6-amino-2-(butylamino)-9-((6-chloropyridin-3-yl)methyl)-7H-purin-8(9H)-one | 473930-12-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-amino-2-(butylamino)-9-((6-chloropyridin-3-yl)methyl)-7H-purin-8(9H)-one
• 英文别名: 6-amino-2-(butylamino)-9-[(6-chloropyridin-3-yl)methyl]-7H-purin-8-one
• CAS: 473930-12-0
• 化学式: C₁₅H₁₈ClN₇O
• 分子量: 347.807
• InChiKey: OEUBGVYHYRETGV-UHFFFAOYSA-N

物化性质

• 熔点：
  256-258 °C(Solv: methanol (67-56-1))
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-amino-2-(butylamino)-9-((6-chloropyridin-3-yl)methyl)-7H-purin-8(9H)-one 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.83h， 生成 N-(2-(4-(5-((6-amino-2-(butylamino)-8-oxo-7H-purin-9(8H)-yl)methyl)pyridin-2-yl)piperazin-1-yl)ethyl)-2-(aminooxy)acetamide trifluoroacetic acid
  参考文献：
  名称：

  [EN] ANTIBODY-TLR AGONIST CONJUGATES, METHODS AND USES THEREOF
  [FR] CONJUGUÉS ANTICORPS-AGONISTES DE TLR, PROCÉDÉS ET UTILISATIONS DE CEUX-CI

  摘要：

  本文披露了TLR-激动剂化合物、抗体-TLR激动剂结合物、制药组合物以及使用这些化合物或结合物作为治疗癌症等疾病或病症的治疗剂的方法。

  公开号：

  WO2022040596A1
• 作为产物：
  描述：

  2-氯-6-氨基嘌呤 在 盐酸 、 溴 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 6-amino-2-(butylamino)-9-((6-chloropyridin-3-yl)methyl)-7H-purin-8(9H)-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel 9-Substituted-8-Hydroxyadenine Derivatives as Potent Interferon Inducers

  摘要：

  Recently we reported the adenine derivatives 3a-d as novel interferon (IFN) inducers. In the present study, we conducted a detailed structure-activity relationship study of analogues of 3a-d with respect to their IFN-inducing activity, mainly focusing on the N(9)-position of the adenine. From this study, we found that introduction of the 3-pyridylmethyl moiety was effective to increase in vitro activity, and compound 9ae was identified as being the most potent IFN inducer. This compound gave a minimum effective concentration (MEC) of 3 nM, which is comparable with that of R-848, a second generation IFN inducer. Compound 9ae also demonstrated potent IFN-inducing activity at a dose of 0.1 mg/kg by oral administration in mice. Furthermore, compound 9ae induced IFN in monkeys in a dose dependent manner, with a potency superior to that of R-848. In addition, 9ae did not cause emesis in ferrets even at a dose of 30 mg/kg. In this study the maximum plasma concentration of 9ae was 1019 ng/mL (ca. 3.1 mu M), which was approximately 1000-fold higher than the MEC value. Therefore, with respect to both the efficacy and the safety margin, compound 9ae (SM-276001) is considered to be a promising compound as an orally active IFN inducer.

  DOI：

  10.1021/jm051089s

文献信息

• [EN] USE OF A TLR7 AGONIST FOR THE TREATMENT OF CANCER<br/>[FR] UTILISATION D'UN AGONISTE DE TLR7 POUR LE TRAITEMENT DU CANCER
  申请人：ASTRAZENECA AB

  公开号：WO2010033074A1

  公开（公告）日：2010-03-25

  The invention relates to a novel method of treatment or prophylaxis of cancer, which comprises administering to a patient in need thereof a therapeutically effective amount of a TLR7 agonist of Formula (I), or a pharmaceutically acceptable salt thereof.

  该发明涉及一种治疗或预防癌症的新方法，包括向需要的患者施用公式（I）的TLR7激动剂或其药学上可接受的盐的治疗有效量。
• Novel adenne derivatives
  申请人：——

  公开号：US20040132748A1

  公开（公告）日：2004-07-08

  This invention relates to an adenine derivative, a tautomer thereof, or a pharmaceutically acceptable salt thereof represented by general formula (I): 1 wherein X represents NR 3 (wherein R 3 represents a hydrogen atom or C 1-3 alkyl) or the like; R 1 represents substituted or unsubstituted alkyl or the like; R 2 represents hydroxyl or the like; and Y represents a substituted or unsubstituted aromatic hetero ring or the like. Also, the present invention relates to pharmaceuticals such as an interferon inducer, antiviral agent, anticancer agent, type 2 helper T cell selective immune response inhibitor, antiallergic agent, and immune response modulator comprising the above derivative as an active ingredient.

  本发明涉及一种由通式（I）表示的腺嘌呤衍生物、其互变异构体或其药学上可接受的盐，其中X代表NR3（其中R3代表氢原子或C1-3烷基）或类似物；R1代表取代或未取代的烷基或类似物；R2代表羟基或类似物；Y代表取代或未取代的芳香杂环或类似物。此外，本发明还涉及将上述衍生物作为活性成分的药物，例如干扰素诱导剂、抗病毒剂、抗癌剂、2型辅助T细胞选择性免疫反应抑制剂、抗过敏剂和免疫反应调节剂。
• Novel adenine derivatives
  申请人：Isobe Yoshiaki

  公开号：US20070037832A1

  公开（公告）日：2007-02-15

  This invention relates to an adenine derivative, a tautomer thereof, or a pharmaceutically acceptable salt thereof represented by general formula (I): wherein X represents NR 3 (wherein R 3 represents a hydrogen atom or C 1-3 alkyl) or the like; R 1 represents substituted or unsubstituted alkyl or the like; R 2 represents hydroxyl or the like; and Y represents a substituted or unsubstituted aromatic hetero ring or the like. Also, the present invention relates to pharmaceuticals such as an interferon inducer, antiviral agent, anticancer agent, type 2 helper T cell selective immune response inhibitor, antiallergic agent, and immune response modulator comprising the above derivative as an active ingredient.

  本发明涉及一种腺嘌呤衍生物，其互变异构体或药学上可接受的盐，由下式表示：其中X代表NR3（其中R3代表氢原子或C1-3烷基）或类似物；R1代表取代或未取代的烷基或类似物；R2代表羟基或类似物；Y代表取代或未取代的芳香杂环或类似物。此外，本发明涉及上述衍生物作为活性成分的制备干扰素诱导剂、抗病毒剂、抗癌剂、选择性抑制2型辅助T细胞免疫反应抑制剂、抗过敏剂和免疫反应调节剂等药物。
• Anti PD-L1 conjugates for treating tumors
  申请人：BIRDIE BIOPHARMACEUTICALS, INC.

  公开号：US11130812B2

  公开（公告）日：2021-09-28

  The present invention discloses anti-PD-L/PD-1 Axis antibody conjugates for targeted immunotherapy, as well as compositions comprising said conjugates. Further, the present invention discloses the use of the conjugates in the treatment of tumor/cancer.

  本发明公开了用于靶向免疫疗法的抗-PD-L/PD-1 轴抗体共轭物以及包含上述共轭物的组合物。此外，本发明还公开了共轭物在治疗肿瘤/癌症中的用途。
• Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility
  作者：Tomoaki Nakamura、Hiroki Wada、Hirotaka Kurebayashi、Tom McInally、Roger Bonnert、Yoshiaki Isobe

  DOI：10.1016/j.bmcl.2012.11.114

  日期：2013.2

  We report the discovery of novel series of highly potent TLR7 agonists based on 8-oxoadenines, 1 and 2 by introducing and optimizing various tertiary amines onto the N(9)-position of the adenine moiety. The introduction of the amino group resulted in not only improved water solubility but also enhanced TLR7 agonistic activity. In particular compound 20 (DSR-6434) indicated an optimal balance between the agonistic potency and high water solubility. It also demonstrated a strong antitumor effect in vivo by intravenous administration in a tumor bearing mice model. (c) 2012 Elsevier Ltd. All rights reserved.