N-{3-[(3S)-3-(4-fluorobenzyl)piperidinyl]propyl}-N'-[3-(1,3,4-oxadiazol-2-yl)phenyl]-urea

• 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-[(3S)-3-(4-fluorobenzyl)piperidinyl]propyl}-N'-[3-(1,3,4-oxadiazol-2-yl)phenyl]-urea
• 英文别名: 1-{3-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-yl]-propyl}-3-(3-[1,3,4]oxadiazol-2-yl-phenyl)-urea；1-[3-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-[3-(1,3,4-oxadiazol-2-yl)phenyl]urea
• 化学式: C₂₄H₂₈FN₅O₂
• 分子量: 437.517
• InChiKey: KFPIFLHWICOLPS-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-BOC-3-羟基哌啶 在 palladium on activated charcoal 盐酸 、 正丁基锂 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 4 A molecular sieve 、 氢气 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， -78.0~50.0 ℃ 、275.79 kPa 条件下， 反应 34.0h， 生成 N-{3-[(3S)-3-(4-fluorobenzyl)piperidinyl]propyl}-N'-[3-(1,3,4-oxadiazol-2-yl)phenyl]-urea
  参考文献：
  名称：

  Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists

  摘要：

  The discovery of novel and selective small molecule antagonists of the CC Chemokine Receptor-3 (CCR3) is presented. Simple conversion from a 4- to 3-benzylpiperidine gave improved selectivity for CCR3 over the serotonin 5HT(2A) receptor. Chiral resolution and exploration of mono- and disubstitution of the N-propylurea resulted in several 3-benzylpiperidine N-propylureas with CCR3 binding IC50S under 5 nM. Data from in vitro calcium mobilization and chemotaxis assays for these compounds ranged from high picomolar to low nanomolar EC(50)s and correlated well with antagonist binding IC(50)s. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.059

文献信息

• N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
  申请人：——

  公开号：US20040058960A1

  公开（公告）日：2004-03-25

  The present application describes modulators of CCR3 of formula (I): 1 or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3调节剂的公式(I)：1或其药学上可接受的盐形式，用于预防哮喘和其他过敏性疾病。
• US6605623B1
  申请人：——

  公开号：US6605623B1

  公开（公告）日：2003-08-12
• US6906066B2
  申请人：——

  公开号：US6906066B2

  公开（公告）日：2005-06-14
• Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists
  作者：Jeffrey G Varnes、Daniel S Gardner、Joseph B Santella、John V Duncia、Melissa Estrella、Paul S Watson、Cheryl M Clark、Soo S Ko、Patricia Welch、Maryanne Covington、Nicole Stowell、Eric Wadman、Paul Davies、Kimberley Solomon、Robert C Newton、George L Trainor、Carl P Decicco、Dean A Wacker

  DOI：10.1016/j.bmcl.2004.01.059

  日期：2004.4

  The discovery of novel and selective small molecule antagonists of the CC Chemokine Receptor-3 (CCR3) is presented. Simple conversion from a 4- to 3-benzylpiperidine gave improved selectivity for CCR3 over the serotonin 5HT(2A) receptor. Chiral resolution and exploration of mono- and disubstitution of the N-propylurea resulted in several 3-benzylpiperidine N-propylureas with CCR3 binding IC50S under 5 nM. Data from in vitro calcium mobilization and chemotaxis assays for these compounds ranged from high picomolar to low nanomolar EC(50)s and correlated well with antagonist binding IC(50)s. (C) 2004 Elsevier Ltd. All rights reserved.