1-(5-溴吡啶-2-基)-3-[2-(1H-吲哚-3-基)乙基]硫脲 | 181305-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 1-(5-溴吡啶-2-基)-3-[2-(1H-吲哚-3-基)乙基]硫脲
• 英文名称: 1-(5-Bromo-pyridin-2-yl)-3-[2-(1H-indol-3-yl)-ethyl]-thiourea
• 英文别名: Thiourea, N-(5-bromo-2-pyridinyl)-N'-(2-(1H-indol-3-yl)ethyl)-；1-(5-bromopyridin-2-yl)-3-[2-(1H-indol-3-yl)ethyl]thiourea
• CAS: 181305-55-5
• 化学式: C₁₆H₁₅BrN₄S
• 分子量: 375.292
• InChiKey: GYXKZCBDZOVHQK-UHFFFAOYSA-N

物化性质

• 熔点：
  211-212 °C
• 沸点：
  546.7±60.0 °C(Predicted)
• 密度：
  1.575±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  84.8
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  色胺盐酸盐 、 imidazole-1-carbothionic acid (5-bromopyridin-2-yl)amide 生成 1-(5-溴吡啶-2-基)-3-[2-(1H-吲哚-3-基)乙基]硫脲
  参考文献：
  名称：

  苯乙基噻唑基硫脲（PETT）化合物是一类新的HIV-1逆转录酶抑制剂。2. PETT类似物的合成和进一步的构效关系研究。

  摘要：

  苯乙基噻唑基硫脲（PETT）衍生物已被鉴定为HIV-1 RT的一系列新的非核苷抑制剂。此类化合物的构效关系研究确定了N- [2-（2-吡啶基）乙基] -N'-[2-（5-溴吡啶基）]-硫脲盐酸盐（卓维定； LY300046.HCl）作为高效的抗HIV-1药物。Trovirdine目前正处于一期临床试验中，有望用于治疗AIDS。正在扩展这些结构-活性关系研究以鉴定该系列中具有改进性能的其他化合物。这里描述了这项工作的一部分。研究了各种取代或未取代的杂芳族环取代PETT化合物的两个芳族部分。此外，还研究了苯环上多重取代的影响。在细胞培养测定中，对野生型和构建的HIV-1 RT突变体以及野生型HIV-1及其衍生的突变病毒Ile100和Cys181测定了抗病毒活性。在双突变病毒HIV-1（Ile 100 / Asn103）和HIV-1（Ile100 / Cys181）上确定了一些选定的化合物。合成

  DOI：

  10.1021/jm950639r

文献信息

• Substituted heterocyclic thiourea compounds as a new class of anti-allergic agents inhibiting IgE/FcεRI receptor mediated mast cell leukotriene release
  作者：T.K Venkatachalam、S Qazi、P Samuel、F.M Uckun

  DOI：10.1016/s0968-0896(02)00531-x

  日期：2003.3

  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.
• Inhibition of mast cell leukotriene release by thiourea derivatives
  作者：Taracad K Venkatachalam、Sanjive Qazi、Peter Samuel、Fatih M Uckun

  DOI：10.1016/s0960-894x(02)00992-7

  日期：2003.2

  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/FcERI-mediated mast cell leukotriene release. Of the 22 naphthylethyl thiourea compounds tested, there were seven 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 (5) (IC50 = 0.005 muM) were identified as the lead compounds. Among the I I indolylethyl thiourea compounds tested, there were seven active compounds and the halopyridyl compounds N-[2-(3-indolylethyl)]-N'-[2-(5-chloropyridyl)]thiourea and N-[2-(3-indolylethyl)]-N'-[2-(5-bromopyridyl)]thiourea were the most active agents and inhibited the LTC4 release with low micromolar IC50 values of 4.9 muM and 6.1 muM, respectively. The hydroxylphenyl substituted compounds N-[2-(4-hydroxyphenyl)ethyl]- N'-[2-(5-chloropyridyl)] thiourea (IC50 = 12.6 muM), N-[2-(4-hydroxyphenyl)ethyl]-N'-[2-(5-bromopyridyl)]thiourea (IC50 = 16.8 muM) and N-[2-(4-hydroxyphenyl)ethyl]-N'-[2-(pyridyl)]thiourea (IC50 = 8.5 muM) 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. (C) 2002 Elsevier Science Ltd. All rights reserved.
• N′-[2-(2-thiophene)ethyl]-N′-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of nni-resistant and multidrug-resistant human immunodeficiency virus-1
  作者：Fatih M. Uckun、Sharon Pendergrass、Danielle Maher、Dan Zhu、Lisa Tuel-Ahlgren、Chen Mao、T.K. Venkatachalam

  DOI：10.1016/s0960-894x(99)00624-1

  日期：1999.12

  The thiophene-ethyl thiourea (TET) compound N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridl)]-thiourea (compound HI-443) was five times more potent than trovirdine, 1250 times more potent than nevirapine, 100 times more potent than delavirdine, 75 times more potent than MKC-442, and 50 times more potent than AZT against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation. HI-443 was almost as potent against the NNI-resistant HIV-I strain A17 with a Y181C mutation as it was against HTLVIIIB. The activity of HI-443 against A17 was ten times more potent than that of trovirdine, 2083 times more potent than that of nevirapine, and 1042 times more potent than that of delavirdine. HI-443 inhibited the replication of the NNI-resistant HIV-1 strain A17 variant with Y181C plus K103N mutations in RT with an IC, value of 3.3 mu M, whereas the IC50 values of trovirdine, nevirapine, and delavirdine were all >100 mu M. These findings establish the novel thiophene containing thiourea compound HI-443 as a novel NNI with potent antiviral activity against NNI-sensitive, NNI-resistant and multidrug-resistant strains of HIV-l. (C) 1999 Elsevier Science Ltd. All rights reserved.