(3R,4S)-tert-butyl 3-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)-4-(3-(5-acetyl-4-methylthiazol-2-yl)ureido)pyrrolidine-1-carboxylate | 388105-01-9

• 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: (3R,4S)-tert-butyl 3-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)-4-(3-(5-acetyl-4-methylthiazol-2-yl)ureido)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3S,4R)-3-[(5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamoylamino]-4-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]pyrrolidine-1-carboxylate
• CAS: 388105-01-9
• 化学式: C₂₉H₄₀FN₅O₄S
• 分子量: 573.732
• InChiKey: HUEIIQRYVMJFKL-WMTXJRDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3R,4S)-tert-butyl 3-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)-4-(3-(5-acetyl-4-methylthiazol-2-yl)ureido)pyrrolidine-1-carboxylate 生成 1-(5-acetyl-4-methylthiazol-2-yl)-3-{(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-pyrrolidin-3-yl}-urea
  参考文献：
  名称：

  CC chemokine receptor-3 (CCR3) antagonists: Improving the selectivity of DPC168 by reducing central ring lipophilicity

  摘要：

  DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2136 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.065
• 作为产物：
  描述：

  N-BOC-4-氧代-3-吡咯烷甲酸乙酯 在 palladium dihydroxide 硼烷 、 氢气 、 sodium cyanoborohydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 生成 (3R,4S)-tert-butyl 3-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)-4-(3-(5-acetyl-4-methylthiazol-2-yl)ureido)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  CC chemokine receptor-3 (CCR3) antagonists: Improving the selectivity of DPC168 by reducing central ring lipophilicity

  摘要：

  DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2136 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.065

文献信息

• 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。
• 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.
• CC chemokine receptor-3 (CCR3) antagonists: Improving the selectivity of DPC168 by reducing central ring lipophilicity
  作者：James R. Pruitt、Douglas G. Batt、Dean A. Wacker、Lori L. Bostrom、Shon K. Booker、Erin McLaughlin、Gregory C. Houghton、Jeffrey G. Varnes、David D. Christ、Maryanne Covington、Anuk M. Das、Paul Davies、Danielle Graden、Ilona Kariv、Yevgeniya Orlovsky、Nicole C. Stowell、Krishna G. Vaddi、Eric A. Wadman、Patricia K. Welch、Swamy Yeleswaram、Kimberly A. Solomon、Robert C. Newton、Carl P. Decicco、Percy H. Carter、Soo S. Ko

  DOI：10.1016/j.bmcl.2007.03.065

  日期：2007.6

  DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2136 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. (C) 2007 Elsevier Ltd. All rights reserved.