(2R)-2-[[7-amino-2-[[(2,3-difluorophenyl)methyl]thio]-4-pteridinyl]amino]-1-propanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: (2R)-2-[[7-amino-2-[[(2,3-difluorophenyl)methyl]thio]-4-pteridinyl]amino]-1-propanol
• 英文别名: (2R)-2-[[7-amino-2-[(2,3-difluorophenyl)methylsulfanyl]pteridin-4-yl]amino]propan-1-ol
• 化学式: C₁₆H₁₆F₂N₆OS
• 分子量: 378.405
• InChiKey: BJILNBJSTFTMIK-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2R)-2-[[7-amino-2-[[(2,3-difluorophenyl)methyl]thio]-4-pteridinyl]amino]-1-propanol 在 Oxone 作用下， 以 水 、 乙腈 为溶剂， 生成 (2R)-2-[[7-amino-2-[[(2,3-difluorophenyl)methyl]sulphonyl]-4-pteridinyl]amino]-1-propanol
  参考文献：
  名称：

  7-amino-2-alkylthiopteridin-4-yl-amines for the treatment of chemokine-related diseases

  摘要：

  式(I)的蝶啶化合物，其中R1、R2、R3和R4如权利要求中所定义，用于其制备的方法和中间体，含有它们的药物组合物，以及它们在治疗如牛皮癣、类风湿性关节炎、与升高的CXCR2趋化因子水平相关的血管生成疾病（糖尿病性视网膜病变）和慢性阻塞性肺病（COPD）等炎症性疾病中的用途。这些化合物是趋化因子受体的配体，描述中提到的医疗适应症包括：呼吸道疾病（COPD、哮喘、支气管炎、鼻炎、纤维化肺、肺炎等）、骨关节疾病（关节炎等）、皮肤病（牛皮癣等）、胃肠道疾病、其他组织疾病和全身性疾病（多发性硬化症、动脉粥样硬化、艾滋病、1型糖尿病、麻风病、败血症等）、异体移植排斥、癌症、囊性纤维化、中风、烧伤伤口、皮肤溃疡、生殖疾病等。

  公开号：

  US20040102447A1
• 作为产物：
  描述：

  2,4-bis[[(2,3-difluorophenyl)methyl]thio]-7-pteridinamine 、 D-氨基丙醇 反应 0.5h， 生成 (2R)-2-[[7-amino-2-[[(2,3-difluorophenyl)methyl]thio]-4-pteridinyl]amino]-1-propanol
  参考文献：
  名称：

  7-amino-2-alkylthiopteridin-4-yl-amines for the treatment of chemokine-related diseases

  摘要：

  式(I)的蝶啶化合物，其中R1、R2、R3和R4如权利要求中所定义，用于其制备的方法和中间体，含有它们的药物组合物，以及它们在治疗如牛皮癣、类风湿性关节炎、与升高的CXCR2趋化因子水平相关的血管生成疾病（糖尿病性视网膜病变）和慢性阻塞性肺病（COPD）等炎症性疾病中的用途。这些化合物是趋化因子受体的配体，描述中提到的医疗适应症包括：呼吸道疾病（COPD、哮喘、支气管炎、鼻炎、纤维化肺、肺炎等）、骨关节疾病（关节炎等）、皮肤病（牛皮癣等）、胃肠道疾病、其他组织疾病和全身性疾病（多发性硬化症、动脉粥样硬化、艾滋病、1型糖尿病、麻风病、败血症等）、异体移植排斥、癌症、囊性纤维化、中风、烧伤伤口、皮肤溃疡、生殖疾病等。

  公开号：

  US20040102447A1

文献信息

• 7-AMINO-2-ALKYLTHIOPTERIDIN-4-YL-AMINES FOR THE TREATMENT OF CHEMOKINE-RELATED DISEASES
  申请人：AstraZeneca AB

  公开号：EP1328319A1

  公开（公告）日：2003-07-23
• US7071193B2
  申请人：——

  公开号：US7071193B2

  公开（公告）日：2006-07-04
• [EN] 7-AMINO-2-ALKYLTHIOPTERIDIN-4-YL-AMINES FOR THE TREATMENT OF CHEMOKINE-RELATED DISEASES<br/>[FR] 7-AMINO-2-ALKYLTHIOPTERIDINE-4-YL-AMINES POUR LE TRAITEMENT DE MALADIES ASSOCIEES A LA CHIMIOKINE
  申请人：ASTRAZENECA AB

  公开号：WO2002032507A1

  公开（公告）日：2002-04-25

  Pteridine compounds of formula (I) in which R?1, R2, R3 and R4¿ are as specified in the claims, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in the treatment of inflammatory diseases such as psoriasis, rheumatoid arthritis, diseases in which angiogenesis is assocated with raised CXCR2 chemokine levels (diabetic retinopathy) and COPD. The compounds are ligands for chemokine receptors and medical indications mentioned in the description include: diseases of the respiratory tract (COPDD, asthma, bronchitis, rhinitis, fibroid lung, pneumonia, etc.), diseases of the bones and joints (arthritis, etc.), skin-diseases (psoriasis, etc), diseases of the gastrointestinal tract, diseases in other tissues and systemic disease (multipe sclerosis, atherosclerosis, AIDS, type 1 diabetes, leprosy, sepsis, etc.), allograft rejection, cancers, cystic fibrosis, stroke, burn wounds, skin ulcers, reproductive disease and more.
• 7-amino-2-alkylthiopteridin-4-yl-amines for the treatment of chemokine-related diseases
  申请人：——

  公开号：US20040102447A1

  公开（公告）日：2004-05-27

  Pteridine compounds of formula (I) in which R 1 , R 2 , R 3 and R 4 are as specified in the claims, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in the treatment of inflammatory diseases such as psoriasis, rheumatoid arthritis, diseases in which angiogenesis is assocated with raised CXCR2 chemokine levels (diabetic retinopathy) and COPD. The compounds are ligands for chemokine receptors and medical indications mentioned in the description include: diseases of the respiratory tract (COPDD, asthma, bronchitis, rhinitis, fibroid lung, pneumonia, etc.), diseases of the bones and joints (arthritis, etc.), skin-diseases (psoriasis, etc), diseases of the gastrointestinal tract, diseases in other tissues and systemic disease (multipe sclerosis, atherosclerosis, AIDS, type 1 diabetes, leprosy, sepsis, etc.), allograft rejection, cancers, cystic fibrosis, stroke, burn wounds, skin ulcers, reproductive disease and more.

  式(I)的蝶啶化合物，其中R1、R2、R3和R4如权利要求中所定义，用于其制备的方法和中间体，含有它们的药物组合物，以及它们在治疗如牛皮癣、类风湿性关节炎、与升高的CXCR2趋化因子水平相关的血管生成疾病（糖尿病性视网膜病变）和慢性阻塞性肺病（COPD）等炎症性疾病中的用途。这些化合物是趋化因子受体的配体，描述中提到的医疗适应症包括：呼吸道疾病（COPD、哮喘、支气管炎、鼻炎、纤维化肺、肺炎等）、骨关节疾病（关节炎等）、皮肤病（牛皮癣等）、胃肠道疾病、其他组织疾病和全身性疾病（多发性硬化症、动脉粥样硬化、艾滋病、1型糖尿病、麻风病、败血症等）、异体移植排斥、癌症、囊性纤维化、中风、烧伤伤口、皮肤溃疡、生殖疾病等。
• Evaluation of a series of bicyclic CXCR2 antagonists
  作者：Iain Walters、Caroline Austin、Rupert Austin、Roger Bonnert、Peter Cage、Mark Christie、Mark Ebden、Stuart Gardiner、Caroline Grahames、Steven Hill、Fraser Hunt、Robert Jewell、Shirley Lewis、Iain Martin、David Nicholls、David Robinson

  DOI：10.1016/j.bmcl.2007.11.039

  日期：2008.1

  The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity. (c) 2007 Elsevier Ltd. All rights reserved.