1-(4-Methyl-thiazol-2-yl)-3-((R)-1-naphthalen-1-yl-ethyl)-thiourea | 402955-20-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(4-Methyl-thiazol-2-yl)-3-((R)-1-naphthalen-1-yl-ethyl)-thiourea
• 英文别名: Thiourea, N-(4-methyl-2-thiazolyl)-N'-[(1R)-1-(1-naphthalenyl)ethyl]-；1-(4-methyl-1,3-thiazol-2-yl)-3-[(1R)-1-naphthalen-1-ylethyl]thiourea
• CAS: 402955-20-8
• 化学式: C₁₇H₁₇N₃S₂
• 分子量: 327.474
• InChiKey: ACIJRUFDQJLQDX-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-(+)-1-(2-萘基)乙胺 、 N-(4-methyl-1,3-thiazol-2-yl)imidazole-1-carbothioamide 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 1-(4-Methyl-thiazol-2-yl)-3-((R)-1-naphthalen-1-yl-ethyl)-thiourea
  参考文献：
  名称：

  Inhibition of mast cell leukotriene release by thiourea derivatives

  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/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.

  DOI：

  10.1016/s0960-894x(02)00992-7

文献信息

• Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives
  作者：Taracad K. Venkatachalam、Chen Mao、Fatih M. Uckun

  DOI：10.1016/j.bcp.2004.01.019

  日期：2004.5

  Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV- 1). Molecular modeling studies indicated that because of the asymmetric geometry of the non-nucleoside inhibitors (NNRTI) binding pocket, the 'R' stercoisomers would fit the NNRTI binding pocket of the HIV-1 RT much better than the corresponding 'S' stereoisomers, as reflected by their 10(4)-fold lower K-i values. The 'R' stereoisomers of several PETT derivatives inhibited the recombinant RT in vitro with lower IC50 values than their enantiomers. The active compounds were further evaluated for their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMCs). All the 'R' isomers again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strains HTLVIIIB in PBMCs at nanomolar concentrations whereas their enantiomers were less potent. The lead compounds for the respective groups were further tested against A17 (NNRTI-resistant, Y181C mutant RT), and A17Var (NNI-resistant Y181C +/- K103N mutant RT) as well as multidrug resistant viral strains. The results indicated that the lead compounds were several logs more potent than the standard NNRTI drug nevirapine. Structure-activity relationship among the derivatives showed preference of pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of both the stereochemistry as well as regiochemistry. Our data provides experimental evidence that the stereochemistry and the regiochemistry of non-nucleoside inhibitors can profoundly affect their anti-HIV activity. (C) 2004 Elsevier Inc. All rights reserved.
• 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.