1-(4-methoxyphenyl)-3-[N-(4-methylphenyl)benzamidoyl]-2-thiourea | 303024-53-5

• 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: 1-(4-methoxyphenyl)-3-[N-(4-methylphenyl)benzamidoyl]-2-thiourea
• 英文别名: N-[(4-methoxyphenyl)carbamothioyl]-N'-(4-methylphenyl)benzenecarboximidamide；(3E)-1-(4-methoxyphenyl)-3-[(4-methylanilino)-phenylmethylidene]thiourea
• CAS: 303024-53-5
• 化学式: C₂₂H₂₁N₃OS
• 分子量: 375.494
• InChiKey: FYPUTZKSYZAYPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-3-[N-(4-methylphenyl)benzamidoyl]-2-thiourea 在 吡啶 、 溴 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 5.0h， 生成 methyl 4-N-methoxyphenyl-5-[(E)-N-tolylbenzimidoyl-(Z)-imino]-3-trichloromethyl-1,2,4-thiadiazolidyne 2-carboxylate
  参考文献：
  名称：

  N-(2,2,2-三氯亚乙基)-取代的羧酰胺和氨基甲酸酯环加成为1,2,4-噻二唑-5(2H)-亚胺

  摘要：

  1,2,4-噻二唑-5(2H)-亚胺 4 与 N-(2,2,2-三氯亚乙基)-取代的酰胺 5 反应形成 [3 + 2]-环加成产物 6，其特征在于通过 X 射线衍射研究确定，环硫原子与 1,3-二氮杂亚丙基侧基的末端氮原子相连。这种配位显然在温和条件下在氧原子上将化合物 6 烷基化为 8 中起重要作用。SN 键“转换”恢复原来的 1,2,4-噻二唑环随之发生。© 2003 Wiley Periodicals, Inc. 杂原子化学 14:474–480, 2003; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.10182

  DOI：

  10.1002/hc.10182
• 作为产物：
  描述：

  2-(4-methylphenyl)-3-phenyl-5-(4-methoxyphenylamino)[1,2,4]thiadiazol-2-ium bromide 在 1,4-dithio-erythritol 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 1-(4-methoxyphenyl)-3-[N-(4-methylphenyl)benzamidoyl]-2-thiourea
  参考文献：
  名称：

  2,3-Diaryl-5-anilino[1,2,4]thiadiazoles as melanocortin MC4 receptor agonists and their effects on feeding behavior in rats

  摘要：

  The melanocortin-4 receptor (MC4) modulates physiological functions such as feeding behavior, nerve regeneration, and drug addiction. Using a high throughput screen based on I-121-NDP-MSH binding to the human MC4 receptor, we discovered 2,3-diaryl-5-anilino[1,2,4]thiadiazoles 3 as potent and selective MC4 receptor agonists. Through SAR development on the three attached aryl rings, we improved the binding affinity from 174 nM to 4.4 nM IC50. When delivered intraperitoneally, compounds 3a, 3b, and 3c induced significant inhibition of food intake in a fasting-induced feeding model in rats. When delivered orally, these compounds lost activity, mainly due to rapid metabolism to inactive imidoylthiourea reduction products. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00428-5

文献信息

• Synthesis and regioselective [4+2] cycloaddition/nucleophilic reactions of N-arylamino-1:3-diaza-1:3-butadienes with ketenes and accompanying rearrangements
  作者：Paramita D. Dey、Arun K. Sharma、Sachchida N. Rai、Mohinder P. Mahajan

  DOI：10.1016/0040-4020(95)00372-f

  日期：1995.7

  -butadienes 4 are shown to undergo regioselective reactions with phenyl- and chloroketenes resulting in high yields of 3-aryl-2-methylthio6-phenyl-4(3H)-pyrimidinones 7. Similar reactions with bromo- and iodoketenes, resulted, via aziridinium intermediates 12, in good yields of 3-aryl-S-(N-arylamino)-2-methylthio-6-phenyl4(3H)-pyrimidinones 13, The mechanistic aspects of cycloadditions and semi-empirical

  N-Arylamino-1：3-diaza-1：3-butadienes 4与苯基和氯乙烯酮发生区域选择性反应，导致3-芳基-2-甲基硫代6-苯基-4（3H）-嘧啶酮7的高收率。经由叠氮鎓中间体12与溴和碘酮的类似反应，以高收率产生了3-芳基-S-（N-芳基氨基）-2-甲硫基-6-苯基4（3H）-嘧啶酮13，环加成反应的机理还报道了这些二氮杂丁二烯的​​半经验AM1计算结果。
• Cycloaddition ofN-(2,2,2-trichloroethylidene)-substituted carboxamides and carbamates to 1,2,4-thiadiazol-5(2H)-imines
  作者：Vladimir S. Zyabrev、Mikhail A. Rensky、Eduard B. Rusanov、Boris S. Drach

  DOI：10.1002/hc.10182

  日期：——

  1,2,4-Thiadiazol-5(2H)-imines 4 react with N-(2,2,2-trichloroethylidene)-substituted amides 5 to form [3 + 2]-cycloaddition products 6 featured by an extra coordination of the ring sulfur atom to the terminal nitrogen atom of the side 1,3-diazapropenylidene group, as established by X-ray diffraction investigation. This coordination evidently plays an important role in the alkylation of compounds 6

  1,2,4-噻二唑-5(2H)-亚胺 4 与 N-(2,2,2-三氯亚乙基)-取代的酰胺 5 反应形成 [3 + 2]-环加成产物 6，其特征在于通过 X 射线衍射研究确定，环硫原子与 1,3-二氮杂亚丙基侧基的末端氮原子相连。这种配位显然在温和条件下在氧原子上将化合物 6 烷基化为 8 中起重要作用。SN 键“转换”恢复原来的 1,2,4-噻二唑环随之发生。© 2003 Wiley Periodicals, Inc. 杂原子化学 14:474–480, 2003; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.10182
• 2,3-Diaryl-5-anilino[1,2,4]thiadiazoles as melanocortin MC4 receptor agonists and their effects on feeding behavior in rats
  作者：Kevin Pan、Malcolm K Scott、Daniel H.S Lee、Louis J Fitzpatrick、Jeffery J Crooke、Ralph A Rivero、Daniel I Rosenthal、Anil H Vaidya、Boyu Zhao、Allen B Reitz

  DOI：10.1016/s0968-0896(02)00428-5

  日期：2003.1

  The melanocortin-4 receptor (MC4) modulates physiological functions such as feeding behavior, nerve regeneration, and drug addiction. Using a high throughput screen based on I-121-NDP-MSH binding to the human MC4 receptor, we discovered 2,3-diaryl-5-anilino[1,2,4]thiadiazoles 3 as potent and selective MC4 receptor agonists. Through SAR development on the three attached aryl rings, we improved the binding affinity from 174 nM to 4.4 nM IC50. When delivered intraperitoneally, compounds 3a, 3b, and 3c induced significant inhibition of food intake in a fasting-induced feeding model in rats. When delivered orally, these compounds lost activity, mainly due to rapid metabolism to inactive imidoylthiourea reduction products. (C) 2002 Elsevier Science Ltd. All rights reserved.