N-环戊基-9-甲基嘌呤-6-胺 | 109292-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: N-环戊基-9-甲基嘌呤-6-胺
• 英文名称: N6-cyclopentyl-9-methyladenine
• 英文别名: N 0840；N⁶-cyclopentyl-9-methyladenine；N-Cyclopentyl-9-methyladenine；NCGC00015717-04；n6-cyclopentyl 9-methyladenine；N-cyclopentyl-9-methylpurin-6-amine
• CAS: 109292-91-3
• 化学式: C₁₁H₁₅N₅
• mdl: MFCD00153844
• 分子量: 217.274
• InChiKey: LZMRVYPPUVMKOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-环戊基-9-甲基嘌呤-6-胺 在 disodium hydrogenphosphate 、 溴 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 生成 LUF5666
  参考文献：
  名称：

  Synthesis and biological evaluation of disubstituted N6-cyclopentyladenine analogues

  摘要：

  Novel 3,8- and 8,9-disubstituted N(6)-cyclopentyladenine derivatives were synthesised in moderate overall yield from 6-chloropurine. The derivatives were made in an attempt to find a new neutral antagonist with high affinity for adenosine A(1) receptors. N(6)-Cyclopentyl-9-methyladenine (N-0840) was used as a lead compound. Binding affinities of the new analogues were determined for human adenosine A(1) and A(3) receptors. Their intrinsic activity was assessed in [35S]GTPgammaS binding experiments. Elongation of the 9-methyl of N-0840 to a 9-propyl substituent was very well tolerated. A 9-benzyl group, on the other hand, caused a decrease in adenosine A(1) receptor affinity. Next, the 8-position was examined in detail, and affinity was increased with appropriate substitution. Most derivatives were A(1)-selective and 20 of the new compounds (6-9, 15-21, 23-26, 28, 31, 33, 35, and 36) had higher adenosine A(1) receptor affinity than the reference substance, N-0840. Compound 31 (N(6)-cyclopentyl-8-(N-methylisopropylamino)-9-methyladenine, LUF 5608) had the highest adenosine A(1) receptor affinity, 7.7 nM. In the [35S]GTPgammaS binding experiments, derivatives 5, 14, 22, 23, 25, 26, 33 and 34 did not significantly change basal [35S]GTPgammaS binding, thus behaving as neutral antagonists. Moreover, four of these compounds (23, 25, 26, and 33) displayed a 4- to 10-fold increased adenosine A(1) receptor affinity (75-206 nM) compared to N-0840 (852 nM). In summary, we synthesised a range of N-0840 analogues with higher affinity for adenosine A(1) receptors. In addition, four new derivatives, LUF 5666 (23), LUF 5668 (25), LUF 5669 (26) and LUF 5674 (33), behaved as neutral antagonists when tested in [35S]GTPgammaS binding studies. Thus, these compounds have improved characteristics as neutral adenosine A(1) receptor antagonists.

  DOI：

  10.1016/j.bmc.2003.10.023
• 作为产物：
  描述：

  6-氯嘌呤 在 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 32.0h， 生成 N-环戊基-9-甲基嘌呤-6-胺
  参考文献：
  名称：

  Synthesis and biological evaluation of disubstituted N6-cyclopentyladenine analogues

  摘要：

  Novel 3,8- and 8,9-disubstituted N(6)-cyclopentyladenine derivatives were synthesised in moderate overall yield from 6-chloropurine. The derivatives were made in an attempt to find a new neutral antagonist with high affinity for adenosine A(1) receptors. N(6)-Cyclopentyl-9-methyladenine (N-0840) was used as a lead compound. Binding affinities of the new analogues were determined for human adenosine A(1) and A(3) receptors. Their intrinsic activity was assessed in [35S]GTPgammaS binding experiments. Elongation of the 9-methyl of N-0840 to a 9-propyl substituent was very well tolerated. A 9-benzyl group, on the other hand, caused a decrease in adenosine A(1) receptor affinity. Next, the 8-position was examined in detail, and affinity was increased with appropriate substitution. Most derivatives were A(1)-selective and 20 of the new compounds (6-9, 15-21, 23-26, 28, 31, 33, 35, and 36) had higher adenosine A(1) receptor affinity than the reference substance, N-0840. Compound 31 (N(6)-cyclopentyl-8-(N-methylisopropylamino)-9-methyladenine, LUF 5608) had the highest adenosine A(1) receptor affinity, 7.7 nM. In the [35S]GTPgammaS binding experiments, derivatives 5, 14, 22, 23, 25, 26, 33 and 34 did not significantly change basal [35S]GTPgammaS binding, thus behaving as neutral antagonists. Moreover, four of these compounds (23, 25, 26, and 33) displayed a 4- to 10-fold increased adenosine A(1) receptor affinity (75-206 nM) compared to N-0840 (852 nM). In summary, we synthesised a range of N-0840 analogues with higher affinity for adenosine A(1) receptors. In addition, four new derivatives, LUF 5666 (23), LUF 5668 (25), LUF 5669 (26) and LUF 5674 (33), behaved as neutral antagonists when tested in [35S]GTPgammaS binding studies. Thus, these compounds have improved characteristics as neutral adenosine A(1) receptor antagonists.

  DOI：

  10.1016/j.bmc.2003.10.023

文献信息

• N.sup.6 -substituted 9-methyladenines: a new class of adenosine receptor
  申请人：Discovery Therapeutics, Inc.

  公开号：US05565566A1

  公开（公告）日：1996-10-15

  Novel compounds and a method of using them to antagonize adenosine receptors are provided wherein the compounds are selected from the group of racemic mixtures or optically active compounds represented by the general formula: ##STR1## wherein R.sub.2 is selected from the group consisting of cycloalkyl radicals having from 3 to 8, preferably 3 to 7, ring carbon atoms, alkyl radicals having from 1 to 10, carbon atoms, aralkyl radicals having from 7 to 14, preferably 7 to 10, carbon atoms, and heteroatom- and halogen-substituted derivatives thereof wherein said heteroatom may be selected from the group consisting of nitrogen, phosphorus, sulfur and oxygen; R.sub.1 may be hydrogen or R.sub.2, and R.sub.3 is selected from the group consisting of hydrogen, halogen, amine, carboxy, thio, sufonate, sulfonamide, sulfone, sulfoxamide, phenyl, alkyl-substituted amine, cycloalkyl-substituted amine, alkyl radicals having from 1 to 10 carbon atoms, and cycloalkyl radicals having from 3 to 8, preferably 5 to 6, ring carbon atoms. R.sub.4 is selected from the group consisting of benzyl, phenyl, and alkyl groups comprising from 1 to 4 carbon atoms, wherein said alkyl group can be substituted with oxygen, for example ethers and alcohols. R.sub.5 is selected from the group consisting of hydrogen; hydroxy; sulfonate; halogen; alkoxy and cycloalkoxy groups comprising 1 to 6 carbon atoms, wherein said alkoxy and cycloalkoxy groups can be substituted with phenyl; and amine, wherein said amine can be substituted with alkyl, cycloalkyl, or phenyl. Optically active compounds are especially active as antagonists of A.sub.1 adenosine receptors.

  提供了一种小说化合物及其使用方法，用于拮抗腺苷受体，其中所述化合物选自旋光混合物或光学活性化合物组中，该组化合物由下式表示： ##STR1## 其中R.sub.2选自环烷基，其具有3到8个，优选3到7个环碳原子，1到10个碳原子的烷基，7到14个，优选7到10个碳原子的芳基烷基，以及其杂原子和卤素取代衍生物，其中所述杂原子可以选自氮、磷、硫和氧组成的群；R.sub.1可以是氢或R.sub.2，R.sub.3选自氢、卤素、胺、羧基、硫醇、磺酸盐、磺酰胺、磺酮、亚磺酰胺、苯基、烷基取代的胺、环烷基取代的胺、1到10个碳原子的烷基以及3到8个，优选5到6个环碳原子的环烷基。R.sub.4选自苄基、苯基和由1到4个碳原子组成的烷基，其中所述烷基可以用氧取代，例如醚和醇。R.sub.5选自氢、羟基、磺酸盐、卤素、1到6个碳原子的烷氧基和环烷氧基，其中所述烷氧基和环烷氧基可以用苯基取代，以及胺，其中所述胺可以用烷基、环烷基或苯基取代。光学活性化合物特别活跃，可作为A.sub.1腺苷受体拮抗剂。
• Combination of loop diuretics with adenosine A1-receptor antagonists
  申请人：KYOWA HAKKO KOGYO CO., Ltd.

  公开号：EP0970696A1

  公开（公告）日：2000-01-12

  The invention relates to a combination of a loop diuretic and a adenosine A1 receptor antagonist; a pharmaceutical composition containing a loop diuretic and an adenosine A1-receptor antagonist; the preparation of a pharmaceutical composition which comprises bringing a mixture of a loop diuretic and an adenosine A1 receptor antagonist into a galenic administration form; the use of a combination of a loop diuretic and an adenosine A1-receptor antagonist or of a pharmaceutical composition containing a loop diuretic and an adenosine A1-receptor antagonist for the simultaneous, separate or sequential administration in the treatment and/or prophylaxis of hypertension, renal failure or disorders with increased proximal tubular reabsorption, e.g. congestive heart failure, liver cirrhosis or nephrotic syndrome.

  本发明涉及一种襻利尿剂和腺苷 A1 受体拮抗剂的组合物；一种含有襻利尿剂和腺苷 A1 受体拮抗剂的药物组合物；一种药物组合物的制备方法，其中包括将襻利尿剂和腺苷 A1 受体拮抗剂的混合物制成加仑给药形式；将襻利尿剂和腺苷 A1 受体拮抗剂的复方制剂或含有襻利尿剂和腺苷 A1 受体拮抗剂的药物组合物用于同时、单独或连续给药，以治疗和/或预防高血压、肾功能衰竭或近端肾小管重吸收增加的病症，例如如充血性心力衰竭、肝硬化或肾病综合征。
• Modulation of the P2Y2 receptor pathway
  申请人：P2-Science APS

  公开号：EP2036567A2

  公开（公告）日：2009-03-18

  The present invention relates to the field of regulating the activity of the purinergic receptors for the modulation of the vascular tone, particularly for the purpose of treatment of haemodynamic conditions by overriding of vasoconstriction activity, such as increases in sympathic vasoconstriction. Modulators, such as UTP analogues as described herein are preferably specific for P2Y2. Compounds capable of stimulating the P2Y2 receptor are suitable for the treatment or prevention wherein inhibition of vasoconstriction activity is desirable such as hypertension and hypertension relates disorders or diseases, whereas compound capable of counteracting the activity of the P2Y2 receptor are suitable for the treatment of or prevention wherein inhibition of vasodilatation is desirable.

  本发明涉及调节嘌呤能受体活性以调节血管张力的领域，特别是通过抑制血管收缩活性（如交感血管收缩增加）来治疗血流动力学疾病。调节剂，如本文所述的UTP 类似物，最好对 P2Y2 具有特异性。能够刺激 P2Y2 受体的化合物适用于治疗或预防需要抑制血管收缩活性的疾病，如高血压和高血压相关失调或疾病，而能够抵消 P2Y2 受体活性的化合物适用于治疗或预防需要抑制血管舒张的疾病。
• Biodegradable polymeric nanoparticle conjugates and use thereof
  申请人：NEW YORK UNIVERSITY

  公开号：US10744209B2

  公开（公告）日：2020-08-18

  The present invention relates to a polymeric nanoparticle conjugate of formula (I). The present invention also relates to pharmaceutical compositions including these polymeric nanoparticle conjugates, and methods of preparation and use thereof.

  本发明涉及式（I）的聚合物纳米颗粒共轭物。本发明还涉及包括这些聚合物纳米颗粒共轭物的药物组合物及其制备和使用方法。
• Pharmaceutical compositions for the treatment of chemoresistant acute myeloid leukemia (AML)
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US11376269B2

  公开（公告）日：2022-07-05

  The present invention relates to pharmaceutical compositions for use in the treatment of chemoresistant acute myeloid leukemia (AML). The inventors have established a powerful preclinical model to screen in vivo responses to conventional genotoxics and to mimic the chemoresistance and minimal residual disease as observed in AML patients after chemotherapy. The inventors showed that cytarabine-resistance mechanism involves the CD39-dependent crosstalk between energetic niche and AML mitochondrial functions through CD39-P2Y13-cAMP-PKA signaling axis. In particular, the present invention relates to an inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis for use in a method of treating chemoresistant acute myeloid leukemia (AML) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of said inhibitor.

  本发明涉及用于治疗化疗耐药急性髓性白血病（AML）的药物组合物。本发明者建立了一个强大的临床前模型，用于筛选体内对传统基因毒性药物的反应，并模拟急性髓性白血病患者化疗后观察到的化疗耐药性和最小残留病。本发明人发现，细胞抗药性机制涉及 CD39 依赖性能量龛和 AML 线粒体功能之间通过 CD39-P2Y13-cAMP-PKA 信号轴的串扰。特别是，本发明涉及一种CD39-P2Y13-cAMP-PKA信号轴抑制剂，用于治疗有需要的患者的化疗耐药急性髓性白血病（AML）的方法，包括向患者施用治疗有效量的所述抑制剂。