1-deaza-2-amino-6-chloropurine | 37436-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 1-deaza-2-amino-6-chloropurine
• 英文别名: 7-chloro-1(3)H-imidazo[4,5-b]pyridin-5-ylamine；7-Chlor-1(3)H-imidazo[4,5-b]pyridin-5-ylamin；7-chloro-1H-imidazo[4,5-b]pyridin-5-amine
• CAS: 37436-96-7
• 化学式: C₆H₅ClN₄
• 分子量: 168.585
• InChiKey: YCKDTQDJPNPXGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-deaza-2-amino-6-chloropurine 在 copper(l) iodide 、 trans-bis(triphenylphosphine)palladium dichloride 、 二碘甲烷 、 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 碘 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 29.17h， 生成 (3aR,3bS,4aS,5R,5aS)-5-(5-((5-chlorothiophen-2-yl)ethynyl)-7-(ethylamino)-3H-imidazo[4,5-b]pyridin-3-yl)-N,2,2-trimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxamide
  参考文献：
  名称：

  Rigidified A₃ Adenosine Receptor Agonists: 1-Deazaadenine Modification Maintains High in Vivo Efficacy

  摘要：

  Substitution of rigidified A(3) adenosine receptor (AR) agonists with a 2-((5-chlorothiophen-2-y1)ethynyl) or a 2-(4-(5-chlorothiophen-2-y1)-1H-1,2,3-triazol-1-yl)) group provides prolonged protection in a model of chronic neuropathic pain. These agonists contain a bicyclo[3.1.0]hexane ((N)-methanocarba) ring system in place of ribose, which adopts a receptor-preferred conformation. N-6-Small alkyl derivatives were newly optimized for A(3)AR affinity and the effects of a 1-deaza-adenine modification probed. 1-Deaza-N-6-ethyl alkyne 20 (MRS7144, K-i 1.7 nM) and 1-aza N-6-propyl alkyne 12 (MRS7154, K-i 1.1 nM) were highly efficacious in vivo. Thus, the presence of N1 is not required for nanomolar binding affinity or potent, long-lasting functional activity. Docking of 1-deaza compounds to a receptor homology model confirmed a similar binding mode as previously reported 1-aza derivatives. This is the first demonstration in nonribose adenosine analogues that the 1-deaza modification can maintain high A(3)AR affinity, selectivity, and efficacy.

  DOI：

  10.1021/acsmedchemlett.5b00150
• 作为产物：
  描述：

  N-(7-chloro-1(3)H-imidazo[4,5-b]pyridin-5-yl)-formamide 在 盐酸 作用下， 生成 1-deaza-2-amino-6-chloropurine
  参考文献：
  名称：

  The Synthesis of 5-Amino-7-hydroxy-1,3,4-imidazopyridine (1-Deazaguanine) and Related Compounds

  摘要：

  DOI：

  10.1021/ja01597a074

文献信息

• [EN] A3 ADENOSINE RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR DE L'ADÉNOSINE A3
  申请人：US HEALTH

  公开号：WO2015080940A1

  公开（公告）日：2015-06-04

  Disclosed are compounds of the formula (I) and (II) which are A3 adenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R2-R6, and R103-R106 are as defined in the specification. These compounds are selective to the A3 receptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain.

  揭示了公式(I)和(II)的化合物，这些化合物是A3腺苷受体激动剂，包括这些化合物的药物组合物，以及使用这些化合物的方法，其中X、Y、Z、R2-R6和R103-R106如规范中所定义。这些化合物对A3受体具有选择性，可用于治疗或预防多种疾病或症状，例如神经病性疼痛。
• Certain imidazo[4,5-b]pyridine derivatives
  申请人：CIBA-GEIGY AG

  公开号：EP0354180A2

  公开（公告）日：1990-02-07

  Disclosed are imidazo[4,5-b]pyridine derivatives of the formula I wherein R₁, R₂ and R₃ are as defined in the specification, which exhibit valuable pharmacological properties, especially as adenosine-2 (A-2) receptor agonists, and the preparation thereof.

  所公开的是式 I 的咪唑并[4,5-b]吡啶衍生物 其中 R₁、R₂ 和 R₃ 如说明书中所定义，这些衍生物具有重要的药理特性，特别是作为腺苷-2 (A-2) 受体激动剂，以及其制备方法。
• A3 adenosine receptor agonists
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：US10577368B2

  公开（公告）日：2020-03-03

  Disclosed are compounds of the formula (I) and (II): which are A3 adenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R2-R6, and R103-R106 are as defined in the specification. These compounds are selective to the A3 receptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain.

  所公开的是式 (I) 和 (II) 的化合物： 其中X、Y、Z、R2-R6和R103-R106如说明书中所定义。这些化合物对 A3 受体具有选择性，可用于治疗或预防多种疾病或病症，例如神经性疼痛。
• Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines
  作者：Christopher R. Coxon、Elizabeth Anscombe、Suzannah J. Harnor、Mathew P. Martin、Benoit Carbain、Bernard T. Golding、Ian R. Hardcastle、Lisa K. Harlow、Svitlana Korolchuk、Christopher J. Matheson、David R. Newell、Martin E. M. Noble、Mangaleswaran Sivaprakasam、Susan J. Tudhope、David M. Turner、Lan Z. Wang、Stephen R. Wedge、Christopher Wong、Roger J. Griffin、Jane A. Endicott、Céline Cano

  DOI：10.1021/acs.jmedchem.6b01254

  日期：2017.3.9

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.
• Gene Therapy of Cancer: Activation of Nucleoside Prodrugs with<i>E. coli</i>Purine Nucleoside Phosphorylase
  作者：John A. Secrist、William B. Parker、Paula W. Allan、L. Lee Bennett、William R. Waud、Jackie W. Truss、Anita T. Fowler、John A. Montgomery、Steven E. Ealick、Alan H. Wells、G. Yancey Gillespie、V. K. Gadi、Eric J. Sorscher

  DOI：10.1080/15257779908041562

  日期：1999.4

  During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery off. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data.