)-1,3-噻唑-2-胺
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

  摘要：

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.006

文献信息

• [EN] COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS
  申请人：YUMANITY THERAPEUTICS INC

  公开号：WO2020198026A1

  公开（公告）日：2020-10-01

  The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.

  本发明涉及对神经系统疾病和原发性脑癌治疗中有用的化合物。本发明的化合物，单独或与其他药用活性剂结合使用，可用于治疗或预防神经系统疾病和原发性脑癌。
• NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
  申请人：Florjancic S. Alan

  公开号：US20080064699A1

  公开（公告）日：2008-03-13

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R 1 , R 2 , R 3 , R 4 , and L 2 , are defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

  本发明涉及式（I）的化合物，或其药学上可接受的盐，前药，前药盐或其组合物，其中R1，R2，R3，R4和L2在规范中有定义，包括这些化合物的组合物，以及使用这些化合物和组合物治疗疾病和病症的方法。
• NRF2 SMALL MOLECULE INHIBITORS FOR CANCER THERAPY
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20160046616A1

  公开（公告）日：2016-02-18

  Small molecule inhibitors of Nrf2 and methods of their use are provided for treating or preventing a disease, disorder or condition associated with an Nrf2-regulated pathway. The compound can be administered as a single agent or can be administered to enhance the efficacy of a chemotherapeutic drug and/or radiation therapy.

  提供了Nrf2的小分子抑制剂及其使用方法，用于治疗或预防与Nrf2调节通路相关的疾病、疾患或病情。该化合物可以作为单一药剂使用，也可以用于增强化疗药物和/或放射治疗的疗效。
• Discovery of an Allosteric, Inactive Conformation-Selective Inhibitor of Full-Length HPK1 Utilizing a Kinase Cascade Assay
  作者：Weixue Wang、Laurence Mevellec、Annie Liu、Geoff Struble、Robyn Miller、Samantha J. Allen、Kelly Federowicz、Berthold Wroblowski、Jorge Vialard、Kay Ahn、Daniel Krosky

  DOI：10.1021/acs.biochem.1c00486

  日期：2021.10.19

  Achieving selectivity across the human kinome is a major hurdle in kinase inhibitor drug discovery. Assays using active, phosphorylated protein kinases bias hits toward poorly selective inhibitors that bind within the highly conserved adenosine triphosphate (ATP) pocket. Targeting inactive (vs active) kinase conformations offers advantages in achieving selectivity because of their more diversified

  在人类激酶组中实现选择性是激酶抑制剂药物发现的主要障碍。使用活性磷酸化蛋白激酶的分析偏向于结合在高度保守的三磷酸腺苷 (ATP) 口袋内的选择性差的抑制剂。定位无效（与活性）激酶构象因其更多样化的结构而在实现选择性方面具有优势。激酶级联分析通常以未磷酸化的非活性形式的靶激酶启动，这些激酶在分析过程中被激活。因此，这些测定能够鉴定除与活性形式结合的抑制剂外，优先结合酶的非磷酸化形式的抑制剂。我们将这种级联分析应用于新兴的癌症免疫疗法靶向造血祖细胞激酶 1 (HPK1)，这是一种负调节 T 细胞受体信号传导的丝氨酸/苏氨酸激酶。使用这种方法，我们发现了一种变构的、无活性的构象选择性三唑并嘧啶酮 HPK1 抑制剂，即化合物1。化合物1与未磷酸化的 HPK1 的结合比活性 HPK1 强 24 倍以上，不与 ATP 竞争，并且对对于 T 细胞信号传导至关重要的激酶具有高度选择性。此外，化合物1不单独与分离的
• COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
  申请人：AbbVie Inc.

  公开号：EP2024349B1

  公开（公告）日：2017-08-02