2-(4-fluorophenyl)-N-[(2R)-1-piperazin-1-ylpropan-2-yl]-4-propyl-1,3-oxazole-5-carboxamide | 924644-21-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)-N-[(2R)-1-piperazin-1-ylpropan-2-yl]-4-propyl-1,3-oxazole-5-carboxamide
• CAS: 924644-21-3
• 化学式: C₂₀H₂₇FN₄O₂
• 分子量: 374.458
• InChiKey: FYZHAKNQDYYIDV-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  potassium cyanate 、 2-(4-fluorophenyl)-N-[(2R)-1-piperazin-1-ylpropan-2-yl]-4-propyl-1,3-oxazole-5-carboxamide 在 溶剂黄146 作用下， 以 水 为溶剂， 生成 N-[(2R)-1-(4-carbamoylpiperazin-1-yl)propan-2-yl]-2-(4-fluorophenyl)-4-propyl-1,3-oxazole-5-carboxamide
  参考文献：
  名称：

  Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist

  摘要：

  Despite the extensive literature describing the role of the ATP-gated P2X(3) receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X(3) antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.044
• 作为产物：
  描述：

  benzyl 4-[(2R)-2-[[2-(4-fluorophenyl)-4-propyl-1,3-oxazole-5-carbonyl]amino]propyl]piperazine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 生成 2-(4-fluorophenyl)-N-[(2R)-1-piperazin-1-ylpropan-2-yl]-4-propyl-1,3-oxazole-5-carboxamide
  参考文献：
  名称：

  Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist

  摘要：

  Despite the extensive literature describing the role of the ATP-gated P2X(3) receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X(3) antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.044

文献信息

• PIPERIDINE AND PIPERAZINE DERIVATIVES AS P2X3 ANTAGONISTS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1917262A1

  公开（公告）日：2008-05-07
• [EN] PIPERIDINE AND PIPERAZINE DERIVATIVES AS P2X3 ANTAGONISTS<br/>[FR] DERIVES DE PIPERIDINE ET DE PIPERAZINE EN TANT QU'ANTAGONISTES DE P2X3
  申请人：HOFFMANN LA ROCHE

  公开号：WO2007020194A1

  公开（公告）日：2007-02-22

  [EN] Compounds of formula (I) wherein R¹, R^2a, R^2b, R³, Y, X, A, R⁶, R⁷ and R⁸ are as described herein, are modulators of P2X₃ useful for the treatment of pain and genitourinary, gastrointestinal, and respiratory disorders.
  [FR] La présente invention concerne des composés répondant à la formule (I) dans laquelle R¹, R^2a, R^2b, R³, Y, X, A, R⁶, R⁷ et R⁸ sont tels que décrits dans la description, lesquels sont des modulateurs de P2X₃ utiles pour le traitement de la douleur et de troubles génito-urinaires, gastro-intestinaux et respiratoires.
• Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist
  作者：Christine E. Brotherton-Pleiss、Michael P. Dillon、Anthony P.D.W. Ford、Joel R. Gever、David S. Carter、Shelley K. Gleason、Clara J. Lin、Amy G. Moore、Anthony W. Thompson、Marzia Villa、Yansheng Zhai

  DOI：10.1016/j.bmcl.2009.12.044

  日期：2010.2

  Despite the extensive literature describing the role of the ATP-gated P2X(3) receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X(3) antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85. (C) 2009 Elsevier Ltd. All rights reserved.