2-[(4-bromophenyl)amino]-4-methylpyrimidine-5-carbaldehyde | 926304-98-5

• 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: 2-[(4-bromophenyl)amino]-4-methylpyrimidine-5-carbaldehyde
• 英文别名: 2-(4-Bromo-phenylamino)-4-methyl-pyrimidine-5-carbaldehyde；2-(4-bromoanilino)-4-methylpyrimidine-5-carbaldehyde
• CAS: 926304-98-5
• 化学式: C₁₂H₁₀BrN₃O
• 分子量: 292.135
• InChiKey: MPLGZYGIURYXKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(4-bromophenyl)amino]-4-methylpyrimidine-5-carbaldehyde 、 氰化锌 在 tris-(dibenzylideneacetone)dipalladium(0) 1,1'-双(二苯基膦)二茂铁 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以57%的产率得到4-[(5-formyl-4-methylpyrimidin-2-yl)amino]benzonitrile
  参考文献：
  名称：

  WO2007/22371

  摘要：

  公开号：
• 作为产物：
  描述：

  1,4-二溴苯 在 manganese(IV) oxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 二异丁基氢化铝 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 2-[(4-bromophenyl)amino]-4-methylpyrimidine-5-carbaldehyde
  参考文献：
  名称：

  Design of Substituted Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor 5 Antagonists: Potent Inhibitors of R5 HIV-1 Replication

  摘要：

  The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (RS) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.

  DOI：

  10.1021/jm401101p

文献信息

• Chemokine receptor binding compounds
  申请人：Zhou Yuanxi

  公开号：US20070066624A1

  公开（公告）日：2007-03-22

  The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR4 or CCR5. In one aspect, these compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  本发明涉及化学因子受体结合化合物、药物组合物及其使用。更具体地，本发明涉及化学因子受体活性调节剂，优选地为CCR4或CCR5的调节剂。在一个方面，这些化合物表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护效应。
• CHEMOKINE RECEPTOR BINDING COMPOUNDS
  申请人：Genzyme Corporation

  公开号：EP1924265A2

  公开（公告）日：2008-05-28
• [EN] CHEMOKINE RECEPTOR BINDING COMPOUNDS<br/>[FR] COMPOSES SE LIANT AUX RECEPTEURS DE CHIMIOKINE
  申请人：ANORMED INC

  公开号：WO2007022371A2

  公开（公告）日：2007-02-22

  [EN] The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR4 or CCR5. In one aspect, these compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
  [FR] La présente invention concerne des composés se liant aux récepteurs de chimiokine, des compositions pharmaceutiques et leur utilisation. Plus spécifiquement, cette invention concerne des modulateurs de l'activité des récepteurs de chimiokine, de préférence des modulateurs de CCR4 ou de CCR5. Dans un aspect, ces composés démontrent des effets de protection contre l'infection de cellules cible par un virus d'immunodéficience humain (VIH).
• WO2007/22371
  申请人：——

  公开号：——

  公开（公告）日：——
• Design of Substituted Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor 5 Antagonists: Potent Inhibitors of R5 HIV-1 Replication
  作者：Renato Skerlj、Gary Bridger、Yuanxi Zhou、Elyse Bourque、Ernest McEachern、Markus Metz、Curtis Harwig、Tong-Shuang Li、Wen Yang、David Bogucki、Yongbao Zhu、Jonathan Langille、Duane Veale、Tuya Ba、Michael Bey、Ian Baird、Alan Kaller、Maria Krumpak、David Leitch、Michael Satori、Krystyna Vocadlo、Danielle Guay、Susan Nan、Helen Yee、Jason Crawford、Gang Chen、Trevor Wilson、Bryon Carpenter、David Gauthier、Ron MacFarland、Renee Mosi、Veronique Bodart、Rebecca Wong、Simon Fricker、Dominique Schols

  DOI：10.1021/jm401101p

  日期：2013.10.24

  The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (RS) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.