1-(4-bromophenyl)-3-(cyclohexylmethyl)urea

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-bromophenyl)-3-(cyclohexylmethyl)urea
• 英文别名: 1-(4-Bromophenyl)-3-(cyclohexylmethyl)urea
• 化学式: C₁₄H₁₉BrN₂O
• 分子量: 311.222
• InChiKey: RKDLYTAAJGVJLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-吡唑硼酸频哪醇酯 、 1-(4-bromophenyl)-3-(cyclohexylmethyl)urea 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 生成 1-(4-(1H-pyrazol-4-yl)phenyl)-3-(cyclohexylmethyl)urea
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

  摘要：

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

  DOI：

  10.1021/jm400062r
• 作为产物：
  描述：

  4-溴异氰酸苯酯 、 环己甲胺 以 甲苯 为溶剂， 反应 1.0h， 以79%的产率得到1-(4-bromophenyl)-3-(cyclohexylmethyl)urea
  参考文献：
  名称：

  N-芳基脲衍生物对分枝杆菌和分枝杆菌水解酶的生化和微生物学评估。

  摘要：

  制备了聚焦的24种N-芳基脲衍生物文库，并针对结核分枝杆菌（Mtb）Rv3802c和Mtb Ag85C的丝氨酸酯酶进行了评估。对文库成员的选择性和抑制方式进行了评估。发现呋喃基尿素衍生物6c是Rv3802c最有效的非共价抑制剂，K i值为5.2±0.7μM。另一方面，基于三唑的脲10a和10b不可逆地选择性地抑制Ag85C，其ak inact / K i值分别为2.3±0.3和5.5±0.4×10-3μM-1min-1。还评估了文库对两种Mtb菌株（耻垢分枝杆菌和脓肿分枝杆菌）的最低抑制浓度（MIC）。化合物4a和4c具有抗Mtb H37Rv mc26206的活性，MIC值分别为3.12和1.5μM。密切相关的4e对Mtb H37Rv mc26206具有相似的活性，但对Mtb H37Ra，耻垢分枝杆菌和脓肿分枝杆菌也具有活性。化合物4a，4c和4e均包含一个共同的1-（环己基甲基）-3-苯

  DOI：

  10.1039/c9md00122k

文献信息

• Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors
  作者：Yan Yin、Li Lin、Claudia Ruiz、Susan Khan、Michael D. Cameron、Wayne Grant、Jennifer Pocas、Nibal Eid、HaJeung Park、Thomas Schröter、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1021/jm400062r

  日期：2013.5.9

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.
• Biochemical and microbiological evaluation of <i>N</i>-aryl urea derivatives against mycobacteria and mycobacterial hydrolases
  作者：Abhishek Vartak、Christopher Goins、Vinicius Calado Nogueira de Moura、Celine M. Schreidah、Alexander D. Landgraf、Boren Lin、Jianyang Du、Mary Jackson、Donald R. Ronning、Steven J. Sucheck

  DOI：10.1039/c9md00122k

  日期：——

  k inact/K i value of 2.3 ± 0.3 and 5.5 ± 0.4 × 10-3 μM-1 min-1, respectively. The library was also evaluated for minimum inhibitory concentration (MIC) against two strains of Mtb, Mycobacterium smegmatis, and Mycobacterium abscessus. Compounds 4a and 4c were active against Mtb H37Rv mc26206 with MIC values of 3.12 and 1.5 μM, respectively. Closely related 4e showed similar activity against Mtb H37Rv

  制备了聚焦的24种N-芳基脲衍生物文库，并针对结核分枝杆菌（Mtb）Rv3802c和Mtb Ag85C的丝氨酸酯酶进行了评估。对文库成员的选择性和抑制方式进行了评估。发现呋喃基尿素衍生物6c是Rv3802c最有效的非共价抑制剂，K i值为5.2±0.7μM。另一方面，基于三唑的脲10a和10b不可逆地选择性地抑制Ag85C，其ak inact / K i值分别为2.3±0.3和5.5±0.4×10-3μM-1min-1。还评估了文库对两种Mtb菌株（耻垢分枝杆菌和脓肿分枝杆菌）的最低抑制浓度（MIC）。化合物4a和4c具有抗Mtb H37Rv mc26206的活性，MIC值分别为3.12和1.5μM。密切相关的4e对Mtb H37Rv mc26206具有相似的活性，但对Mtb H37Ra，耻垢分枝杆菌和脓肿分枝杆菌也具有活性。化合物4a，4c和4e均包含一个共同的1-（环己基甲基）-3-苯