9H-嘌呤-6-胺,2-氯-N-[(3-碘苯基)甲基]-9-甲基- | 163042-66-8

• 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: 9H-嘌呤-6-胺,2-氯-N-[(3-碘苯基)甲基]-9-甲基-
• 英文名称: 2-chloro-N⁶-(3-iodobenzyl)-9-methyladenine
• 英文别名: 2-chloro-N6-(3-iodobenzyl)-9-methyladenine；2-chloro-N-[(3-iodophenyl)methyl]-9-methylpurin-6-amine
• CAS: 163042-66-8
• 化学式: C₁₃H₁₁ClIN₅
• 分子量: 399.621
• InChiKey: ATOXAERIKXFYQV-UHFFFAOYSA-N

物化性质

• 沸点：
  509.0±60.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 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：

  9H-嘌呤-6-胺,2-氯-N-[(3-碘苯基)甲基]-9-甲基- 在 甲胺 作用下， 以 四氢呋喃 、 水 为溶剂， 以89%的产率得到N⁶-(3-iodobenzyl)-2-(methylamino)-9-methyladenine
  参考文献：
  名称：

  A.sub.3 adenosine receptor agonists

  摘要：

  本发明提供了A.sub.3选择性激动剂，特别是在2、6和9位置具有选择性取代基的腺嘌呤化合物，以及相关的取代化合物，特别是那些在苄基和/或糖酰胺基团上含有取代基的化合物，以及包含这些化合物的药物组合物。本发明还提供了一种在哺乳动物中选择性激活A.sub.3腺苷受体的方法，该方法包括向需要选择性激活其A.sub.3腺苷受体的哺乳动物急性或慢性地给予与A.sub.3受体结合以刺激A.sub.3受体依赖性反应的治疗或预防有效量的化合物。

  公开号：

  US05688774A1
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 121.67h， 生成 9H-嘌呤-6-胺,2-氯-N-[(3-碘苯基)甲基]-9-甲基-
  参考文献：
  名称：

  Structure-Activity Relationships of 9-Alkyladenine and Ribose-Modified Adenosine Derivatives at Rat A3 Adenosine Receptors

  摘要：

  9-Alkyladenine derivatives and ribose-modified N-6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A(3) adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A(3) selectivity in adenosine derivatives, such as an N-6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A(3) receptors stably expressed in Chinese hamster ovary (CHO) cells, using [I-125]]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamid)), and at rat brain A(1) and A(2a) receptors using [H-3]-N-6-PIA ((R)-N-6-phenylisopropyladenosine) and [H-3]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5'-(N-ethylcarbamoyl)adenosine), respectively. A series of N-6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A(3) receptors. N-6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A(3) receptors and of comparable affinity at A(1) and A(2a) receptors, resulting in a 3-6-fold selectivity for A(3) receptors. A pair of chiral N-6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A(3) receptors by 5.7-fold. 2-Chloro-9-(beta-D-erythrofuranosyl)-N-6-(3-iodobenzyl)adenine had a K-i value at A(3) receptors of 0.28 mu M. 2-Chloro-9-[2-amino-2,3-dideoxy-beta-D-5-(methylcarbamoyl)-arabinofuranosyl]-N-6-(3-iodobenzyl)adenine was moderately selective for A(1) and A(3) VS A(2a) receptors. A 3'-deoxy analogue of a highly A(3)-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A(3) receptors expressed in CHO cells. The 3'-OH and 4'-CH2OH groups of adenosine are not required for activation at A(3) receptors. A number of 2',3'-dideoxyadenosines and 9-acyclic-substituted adenines appear to inhibit adenylyl cyclase at the allosteric ''P'' site.

  DOI：

  10.1021/jm00010a017

文献信息

• Use of A3 adenosine receptor agonist in osteoarthritis treatment
  申请人：CAN-FITE BIOPHARMA LTD.

  公开号：US10265337B2

  公开（公告）日：2019-04-23

  Provided is an A3 adenosine receptor agonist (A3AR agonist) for the preparation of a pharmaceutical composition for the treatment of a mammal subject having osteoarthritis (OA), as well as to a method for the treatment of OA in a mammal subject, the method includes administering to said subject in need of said treatment an amount of A3AR agonist, the amount being effective to treat or prevent the development of OA. Preferred but not exclusive A3AR agonists in accordance with the present subject matter are IB-MECA and Cl-IB-MECA. The A3AR agonist may be administered in combination with another drug, such as Methotrexate (MTX). Also provided are pharmaceutical compositions for treatment of osteoarthritis including an amount of an A3AR agonist.

  本发明提供了一种A3腺苷受体激动剂（A3AR激动剂），用于制备治疗患有骨关节炎（OA）的哺乳动物的药物组合物，以及用于治疗哺乳动物OA的方法，该方法包括向需要所述治疗的所述受试者施用一定量的A3AR激动剂，所述量可有效治疗或预防OA的发展。根据本发明的主题，优选但并非唯一的 A3AR 激动剂是 IB-MECA 和 Cl-IB-MECA。A3AR 激动剂可与另一种药物（如甲氨蝶呤 (MTX)）联合使用。还提供了治疗骨关节炎的药物组合物，包括一定量的 A3AR 激动剂。
• 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。
• Method for treating NASH accompanied by fibrosis using Cl-IB-MECA
  申请人：CAN-FITE BIOPHARMA LTD.

  公开号：US10780106B2

  公开（公告）日：2020-09-22

  Provided is an A3AR ligand for reducing ectopic fat accumulation, particularly in fatty liver. Further provided is the use of A3AR ligand for the preparation of a pharmaceutical composition for reducing such fat accumulation, method of treating a condition associates with fat accumulation making use of the ligand and kits including pharmaceutical compositions including the ligand, and instructions for use of same, for treating a condition associated with ectopic fat accumulation. Further provided is the use of an A3AR agonist, such as 2-Chloro-N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA, CF102) for treating fatty liver, specifically, non-alcoholic fatty liver disease (NAFLD).

  本发明提供了一种 A3AR 配体，用于减少异位脂肪堆积，特别是脂肪肝中的异位脂肪堆积。还提供了 A3AR 配体用于制备减少此类脂肪蓄积的药物组合物的用途、利用该配体治疗与脂肪蓄积有关的疾病的方法，以及包括该配体的药物组合物的试剂盒及其使用说明，用于治疗与异位脂肪蓄积有关的疾病。进一步提供的是A3AR激动剂，如2-氯-N6-(3-碘苄基)-腺苷-5′-N-甲基尿酰胺(Cl-IB-MECA，CF102)用于治疗脂肪肝，特别是非酒精性脂肪肝(NAFLD)。
• Pharmaceutical compositions comprising an adenosine receptor agonist or antagonist
  申请人：Fishman Pina

  公开号：US20060084626A1

  公开（公告）日：2006-04-20

  Adenosine receptor agonists, particularly an agonist which binds to the A3 adenosine receptor, are used for induction of production or secretion of G-CSF within the body, prevention or treatment of toxic side effects of a drug or prevention or treatment of leukopenia, particularly drug-induced leukopenias; and inhibition of abnormal cell growth and proliferation.

  腺苷受体激动剂，特别是与 A3 腺苷受体结合的激动剂，可用于诱导体内产生或分泌 G-CSF，预防或治疗药物的毒副作用，或预防或治疗白细胞减少症，特别是药物引起的白细胞减少症；以及抑制细胞的异常生长和增殖。
• ADENOSINE A3 RECEPTOR AGONISTS FOR THE TREATMENT OF DRY EYE DISORDERS INCLUDING SJOGREN'S SYNDROME
  申请人：Can-Fite Biopharma Ltd.

  公开号：EP1778239A1

  公开（公告）日：2007-05-02