2-氯-N-环己基腺苷 | 38583-85-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2-氯-N-环己基腺苷
• 英文名称: 2-chloro-N⁶-cyclohexyladenosine
• 英文别名: 2-chloro-N6-cyclohexyladenosine；(2R,3R,4S,5R)-2-[2-chloro-6-(cyclohexylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 38583-85-6
• 化学式: C₁₆H₂₂ClN₅O₄
• 分子量: 383.835
• InChiKey: HBIOOKQCPKDFHZ-SDBHATRESA-N

物化性质

• 沸点：
  660.1±65.0 °C(Predicted)
• 密度：
  1.79

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-氯-N-环己基腺苷 在 10percent Pd/C sodium hydroxide 、 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以68%的产率得到N6-cyclohexyladenosine
  参考文献：
  名称：

  N-Cycloalkyl Derivatives of Adenosine and 1-Deazaadenosine as Agonists and Partial Agonists of the A₁ Adenosine Receptor

  摘要：

  A number of cycloalkyl substituents (from C-3 to C-8) have been int-reduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guanosine 5'-triphosphate (GTP) shift and the maximal induction of guanosine 5'-(gamma-thio)triphosphate ([S-35]GTP gamma S) binding to G proteins in rat brain membranes were used to determine the intrinsic activity of these nucleosides at the A(1) adenosine receptor. All compounds of the ribose-bearing series proved to be full agonists, the 1-deaza derivatives showing affinities for the Al receptor about 10-fold lower than the corresponding adenosines. On the other hand, all the 2'-deoxyribose derivatives bind to the A(1) receptor with affinities in the high nanomolar range, with the 2-chloro substituted compounds showing slightly higher affinities than the 2-unsubstituted counterparts. In terms of the potencies, the most potent compounds proved to be those bearing four- and five-membered rings. Both GTP shifts and [S-35]-GTP gamma S experiments showed that most of the 2'-deoxyadenosine derivatives are partial agonists, The 2'-deoxyadenosine derivatives which were identified as partial agonists consistently detected fewer Az receptors in the high-affinity state than full agonists. However, it is worthwhile noting that there was not a simple Linear relationship between receptor occupancy and activation. These results indicate that a critical density of A(1) adenosine receptors in the high-affinity state is required for G protein activation.

  DOI：

  10.1021/jm9911231
• 作为产物：
  描述：

  (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate 、 环己胺 在 氨 作用下， 以 甲醇 为溶剂， 反应 28.0h， 以92%的产率得到2-氯-N-环己基腺苷
  参考文献：
  名称：

  N-Cycloalkyl Derivatives of Adenosine and 1-Deazaadenosine as Agonists and Partial Agonists of the A₁ Adenosine Receptor

  摘要：

  A number of cycloalkyl substituents (from C-3 to C-8) have been int-reduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guanosine 5'-triphosphate (GTP) shift and the maximal induction of guanosine 5'-(gamma-thio)triphosphate ([S-35]GTP gamma S) binding to G proteins in rat brain membranes were used to determine the intrinsic activity of these nucleosides at the A(1) adenosine receptor. All compounds of the ribose-bearing series proved to be full agonists, the 1-deaza derivatives showing affinities for the Al receptor about 10-fold lower than the corresponding adenosines. On the other hand, all the 2'-deoxyribose derivatives bind to the A(1) receptor with affinities in the high nanomolar range, with the 2-chloro substituted compounds showing slightly higher affinities than the 2-unsubstituted counterparts. In terms of the potencies, the most potent compounds proved to be those bearing four- and five-membered rings. Both GTP shifts and [S-35]-GTP gamma S experiments showed that most of the 2'-deoxyadenosine derivatives are partial agonists, The 2'-deoxyadenosine derivatives which were identified as partial agonists consistently detected fewer Az receptors in the high-affinity state than full agonists. However, it is worthwhile noting that there was not a simple Linear relationship between receptor occupancy and activation. These results indicate that a critical density of A(1) adenosine receptors in the high-affinity state is required for G protein activation.

  DOI：

  10.1021/jm9911231

文献信息

• [EN] METHODS OF PREVENTING, REDUCING OR TREATING MACULAR DEGENERATION<br/>[FR] PROCÉDÉS DE PRÉVENTION, DE RÉDUCTION OU DE TRAITEMENT DE LA DÉGÉNÉRESCENCE MACULAIRE
  申请人：INOTEK PHARMACEUTICALS CORP

  公开号：WO2016090005A1

  公开（公告）日：2016-06-09

  The present invention is directed to selective adenosine A1 agonist compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, reduce or prevent age-related macular degeneration.

  本发明涉及选择性腺苷A1激动剂化合物，包括这种化合物的药物组合物，以及使用这种化合物来治疗、减少或预防年龄相关性黄斑变性的方法。
• [EN] METHOD OF REDUCING INTRAOCULAR PRESSURE IN HUMANS<br/>[FR] PROCÉDÉ DE RÉDUCTION DE LA PRESSION INTRAOCULAIRE CHEZ LES HUMAINS
  申请人：INOTEK PHARMACEUTICALS CORP

  公开号：WO2010127210A1

  公开（公告）日：2010-11-04

  Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for reducing intraocular pressure comprising administering an effective amount of compounds of Formula I to a subject in need thereof.

  本文提供了公式I的化合物，包含有效量的公式I化合物的组合物，以及用于降低眼压的方法，包括向需要的受试者施用公式I化合物的有效量。
• METHOD OF REDUCING INTRAOCULAR PRESSURE IN HUMANS
  申请人：BARMAN Shikha

  公开号：US20100279970A1

  公开（公告）日：2010-11-04

  Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for reducing intraocular pressure comprising administering an effective amount of compounds of Formula I to a subject in need thereof.

  本文提供的是I式化合物、包含有效量I式化合物的组合物以及减少眼压的方法，该方法包括向需要的受体中施用有效量的I式化合物。
• Method of reducing intraocular pressure in humans
  申请人：Barman Shikha

  公开号：US08470800B2

  公开（公告）日：2013-06-25

  Provided herein are compounds, compositions, and methods for reducing intraocular pressure. Also provided herein are compounds, compositions and methods for the treatment of glaucoma or ocular hypertension.

  本文提供了降低眼压的化合物、组合物和方法。还提供了治疗青光眼或眼压增高的化合物、组合物和方法。
• METHODS OF PREVENTING, REDUCING OR TREATING MACULAR DEGENERATION
  申请人：Inotek Pharmaceuticals Corporation

  公开号：US20160158267A1

  公开（公告）日：2016-06-09

  The present invention is directed to selective adenosine A 1 agonist compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, reduce or prevent age-related macular degeneration.

  本发明涉及选择性腺苷酸A1激动剂化合物、包含这些化合物的药物组成物以及使用这些化合物治疗、减少或预防与年龄相关的黄斑退化的方法。