Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists

Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists

Ana Mallo-AbreuRubén Prieto-DíazWillem JespersJhonny AzuajeMaria MajellaroCarmen VelandoXerardo García-MeraOlga CaamañoJosé BreaMaría I. LozaHugo Gutiérrez-de-Terán, and Eddy Sotelo

 

Journal of Medicinal Chemistry, 2020, 63, 7721-7739.

 

https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00564

 

 


X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists
Willem Jespers, Grégory Verdon, Jhonny Azuaje, Maria Majellaro, Henrik Keränen,Xerardo García-Mera, Miles Congreve, Francesca Deflorian, Chris de Graaf, Andrei Zhukov, Andrew S. Doré, Jonathan S. Mason, Johan Åqvist,Robert M. Cooke, Eddy Sotelo and Hugo Gutiérrez-de-Terán

Angew. Chem. Int. Ed., 2020, 59

 

https://doi.org/10.1002/anie.202003788


The European Research Network on Signal Transduction (ERNEST): Toward a Multidimensional Holistic Understanding of G Protein- Coupled Receptor Signaling

Martha E. Sommer, Jana Selent, Jens Carlsson, Chris De Graaf, David E. Gloriam, Gyorgy M. Keseru, Mickey Kosloff, Stefan Mordalski, Aurelien Rizk, Mette M. Rosenkilde, Eddy Sotelo, Johanna K. S. Tiemann, Andrew Tobin, Nina Vardjan, Maria Waldhoer, and Peter Kolb

https://pubs.acs.org/doi/10.1021/acsptsci.0c00024


Trifluorinated Pyrimidine-Based A2B Antagonists: Optimization and Evidence of Stereospecific Recognition

Ana Mallo-Abreu, María Majellaro, Willem Jespers, Jhonny Azuaje, Olga Caamaño, XerardoGarcía-Mera, José M.Brea, MaríaI.Loza, HugoGutieŕrez-de-Terań,
and Eddy Sotelo

J. Med. Chem. 2019, 62, 9315−9330

https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01340


Free-Energy Calculations for Bioisosteric Modifications of A3 Adenosine Receptor Antagonists

Zuzana Jandova, Willem Jespers, Eddy Sotelo, Hugo Gutiérrez-de-Terán and Chris Oostenbrink

Int. J. Mol. Sci. 2019, 20(14), 3499 https://www.mdpi.com/1422-0067/20/14/3499


Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke.

Silva, A., Pérez-Díaz, A., Santamaría, M., Correa-Paz, C., Rodríguez-Yáñez, M., Ardá, A., Pérez-Mato, M., Iglesias-Rey, R., Brea, J., Azuaje, J., Sotelo, E., Sobrino, T., Loza, M., Castillo, J., Campos, F

Annals of Neurology, 2018, 84, 260-273. https://doi.org/10.1002/ana.25286


Structural Mapping ogf Adenosine Receptor Mutations: Ligand Binding and Signaling Mechanisms.

Jespers, W., Schiedel, A. C., Heitman, L., Cooke, R., Leene, L., van Westen, G. J., Glorian, D. E., Muller, C. E., Sotelo, E., Gutiérrez de Terán, H.

Trends in Pharmacological Sciences, 2018, 39, 75-89. https://doi.org/10.1016/j.tips.2017.11.001


Three-Dimensional Printing in Catalysis: Combining 3D Heterogeneous Copper and Palladium Catalysts for Multicatalytic Multicomponent Reactions

Díaz-Marta, A.S. Tubío, C.R., Carbajales, C., Fernandez, C., Escalante, L., Sotelo, E., Guitián, F., Barrio, V. L., Gil, A., Coelho, A.


Development of Fluorescent Probes that Target Serotonin 5HT2B receptors

Azuaje, J., López, Paula, Iglesias, A., De la Fuente, R., Pérez-Rubio, J. M., García, D., Pérez, D., Stepniewski, T., García-Mera, X., Loza, M. I., Cadavid, M. I. Brea, J., Sotelo, E.*

Scientific Reports. 2017, 7, 11370-3. https://www.nature.com/articles/s41598-017-11370-2


Effect of Nitrogen Atom Substitution in A3 Adenosine Receptor Binding: N(4,6-Dirarylpyridin-2-yl)acetamides as Potent and Selective Antagonists

Azuaje, J., Jespers, W., Yaziji, V., Mallo, A., Majellaro, M., Caamaño, O., Loza, M. I., Cadavid, M. I. Brea, J. Gutiérrez de Terán, H., Sotelo, E.*

Journal of Medicinal Chemistry, 2017, 60, 7502-7511. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.7b00860


3-Oxopyridazin-5-yl-Chalcone Hybrids: Potent Antiplatelet Agents that Prevent GP IIb/IIIa Activation

El Maatougui, A., Yañez, M., Crespo, A., Fraiz, N., Coelho, A., Raviña, E., Cano, E., Loza, M. I., Brea, J., Gutiérrez de Terán, H., Sotelo, E.*


Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid

Fernandez-Dueñas, V., Morato, X., Ciruela, F., Azuaje, J., Sotelo, E.* Cordobilla, B., Domingo, J.C.


Enantiospecific Recognition at the A2B Adenosine Receptor by Alkyl 2-Cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahydropyrimiidine-5-carboxylates

Carbajales, C., Azuaje, J., Oliveira, A., Loza, M.I., Brea, J., Cadavid, M.I., Masaguer, C. F., García-Mera, X., Gutiérrez de Terán, H., Sotelo, E.*

Journal of Medicinal Chemistry. 2017, 60, 3372-3382. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.7b00138


An Efficient and Recyclable 3D Printed α-Al2O3 Catalyst for the Multicomponent Assembly of Bioactive Heterocycles

Azuaje, J., Tubio, C.R., Escalante, L., Gomez, M., Coelho, A., Caamaño, O., Gil, A., Sotelo, E.*

Applied Catalysis, A: General, 2017, 530, 203-210. https://www.sciencedirect.com/science/article/pii/S0926860X16305701


Multicomponent Assembly of the Kinesin Spindle Protein Inhibitor CPUYJ039 and Analogues as Antimitotic Agents.

Carbajales, C., Sawada, J-C., Marzano, G., Sotelo, E., Escalante, L., Sanchez-Diaz Marta, A., García-Mera, X., Asai, A., Coelho, A.


Structure-Based Rational Design of Adenosine Receptor Ligands.

Gutiérrez-de-Terán, H. Sallander, J. Sotelo, E.

Current Topics In Medicinal Chemistry, 2017, 17, 40-58. https://www.ingentaconnect.com/contentone/ben/ctmc/2017/00000017/00000001/art00007


Drug Structural Features Affect Drug Delivery from Hyperbranched Polyesteramide Hot Melt Extrudates.

Raviña-Eirín, E., Azuaje, J., Sotelo, E. Gómez-Amoza, J. L., Martínez-Pacheco, R.

European Journal of Pharmaceutics and Biopharmaceutics, 2016, 102, 1-78. https://www.sciencedirect.com/science/article/pii/S0939641116300108


Discovery of Potent and Highly Selective Adenosine A2B Receptor Antagonists Chemotypes.

El Maatougi, A., Azuaje, J., González-Gómez, M., Míguez, G., Crespo, A., García-Mera, X.,  Gutiérrez de Terán, H., Sotelo, E.*

Journal of Medicinal Chemistry, 2016, 59, 1967-1983. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01586


3D-Printing of a Heterogeneous Copper-Based Catalyst

Tubio, C. R., Azuaje, J., Escalante, L., Coelho, A., Sotelo, E. Gil, A.


Pyrazin-2(1H)-ones as a Novel Class of Selective A3 Adenosine Receptor Antagonists.

Azuaje, J., Carbajales, C, González-Gomes, M., Coelho, A., Caamaño, O., Gutierrez de Terán, H., Sotelo, E.

Future Medicinal Chemistry, 2015, 7, 1373-1380. https://www.future-science.com/doi/10.4155/fmc.15.69


Sol-Gel Entrapped Cu in Silica Matrix: An Efficienct Heterogeneous Nanocatalyst For Huisgen, and Ullmann Reactions.

Diz, P., Gil, A., Guitían, F., El Maatougui, A., Azuaje, J., Pernas, P., Sotelo, E., Coelho, A.

Applied Catalysis A: General  , 2015, 502, 86-95. https://www.sciencedirect.com/science/article/pii/S0926860X1530003X


Integrated Ugi-Based Assembly of Functional, Skeletal and Stereochemically Diverse 1,4-Benzodiazepin-2-ones.

Azuaje, J., Pérez-Rubio, J. M., Yaziji, V., El Maatougui, González-Gómez, J. C., Masaguer, C. F., Sánchez-Pedregal, V., Navarro-Vázquez, A., Teijeira, M., Sotelo, E.*

J. Org. Chem. 2015, 80, 1533-1549. https://pubs.acs.org/doi/abs/10.1021/jo502382q


Computer-Aided Design of GPCR Ligands.

Gutiérrez-de-Terán, H., Keranen, H., Azuaje, J., Rodriguez, D., Sotelo, E.

Methods in Molecular Biology, 2015, 1272, 1272-1291. https://link.springer.com/protocol/10.1007%2F978-1-4939-2336-6_19


Structure-Based Design of Novel KSP-Eg5 Inhibitors Assisted by a Targeted Multicomponent Reaction.

Carbajales, C., Prado, M. A., Gutiérrez-de-Terán, H., Cores, A., Azuaje, J., Novio, S., Nuñez, M. J., Fernández, B., Sotelo, E., García-Mera, X., Sánchez-Lazo, P., Freire-Garabal, M., Coelho, A.


Ugi-Based Approaches to Quinoxaline Libraries.

Azuaje, J., El Maatougui, García-Mera, X., Sotelo, E.*

ACS Combinatorial Science, 2014, 16, 403-411. https://pubs.acs.org/doi/abs/10.1021/co500036n


Discovery of 3,4-Dihydropyrimidin-2(1H)-ones as a Novel Class of Potent and Selective A2B Adenosine Receptor Antagonists.

Crespo, A., El Maatougui, A.,Biagini, P., Azuaje, J., Coelho, A., García-Mera, X., Brea, J., Loza, M. I., Cadavid, M. I., Sotelo, E.*

ACS Medicinal Chemistry Letters, 2013, 4, 1031-1036. https://pubs.acs.org/doi/10.1021/ml400185v


Copper-Catalyzed Huisgen 1,3-Dipolar Cycloaddition Under Oxidative Conditions: Polymer-Assisted Assembly of 4-Acyl-1-Substituted-1,2,3-Triazoles

Diz, P., Coelho, A., El Maatougui, A., Azuaje, J., Caamaño, O., Gil, A., Sotelo, E.*

The Journal of Organic Chemistry, 2013, 78, 6540-6549. https://pubs.acs.org/doi/10.1021/jo400800j


Three-Component Assembly of Structurally Diverse 2-Aminopyrimidine-5-carbonitriles.

Val, C., Crespo, A., El Maatougui, A., Azuaje, J. A., Coelho, A., Sotelo, E.*

ACS Comb. Sci., 2013, 15, 370-378. https://pubs.acs.org/doi/abs/10.1021/co4000503


Multicomponent Assembly of Diverse Pyrazin-2(1H)-one Chemotypes

Azuaje, J., El Maatougui, A., Pérez-Rubio, J. M., Coelho, A., Fernández, F. Sotelo, E.*

The Journal of Organic Chemistry, 2013, 78, 4402-4409. https://pubs.acs.org/doi/abs/10.1021/jo4003163


Selective and potent Adenosine A3 Receptor Antagonists by Methoxyaryl Substitution on the N-(2,6-Diarylpyrimidin-4-yl)acetamide scaffold.

Yaziji, V., Rodríguez, D., Gutiérrez de Terán, H., Coelho, A., El Maatougui, A., Brea, J., Loza, M. I., Garcia-Mera, X., Cadavid, M.I., Sotelo, E.*

European Journal of Medicinal Chemistry. 2013, 59, 235-242. https://www.sciencedirect.com/science/article/pii/S0223523412006794


Discovery and Preliminary SAR of 5-Arylidene-2,2,-dimethyl-1,3-dioxane-2,4-diones as Platelet Aggregation Inhibitors.

El Maatougui, A., Azuaje, J., Coelho, A., Cano, E., Yañez, M., Yaziji, V., Carbajales, C., Sotelo, E.*

Combinatorial Chemistry & High Throughput Screening, 2012, 15, 551-554. http://www.eurekaselect.com/100357


Pyrimidine Derivatives as Potent and Selective A3 Adenosine Receptor Antagonists.

. Yaziji, V., Rodríguez, D., Gutiérrez de Terán, H., Coelho, A., Brea, J., Loza, M. I., Garcia-Mera, X., Cadavid, M.I., Caamaño, Sotelo, E.*

Journal of Medicinal Chemistry. 2011, 54, 457-471. https://pubs.acs.org/doi/abs/10.1021/jm100843z


Supported Tosic Acid as Highly Robust and Eco-Friendly Isocyanide´s Scavengers.

Azuaje, J., Al Maatougui, A., Blanco, J.M., Coelho, A., Sotelo, E.*

ACS Combinatorial Science, 2011, 13, 89-95. https://pubs.acs.org/doi/10.1021/co100035z


Silica-Supported Aluminum Chloride-Assisted Solution Phase Synthesis of Pyridazinone-Based Antiplatelet Agents.

El Maatougui, A., Azuaje, J., Sotelo, E., Caamaño, O., Coelho, A.

ACS Combinatorial Science 2011, 13, 7-12. https://pubs.acs.org/doi/abs/10.1021/co100017h


Convergent Assembly of Structurally Diverse Quinazolines.

Crespo, A., Coelho, A., Diz, P., Fernández, F., Novoa de Armas, H., Sotelo, E.*

Organic & Biomolecular Chemistry, 2011, 9, 351-357. https://pubs.acs.org/doi/abs/10.1021/co100017h


Polymer Supported 1,5,7-triazabicylo[4,4,0]dec-5-ene as Polyvalent Ligands in the Copper Catalysed Huisgen 1,3-Dipolar Cycloaddition.

Coelho, A., Díz, P., Caamaño, O., Sotelo, E.*

Advanced Synthesis & Catalysis, 2010, 352, 1179-1192. https://onlinelibrary.wiley.com/doi/10.1002/adsc.200900680


Divergent Solution Phase Synthesis of Diarylpirimidines as Selective A3 Adenosine Receptor Antagonsits

Yaziji, V., Coelho, A., El Maatougui, Brea, J., Loza, M. I., Garcia-Mera, X., Sotelo, E.*

Journal of Combinatorial Chemistry, 2009, 11, 519-522. https://pubs.acs.org/doi/10.1021/cc900044k


Synthetic Applications of Polystyrene 1,1,3,3-Tetramethylguanidine

Coelho, A., Crespo, A., Fernández, F., Biagini, P., Stefanachi, A., Sotelo, E.*

Combinatorial Chemistry & Highthroughput Screening, 2008, 11, 843-847. http://www.eurekaselect.com/68075


Click Chemistry Approach to Assembly Proline Mimetic Libraries Containing 1,4-Substituted 1,2,3-Triazoles.

Rodriguez-Borges, J. E., Gonçalves, S., do Vale, M. L., García-Mera, X., Coelho, A., Sotelo, E.

Journal of Combinatorial Chemistry, 2008, 10, 372-375. https://pubs.acs.org/doi/10.1021/cc800035z


Design, Synthesis and Biological Evaluation of Glycine-Based Molecular Tongs as Inhibitors of α-β 1-40 Aggregation in Vitro.

Cellamare, S., Stefanachi, A., Antonella, S., Basile, T., Catto, M., Campagna, F., Sotelo, E., Carotti, A.

Bioorganic & Medicinal Chemistry, 2008, 16, 4810-4822. https://www.sciencedirect.com/science/article/pii/S096808960800271X


1,3- and 8-Substituted-9-Deazaxanthines as Potent and Selective Antagonists at the Human A2B Adenosine Receptor

Stefanachi, A., Brea, J. M., Cadavid M. I., Centeno, N. B., Esteve, C., Loza, M. I., Martínez, A., Nieto, R., Raviña, E., Sanz, F., Segarra, V., Sotelo, E., Vidal, B., Carotti, A.

Bioorganic & Medicinal Chemistry, 2008, 16, 2852-2859. https://www.sciencedirect.com/science/article/pii/S0968089608000035


2-Substituted 4-, 5- and 6-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones and 2-Substituted 4,5-bis[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones as Potent Platelet Aggregation Inhibitors: Design, Synthesis and SAR Studies.

Meyers, C., Yáñez, M., Elmatougi, A., Verhest, T., Coelho, A., Fraiz, N., Lemière, G. L. F., García-Mera, X., Laguna, R., Cano, E., Maes, B. U. W., Sotelo, E.*

Bioorganic & Medicinal Chemistry Lett. 2008, 18, 793-797. https://www.sciencedirect.com/science/article/pii/S0960894X07013431


Synthesis, Adenosine Receptor Binding and 3D-QSAR- of 4-Substituted 2-(2´-furyl)-1,2,4-triazolo[1,5-a]quinoxalines.

Martínez A., Gutierrez de Terán, H., Brea, J. M., Raviña, E., Loza, M. I., Cadavid, M. I., Sanz, F., Segarra, V., Vidal, B. Sotelo, E.*

Bioorganic & Medicinal Chemistry, 2008, 16, 2103-2113. https://www.sciencedirect.com/science/article/pii/S0968089608000515


Design, Synthesis and Structure Activity Relationships of a Novel Series of 5-Alkylidenenpyridazin-3-ones with a non c-AMP-Based Antiplatelet Activity.

Coelho, A., Raviña, E., Yáñez, M., Fraiz, N., Laguna, R., Cano, E., Sotelo, E.*

Journal of Medicinal Chemistry, 2007, 50, 6476-6484. https://pubs.acs.org/doi/10.1021/jm061401d


Parallel Regulation By Olanzapine Of The Patterns Of Expression Of 5-Ht2a And D3 Receptors In Rat Central Nervous System And Blood Cells.

Padín; J. F., Rodríguez; M.A., Domínguez; E., Dopeso-Reyes; I. G., Buceta; M., Cano; E., Sotelo, E., Caruncho; H. J., Cadavid; M. I., Castro; M., Loza, M.I.


Expanding the Chemical Diversity of Azinone Libraries by A Consecutive Alkylation/Palladium-Catalysed Functionalization Strategy

Coelho, A., Sotelo, E.*

Journal of Combinatorial Chemistry, 2005, 7, 526-529. https://pubs.acs.org/doi/10.1021/cc050036t


Reactivity of 5-Alkynylpyridazinones Toward Hydrochloric Acid

Coelho, A., Novoa, H., Peeters, O.M., Blaton, N., Sotelo, E.*


Reactivity of 5-Iodopyridazin-3(2H)-ones in Palladium-Catalysed Reactions

Coelho, A., Sotelo, E., Novoa, H., Peeters, O.M., Blaton, N., Raviña, E.


8-Substituted-9-deazaxanthines as Adenosine Receptor Ligands: Design, Synthesis and Structure-affinity Relationships at A2B

Carotti, A., Stefanachi, A., Raviña, E., Sotelo, E., Loza, M. I., Cadavid, M. I., Centeno, N. B.

European Journal of Medicinal Chemistry, 2004, 39, 879-887. https://www.sciencedirect.com/science/article/pii/S0223523404001618


Efficient Heck Alkenylation at position 5 of the 6-phenyl-3(2H)-pyridazinone System.

Coelho, A., Sotelo, E., Novoa, H., Blaton, N., Peeters, O.M., Raviña, E.


Facile Solution Phase Combinatorial Synthesis of Highly Substituted Pyridazinones

Sotelo, E.*


Stille-Based Approaches in the Synthesis of 6-phenyl-5-Substituted-3(2H)-pyridazinones.

Sotelo, E., Coelho, A., Raviña, E.


Sonogashira Approaches in The Synthesis of 5-Substituted-6-phenyl-3(2H)-pyridazinones.

Coelho, A., Sotelo, E., Raviña, E.


Retro-Ene-Assisted Palladium-Catalysed Synthesis of 4,5-Disubstituted-3(2H)-pyridazinones.

Sotelo, E., Coelho, A., Raviña, E.


Traceless Solid Phase Synthesis of 4,5- and 5,6-Diaryl-3(2H)-pyridazinones.

Sotelo, E., Raviña, E.