N-[5-(trifluoromethyl)pyridin-2-yl]imidazole-1-carbothioamide | 250208-70-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-[5-(trifluoromethyl)pyridin-2-yl]imidazole-1-carbothioamide
• CAS: 250208-70-9
• 化学式: C₁₀H₇F₃N₄S
• 分子量: 272.254
• InChiKey: BURFNQGCQRMGQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-苯乙胺 、 N-[5-(trifluoromethyl)pyridin-2-yl]imidazole-1-carbothioamide 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-Phenethyl-3-(5-trifluoromethyl-pyridin-2-yl)-thiourea
  参考文献：
  名称：

  Substituted heterocyclic thiourea compounds as a new class of anti-allergic agents inhibiting IgE/FcεRI receptor mediated mast cell leukotriene release

  摘要：

  Mast cell derived leukotrienes (LT's) play a vital role in pathophysiology of allergy and asthma. We synthesized various analogues of indolyl, naphthyl and phenylethyl substituted halopyridyl, thiazolyl and benzothiazolyl thioureas and examined their in vitro effects on the high affinity IgE receptor/FcepsilonRI-mediated mast cell leukotriene release. Of the 22 naphthylethyl thiourea compounds tested, there were 7 active compounds and N-[1-(1-naphthyl)ethyl]-N'-[2-(ethyl-4-acetylthiazolyl)]thiourea (17 and 16) (IC50=0.002 muM) and N-[1-(1R)-naphthylethyl]-N'-[2-(5-methylpyridyl)]thiourea (compound 5) (IC50 = 0.005 muM) were identified as the lead compounds. Among the 1l indolylethyl thiourea compounds tested, there were seven active compounds and the halopyridyl compounds N-[2-(3-indolylethyl)]-N'-[2-(5-chloropyridyl)lthiourea (24) and N-[2-(3-indolylethyl)]-N'-[2-(5-bromopyridyl)]thiourea (25) were the most active agents and inhibited the LTC4 release with low micromolar IC50 values of 4.9 and 6.1 PM, respectively. The hydroxylphenyl substituted compounds N-[2-(4-hydroxyphenyl)ethyl]-N'-[2-(5-chloropyridyl)]thiourea (37; IC50 = 12.6muM), N-[2-(4-hydroxyphenyl)ethyll-AT-[2-(5-bromopyridyl)]thiourea (50; IC50 16.8 muM) and N-[2-(4-hydroxyphenyl)ethyl]-N'-[2-(pyridyl)]thiourea (35; IC50 = 8.5muM) were the most active pyridyl thiourea agents. Notably, the introduction of electron withdrawing or donating groups had a marked impact on the biological activity of these thiourea derivatives and the Hammett sigma values of their substituents were identified as predictors of their potency. In contrast, experimentally determined partition coefficient values did not correlate with the biological activity of the thiourea compounds which demonstrates that their liphophilicity is not an important factor controlling their mast cell inhibitory effects. These results establish the substituted halopyridyl, indolyl and naphthyl thiourea compounds as a new chemical class of anti-allergic agents inhibiting IgE receptor/FcepsilonRI-mediated mast cell LTC4 release. Further lead optimization efforts may provide the basis for new and effective treatment as well as prevention programs for allergic asthma in clinical settings. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00531-x
• 作为产物：
  描述：

  2-氨基-5-三氟甲基吡啶 、 N,N'-硫羰基二咪唑 以 乙腈 为溶剂， 反应 12.0h， 生成 N-[5-(trifluoromethyl)pyridin-2-yl]imidazole-1-carbothioamide
  参考文献：
  名称：

  Substituted heterocyclic thiourea compounds as a new class of anti-allergic agents inhibiting IgE/FcεRI receptor mediated mast cell leukotriene release

  摘要：

  Mast cell derived leukotrienes (LT's) play a vital role in pathophysiology of allergy and asthma. We synthesized various analogues of indolyl, naphthyl and phenylethyl substituted halopyridyl, thiazolyl and benzothiazolyl thioureas and examined their in vitro effects on the high affinity IgE receptor/FcepsilonRI-mediated mast cell leukotriene release. Of the 22 naphthylethyl thiourea compounds tested, there were 7 active compounds and N-[1-(1-naphthyl)ethyl]-N'-[2-(ethyl-4-acetylthiazolyl)]thiourea (17 and 16) (IC50=0.002 muM) and N-[1-(1R)-naphthylethyl]-N'-[2-(5-methylpyridyl)]thiourea (compound 5) (IC50 = 0.005 muM) were identified as the lead compounds. Among the 1l indolylethyl thiourea compounds tested, there were seven active compounds and the halopyridyl compounds N-[2-(3-indolylethyl)]-N'-[2-(5-chloropyridyl)lthiourea (24) and N-[2-(3-indolylethyl)]-N'-[2-(5-bromopyridyl)]thiourea (25) were the most active agents and inhibited the LTC4 release with low micromolar IC50 values of 4.9 and 6.1 PM, respectively. The hydroxylphenyl substituted compounds N-[2-(4-hydroxyphenyl)ethyl]-N'-[2-(5-chloropyridyl)]thiourea (37; IC50 = 12.6muM), N-[2-(4-hydroxyphenyl)ethyll-AT-[2-(5-bromopyridyl)]thiourea (50; IC50 16.8 muM) and N-[2-(4-hydroxyphenyl)ethyl]-N'-[2-(pyridyl)]thiourea (35; IC50 = 8.5muM) were the most active pyridyl thiourea agents. Notably, the introduction of electron withdrawing or donating groups had a marked impact on the biological activity of these thiourea derivatives and the Hammett sigma values of their substituents were identified as predictors of their potency. In contrast, experimentally determined partition coefficient values did not correlate with the biological activity of the thiourea compounds which demonstrates that their liphophilicity is not an important factor controlling their mast cell inhibitory effects. These results establish the substituted halopyridyl, indolyl and naphthyl thiourea compounds as a new chemical class of anti-allergic agents inhibiting IgE receptor/FcepsilonRI-mediated mast cell LTC4 release. Further lead optimization efforts may provide the basis for new and effective treatment as well as prevention programs for allergic asthma in clinical settings. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00531-x

文献信息

• N-[2-(1-cyclohexenyl)ethyl]-N′-[2-(5-bromopyridyl)]-thiourea and N′-[2-(1-cyclohexenyl)ethyl]-N′-[2-(5-chloropyridyl)]- thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1
  作者：Fatih M. Uckun、Chen Mao、Sharon Pendergrass、Danielle Maher、Dan Zhu、Lisa Tuel-Ahlgren、T.K. Venkatachalam

  DOI：10.1016/s0960-894x(99)00460-6

  日期：1999.9

  We have replaced the pyridyl ring of trovirdine with an alicyclic cyclohexenyl, adamantyl or cis-myrtanyl ring. Only the cyclohexenyl-containing thiourea compound N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5bromopyridyl)]- thiourea (HI-346) las well as its chlorine-substituted derivative N-[2-(1-cyclohexenyl)ethyl]-N'[2-(5-chloropyridyl)]- thiourea/HI-445) showed RT inhibitory activity. HI-346 and HI-445 effectively inhibited recombinant RT with better IC50 values than other anti-HIV agents tested. The ranking order of efficacy in cell-free RT inhibition assays was: HI-346 (IC50 = 0.4 mu M) > HI-445 (IC50 = 0.5 mu M) > trovirdine (IC50 = 0.8 mu M) > MKC-442 (IC50 = 0.8 mu M) = delavirdine (IC50 1.5 mu M) > nevirapine (IC50 = 23 mu M). In accord with this data, both compounds inhibited the replication of the drug-sensitive HIV-1 strain HTLVIIIB with better IC50 values than other anti-HIV agents tested. The ranking order of efficacy in cellular HIV-1 inhibition assays was: HI-445 = HI-346 (IC50 = 3 nM) > MKC-442 (IC50 = 4 nM) = AZT (IC50 = 4 nM) > trovirdine (IC50 = 7 nM) > delavirdine (IC50 = 9 nM)> nevirapine (IC50 = 34 nM). Surprisingly, the lead compounds HI-346 and HI-445 were 3-times more effective against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation las well as additional mutations involving the RT residues 74V,41L, and 215Y) than they were against HTLVIIIB with wild-type RT. HI-346 and HI-445 were 20-times more potent than trovirdine, 200-times more potent than AZT, 300-times more potent than MKC-442, 400-times more potent than delavirdine, and 5000-times more potent than nevirapine against the multidrug resistant HIV-1 strain RT-MDR. HI-445 was also tested against the RT Y181C mutant A17 strain of HIV-1 and found to be >7-fold more effective than trovirdine and >1,400-fold more effective than nevirapine or delavirdine. Similarly, both HI-346 and HI-445 were more effective than trovirdine, nevirapine, and delavirdine against the problematic NNI-resistant HIV-1 strain A17-variant with both Y181C and K103N mutations in RT, although their activity was markedly reduced against this strain. Neither compound exhibited significant cytotoxicity at effective concentrations (CC50 >100 mu M). These findings establish the lead compounds HI-346 and HI-445 as potent inhibitors of drug-sensitive as well as multidrug-resistant stains of HIV-1. (C) 1999 Elsevier Science Ltd. All rights reserved.