(1S,2R,3S,4R)-4-(6-amino-2-chloro-9H-purin-9-yl)cyclopentane-1,2,3-triol | 162254-49-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1S,2R,3S,4R)-4-(6-amino-2-chloro-9H-purin-9-yl)cyclopentane-1,2,3-triol
• 英文别名: 2-chloronoraristeromycin；(1S,2R,3S,4R)-4-(6-amino-2-chloro-9H-purin-9-yl) cyclopentane-1,2,3-triol；(1S,2R,3S,4R)-4-(6-amino-2-chloro-9H-purin-9-yl)-cyclopentane-1,2,3-triol；(1S, 2R, 3S, 4R)-4-(6-Amino-2-Chloro-9H-Purin-9-yl) Cyclopentane-1,2,3-triol；(1S,2R,3S,4R)-4-(6-amino-2-chloropurin-9-yl)cyclopentane-1,2,3-triol
• CAS: 162254-49-1
• 化学式: C₁₀H₁₂ClN₅O₃
• 分子量: 285.69
• InChiKey: UMMMZHIKPLYIHG-LPWJYYESSA-N

物化性质

• 沸点：
  541.1±60.0 °C(Predicted)
• 密度：
  2.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  130
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,2R,3S,4R)-4-(6-amino-2-chloro-9H-purin-9-yl)cyclopentane-1,2,3-triol 、 2-苯乙胺 以 乙醇 为溶剂， 反应 72.0h， 以to give compound 51 (272 mg, 70%) as a yellow solid的产率得到(1S,2R,3S,4R)-4-<6-amino-2-<(phenylethyl)amino>-9H-purin-9-yl>cyclopentane-1,2,3-triol
  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位置具有选定取代基的腺嘌呤化合物，以及相关的取代化合物，特别是那些在苯甲基和/或尿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给予治疗或预防有效量的与A.sub.3受体结合以刺激A.sub.3受体依赖反应的化合物。

  公开号：

  US05688774A1
• 作为产物：
  描述：

  在 甲醇 、 氨 作用下， 反应 4.0h， 以60%的产率得到(1S,2R,3S,4R)-4-(6-amino-2-chloro-9H-purin-9-yl)cyclopentane-1,2,3-triol
  参考文献：
  名称：

  碳环 2-取代腺嘌呤核苷和相关类似物的合成

  摘要：

  合成了 2-Iodonoraristeromycin、2-iodoaristeromycin 和相关类似物，以研究它们对人和恶性疟原虫 S-腺苷-L-高半胱氨酸水解酶的抑制活性。

  DOI：

  10.1080/15257770802341459

文献信息

• 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。
• Search for New Purine- and Ribose-Modified Adenosine Analogs as Selective Agonists and Antagonists at Adenosine Receptors
  作者：Suhaib M. Siddiqi、Kenneth A. Jacobson、John L. Esker、Mark E. Olah、Xiao-duo Ji、Neli Melman、Kamal N. Tiwari、John A. Secrist、Stewart W. Schneller

  DOI：10.1021/jm00007a014

  日期：1995.3

  The binding affinities at rat A(1), A(2a), and A(3) adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6(-)CH(2)-ring, -hydrazino, and -hydroxylamino) and the ribose moiety (2'-, 3'-, and 5'-deoxy; 2'- and 3'-O-methyl;2'-deoxy 2'-fluoro;6'-thio;5'-uronamide;carbocyclic;4'- or 3'-methyl; and inversion of configuration. (-)- and (+)-5'-Noraristeromycin were 48- and 21-fold selective, respectively, for A(2a), vs A(1) receptors. 2-Chloro-6'-thioadenosine displayed a K-i value of 20 nM at A(2a) receptors (15-fold selective vs A(1)). 2-Chloroadenin-9-yl(beta-L-2'-deoxy-6'-thiolyxofuranoside) displayed a K-i value of 8 mu M at A(1) receptors and appeared to be an antagonist, on the basis of the absence of a GTP-induced shift in binding vs a radiolabeled antagonist (8-cyclopentyl-1,3-dipropylxanthine). 2-Chloro-2'-deoxyadenosine and 2-chloroadenin-9-yl(beta-D-6'-thioarabinoside) were putative partial agonists at A(1) receptors, with K-i values of 7.4 and 5.4 mu M, respectively. The A(2a) selective agonist 2-(1-hexynyl)-5'-(N-ethylcarbamoyl)adenosine displayed a K-i value of 26 nM at A(3) receptors. The 4'-methyl substitution of adenosine was poorly tolerated, yet when combined with other favorable modifications, potency was restored. Thus, N-6-benzyl-4'methyladenosine-5'-(N-methyluronamide) displayed a K-i value of 604 nM at A(3) receptors and was 103- and 88-fold selective vs A(1) and A(2a) receptors, respectively. This compound was a full agonist in the A(3)-mediated inhibition of adenylate cyclase in transfected CHO cells. The carbocyclic analogue of N-6-(3-iodobenzyl)adenosine-5'-(N-methyluronamide) was 2-fold selective for A(3) VS A(1) receptors and was nearly inactive at A(2a) receptors.
• Use of A3 Adenosine Receptor Agonist in Osteoarthritis Treatment
  申请人：Fishman Pnina

  公开号：US20080300213A1

  公开（公告）日：2008-12-04

  The present invention provides the use of an A 3 adenosine receptor agonist (A 3 AR 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 comprises administering to said subject in need of said treatment an amount of an A 3 AR agonist, the amount being effective to treat or prevent the development of OA. Preferred but not exclusive A 3 AR agonists in accordance with the invention are IB-MECA and Cl—IB-MECA. The A 3 AR agonist may be administered in combination with another drug, such as, Methotrexate (MTX). The invention also provides pharmaceutical compositions for treatment of osteoarthritis comprising an amount of an A 3 AR agonist.
• TREATMENT FOR DRY EYE CONDITIONS
  申请人：FISHMAN Pnina

  公开号：US20100222369A1

  公开（公告）日：2010-09-02

  The present invention provides a method for treating dry eye condition in an individual comprising administrating to said individual an amount of A 3 adenosine receptor (A 3 AR) agonist, the amount being effective to ameliorate symptoms of dry eye in the individual. In accordance with one embodiment, the dry eye condition is manifested by one or more opthalmologic clinical symptoms selected from foreign body sensation, burning, itching, irritation, redness, eye pain, blurred vision, degraded vision and excessive tearing. A preferred A 3 RAg in accordance with the invention is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA).
• A3 ADENOSIDE RECEPTOR AGONISTS FOR THE REDUCTION OF INTRAOCULAR PRESSURE
  申请人：Fishman Pnina

  公开号：US20120065155A1

  公开（公告）日：2012-03-15

  The present disclosure provides the use of an A3R agonist, such as IB-MECA, for reducing in a subject, preferably, human subject, intra ocular pressure (IOP). Similarly, the invention provides a pharmaceutical composition and a method for reducing IOP in a subject making use of the A 3 R agonist.