4-(4-methoxy-phenyl)-thioallophanonitrile | 144264-59-5

• 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: 4-(4-methoxy-phenyl)-thioallophanonitrile
• 英文别名: N-Cyano-N'-(4-methoxy)phenylthiourea；1-Cyano-3-(4-methoxyphenyl)thiourea
• CAS: 144264-59-5
• 化学式: C₉H₉N₃OS
• 分子量: 207.256
• InChiKey: YHPFFGGCCGMZSW-UHFFFAOYSA-N

物化性质

• 熔点：
  181-182 °C
• 沸点：
  322.1±44.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

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：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  89.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methoxy-phenyl)-thioallophanonitrile 以 乙醇 为溶剂， 反应 18.0h， 生成 2-((4-methoxyphenyl)amino)thiazolo[4,5-d]pyrimidin-7(6H)-one
  参考文献：
  名称：

  设计，合成和生物评价的6-取代的Thieno [3,2-d]嘧啶类似物作为双表皮生长因子受体激酶和微管抑制剂。

  摘要：

  酪氨酸激酶抑制剂与微管靶向剂成功结合的临床证据促使我们设计和开发具有表皮生长因子受体（EGFR）激酶和微管蛋白聚合抑制特性的单一药物。发现了一系列6-芳基/杂芳基-4-（3'，4'，5'-三甲氧基苯胺基）噻吩并[3,2-d]嘧啶衍生物，它们是新型的双微管蛋白聚合和EGFR激酶抑制剂。4-（3'，4'，5'-三甲氧基苯胺基）-6-（对甲苯基）噻吩并[3,2-d]嘧啶衍生物6g是该系列中最有效的化合物，具有抗增殖作用，其中一半最大抑制浓度（IC50）值在一位或两位数纳摩尔范围内。化合物6g与秋水仙碱位点的微管蛋白结合并抑制微管蛋白组装，IC50值为0.71μM，6g抑制EGFR活性，IC50值为30 nM。我们的数据表明，6g优异的体外和体内特性可能源于其对微管蛋白聚合和EGFR激酶的双重抑制作用。

  DOI：

  10.1021/acs.jmedchem.8b01391
• 作为产物：
  描述：

  在 三光气 、 sodium ethanolate 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 1.0h， 生成 4-(4-methoxy-phenyl)-thioallophanonitrile
  参考文献：
  名称：

  Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

  摘要：

  Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.

  DOI：

  10.1021/jm501127s

文献信息

• Cardioselective Anti-Ischemic ATP-Sensitive Potassium Channel Openers. 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Cyanoguanidine Portion
  作者：Karnail S. Atwal、Gary J. Grover、Syed Z. Ahmed、Paul G. Sleph、Steven Dzwonczyk、Anne J. Baird、Diane E. Normandin

  DOI：10.1021/jm00017a007

  日期：1995.8

  Structure-activity relationships for the cyanoguanidine portion of the lead cardiac selective ATP-sensitive potassium channel (KATP) opener (3) are described. The cyanoguanidine moity appears to be optimal since increasing or decreasing the distance between the aniline nitrogen and the pendant aromatic ring attenuates anti-ischemic potency/selectivity. Similarly, unfavorable results are obtained by replacement of

  描述了先导心脏选择性ATP敏感性钾通道（KATP）开放剂（3）氰基胍部分的结构活性关系。由于增加或减少苯胺氮与侧链芳香环之间的距离会减弱抗缺血能力/选择性，因此氰基胍活性似乎是最佳的。同样，通过用其他接头（CH2，S，O）代替苯胺氮也获得了不利的结果。用甲基取代苯环会降低心脏选择性。将尿素部分限制在苯并咪唑酮或咪唑啉酮环中可保持抗缺血性，并显着改善心脏选择性。如血管舒张药和抗缺血药的药效之比所示，体外心脏选择性变化超过三个数量级。这些数据与先前的结果一致，表明对于抗缺血和血管松弛活性存在不同的结构-活性关系。由于用结构上不同的KATP阻滞剂（格列本脲，5-羟基癸酸钠，甲氧芬那酸）预处理可取消该系列化合物的抗缺血作用，因此这些化合物的抗缺血作用机制似乎仍涉及开放KATP。
• Hindered phenolic aminothiazoles - synthesis, α-glucosidase, α-amylase inhibitory and antioxidant activities
  作者：Sandhya Satheesh、Akhila Radha、Krishnapriya Girija、Kallikat Rajasekharan、Priya Maheswari

  DOI：10.2298/jsc161005084s

  日期：——

  -glucosidase inhibition activity with an IC 50 value of 117 µM while the standard com­pound acarbose showed an IC 50 value of 48.3 µM and 4-amino-2-[(4-methylphenyl)amino]-5-thiazolyl}(3,5-di- t -butyl-4-hydroxyphenyl)methanone showed good α -amylase inhibition activity with an IC 50 value of 283 µM compared to acarbose ( IC 50 532 µM). The antioxidant activities of the hindered phenolic thiazoles were

  N-芳基-N'-[亚氨基（硝基氨基）甲基]硫脲或N-芳基-N'-氰基硫脲与2-溴-1-（2,6-二叔丁基-）反应的碱催化杂环化4-羟基苯基）乙酮提供4-氨基-2-（芳基氨基）-5-（3,5-二叔丁基-4-羟基苯甲酰基）噻唑，其被设计为受阻酚和2-氨基噻唑部分的分子杂化物。筛选这些化合物对碳水化合物水解酶的抑制活性。因此，[4-氨基-2-（苯基氨基）-5-噻唑基]（3,5-二叔丁基-4-羟基苯基）甲酮具有α-葡萄糖苷酶抑制活性，IC 50值为117 µM，而标准化合物阿卡波糖的IC 50值为48.3 µM，4-氨基-2-[（4-甲基苯基）氨基] -5-噻唑基}（3，5-二叔丁基-4-羟基苯基）甲酮与阿卡波糖（IC 50 532 µM）相比，显示出良好的α-淀粉酶抑制活性，IC 50值为283 µM。还研究了受阻酚噻唑的抗氧化活性，在2,2-二苯基-1-吡啶并肼基自由基清除试验中，2-[（（
• Pyranyl cyanoguanidine derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05140031A1

  公开（公告）日：1992-08-18

  Novel compounds having the formula ##STR1## wherein ##STR2## are disclosed. These compounds have potassium channel activating activity and are useful, for example, as cardiovascular agents, especially as antiischemic agents.

  揭示了具有以下化学式##STR1##的新化合物。这些化合物具有钾通道激活活性，例如作为心血管药物，特别是作为抗缺血药物时具有用途。
• Inhibitors for Human Glutaminyl Cyclase by Structure Based Design and Bioisosteric Replacement
  作者：Mirko Buchholz、Antje Hamann、Susanne Aust、Wolfgang Brandt、Livia Böhme、Torsten Hoffmann、Stephan Schilling、Hans-Ulrich Demuth、Ulrich Heiser

  DOI：10.1021/jm900969p

  日期：2009.11.26

  The inhibition of human glutaminyl cyclase (hQC) has come into focus as a new potential approach for the treatment of Alzheimer's disease. The hallmark of this principle is the prevention of the formation of A beta(3,11(pE)-40,42), as these A beta-species were shown to be of elevated neurotoxicity and likely to act as a seeding core leading to an accelerated formation of A beta-oligomers and fibrils. Starting from 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea, bioisosteric replacements led to the development of new classes of inhibitors. The optimization of the metal-binding group was achieved by homology modeling and afforded a first insight into the probable binding mode of the inhibitors in the hQC active site. The efficacy assessment of the hQC inhibitors was performed in cell culture, directly monitoring the inhibition of A beta(3,11(pE)-40,42) formation.
• US5140031A
  申请人：——

  公开号：US5140031A

  公开（公告）日：1992-08-18