N-(3,4-dichlorophenyl)-[3-(2-oxopropyl)[1,2,4]-thiadiazol-5-yl]amine | 726160-27-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,4-dichlorophenyl)-[3-(2-oxopropyl)[1,2,4]-thiadiazol-5-yl]amine
• 英文别名: 1-[5-(3,4-Dichloroanilino)-1,2,4-thiadiazol-3-yl]propan-2-one
• CAS: 726160-27-6
• 化学式: C₁₁H₉Cl₂N₃OS
• 分子量: 302.184
• InChiKey: HRKVNVMQORCPIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,4-dichlorophenyl)-[3-(2-oxopropyl)[1,2,4]-thiadiazol-5-yl]amine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 N-(3,4-dichlorophenyl)-N-[3-(2-methylaminoprop-1-yl)-[1,2,4]thiadiazol-5-yl]amine
  参考文献：
  名称：

  1,2,4-噻二唑衍生物作为有效的 NMDA 受体阻滞剂，具有抗胆碱酯酶活性和抗氧化特性

  摘要：

  合成了新的3位不同取代基的5-苯胺基-1,2,4-噻二唑衍生物，并研究了它们对NMDA受体关键结合位点、乙酰胆碱酯酶、丁酰胆碱酯酶和羧酸酯酶的抑制活性以及抗氧化性能的影响. 发现具有 2-氨基丙基片段的化合物是含有 NR2B 的 NMDA 受体和中度丁酰胆碱酯酶抑制剂的变构调节剂 [3H] 芬普地尔结合位点的有效阻断剂。发现一些化合物能够同时阻断 NMDA 受体的 [3H] 芬普地尔和通道内 [3H]MК-801 结合位点。含有 2-氨基丙烯基片段的化合物不表现出对 NMDA 受体和丁酰胆碱酯酶的活性，但表现出高自由基清除活性。

  DOI：

  10.1007/s11172-017-1890-9
• 作为产物：
  描述：

  3-氨基-5-甲基异恶唑 、 3,4-二氯异硫氰酸苯酯 以 乙腈 为溶剂， 生成 N-(3,4-dichlorophenyl)-[3-(2-oxopropyl)[1,2,4]-thiadiazol-5-yl]amine
  参考文献：
  名称：

  5-Amino-3-(2-aminopropyl)-1,2,4-thiadiazoles as the basis of hybrid multifunctional compounds

  摘要：

  从侧链中含有氨基的 1,2,4-噻二唑开始，我们开发了一种合成混合多功能化合物的方法。

  DOI：

  10.1007/s11172-014-0563-1

文献信息

• Screening of a series of 3,5-disubstituted 1,2,4-thiadiazoles for selectivity of cytotoxic action to cancer cells
  作者：A. N. Proshin、T. P. Trofimova、O. N. Zefirova、I. V. Zhirkina、D. A. Skvortsov、S. O. Bachurin

  DOI：10.1007/s11172-021-3116-4

  日期：2021.3

  New 3,5-disubstituted-1,2,4-thiadiazoles were synthesized and together with a series of their analogs obtained earlier were tested for cytotoxic activity to breast adenocarcinoma MCF-7 and lung carcinoma A 549 cells. The selectivity of cytotoxic action was determined in comparison to etiologically noncancerous breast epithelial cells MCF-10A and lung fibroblasts VA13. From five- to six-fold selectivity of cytotoxic action was revealed for 3,4-dichlorophenyl-3-[2-(2-morpholin-4-ylethylamino)propyl]-[1,2,4]thiadiazol-5-yl}amine and (2-5-[(4-diethylami-nobenzyl)pyridin-3-ylmethylamino]-[1,2,4]thiadiazol-3-yl}-1-methylvinyl)-(2,2,6,6-tetra-methylpiperidin-4-yl)amine in the pairs A 549/VA13 and MCF-7/MCF-10A, respectively. Some structure—property relationships for the compounds under study were discussed.

  合成了新的 3,5-二取代-1,2,4-噻二唑，并与之前获得的一系列类似物一起测试了对乳腺癌 MCF-7 和肺癌 A 549 细胞的细胞毒活性。与病因学上的非癌性乳腺上皮细胞 MCF-10A 和肺成纤维细胞 VA13 相比，确定了细胞毒作用的选择性。 3,4-二氯苯基-3-[2-(2-吗啉-4-基乙基氨基)丙基]-[1,2,4]噻二唑-5-基的细胞毒性作用选择性提高了五到六倍}胺和(2-5-[(4-二乙基氨基苄基)吡啶-3-基甲基氨基]-[1,2,4]噻二唑-3-基}-1-甲基乙烯基)-(2,2,6, 6-四甲基哌啶-4-基)胺分别为 A 549/VA13 和 MCF-7/MCF-10A 对。讨论了所研究化合物的一些结构-性质关系。
• 5-Amino-3-(2-aminopropyl)-1,2,4-thiadiazoles as the basis of hybrid multifunctional compounds
  作者：A. N. Proshin、I. V. Serkov、L. N. Petrova、S. O. Bachurin

  DOI：10.1007/s11172-014-0563-1

  日期：2014.5

  An approach to the synthesis of hybrid multifunctional compounds starting from 1,2,4-thiadiazoles containing an amino group in the side chain was developed.

  从侧链中含有氨基的 1,2,4-噻二唑开始，我们开发了一种合成混合多功能化合物的方法。
• 1,2,4-Thiadiazoles as promising multifunctional agents for treatment of neurodegenerative diseases
  作者：G. F. Makhaeva、A. N. Proshin、N. P. Boltneva、E. V. Rudakova、N. V. Kovaleva、O. G. Serebryakova、I. V. Serkov、S. O. Bachurin

  DOI：10.1007/s11172-016-1486-9

  日期：2016.6

  substituents at position 3 of the thiadiazole ring were carried out, in particular, their esterase profile and antioxidant properties. It was found that the presence in the molecule of 2-aminopropyl fragment determines an efficient and selective inhibition of butyrylcholinesterase as compared to acetylcholinesterase and carboxylesterase, with radical-scavenging activity being weak. The compounds containing

  对在噻二唑环的第 3 位含有不同取代基的新型 3-取代 5-苯胺基-1,2,4-噻二唑的性质进行了详细研究，特别是它们的酯酶谱和抗氧化性质。发现与乙酰胆碱酯酶和羧酸酯酶相比，2-氨基丙基片段分子中的存在决定了对丁酰胆碱酯酶的有效和选择性抑制，自由基清除活性较弱。含有2-氨基丙烯基片段的化合物具有高自由基清除活性，弱抑制胆碱酯酶，并表现出抗羧酸酯酶活性。3-取代 5-anilino-1,2 的广泛活性，
• 5-AMINO-1,2,4-THIADIAZOLE DERIVATIVES
  申请人：Federalnoe Gosudarstvennoe Bydzhetnoe Uchrezhdenie Nauki Institut Fiziologicheski Aktivnikh Veschestv Rossiiskoi Akademii Nauk (IFAV RAN)

  公开号：EP2628734A2

  公开（公告）日：2013-08-21

  The present invention relates in general to the field of organic chemistry and, in particular, to novel biologically active compounds of 5-amino[1,2,4]thiadiazole derivatives of the general formula: wherein X is ONO2 or NHR3; R1, R2, and R3 may be the same or different and independently represent hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, as well as R1 together with R2 may represent heterocyclyl (for example, optionally substituted pyrrolidine, piperidine, azepane, piperazine, morpholine, etc.) provided that, when R1 is H, then R2 is other than hydrogen or methyl. 5-Amino-[1,2,4]thiadiazole derivatives are of special interest as drug candidates for prevention and treatment of neurodegenerative diseases, for example, Alzheimer's disease.

  本发明总体上涉及有机化学领域，特别是通式为 5-氨基[1,2,4]噻二唑衍生物的新型生物活性化合物： 其中 X 是 ONO2 或 NHR3； R1、R2和R3可以相同或不同，并独立地代表氢、烷基、芳基、芳烷基、杂芳基、杂烷基、环烷基，以及R1与R2一起代表杂环烷基（例如，任选取代的吡咯烷、哌啶、氮杂环烷、哌嗪、吗啉等），条件是当R1为H时，R2不是氢或甲基。 5-氨基-[1,2,4]噻二唑衍生物作为预防和治疗神经退行性疾病（例如阿尔茨海默病）的候选药物具有特殊的意义。
• Novel 1,2,4-Thiadiazole Derivatives as Potent Neuroprotectors: Approach to Creation of Bioavailable Drugs
  作者：German L. Perlovich、Alexey N. Proshin、Tatyana V. Volkova、Ludmila N. Petrova、Sergey O. Bachurin

  DOI：10.1021/mp300011r

  日期：2012.8.6

  Novel 1,2,4-thiadiazole derivatives as potent neuroprotectors were synthesized and identified. Their ability to inhibit the glutamate stimulated Ca uptake was measured. Permeation experiments on the phospholipid membranes were conducted, and the apparent permeability coefficients were obtained. The partition coefficients in n-octanol/buffer (pH 7.4) and n-hexane/buffer (pH 7.4) immiscible phases (as model systems for characterizing gastrointestinal tract membranes and BBB) were determined. A classification of the studied compounds from the standpoint of "permeability-activity" properties was proposed.