(R)-4-(2-(1-aminoethyI)-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)benzonitrile | 873191-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: (R)-4-(2-(1-aminoethyI)-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)benzonitrile
• 英文别名: (R)-4-(2-(1-aminoethyl)-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)benzonitrile；4-[2-[(1R)-1-aminoethyl]-4-oxopyrido[2,3-d]pyrimidin-3-yl]benzonitrile
• CAS: 873191-26-5
• 化学式: C₁₆H₁₃N₅O
• 分子量: 291.312
• InChiKey: KDAPXRNXTLNTRN-SNVBAGLBSA-N

物化性质

• 沸点：
  540.6±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-4-(2-(1-aminoethyI)-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)benzonitrile 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 生成 (R)-N-(1-(3-(4-cyanophenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl)ethyl)-N-(2-(ethyIsulfonyI)ethyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-acetamide
  参考文献：
  名称：

  Discovery of potent and specific CXCR3 antagonists

  摘要：

  The optimization of a series of 8-aza-quinazolinone analogs for antagonist activity against the CXCR3 receptor is reported. Compounds were optimized to avoid the formation of active metabolites and time-dependent- inhibitors of CYP3A4. In addition, antagonists showed potent against CXCR3 activity in whole blood and optimized to avoid activity in the chromosomal aberration assay. Compound 25 was identified as having the optimal balance of CXCR3 activity and pharmacokinetic properties across multiple pre-clinical species, which are reported herein. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.120
• 作为产物：
  描述：

  2-氨基烟酸 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-氯代丁二酰亚胺 、 sodium azide 、 L-苹果酸 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-4-(2-(1-aminoethyI)-4-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)benzonitrile
  参考文献：
  名称：

  Discovery of potent and specific CXCR3 antagonists

  摘要：

  The optimization of a series of 8-aza-quinazolinone analogs for antagonist activity against the CXCR3 receptor is reported. Compounds were optimized to avoid the formation of active metabolites and time-dependent- inhibitors of CYP3A4. In addition, antagonists showed potent against CXCR3 activity in whole blood and optimized to avoid activity in the chromosomal aberration assay. Compound 25 was identified as having the optimal balance of CXCR3 activity and pharmacokinetic properties across multiple pre-clinical species, which are reported herein. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.120

文献信息

• [EN] FUSED PYRIMIDINE DERIVATIVES AND COMPOSITIONS THEREOF AS CXCR3 RECEPTOR MODULATORS, USEFUL IN PREVENTION AND TREATMENT OF INFLAMMATORY AND IMMUNOREGULATORY DISORDERS AND DISEASES<br/>[FR] DERIVES DE PYRIMIDINE FUSIONNES ET COMPOSITIONS SUR LEUR BASE, UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR DE CXCR3, UTILES DANS LA PREVENTION ET LE TRAITEMENT DE MALADIES ET TROUBLES INFLAMMATOIRES OU IMMUNOREGULATEURS
  申请人：AMGEN INC

  公开号：WO2006004915A1

  公开（公告）日：2006-01-12

  Compounds are provided having the formula: wherein variables Ra, R1, R2, R3, R4, A1, A4, L, Q, X and subscript n as described herein. The subject compounds are useful for treatment of inflammatory and immune conditions and diseases. Compositions and methods of treatment using the subject compounds are also provided. For example, the subject methods are useful for treatment of inflammatory and immune disorders and disease such as multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

  提供具有以下公式的化合物：其中变量Ra、R1、R2、R3、R4、A1、A4、L、Q、X和下标n如本文所述。所述化合物对于治疗炎症和免疫状况和疾病有用。还提供使用所述化合物的组合物和治疗方法。例如，所述方法对于治疗炎症和免疫紊乱和疾病如多发性硬化症、类风湿关节炎、银屑病和炎症性肠病有用。
• Compounds, compositions and methods for prevention and treatment of inflammatory and immunoregulatory disorders and diseases
  申请人：Fu Zice

  公开号：US20060069099A1

  公开（公告）日：2006-03-30

  Compounds are provided having the formula: wherein variables R a , R 1 , R 2 , R 3 , R 4 , A 1 , A 4 , L, Q, X and subscript n as described herein. The subject compounds are useful for treatment of inflammatory and immune conditions and diseases. Compositions and methods of treatment using the subject compounds are also provided. For example, the subject methods are useful for treatment of inflammatory and immune disorders and disease such as multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

  提供具有以下公式的化合物：其中变量Ra，R1，R2，R3，R4，A1，A4，L，Q，X和下标n如此描述。这些化合物可用于治疗炎症和免疫性疾病。还提供使用这些化合物的组合物和治疗方法。例如，这些方法可用于治疗多发性硬化症、类风湿性关节炎、银屑病和炎症性肠病等炎症和免疫性疾病的治疗。
• Aryl nitrile compounds and compositions and their uses in treating inflammatory and related disorders
  申请人：Bergeron Philippe

  公开号：US20070015773A1

  公开（公告）日：2007-01-18

  Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides aryl nitrile compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis, type I diabetes, asthma, psoriasis and inflammatory bowel disease.

  本文提供了在治疗炎症和免疫相关疾病中有用的化合物、组合物和方法。具体来说，本发明提供了可以调节趋化因子受体的表达和/或功能的芳基腈化合物。这些方法适用于治疗炎症和免疫调节性疾病，例如多发性硬化症、类风湿性关节炎、1型糖尿病、哮喘、牛皮癣和炎症性肠病。
• WO2007/2701
  申请人：——

  公开号：——

  公开（公告）日：——
• Optimization of a series of quinazolinone-derived antagonists of CXCR3
  作者：Jiwen Liu、Zice Fu、An-Rong Li、Michael Johnson、Liusheng Zhu、Andrew Marcus、Jay Danao、Tim Sullivan、George Tonn、Tassie Collins、Julio Medina

  DOI：10.1016/j.bmcl.2009.07.032

  日期：2009.9

  The evaluation of the CXCR3 antagonist AMG 487 in clinic trials was complicated due to the formation of an active metabolite. In this Letter, we will discuss the further optimization of the quinazolinone series that led to the discovery of compounds devoid of the formation of the active metabolite that was seen with AMG 487. In addition, these compounds also feature increased potency and good pharmacokinetic properties. We will also discuss the efficacy of the lead compound 34 in a mouse model of cellular recruitment induced by bleomycin. (C) 2009 Elsevier Ltd. All rights reserved.