179112-79-9Relevant articles and documents
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Kissmann,Weiss
, p. 1053 (1956)
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A One-Pot Synthesis of Highly Functionalized Purines
Zelli, Renaud,Zeinyeh, Wa?l,Haudecoeur, Romain,Alliot, Julien,Boucherle, Benjamin,Callebaut, Isabelle,Décout, Jean-Luc
supporting information, p. 6360 - 6363 (2017/12/08)
Highly substituted purines were synthesized in good to high yields through a one-pot straightforward metal-free scalable method, using the Traube synthesis adapted to Vilsmeier-type reagents. From 5-amino-4-chloropyrimidines, new 9-aryl-substituted chloropurines and intermediates for peptide nucleic acid synthesis were prepared. Variant procedures allowing a rapid synthesis of ribonucleosides and 7-benzylpurine from 5-amidino-6-aminopyrimidines are also reported to illustrate the high potential of this versatile toolbox. This route appears to be particularly interesting in the field of nucleic acids for a direct and rapid access to various new 8-alkylpurine nucleosides.
Synthesis, Biological Activity and Molecular Modeling of 6-Benzylthioinosine Analogues as Subversive Substrates of Toxoplasma gondii Adenosine Kinase
Yadav, Vikas,Chu, Chung K.,Rais, Reem H.,Al Safarjalani, Omar N.,Guarcello, Vincenzo,Naguib, Fardos N. M.,El Kouni, Mahmoud H.
, p. 1987 - 1996 (2007/10/03)
Toxoplasma gondii is the most common cause of secondary CNS infections in immunocompromised persons such as AIDS patients. The major route of adenosine metabolism in T. gondii is direct phosphorylation to adenosine 5′-monophosphate (AMP) catalyzed by the enzyme adenosine kinase (EC 2.7.1.20). Adenosine kinase in T. gondii is significantly more active than any other purine salvage enzyme in this parasite and has been established as a potential chemotherapeutic target for the treatment of toxoplasmosis. Subversive substrates of T. gondii, but not the human, adenosine kinase are preferentially metabolized to their monophosphorylated forms and become selectively toxic to the parasites but not their host. 6-Benzylthioinosine (BTI) was identified as an excellent subversive substrate of T. gondii adenosine kinase. Herein, we report the synthesis of new analogues of BTI as subversive substrates for T. gondii adenosine kinase. These new subversive substrates were synthesized starting from tribenzoyl protected D-ribose. To accomplish the lead optimization process, a divergent and focused combinatorial library was synthesized using a polymer-supported trityl group at the 5′-position. The combinatorial library of 20 compounds gave several compounds more active than BTI. Structure-activity relationship studies showed that substitution at the para position plays a crucial role. To investigate the reasons for this discrimination, substrates with different substituents at the para position were studied by molecular modeling using Monte Carlo Conformational Search followed by energy minimization of the enzyme-ligand complex.
