2',3'-O-isopropylidene-5'-O-tosyl-2-MeS-adenosine | 1157870-27-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-O-isopropylidene-5'-O-tosyl-2-MeS-adenosine
• 英文别名: 5'-O-tosyl-2',3'-acetonide-2-MeS-adenosine；[(3aR,4R,6R,6aR)-4-(6-amino-2-methylsulfanylpurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 4-methylbenzenesulfonate
• CAS: 1157870-27-3
• 化学式: C₂₁H₂₅N₅O₆S₂
• 分子量: 507.591
• InChiKey: OCWMTLAXPSHKPZ-NVQRDWNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  174
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl 2-(R,S)-2-(tert-butoxycarbonylamino)-4-mercaptobutanoate 、 2',3'-O-isopropylidene-5'-O-tosyl-2-MeS-adenosine 以 甲醇 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes

  摘要：

  The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N-6-amino moiety favors the inhibition of DNMT3b2 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.113
• 作为产物：
  描述：

  (2R,3R,4S,5R)-2-(6-amino-2-methylsulfanyl-9H-purin-9-yl)tetrahydrofuran-3,4-(O-isopropylidene) 、 对甲苯磺酰氯 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以52%的产率得到2',3'-O-isopropylidene-5'-O-tosyl-2-MeS-adenosine
  参考文献：
  名称：

  [EN] NON-HYDROLYZABLE NUCLEOSIDE DI- OR TRI-PHOSPHATE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS DE NUCLÉOSIDES DI- OU TRI-PHOSPHATES NON HYDROLYSABLES ET LEURS UTILISATIONS

  摘要：

  该发明提供了非水解核苷酸多聚物衍生物，例如2MeS-腺苷-β，γ-CH2-5'-O-(1-硼酸三磷酸盐)、2MeS-腺苷-β，γ-CC12-5'-O-(1-硼酸三磷酸盐)、2-MeS-腺苷-5'-二氯甲基二磷酸盐、2-MeS-腺苷-5'-二氟甲基二磷酸盐和2MeS-腺苷-5'-O-(1-硼二磷酸盐)，以及其制备的药物组合物。这些化合物对于预防或治疗由P2Y受体调节的疾病或紊乱，如2型糖尿病，以及疼痛控制非常有用。

  公开号：

  WO2009066298A1

文献信息

• [EN] NON-HYDROLYZABLE NUCLEOSIDE DI- OR TRI-PHOSPHATE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE NUCLÉOSIDES DI- OU TRI-PHOSPHATES NON HYDROLYSABLES ET LEURS UTILISATIONS
  申请人：UNIV BAR ILAN

  公开号：WO2009066298A1

  公开（公告）日：2009-05-28

  The invention provides non-hydrolyzable nucleoside polyphosphate derivatives, e.g., 2MeS-adenosine- β,γ-CH2-5'-O-(1-boranotriphosphate), 2MeS-adenosine- β,γ-CC12-5'-O-(1-boranotriphosphate), 2-MeS-adenosine-5'-dichloro methylene-diphosphate, 2-MeS-adenosine-5'-difluoromethylene- diphosphate and 2MeS-adenosine-5'-O-(1-boranodiphosphate), as well as pharmaceutical compositions thereof. These compounds are useful for prevention or treatment of diseases or disorders modulated by P2Y-receptors such as type 2 diabetes, and for pain control.

  该发明提供了非水解核苷酸多聚物衍生物，例如2MeS-腺苷-β，γ-CH2-5'-O-(1-硼酸三磷酸盐)、2MeS-腺苷-β，γ-CC12-5'-O-(1-硼酸三磷酸盐)、2-MeS-腺苷-5'-二氯甲基二磷酸盐、2-MeS-腺苷-5'-二氟甲基二磷酸盐和2MeS-腺苷-5'-O-(1-硼二磷酸盐)，以及其制备的药物组合物。这些化合物对于预防或治疗由P2Y受体调节的疾病或紊乱，如2型糖尿病，以及疼痛控制非常有用。
• SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes
  作者：Oscar M. Saavedra、Ljubomir Isakovic、David B. Llewellyn、Lijie Zhan、Naomy Bernstein、Stephen Claridge、Franck Raeppel、Arkadii Vaisburg、Nadine Elowe、Andrea J. Petschner、Jubrail Rahil、Norman Beaulieu、A. Robert MacLeod、Daniel Delorme、Jeffrey M. Besterman、Amal Wahhab

  DOI：10.1016/j.bmcl.2009.03.113

  日期：2009.5

  The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N-6-amino moiety favors the inhibition of DNMT3b2 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.
• 2-MeS-β,γ-CCl₂-ATP is a Potent Agent for Reducing Intraocular Pressure
  作者：Shay Eliahu、Alba Martín-Gil、María Jesús Perez de Lara、Jesús Pintor、Jean Camden、Gary A. Weisman、Joanna Lecka、Jean Sévigny、Bilha Fischer

  DOI：10.1021/jm100030u

  日期：2010.4.22

  Extracellular nucleotides can modify the production or drainage of the aqueous humor via activation of P2 receptors and therefore affect the intraocular pressure (IOP). We have synthesized slowly hydrolyzable nucleoside di- and triphosphate analogues, 1, and 8-14. Analogues 8-14 were completely resistant to hydrolysis by alkaline phosphatase over 30 min at 37 degrees C. In human blood serum, analogues 8-14 exhibited high stability, e.g., analogues 9 and 10-14 were only 15% and 0% degraded after 24 h, respectively. Moreover, analogues 8-14 were highly stable at pH 1.4 (t(1/2) 1 h-30 days). Analogues 8-14 were agonists of the P2Y(1) receptor (EC50 0.57-9.54 mu M). Ocular administration of most analogues into rabbits reduced IOP, e.g., analogue 9 reduced IOP by 32% (EC50 95.5 nM). Analogue 9 was more effective at reducing IOP than several common glaucoma drugs and represents a promising alternative to timolol maleate, which cannot be used for the treatment of patients suffering from asthma or cardiac problems.