Structural investigation on thiazolo[5,4-d]pyrimidines to obtain dual-acting blockers of CD73 and adenosine A2A receptor as potential antitumor agents
| Autor: | Juliana Lopes Rangel Fietto, Fabrizio Vincenzi, Vittoria Colotta, Marine Sarlandie, Silvia Pasquini, Flavia Varano, Katia Varani, Daniela Catarzi, Audrey Guilbaud, Julie Pelletier, Jean Sévigny, Nicolly Espindola Gelsleichter |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pyrimidine
Stereochemistry medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Adenosine A2A receptor Cancer immunotherapy CD73 inhibitors 01 natural sciences Biochemistry Thiazolo[5 chemistry.chemical_compound Economica Drug Discovery 4-d]pyrimidine medicine Inverse agonist Adenosine A2A receptor inverse agonists Receptor Molecular Biology chemistry.chemical_classification Antitumor agents 010405 organic chemistry Chemistry Organic Chemistry Adenosine receptor Adenosine 0104 chemical sciences 3. Good health 010404 medicinal & biomolecular chemistry Enzyme Molecular Medicine Thiazolo[5 4-d]pyrimidine medicine.drug |
| Popis: | Adenosine pathway, including its generating enzyme (CD73) and its receptors represents a key target for cancer immunotherapy. Here we aimed to search for novel compounds able to co-target the CD73 and the A2A adenosine receptor (A2A AR) as dual-blockers of adenosine generation and activity. The design project was to combine in the same molecule the thiazolo[5,4-d]pyrimidine core, an essential pharmacophoric feature to block the A2A AR, with a benzenesulfonamide group which is a characteristic group of CD73 inhibitors. Most of the reported compounds resulted in inverse agonists of the human (h) A2A AR endowed with high affinity, selectivity and potency. However they were weak inhibitors of CD73 enzyme. Nevertheless, this study can be considered as a starting point to develop more active compounds. |
| Databáze: | OpenAIRE |
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