N-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-N'-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}urea | 675122-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-N'-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}urea
• 英文别名: N-[3-ethyl-5-(1-methyl-1H-tetraazol-5-yl)phenyl]-N'-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}urea；1-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R,3S)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-3-hydroxybutan-2-yl]urea
• CAS: 675122-43-7
• 化学式: C₂₇H₃₆FN₇O₂
• 分子量: 509.627
• InChiKey: SGWACYVRKXWJNK-QLWBXOBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2S,3R)-3-amino-1-[(3S)-3-(4-fluorobenzyl)piperidin-1-yl]-2-butanol 、 phenyl 3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenylcarbamate 以 乙腈 为溶剂， 生成 N-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-N'-{(1R,2S)-3-[(3S)-3-(4-fluorobenzyl)-1-piperidinyl]-2-hydroxy-1-methylpropyl}urea
  参考文献：
  名称：

  从刚性环状模板到构象稳定的非环状支架。第一部分：CCR3拮抗剂开发候选药物BMS-639623的发现具有针对嗜酸性粒细胞趋化性的皮摩尔抑制能力。

  摘要：

  反式1,2-二取代的环己烷CCR3拮抗剂2的构象分析表明，环己烷接头可被无环的顺式α-甲基-β-羟丙基接头取代。单取代和双取代丙基连接基的合成和生物学评估支持这种构象相关性。还发现与尿素的α-甲基降低了蛋白结合，而β-羟基降低了对CYP2D6的亲和力。从头算计算表明，α-甲基基团控制着分子内三个关键功能的空间取向。具有嗜酸性粒细胞趋化性IC（50）= 38 pM的α-甲基-β-羟丙基尿素31被选择进入临床治疗哮喘的研究。

  DOI：

  10.1016/j.bmcl.2007.11.067

文献信息

• N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
  申请人：Duncia V. John

  公开号：US20060069128A1

  公开（公告）日：2006-03-30

  The present application describes N-ureidoalkyl piperidines as modulators of chemokine receptors, or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了N-尿素基烷基哌啶作为趋化因子受体调节剂，或其药学上可接受的盐形式，对于预防哮喘和其他过敏性疾病有用。
• Inhibition of chemokine CCL7 or receptor CCR3 of same for the treatment and diagnosis of prostate cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US10401365B2

  公开（公告）日：2019-09-03

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumor in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumor cells obtained from said subject.

  本发明涉及一种趋化因子CCL7表达抑制剂或受体CCR3表达抑制剂或CCL7/CCR3相互作用抑制剂，用于预防或治疗受试者的前列腺癌向前列腺囊外延伸。本发明还涉及一种确定前列腺癌患者前列腺癌肿瘤侵袭程度的方法，该方法包括一个步骤，即确定从所述患者处获得的前列腺肿瘤细胞样本中受体CCR3的浓度或表达水平。
• [EN] N-UREIDOALKYL-PIPERIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY.<br/>[FR] N-UREIDOALKYL-PIPERIDINES UTILISEES EN TANT QUE MODULATEURS DE L'ACTIVITE DU RECEPTEURS DE CHIMIOKINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004024682A3

  公开（公告）日：2004-07-08
• N-UREIDOALKYL-PIPERIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY.
  申请人：Bristol-Myers Squibb Company

  公开号：EP1545524A2

  公开（公告）日：2005-06-29
• Inhibition of Chemokine CCL7 or Receptor CCR3 of Same for the Treatment and Diagnosis of Prostate Cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US20170131282A1

  公开（公告）日：2017-05-11

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumour in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumour cells obtained from said subject.