6-amino-2-(butyloxy)-9-[3-(1-piperidinyl)propyl]-7,9-dihydro-8H-purin-8-one | 1207629-70-6

• 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-(butyloxy)-9-[3-(1-piperidinyl)propyl]-7,9-dihydro-8H-purin-8-one
• 英文别名: 6-amino-2-butoxy-9-(3-piperidin-1-ylpropyl)-7H-purin-8-one
• CAS: 1207629-70-6
• 化学式: C₁₇H₂₈N₆O₂
• 分子量: 348.448
• InChiKey: BMFALWWMQXNHKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  96.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-butoxy-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 103.0h， 生成 6-amino-2-(butyloxy)-9-[3-(1-piperidinyl)propyl]-7,9-dihydro-8H-purin-8-one
  参考文献：
  名称：

  A Chemical Switch for Transforming a Purine Agonist for Toll-like Receptor 7 to a Clinically Relevant Antagonist

  摘要：

  Toll-like receptor 7 (TLR7) is an established therapeutic target in myriad autoimmune disorders, but no TLR7 antagonist is available for clinical use to date. Herein, we report a purine scaffold TLR7 antagonist, first-of-its-kind to our knowledge, which was developed by rationally dissecting the structural requirements for TLR7-targeted activity for a purine scaffold. Specifically, we identified a singular chemical switch at C-2 that could make a potent purine scaffold TLR7 agonist to lose agonism and acquire antagonist activity, which could further be potentiated by the introduction of an additional basic center at C-6. We ended up developing a clinically relevant TLR7 antagonist with favorable pharmacokinetics and 70.8% oral bioavailability in mice. Moreover, the TLR7 antagonists depicted excellent selectivity against TLR8. To further validate the in vivo applicability of this novel TLR7 antagonist, we demonstrated its excellent efficacy in preventing TLR7-induced pathology in a preclinical murine model of psoriasis.

  DOI：

  10.1021/acs.jmedchem.0c00011

文献信息

• [EN] PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES<br/>[FR] DÉRIVÉS PURINES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES ALLERGIQUES, INFLAMMATOIRES ET INFECTIEUSES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2010018133A1

  公开（公告）日：2010-02-18

  Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

  公式（I）的化合物：其中R1是C1-6烷基氨基，C1-6烷氧基，或C3-7环烷氧基；m是一个取值为3到6的整数；n是一个取值为0到4的整数；它们的盐是人类干扰素的诱导剂。诱导人类干扰素的化合物可能在治疗各种疾病中有用，例如治疗过敏性疾病和其他炎症性疾病，例如过敏性鼻炎和哮喘，治疗传染病和癌症，并且可能还可用作疫苗佐剂。
• COMPOUNDS
  申请人：Biggadike Keith

  公开号：US20100075995A1

  公开（公告）日：2010-03-25

  Compounds of formula (I): wherein R 1 is C 1-6 alkylamino, C 1-6 alkoxy, or C 3-7 cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

  化合物的公式（I）：其中R1是C1-6烷基氨基，C1-6烷氧基或C3-7环烷氧基；m是一个整数，取值为3到6；n是一个整数，取值为0到4；它们的盐是人类干扰素的诱导剂。诱导人类干扰素的化合物可能在治疗各种疾病方面有用，例如治疗过敏性疾病和其他炎症性疾病，例如过敏性鼻炎和哮喘，治疗传染病和癌症，也可能作为疫苗佐剂有用。
• 6-AMINO-PURIN-8-ONE COMPOUNDS
  申请人：Biggadike Keith

  公开号：US20120035193A1

  公开（公告）日：2012-02-09

  Compounds of formula (I): wherein R 1 is C 1-6 alkylamino, C 1-6 alkoxy, or C 3-7 cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

  化学式为（I）的化合物：其中R1是C1-6烷基氨基，C1-6烷氧基或C3-7环烷氧基；m是一个整数，其值为3到6；n是一个整数，其值为0到4；以及它们的盐是人类干扰素的诱导剂。诱导人类干扰素的化合物可能在治疗各种疾病方面有用，例如治疗过敏性疾病和其他炎症性疾病，例如过敏性鼻炎和哮喘，治疗感染性疾病和癌症，并且还可能作为疫苗佐剂有用。
• PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
  申请人：Biggadike Keith

  公开号：US20110229500A1

  公开（公告）日：2011-09-22

  The present invention relates to compounds of formula (I): wherein R 1 is C 1-6 alkylamino, C 1-6 alkoxy, or C 3-7 cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

  本发明涉及以下式子的化合物（I）：其中，R1是C1-6烷基氨基，C1-6烷氧基或C3-7环烷氧基；m是一个整数，其值为3到6；n是一个整数，其值为0到4；其盐是人干扰素的诱导剂。诱导人干扰素的化合物可用于治疗各种疾病，例如过敏性疾病和其他炎症性疾病的治疗，例如过敏性鼻炎和哮喘，感染性疾病和癌症的治疗，并且还可以用作疫苗佐剂。
• 6-amino-purin-8-one compounds
  申请人：GlaxoSmithKline LLC

  公开号：US10117873B2

  公开（公告）日：2018-11-06

  Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

  式(I)化合物： 其中 R1 是 C1-6 烷基氨基、C1-6 烷氧基或 C3-7 环烷氧基；m 是数值为 3-6 的整数；n 是数值为 0-4 的整数；及其盐类是人类干扰素的诱导剂。诱导人类干扰素的化合物可用于治疗各种疾病，例如治疗过敏性疾病和其他炎症，如过敏性鼻炎和哮喘，治疗传染性疾病和癌症，也可用作疫苗佐剂。