6-氯-4-(3-甲基丁-1-炔基)-4-(三氟甲基)-1,3-二氢喹唑啉-2-酮 | 214287-63-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 6-氯-4-(3-甲基丁-1-炔基)-4-(三氟甲基)-1,3-二氢喹唑啉-2-酮
• 英文名称: 6-chloro-3,4-dihydro-4-(3-methylbutyn-1-yl)-4-(trifluoromethyl)-2(1H)-quinazolinone
• 英文别名: (+/-)-6-Chloro-4-isopropylethynyl-4-trifluoromethyl-3,4-dihydro-2(1H)-quinazolinone；6-Chloro-4-(3-methylbut-1-yn-1-yl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1h)-one；6-chloro-4-(3-methylbut-1-ynyl)-4-(trifluoromethyl)-1,3-dihydroquinazolin-2-one
• CAS: 214287-63-5
• 化学式: C₁₄H₁₂ClF₃N₂O
• 分子量: 316.71
• InChiKey: QBABWUINNOHOBD-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C
• 沸点：
  360.6±42.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-氨基-5-氯苯基)-2,2,2-三氟乙酮 在 三氟化硼乙醚 作用下， 以 四氢呋喃 、 xylene 为溶剂， 生成 6-氯-4-(3-甲基丁-1-炔基)-4-(三氟甲基)-1,3-二氢喹唑啉-2-酮
  参考文献：
  名称：

  Expanded-Spectrum Nonnucleoside Reverse Transcriptase Inhibitors Inhibit Clinically Relevant Mutant Variants of Human Immunodeficiency Virus Type 1

  摘要：

  摘要：针对鉴定对K103N突变型人类免疫缺陷病毒（HIV）具有增强效力且保持一日一次剂量的药代动力学一致性的扩展谱非核苷类逆转录酶抑制剂的研究项目已经取得成果，发现了4-环丙炔基-4-三氟甲基-3,4-二氢-2(1H)喹唑啉酮DPC 961和DPC 963，以及4-环丙烯基-4-三氟甲基-3,4-二氢-2(1H)喹唑啉酮DPC 082和DPC 083用于临床开发。DPC 961、DPC 963、DPC 082和DPC 083均对野生型病毒、K103N和L100I单突变变种以及许多多种氨基酸替换的HIV-1突变体表现出低纳摩尔级别的效力。这种高度的效力与口服生物利用度高度结合，如在恒河猴和黑猩猩中展示的那样，并且具有可以导致显著药物自由水平的血浆血清蛋白结合。

  DOI：

  10.1128/aac.43.12.2893

文献信息

• Expanded-Spectrum Nonnucleoside Reverse Transcriptase Inhibitors Inhibit Clinically Relevant Mutant Variants of Human Immunodeficiency Virus Type 1
  作者：Jeffrey W. Corbett、Soo S. Ko、James D. Rodgers、Susan Jeffrey、Lee T. Bacheler、Ronald M. Klabe、Sharon Diamond、Chii-Ming Lai、Shelley R. Rabel、Jo Anne Saye、Stephen P. Adams、George L. Trainor、Paul S. Anderson、Susan K. Erickson-Viitanen

  DOI：10.1128/aac.43.12.2893

  日期：1999.12

  A research program targeted toward the identification of expanded-spectrum nonnucleoside reverse transcriptase inhibitors which possess increased potency toward K103N-containing mutant human immunodeficiency virus (HIV) and which maintain pharmacokinetics consistent with once-a-day dosing has resulted in the identification of the 4-cyclopropylalkynyl-4-trifluoromethyl-3,4-dihydro-2(1 H )quinazolinones DPC 961 and DPC 963 and the 4-cyclopropylalkenyl-4-trifluoromethyl-3,4-dihydro-2(1 H )quinazolinones DPC 082 and DPC 083 for clinical development. DPC 961, DPC 963, DPC 082, and DPC 083 all exhibit low-nanomolar potency toward wild-type virus, K103N and L100I single-mutation variants, and many multiply amino acid-substituted HIV type 1 mutants. This high degree of potency is combined with a high degree of oral bioavailability, as demonstrated in rhesus monkeys and chimpanzees, and with plasma serum protein binding that can result in significant free levels of drug.

  摘要：针对鉴定对K103N突变型人类免疫缺陷病毒（HIV）具有增强效力且保持一日一次剂量的药代动力学一致性的扩展谱非核苷类逆转录酶抑制剂的研究项目已经取得成果，发现了4-环丙炔基-4-三氟甲基-3,4-二氢-2(1H)喹唑啉酮DPC 961和DPC 963，以及4-环丙烯基-4-三氟甲基-3,4-二氢-2(1H)喹唑啉酮DPC 082和DPC 083用于临床开发。DPC 961、DPC 963、DPC 082和DPC 083均对野生型病毒、K103N和L100I单突变变种以及许多多种氨基酸替换的HIV-1突变体表现出低纳摩尔级别的效力。这种高度的效力与口服生物利用度高度结合，如在恒河猴和黑猩猩中展示的那样，并且具有可以导致显著药物自由水平的血浆血清蛋白结合。
• Inhibition of Clinically Relevant Mutant Variants of HIV-1 by Quinazolinone Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Jeffrey W. Corbett、Soo S. Ko、James D. Rodgers、Lisa A. Gearhart、Nicholas A. Magnus、Lee T. Bacheler、Sharon Diamond、Susan Jeffrey、Ronald M. Klabe、Beverly C. Cordova、Sena Garber、Kelly Logue、George L. Trainor、Paul S. Anderson、Susan K. Erickson-Viitanen

  DOI：10.1021/jm990580e

  日期：2000.5.1

  A series of 4-alkenyl and 4-alkynyl-3,4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones were found to be potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of human immunodeficiency virus type-1 (HIV-1). The 4-alkenyl-3,4-dihydro-4-(trifluoromethyl) quinazolinones DPC 082 and DPC 083 and the 4-alkynyl-3,4-dihydro-4-(trifluoromethyl) (LK)-quinazolinones DPC 961 and DPC 963 were found to exhibit low nanomolar potency toward wild-type RF virus (IC90 = 2.0, 2.1, 2.0, and 1.3 nM, respectively) and various single and many multiple amino acid substituted HIV-1 mutant viruses.-The increased potency is combined with favorable plasma serum protein binding as demonstrated by improvements in the percent free drug in human plasma when compared to efavirenz: 3.0%, 2.0%, 1.5% 2.8%, and 0.2- 0.5% for DPC 082, DPC 083, DPC 961, DPC 963, and efavirenz, respectively.