C-甲基分支嘌呤核苷类似物的发展：化学、生物活性和治疗潜力

Title:Development of C-Methyl Branched Purine Ribonucleoside Analogs: Chemistry, Biological Activity and Therapeutic Potential

Volume: 23 Issue: 28

Author(s): Riccardo Petrelli, Mario Grifantini, Loredana Cappellacci

Affiliation:

关键词: 2'-C-甲基和3’-C-甲基支链核苷/潮，丙型肝炎病毒，抗肿瘤核苷，腺苷受体，激动剂， A1AR 激动剂，P2Y1和P2Y2受体配体，IMPDH抑制剂，NAD类似物。

摘要: In this review, we first highlighted on C-methyl-branched nucleosides and nucleotides approved as anti-hepatitis C infection (HCV) drugs, their mechanism of action and recent progress in the development of new clinical candidates. Then, we report on our attempt to develop several C-methyl nucleosides/tides potentially useful for treatment of various diseases such cancer, pain, epilepsy and glaucoma. Design, synthesis and pharmacological screening of 1′-C-, 2′-C-, 3'-C-methyladenosine or other purine/pyrimidine nucleosides allowed us to discover some promising new molecules. 3'-C-Methyladenosine showed antitumor activity against several human tumor cell lines. We have investigated the mechanism of action of 3'-C-methyladenosine that proved to be an effective inhibitor of ribonucleotide reductase. Moreover, we will also summarize the chemical and biological properties of some of the recent N6-substituted and 5', N6-disubstituted 2'-C-methyladenosine derivatives that were synthetized in our laboratory and evaluated as A1 adenosine receptor agonists. 2-Chloro-2'- C-methyl-N6-cyclopentyladenosine (2'-Me-CCPA), 5′-chloro-5′-deoxy-N6-(±)-(endo-norborn- 2-yl)adenosine (5′Cl5′d-(±)-ENBA) and 2'-C-methyl-5'-chloro-5'-deoxy-N6-(±)-(endonorborn- 2-yl)adenosine (2'-Me-5′Cl5′d-(±)-ENBA) displayed high hA1AR affinity and selectivity. 2'-Me-CCPA and 5′Cl5′d-(±)-ENBA showed significant analgesic properties.

Cite this article as:

Riccardo Petrelli, Mario Grifantini, Loredana Cappellacci , Development of C-Methyl Branched Purine Ribonucleoside Analogs: Chemistry, Biological Activity and Therapeutic Potential, Current Medicinal Chemistry 2016; 23 (28) . https://dx.doi.org/10.2174/0929867323666160627100755