Secció de Química Terapèutica

Unitat de Química Farmacèutica

Santiago Vázquez

Novel polycyclic Compounds with Biological Activity

 

Our group:

 PI: Dr. Santiago Vázquez

PhD students:

Matías Rey-Carrizo

                Elena Valverde Murillo

                Marta Barniol-Xicota

                Rosana Leiva Martínez

MSc students:

                Marta Montes Pedrazo

Undergraduate students:

                Marta Frigolé Vivas

                Sandra Codony Gisbert

                Enric Ros Simó

Andreea L. Turcu

 

About Dr. Santiago Vázquez

Dr. Santi Vázquez studied Pharmacy (1986-91) and obtained his PhD (1996) in Organic and Medicinal Chemistry at the Universitat de Barcelona under the direction of Professor Pelayo Camps. After spending two years (1998-2000) in the Christopher Ingold Laboratories (University College London) with Professor William B. Motherwell as a Marie Curie Research Fellow, he returned to Barcelona. In 2001 he took up a researcher position as “Investigador Ramón y Cajal” and in 2005 he was promoted to his current permanent position as Professor at the Laboratori de Química Farmacèutica de la Universitat de Barcelona. Dr. Vázquez is a founder member of the Institut de Biomedicina de la Universitat de Barcelona (IBUB) and acts regularly as consultant for several chemical and pharmaceutical companies. His scientific interests include polycyclic cage compounds, drug synthesis, process optimization and free radical and computational chemistry. He is co-author of more than 50 papers and has coauthored three books on drug synthesis for undergraduates.

 

Research:

Our research group is currently working in the design, synthesis and characterization of new compounds with potential therapeutic activity. Taking into account the expertise of our group in the synthesis of polycyclic compounds, in 2008 we started a new project directed to the synthesis of analogs of the approved drugs amantadine, rimantadine and memantine.

 

We synthesize new analogs of these drugs and the products are pharmacologically tested in order to determine their biological activity as:

 

a) NMDA receptor antagonists, of interest in Alzheimer’s disease; in collaboration with Prof. F. X. Sureda (Facultad de Medicina, from Universitat Rovira i Virgili, Tarragona, Spain);

b) as antivirals agents, mainly against variola virus and influenza virus; in collaboration with the groups of Prof. L. Naesens (Rega Institute for Medical Research, Leuven, Belgium), Prof. L. H. Pinto (Northwestern University, Evanston, USA), and Prof. A. Moroni and S. Gazzarrini (University of Milano, Italy);

c) as anti?trypanosoma agents, mainly against Trypanosoma brucei, the causative agent of the sleeping disease; in collaboration with the group of Prof. J. M. Kelly from the London School of Hygiene and Tropical Medicine (London, United Kingdom).

Much more recently we have started working in the synthesis of novel compounds against novel therapeutics targets such as:

d) soluble epoxide hydrolase inhibitors, in collaboration with Prof. Manuel Vázquez, from the Laboratori de Farmacologia (Universitat de Barcelona and the IBUB).

e) P2X7 receptor antagonists, in collaboration with Prof. Yong-Chul Kim, from the Laboratory of Drug Discovery of the Gwangju Institute of Science & Technology (Gwangju, Korea).

 

After the evaluation of the compounds, and in collaboration with the group of Prof. F. Javier Luque (Departament de Físico?Química de la Universitat de Barcelona and IBUB), we carry out the design and synthesis of new analogs with the aim of improving the activity of the previously synthesized compounds.

 

As a consequence of our research, we have synthesized and pharmacologically characterized a series of new NMDA receptor antagonists with inhibitory activities similar to that of the reference compound, memantine. Moreover, we have described new compounds with potent activity against vaccinia virus and, recently, we have discovered new amines with activity against influenza virus, the virus that causes the flu.

 

Selected publications:

P. Camps, M. D. Duque, S. Vázquez, L. Naesens, E. De Clercq, F. X. Sureda, M. López?Querol, A. Camins, M. Pallàs, S. R. Prathalingam, J. M. Kelly, V. Romero, D. Ivorra, D. Cortés. “Synthesis and pharmacological evaluation of several ring?contracted amantadine analogs”. Bioorg. Med. Chem. 2008, 16, 9925?9936.

 

M. D. Duque, P. Camps, L. Profire, S. Montaner, S. Vázquez, F. X. Sureda, J. Mallol, M. López?Querol, L. Naesens, E. De Clercq, S. R. Prathalingam, J. M. Kelly. “Synthesis and pharmacological evaluation of (2?oxaadamant?1?yl)amines”. Bioorg. Med. Chem. 2009, 17, 3198?3206.

 

M. D. Duque, P. Camps, E. Torres, E. Valverde, F. X. Sureda, M. López?Querol, A. Camins, S. R. Prathalingam, J. M. Kelly, S. Vázquez. “Synthesis and pharmacological evaluation of (2?oxaadamant?1?yl)amines”. Bioorg. Med. Chem. 2010, 18, 46?57.

 

E. Torres, M. D. Duque, P. Camps, L. Naesens, Teresa Calvet, Mercè Font?Bardia, S. Vázquez. “Polycyclic N?benzamido imides with potent activity against vaccinia virus”. ChemMedChem. 2010, 5, 2072-2078.

 

M. D. Duque, C. Ma, E. Torres, J. Wang, L. Naesens, J. Juárez?Jiménez, P. Camps, F. J. Luque, W. DeGrado, R. A. Lamb, L. H. Pinto, S. Vázquez. “Exploring the size limit of templates for inhibitors of the M2 ion channel of influenza A virus”. J. Med. Chem. 2011, 54, 2646-2657.

 

Torres, E. M. D. Duque, M. López-Querol, M. C. Taylor, L. Naesens, C. Ma, L. H. Pinto, F. X. Sureda, J. M. Kelly, S. Vázquez. “Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities”. Bioorganic & Medicinal Chemistry 2012, 20, 942-948.

 

E. Torres, E. Vanderlinden, R. Fernández, S. Miquet, M. Font-Bardia, L. Naesens, S. Vázquez. “Synthesis and Anti-Influenza A Virus Activity of 2,2-dialkylamantadines”. ACS Medicinal Chemistry Letters 2012, 20, 1065-1069.

 

E. Torres, M. D. Duque, E. Vanderlinden, C. Ma, L. H. Pinto, P. Pelayo, M. Froeyen, S. Vázquez, L. Naesens. “Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds”. Antiviral Research 2013, 99, 281-291.

 

M. Rey-Carrizo, E. Torres, C. Ma, M. Barniol-Xicota, J. Wang, Y.; Wu, L. Naesens, W. B. DeGrado, R. A. Lamb, L. H. Pinto, S. Vázquez. “3-Azatetracyclo[5.2.1.15,8.01,5]undecane derivatives: from wild-type inhibitors of the M2 ion channel of influenza A virus to derivatives with potent activity against the V27A mutant”. Journal of Medicinal Chemistry 2013, 56, 9265-9274.

 

Former PhD students:

Dr. Xavier Pujol Ollé (PhD, 2001; currently head of R&D at Farmhispania)

Dr. Gisela Colet Español (PhD, 2001; currently Manager of the Research Support Department at the Institut Català de Investigació Química, ICIQ)

Dr. M. Rosa Muñoz Blasco (PhD, 2007; currently Researcher at the R&D Department of the Prous Institute for Biomedical Research)

Dr. Carles Ayats Rius (PhD, 2007 ; currently “Juan de la Cierva” post-doctoral fellow at the Institut Català de Investigació Química, ICIQ)

Dr. José A. Fernández Pareja (PhD, 2007; currently at Invent-Farma)

Dr. M. Dolores Duque Toral (PhD, 2010; currently Researcher at Medichem, S. A.)

Dr. Eva Torres Costa (PhD, 2013; currently Patent Analyst at Almirall, S. A.)

 

Contact us

Laboratori de Química Farmacèutica, Facultat de Farmàcia, i Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Joan XXIII, s/n; 08028 Barcelona (Spain).

Tel.: +34 934024533

Fax: +34 934035941

E?mail: svazquez@ub.edu