1-[2-(1-Cyclohexenyl)ethyl]-3-(5-chloro-2-pyridinyl)thiourea

• 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: 1-[2-(1-Cyclohexenyl)ethyl]-3-(5-chloro-2-pyridinyl)thiourea
• 英文别名: 1-(5-chloropyridin-2-yl)-3-[2-(cyclohexen-1-yl)ethyl]thiourea
• 化学式: C₁₄H₁₈ClN₃S
• 分子量: 295.836
• InChiKey: DVTYONOGIMBZRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  69
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-(5-chloropyrid-2-yl-thiocarbamoyl)imidazole 、 2-(1-环己烯基)乙胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以51%的产率得到1-[2-(1-Cyclohexenyl)ethyl]-3-(5-chloro-2-pyridinyl)thiourea
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(99)00460-6

文献信息

• Cyclohexenyl-ethyl-thiourea compounds and use
  申请人：Parker Hughes Institute

  公开号：US20030125331A1

  公开（公告）日：2003-07-03

  Novel CycloHexenyl-Ethyl-Thiourea (CHET) compounds as inhibitors of reverse transcriptase and effective agents for the treatment of HIV infection, including mutant, drug-sensitive, drug-resistant, and multi-drug resistant strains of HIV.

  新型环己烯基乙基硫脲（CHET）化合物作为逆转录酶抑制剂和治疗艾滋病毒感染的有效药物，包括艾滋病毒的变异株、药物敏感株、耐药株和多重耐药株。
• CYCLOHEXENYL-ETHYL-THIOUREA COMPOUNDS AND USE
  申请人：Parker Hughes Institute

  公开号：EP1194149A1

  公开（公告）日：2002-04-10
• US6469034B1
  申请人：——

  公开号：US6469034B1

  公开（公告）日：2002-10-22
• [EN] CYCLOHEXENYL-ETHYL-THIOUREA COMPOUNDS AND USE<br/>[FR] COMPOSÉS CYCLOHEXÉNYL-ÉTHYL-THIOURÉE ET LEUR UTILISATION
  申请人：PARKER HUGHES INST

  公开号：WO2000078315A1

  公开（公告）日：2000-12-28

  The use of at least one compound of formula (I) in the manufacture of a medicament for treating drug-resistant HIV in a subject wherein n is 0 to 6; R is H, halogen (C1-C12) alkyl, (C1-C12) alkoxy, amino, cyano, nitro, or hydroxy; and R1 comprises cyclo (C3-C12) alkyl, cyclo (C3-C12) alkenyl, isothiazolyl, tetrazolyl, triazolyl, pyridyl, imidazolyl, phenyl, napthyl, benzoxazolyl, benzimidazolyl, thiazolyl, oxazolyl, benzothiazolyl, pyrazinyl, pyridazinyl, thiadiazolyl, benzotriazolyl, pyrolyl, indolyl, benzothienyl, thienyl, benzofuryl, quinolyl, isoquinolyl, or pyrazolyl; or a pharmaceutically acceptable addition salt thereof.
• 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.