CP 481715 | 212790-31-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: CP 481715
• 英文别名: N-[(1S,2S,4R)-4-(aminocarbonyl)-1-[(3-fluorophenyl)methyl]-2,7-dihydroxy-7-methyloctyl]-2-quinoxalinecarboxamide；CP-481715；CP481715；quinoxaline-2-carboxylic acid [4(R)-carbamoyl-1(S)-(3-fluoro-benzyl)-2(S),7-dihydroxy-7-methyl-octyl]-amide；2-Quinoxalinecarboxamide, N-((1S,2S,4R)-4-(aminocarbonyl)-1-((3-fluorophenyl)methyl)-2,7-dihydroxy-7-methyloctyl)-；N-[(2S,3S,5R)-5-carbamoyl-1-(3-fluorophenyl)-3,8-dihydroxy-8-methylnonan-2-yl]quinoxaline-2-carboxamide
• CAS: 212790-31-3
• 化学式: C₂₆H₃₁FN₄O₄
• 分子量: 482.555
• InChiKey: YEQJVHQCUDMXFG-FHZYATBESA-N

物化性质

• 沸点：
  808.2±65.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  7

制备方法与用途

CP-481715是一种强效且选择性的CCR1拮抗剂，其Ki值为9.2纳摩尔，IC50值为74纳摩尔，不具备内在激动剂活性。

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 CP 481715 在 4-二甲氨基吡啶 吡啶 作用下， 反应 3.0h， 生成 acetic acid 3(R)-carbamoyl-1(S)-{2-(3-fluoro-phenyl)-1(S)-[(quinoxaline-2-carbonyl)-amino]-ethyl}-6-hydroxy-6-methyl-heptyl ester
  参考文献：
  名称：

  Heteroaryl-hexanoic acid amide derivatives as immonomodulatory agents

  摘要：

  本发明涉及式(I)的化合物1，其中R1、R2、R3、R4、R5、R7和L如规范中所述。本发明还涉及包括式(I)的化合物和药学上可接受的载体的制药组合物。此外，本发明涉及使用上述化合物和组合物治疗和预防疾病和病症的方法，包括那些通过拮抗CCR1受体可以治疗或预防的疾病和病症。

  公开号：

  US20040097554A1
• 作为产物：
  描述：

  (3R,5S)-5-((S)-1-amino-2-(3-fluorophenyl)ethyl)-3-(3-hydroxy-3-methylbutyl)-4,5-dihydrofuran-2(3H)-one 在 氨 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 27.0h， 生成 CP 481715
  参考文献：
  名称：

  Process Development of CP-481715, a Novel CCR1 Antagonist

  摘要：

  Process development for the synthesis of 2-quinoxalinecarboxamide, N-[(1S,2S,4R)-4-(aminocarbonyl)-1-[(3-fluorophenyl)methyl]-2,7-dihydroxy-7-methyloctyl] is described. An optimized,and streamlined process starting from lactone 2 was developed: Lactone 2 was alkylated diastereoselectively with prenyl bromide, followed by deprotection of the N-Boc group and concomitant hydration of the olefin. Aminolysis of the lactone in methanolic ammonia afforded the titled compound.

  DOI：

  10.1021/op050059w

文献信息

• [EN] CRYSTAL FORMS OF QUINOXALINE-2-CARBOXYLIC ACID [4-CARBAMOYL-1-(3-FLUOROBENZYL)-2,7-DIHYDROXY-7-METHYL-OCTYL]-AMIDE<br/>[FR] FORMES CRISTALLINES D'ACIDE QUINOXALINE-2-CARBOXYLIQUE [4-CARBAMOYL-1-(3-FLUOROBENZYL)-2,7-DIHYDROXY-7-METHYL-OCTYL]-AMIDE
  申请人：PFIZER PROD INC

  公开号：WO2004014875A1

  公开（公告）日：2004-02-19

  The invention relates to crystal forms of quinoxaline-2-carboxylic acid [4-carbamoyl-1-(3-fluorobenzyl)-2,7-dihydroxy-7-methyl-octyl]-amide, useful in treating or preventing a disorder or condition by antogonizing the CCR1 receptor, and to their methods of preparation and use.

  该发明涉及喹喔啉-2-羧酸[4-氨基甲酰基-1-(3-氟苯基)-2,7-二羟基-7-甲基辛基]-酰胺的晶型，用于通过拮抗CCR1受体来治疗或预防某种疾病或状况，以及其制备和使用方法。
• Dihydoxyhexanoic acid derivatives, their intermediates, and methods of making
  申请人：Pfizer Inc.

  公开号：US20040019217A1

  公开（公告）日：2004-01-29

  This invention relates to dihydroxyhexanoic acid derivatives and their intermediates, as well as to methods of preparing such compounds. Additionally, present invention relates to removing a protecting group from a protected amine wherein the method comprises reacting the protected amine with phosphoric acid.

  这项发明涉及二羟基己酸衍生物及其中间体，以及制备这类化合物的方法。此外，本发明涉及从受保护胺中去除保护基的方法，其中该方法包括将受保护胺与磷酸反应。
• Spirocyclic Heterocycles Medicaments Containing Said Compounds, Use Thereof And Method For Their Production
  申请人：Himmelsbach Frank

  公开号：US20110046148A1

  公开（公告）日：2011-02-24

  The present invention relates to spirocyclic heterocycles of general formula (I) the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids, which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for the treatment of diseases, particularly tumoral diseases as well as benign prostatic hyperplasia (BPH), diseases of the lungs and airways, and the preparation thereof.

  本发明涉及一般式(I)的螺环杂环化合物，其包括其互变异构体、立体异构体、它们的混合物和盐，特别是与无机或有机酸形成的生理上可接受的盐，具有有价值的药理特性，特别是对酪氨酸激酶介导的信号传导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病以及良性前列腺增生（BPH）、肺部和气道疾病，以及其制备方法。
• Pharmaceutical Compositions With Enhanced Performance
  申请人：Babcock Walter C.

  公开号：US20080262107A1

  公开（公告）日：2008-10-23

  Disclosed are polymers of hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and hydroxypropyl methyl cellulose acetate (HPMCA) with unique degrees of substitution of hydroxypropoxy, methoxy, acetyl, and succinoyl groups. When used in making compositions comprising a low-solubility drug and such polymers, the polymers provide enhanced aqueous concentrations and/or improved physical stability.

  本发明涉及羟丙基甲基纤维素乙酸琥珀酸酯（HPMCAS）和羟丙基甲基纤维素乙酸酯（HPMCA）的聚合物，其羟丙氧基，甲氧基，乙酰基和琥珀酰基取代度独特。当用于制备包含低溶解度药物和这些聚合物的组合物时，这些聚合物提供了增强的水溶液浓度和/或改善的物理稳定性。
• PHARMACEUTICAL COMPOSITIONS WITH ENHANCED PERFORMANCE
  申请人：Babcock Walter C.

  公开号：US20120264833A1

  公开（公告）日：2012-10-18

  Disclosed are polymers of hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and hydroxypropyl methyl cellulose acetate (HPMCA) with unique degrees of substitution of hydroxypropoxy, methoxy, acetyl, and succinoyl groups. When used in making compositions comprising a low-solubility drug and such polymers, the polymers provide enhanced aqueous concentrations and/or improved physical stability.

  本发明涉及羟丙基甲基纤维素醋酸琥珀酸酯(HPMCAS)和羟丙基甲基纤维素醋酸酯(HPMCA)的聚合物，其羟丙氧基、甲氧基、乙酰基和琥珀酰基取代度独特。当用于制备含低溶解度药物和上述聚合物的组合物时，聚合物提供了增强的水溶液浓度和/或改善的物理稳定性。