2-cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazole | 940391-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazole
• CAS: 940391-41-3
• 化学式: C₁₃H₁₀FN₃S
• 分子量: 259.307
• InChiKey: RIAQZEKIYSSKAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazole 在 哌啶 、 溶剂黄146 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 4.5h， 生成 2-[5-[[2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
  参考文献：
  名称：

  Design, synthesis and evaluation of small molecule imidazo[2,1-b][1,3,4]thiadiazoles as inhibitors of transforming growth factor-β type-I receptor kinase (ALK5)

  摘要：

  A new series of imidazo[2,1-b][1,3,4]thiadiazoles 5(a-g), 6(a-g), 9(a-i) and 12(a-h) were synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-beta -induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. Compound 6d, 2-(5((2-cyclopropy1-6-(4-fluorophenyl) imidazo [2,1-b][1,3,4]thiadiazol-5-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid, shows prominent ALK5 inhibition (IC50 = 0.0012 mu M) and elective inhibition (91%) against the P38 alpha kinase at10 mu M. The binding mode of compound 6d by XP docking studies shows that it fits well into the active site cavity of ALK5 by forming broad and tight interactions. Lipinski's rule and in silica ADME pharmacokinetic parameters are within the acceptable range defined for human use thereby indicating their potential as a drug-like molecules. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.002
• 作为产物：
  描述：

  2-氨基-5-环丙基-1,3,4-噻二唑 、 2-溴-4'-氟苯乙酮 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 以75 %的产率得到2-cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazole
  参考文献：
  名称：

  含咪唑并[2,1-b][1,3,4]噻二唑基团的吡唑衍生物的合成及抗菌活性评价

  摘要：

  合成了四个系列的新型吡唑衍生物（化合物17a – m、18a – m、19a – g和20a – g ），并评估了它们的抗菌和抗真菌活性。大多数目标化合物（17a – m、18k – m和19b – g）对革兰氏阳性菌和革兰氏阴性菌均表现出很强的抗真菌活性和高选择性。其中，化合物17l（最低抑菌浓度[MIC] = 0.25 µg/mL）和17m（MIC = 0.25 µg/mL）显示出最强的抗真菌活性，比阳性对照加替沙星和氟康唑活性高2倍和4倍， 分别。特别地，化合物17l对人LO2细胞表现出很小的细胞毒性，并且在超高浓度下不表现出溶血，阳性对照化合物加替沙星和氟康唑也是如此。这些结果表明这些化合物对于进一步开发作为抗真菌剂是有价值的。

  DOI：

  10.1002/ardp.202300110

文献信息

• Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives
  作者：Malleshappa N. Noolvi、Harun M. Patel、Navjot Singh、Andanappa K. Gadad、Swaranjit Singh Cameotra、Arvind Badiger

  DOI：10.1016/j.ejmech.2011.07.012

  日期：2011.9

  A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]-thiadiazole derivatives 4(a–k) have been prepared by reaction of 2-amino-5-cyclopropyl-1,3,4-thiadiazole and an appropriate phenacyl bromide. Further 5-bromo 5(a–k) and 5-thiocyanato 6(a–k) derivatives were synthesized in order to study the effect of these substituents on antitumor activity. Structures of these compounds were established by IR

  通过2-氨基-5-环丙基-1的反应制备了一系列2,5,6-三取代的咪唑并[ 2,1 - b ] [1,3,4]-噻二唑衍生物4（a - k）， 3,4-噻二唑和适当的苯甲酰溴。为了研究这些取代基对抗肿瘤活性的影响，还合成了5-溴5（a - k）和5-硫氰酸根6（a - k）衍生物。这些化合物的结构通过IR，1 H NMR，13建立。13 C NMR和质谱。七种化合物在美国国家癌症研究所（NCI）被授予NSC代码，以 在完整的NCI 60细胞组中以单次高剂量（10 -5 M）进行抗癌活性。在测试的化合物中，发现5-溴-6-（4-氯苯基）-2-环丙基咪唑并[ 2,1 - b ] [1,3,4]噻二唑5b（NSC  D - 96022 / 1）是最多的在对白血病癌细胞系具有选择性程度的五个剂量水平筛选中，该系列的有效候选药物。
• Design, synthesis and evaluation of small molecule imidazo[2,1-b][1,3,4]thiadiazoles as inhibitors of transforming growth factor-β type-I receptor kinase (ALK5)
  作者：Harun M. Patel、Baljeet Sing、Varun Bhardwaj、Mahesh Palkar、Mahamadhanif S. Shaikh、Rajesh Rane、Wesam S. Alwan、Andanappa K. Gadad、Malleshappa N. Noolvi、Rajshekhar Karpoormath

  DOI：10.1016/j.ejmech.2014.09.002

  日期：2015.3

  A new series of imidazo[2,1-b][1,3,4]thiadiazoles 5(a-g), 6(a-g), 9(a-i) and 12(a-h) were synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-beta -induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. Compound 6d, 2-(5((2-cyclopropy1-6-(4-fluorophenyl) imidazo [2,1-b][1,3,4]thiadiazol-5-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid, shows prominent ALK5 inhibition (IC50 = 0.0012 mu M) and elective inhibition (91%) against the P38 alpha kinase at10 mu M. The binding mode of compound 6d by XP docking studies shows that it fits well into the active site cavity of ALK5 by forming broad and tight interactions. Lipinski's rule and in silica ADME pharmacokinetic parameters are within the acceptable range defined for human use thereby indicating their potential as a drug-like molecules. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing the imidazo[2,1‐<i>b</i>][1,3,4]thiadiazole moiety
  作者：Jun‐Da Qi、Yu‐Qing Meng、Jingxin Sun、Wan‐Xin Li、Hou‐Xiang Zhai、Changhao Zhang、Jishan Quan、Cheng‐Hua Jin

  DOI：10.1002/ardp.202300110

  日期：2023.8

  Four series of novel pyrazole derivatives (compounds 17a–m, 18a–m, 19a–g, and 20a–g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a–m, 18k–m, and 19b–g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0

  合成了四个系列的新型吡唑衍生物（化合物17a – m、18a – m、19a – g和20a – g ），并评估了它们的抗菌和抗真菌活性。大多数目标化合物（17a – m、18k – m和19b – g）对革兰氏阳性菌和革兰氏阴性菌均表现出很强的抗真菌活性和高选择性。其中，化合物17l（最低抑菌浓度[MIC] = 0.25 µg/mL）和17m（MIC = 0.25 µg/mL）显示出最强的抗真菌活性，比阳性对照加替沙星和氟康唑活性高2倍和4倍， 分别。特别地，化合物17l对人LO2细胞表现出很小的细胞毒性，并且在超高浓度下不表现出溶血，阳性对照化合物加替沙星和氟康唑也是如此。这些结果表明这些化合物对于进一步开发作为抗真菌剂是有价值的。