5-(4-氟苄基)-1,3,4-噻二唑-2-胺 | 39181-55-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-(4-氟苄基)-1,3,4-噻二唑-2-胺
• 中文别名: 5-(4-氟-苄基)-[1,3,4]噻二唑-2-基胺
• 英文名称: 5-(4-fluorobenzyl)-1,3,4-thiadiazol-2-amine
• 英文别名: 5-[(4-fluorophenyl)methyl]-1,3,4-thiadiazol-2-amine
• CAS: 39181-55-0
• 化学式: C₉H₈FN₃S
• mdl: MFCD01364163
• 分子量: 209.247
• InChiKey: XHFWYSOJZBOIDC-UHFFFAOYSA-N

物化性质

• 熔点：
  205-207 °C(Solv: ethanol (64-17-5))
• 沸点：
  390.0±44.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)
• 溶解度：
  26.6 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  5-(4-氟苄基)-1,3,4-噻二唑-2-胺 在 ammonium acetate 、 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 8.33h， 生成 (E)-2-(2-cyano-3-((5-(4-fluorobenzyl)-1,3,4-thiadiazol-2-yl)amino)-3-oxoprop-1-en-1-yl)phenyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells

  摘要：

  A lead compound with the (1,3,4-thiadiazol-2-yl) acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC50, values of 1-5 mu M on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC50 > 50 mu M on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia.

  DOI：

  10.1016/j.bmcl.2020.127114
• 作为产物：
  描述：

  2-[(4-fluorophenyl)acetyl]hydrazinecarbothioamide 在 硫酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 以0.264 g的产率得到5-(4-氟苄基)-1,3,4-噻二唑-2-胺
  参考文献：
  名称：

  THIADIAZOLE AND OXADIAZOLE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

  摘要：

  这项发明涉及到化合物的公式（I），无论是（i）处于碱态或酸盐形式，还是（ii）处于酸态或碱盐形式，以及制备该化合物的方法和其治疗应用。

  公开号：

  US20120040984A1

文献信息

• Synthesis and Anticancer Activity of Thiadiazole Containing Thiourea, Benzothiazole and Imidazo[2,1-b][1,3,4]thiadiazole Scaffolds
  作者：Stephen P. Avvaru、Malleshappa N. Noolvi、Uttam A. More、Sudipta Chakraborty、Ashutosh Dash、Tejraj M. Aminabhavi、Kumar P. Narayan、Vishnu Sutariya

  DOI：10.2174/1573406416666200519085626

  日期：2021.8

  potential scaffolds with promising anticancer activity. Methods: A new series of 5-substituted-1,3,4-thiadiazoles linked with phenyl thiourea, benzothiazole and 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized and tested for invitro anticancer activity on various cancer cell lines. Results: The National Cancer Institute’s preliminary anticancer screening results showed compounds

  背景：大量含氮杂环因其在医学领域的多功能性而被广泛探索，尤其是在抗癌研究中。1,3,4-噻二唑是此类杂环中的一种，对多种癌细胞系具有良好的抗癌活性，可抑制多种生物靶标。 简介： 1,3,4-噻二唑与其他杂环支架配合使用时，显示出增强的抗癌特性。硫脲、苯并噻唑、咪唑并[2,1,b][1,3,4]-噻二唑是具有良好抗癌活性的潜在支架。 方法：合成并测试了一系列与苯基硫脲、苯并噻唑和2,6-二取代咪唑并[2,1-b][1,3,4]噻二唑相连的新系列5-取代-1,3,4-噻二唑用于对各种癌细胞系的体外抗癌活性。 结果：美国国家癌症研究所的初步抗癌筛选结果显示化合物 4b 和 5b 具有有效的抗白血病活性。化合物 4b 对 Human Leukemia-60 细胞系选择性地显示出 32% 的致死率。芳香酶衍生物的对接研究（蛋白质数据库：3S7S）显示活性位点的可逆相互作用具有与来曲唑和依西美坦相当的
• Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4′-fluorophenyl)-imidazo[2,1-b][1,3,4]thiadiazole derivatives as potent anticancer agents
  作者：Subhas S. Karki、Kuppusamy Panjamurthy、Sujeet Kumar、Mridula Nambiar、Sureshbabu A. Ramareddy、Kishore K. Chiruvella、Sathees C. Raghavan

  DOI：10.1016/j.ejmech.2011.02.064

  日期：2011.6

  Levamisole, the imidazo[2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but different side chains namely 2-aralkyl-6-(4′-fluorophenyl)-imidazo[2,1-b][1,3,4]thiadiazoles

  咪唑并[2,1-b]噻唑衍生物左旋咪唑据报道是潜在的抗肿瘤药。在本研究中，我们合成，表征和评估了其新类似物的化学活性，这些新类似物在芳烷基中和具有相同化学主链但侧链不同的咪唑并噻二唑分子即2-芳烷基-6-（4'-氟苯基）-咪唑上具有取代作用[2,1-b] [1,3,4]噻二唑（SCR1），2-芳烷基-5-溴-6-（4'-氟苯基）-咪唑[2,1-b] [1,3,4 ]-噻二唑（SCR2），2-芳烷基-5-甲酰基-6-（4'-氟苯基）-咪唑[2,1-b] [1,3,4]-噻二唑（SCR3）和2-芳烷基-5 -白血病细胞上的-thiocyanato-6-（4'-氟苯基）-咪唑并[2,1-b] [1,3,4]-噻二唑（SCR4）。细胞毒性研究表明3a，4a和4c表现出很强的细胞毒性，而其他的则具有中等的细胞毒性。在这些我们选择了图4a（IC 50，μM8）为理解它的细胞毒性的机制。FACS分析结合
• [EN] 5-AMINO-2-CARBONYLTHIOPHENE DERIVATIVES FOR USE AS P38 MAP KINASE INHIBITORS IN THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] DERIVES DE 5-AMINO-2-CARBONYLTHIOPHENE UTILISES EN TANT QU'INHIBITEURS DE LA P38 MAP KINASE DANS LE TRAITEMENT DES MALADIES INFLAMMATOIRES
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2004089929A1

  公开（公告）日：2004-10-21

  The invention provides the use of a compound for the manufacture of a medicament for the prophylaxis or treatment of a disease state or condition mediated by a p38 MAP kinase; the compound being defined by formula (I): wherein: R1 and R2 are the same or different and each is selected from hydrogen, C1-4 hydrocarbyl, halogen and cyano; X is selected from C=O, C=S, C(=O)NH, C(=S)NH, C(=O)O, C(=O)S, C(=S)O and C(=S)S; R3 is selected from aryl and heteroaryl groups each having from 5 to 12 ring members, the aryl and heteroaryl groups each being unsubstituted or substituted by one or more substituent groups R7 selected from halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group Ra-Rb wherein Ra is a bond, 0, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc or NRcSO2; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 7 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by 0, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; X1 is 0, S or NRc and X2 is =0, =S or =NRc; Rc is hydrogen or C1-4 hydrocarbyl; R4 is a group YR5 or a group R6; Y is is NH, 0 or S; R5 is selected from (a) carbocyclic and heterocyclic groups having from 3 to 12 ring members; and (b) C1-8 hydrocarbyl groups optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, amino, mono- or di- C1-4 hydrocarbylamino, and carbocyclic and heterocyclic groups having from 3 to 12 ring members, wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by 0, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1, provided that when Y is 0, a carbon atom adjacent to the group Y is not replaced by 0; and R6 is a heterocyclic group having from 4 to 12 ring members and containing at least one ring nitrogen atom through which R6 is linked to the adjacent carbonyl group; wherein the carbocyclic and heterocyclic groups of substituents R5 and R6 are each unsubstituted or substituted by one or more substituent groups R7 as hereinbefore defined. Also provided are novel compounds, pharmaceutical compositions containing the compounds and methods for their preparation.

  本发明提供了一种化合物的用途，用于制备用于预防或治疗由p38 MAP激酶介导的疾病状态或病况的药物；该化合物由以下式（I）定义：其中：R1和R2相同或不同，每个均选择自氢、C1-4烃基、卤素和氰基；X选择自C=O、C=S、C(=O)NH、C(=S)NH、C(=O)O、C(=O)S、C(=S)O和C(=S)S；R3选择自含有5至12个环成员的芳基和杂环芳基，芳基和杂环芳基未取代或通过一个或多个取代基R7取代，所述取代基R7选择自卤素、羟基、三氟甲基、氰基、硝基、羧基、氨基、具有3至12个环成员的碳环和杂环基；一个基团Ra-Rb，其中Ra为键，0，CO，X1C(X2)，C(X2)X1，X1C(X2)X1，S，SO，SO2，NRc，SO2NRc或NRcSO2；Rb选择自氢、具有3至7个环成员的碳环和杂环基，以及一个C1-8烃基，可选地通过一个或多个取代基选择自羟基、酮基、卤素、氰基、硝基、氨基、单或双C1-4烃基氨基、具有3至12个环成员的碳环和杂环基取代，并且C1-8烃基的一个或多个碳原子可选地被0、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1替代；X1为0、S或NRc，X2为=0、=S或=NRc；Rc为氢或C1-4烃基；R4为一个基团YR5或一个基团R6；Y为NH、0或S；R5选择自（a）具有3至12个环成员的碳环和杂环基；和（b）可选地通过一个或多个取代基选择自羟基、酮基、卤素、氰基、氨基、单或双C1-4烃基氨基、具有3至12个环成员的碳环和杂环基取代的C1-8烃基，其中C1-8烃基的一个或多个碳原子可选地被0、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1替代，但是当Y为0时，与基团Y相邻的碳原子不被0替代；R6为具有4至12个环成员的杂环基，并且通过其中一个环氮原子与相邻的羰基连接；取代基R5和R6的碳环和杂环基各自未取代或通过一个或多个取代基R7取代，如前所述。还提供了新的化合物、含有该化合物的制剂以及其制备方法。
• [EN] THIOPHENE AMIDE COMPOUNDS FOR USE IN THE TREATMENT OR PROPHYLAXIS OF CANCERS<br/>[FR] COMPOSES D'AMIDE THIOPHENIQUE DESTINES A ETRE UTILISES DANS LE TRAITEMENT OU LA PROPHYLAXIE DU CANCER
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2006040569A1

  公开（公告）日：2006-04-20

  The invention provides the use of a compound for the manufacture of a medicament for the prophylaxis or treatment of a cancer or a para-neoplastic effect associated with a cancer, the para-neoplastic effect being other than cachexia, and the compound being a compound of the formula (I), or a salt, solvate or N-oxide thereof, wherein: R1 and R2 are the same or different and each is selected from hydrogen, C1-4 hydrocarbyl, halogen and cyano; X is selected from C=O, C=S, C(=O)NH, C(=S)NH, C(=O)O, C(=O)S, C(=S)O and C(=S)S; R3 is an aryl or heteroaryl group of 5 to 12 ring members optionally substituted by one or more substituent groups R7 wherein R7 is as defined in the claims; R4 is a group YR5 or a group R6; Y is NH, O or S; R5 is selected from (a) optionally substituted carbocyclic and heterocyclic groups having from 3 to 12 ring members; and (b) optionally substituted C1-8 hydrocarbyl 20 groups; and R6 is an optionally substituted heterocyclic group having from 4 to 12 ring members and containing at least one ring nitrogen atom through which R6 is linked to the adjacent carbonyl group.

  该发明提供了一种化合物的用途，用于制造用于预防或治疗癌症或与癌症相关的癌前病变效应的药物，其中癌前病变效应不包括虚弱症，该化合物为式(I)的化合物，或其盐、溶剂合物或N-氧化物，其中：R1和R2相同或不同，每个均选自氢、C1-4烃基、卤素和氰基；X选自C=O、C=S、C(=O)NH、C(=S)NH、C(=O)O、C(=O)S、C(=S)O和C(=S)S；R3为含有5至12个环成员的芳基或杂芳基，可以选择地被一个或多个取代基R7取代，其中R7如索引中定义；R4为一个基团YR5或一个基团R6；Y为NH、O或S；R5选自(a)从3到12个环成员的可选择取代的碳环和杂环基团；以及(b)可选择取代的C1-8烃基基团；R6为一个含有从4到12个环成员的可选择取代的杂环基团，并且至少包含一个环氮原子，通过该环氮原子，R6与相邻的酰基基团连接。
• Synthesis and Crystal Structure Analysis of 2-(Fluorobenzyl)-6-(4-Nitrophenyl) Imidazo[2,1-b][,,]Thiadiazole
  作者：Afshan Banu、Ravi S. Lamani、I. M. Khazi、Noor Shahina Begum

  DOI：10.1080/15421406.2010.526558

  日期：2010.12.1

  Preparation of 2-(4-fluorobexzyl)-6-(4-nitrophenyl)imidazo[2,1-b][1,3,4]thiadiazole is described and its crystal structure is discussed. The compound crystallizes in the monoclinic space group C2/c with a = 39.941(6) Å, b = 5.698(2) Å, c = 13.272(5) Å β = 90.880°, V = 3020(2) Å3, z = 8. The crystal structure is stabilized by weak intermolecular C-H…N,C-H…O,C-H…S, and C-H…F interactions.

  描述了2-(4-氟苄基)-6-(4-硝基苯基)咪唑并[2,1-b][1,3,4]噻二唑的制备并讨论了其晶体结构。化合物在单斜空间群 C2/c 中结晶，a = 39.941(6) Å, b = 5.698(2) Å, c = 13.272(5) Å β = 90.880°, V = 3020(2) Å3, z = 8. 晶体结构通过弱的分子间 CH…N、CH…O、CH…S 和 CH…F 相互作用来稳定。