2140-11-6Relevant articles and documents
Stereoselective deamination of (5′RS)-5′-methyl-2′,3′-isopropylidene adenosine catalyzed by adenosine deaminase: Preparation of diastereomerically pure 5′-methyl adenosine and inosine derivatives
Ciuffreda, Pierangela,Loseto, Angela,Santaniello, Enzo
, p. 239 - 241 (2002)
Adenosine deaminase from calf intestine catalyzes the stereoselective deamination of (5′S)-5′-methyl-2′,3′-isopropylidene adenosine to the corresponding inosine derivative, so that by enzymatic deamination of (5′RS)-5′-methyl-2′,3′-isopropylidene adenosin
Facile synthesis of N-6 adenosine modified analogue toward S-adenosyl methionine derived probe for protein arginine methyltransferases
Hong, Wei,Dowden, James
, p. 1439 - 1442 (2011)
Chemically modified cellular co-factors that provide function, such as immobilization or incorporation of fluorescent dyes, are valuable probes of biological activity. A convenient route to obtain S-adenosyl methionine (AdoMet) analogues modified at N-6 adenosine to feature a linker terminating in azide functionality is described herein. Subsequent decoration of such AdoMet analogues with guanidinium terminated linkers leads to novel potential bisubstrate inhibitors for protein arginine methyltransferases, PRMTs.
A Structure-Activity Relationship Study of Bitopic N 6-Substituted Adenosine Derivatives as Biased Adenosine A1 Receptor Agonists
Aurelio, Luigi,Baltos, Jo-Anne,Ford, Leigh,Nguyen, Anh T. N.,J?rg, Manuela,Devine, Shane M.,Valant, Celine,White, Paul J.,Christopoulos, Arthur,May, Lauren T.,Scammells, Peter J.
supporting information, p. 2087 - 2103 (2018/03/21)
The adenosine A1 receptor (A1AR) is a potential novel therapeutic target for myocardial ischemia-reperfusion injury. However, to date, clinical translation of prototypical A1AR agonists has been hindered due to dose limiting adverse effects. Recently, we demonstrated that the biased bitopic agonist 1, consisting of an adenosine pharmacophore linked to an allosteric moiety, could stimulate cardioprotective A1AR signaling in the absence of unwanted bradycardia. Therefore, this study aimed to investigate the structure-activity relationship of compound 1 biased agonism. A series of novel derivatives of 1 were synthesized and pharmacologically profiled. Modifications were made to the orthosteric adenosine pharmacophore, linker, and allosteric 2-amino-3-benzoylthiophene pharmacophore to probe the structure-activity relationships, particularly in terms of biased signaling, as well as A1AR activity and subtype selectivity. Collectively, our findings demonstrate that the allosteric moiety, particularly the 4-(trifluoromethyl)phenyl substituent of the thiophene scaffold, is important in conferring bitopic ligand bias at the A1AR.
Synthesis and in vitro stability of nucleoside 5′-phosphonate derivatives
Vertuani, Silvia,Baldisserotto, Anna,Varani, Katia,Borea, Pier Andrea,De Marcos Maria Cruz, Bonache,Ferraro, Luca,Manfredini, Stefano,Dalpiaz, Alessandro
supporting information; experimental part, p. 202 - 209 (2012/09/07)
Nucleoside derivatives are largely synthesized and tested to investigate their influence on platelet aggregation. It's well known that P2Y receptors play an important role in the regulation of platelet function and, as consequence, in controlling atherothrombotic events. The research of compounds that antagonize P2Y1 and, in particular, P2Y12 receptors is of great interest in the aim to obtain platelet aggregation inhibitors that are effective in the prevention and treatment of arterial thrombosis. In this study we present the synthesis and in vitro metabolic stability in human blood and rat liver homogenate of a new class of nucleoside derivatives, in particular 5′-phosphonate adenosine, inosine, guanosine and thioadenosine analogues also modified at the ribose moiety. On the basis of the results obtained we can hypothesize compounds 4 and 18 to have in vivo a relatively high stability.
