Curriculum vitae
1. Dados pessoais
1. Personal data
Nome completo
Full name
Rui Ferreira Alves Moreira
BI
National identity card
5509684
Local e data de Nascimento
Birth place and date
Lisboa 13-10-1960
Pais de nacionalidade
Nationality
PORTUGAL
Morada institucional
Institutional address
Faculdade de Farmácia da Universidade de Lisboa
Av Prof. Gama Pinto
1649-019 Lisboa
PORTUGAL
Contactos
Contact data
Telefone: 217946477
Fax: 217946470
Email: [email protected]
Endereço internet (url): http://www.ff.ul.pt/paginas/rmoreira/
2. Formação académica
2. Academic degrees
Ano Grau académico
Year Academic degree
Instituição
Institution
Classificação
Classification
2004 AGREGAÇÃO
Faculdade de Farmácia
Louvor e Distinção
1991 DOUTORAMENTO
Faculdade de Farmácia
Louvor e Distinção
1985 LICENCIATURA
Faculdade de Farmácia
Muito Bom (18 valores)
3. Actividades anteriores e situação actual em termos científicos e/ou profissionais
3. Previous and current scientific and/or professional activities
Período
Period
Cargo ou categoria
Position or category
Instituição
Institution
from 1986 to 1988
Trainining Research Assistant Faculdade de Farmácia, Universidade de Lisboa
from 1988 to 1991
Research Assistant
Faculdade de Farmácia, Universidade de Lisboa
from 1991 to 2001
Auxiliar Professor
Faculdade de Farmácia, Universidade de Lisboa
from 2001 to 2006
Associate Professor
Faculdade de Farmácia, Universidade de Lisboa
From 2006
Full Professor
Faculdade de Farmácia, Univesidade de Lisboa
4. Área de actividade científica
4. Area of scientific activity
A)Medicinal Chemistry
- Rational design of serine and cysteine protease inhibitors. We have particular interest in developing suicide
or mechanism-based inhibitors capable of achieving long-lasting and selective enzyme inhibition.
- Design of novel chemical drug delivery systems or prodrugs. We are most interested in prodrugs for
antimalarials that have low therapeutic/toxicity ratio. We are also interested in site-specific drug delivery
systems such as those used for Antibody Directed Enzyme-Prodrug Therapy (ADEPT) applied to antitumoral
agents.
- Drug and prodrug metabolism. The study of metabolism is used as a tool to design drugs capable of
reaching their target without being extensively metabolised, or to design prodrugs that are more readily
activated in vivo.
B)Physical Organic Chemistry
We use classical reactivy studies to determine structure-reactivity relationships that can be used to design
more stable drugs or to modulate drug delivery rates from prodrugs.
5. Domínio de especialização
5. Domain of specialization
Domínio de especialização
Domain of specializations
1)Organic Chemistry: synthesis of organic compounds; study of chemical reactivity and of mechanisms of
organic reactions.
2)Medicinal Chemistry: Design and synthesis of bioactive molecules; rational drug design, study of drug
metabolism.
Actuais interesses de investigação
Present research interests
- The design and synthesis of irreversible and suicide-type inhibitors of cysteine and serine proteases based
on heterocyclic scaffolds. This includes the use of mechanism-based and reactivity concepts to design the
inhibitors and to undertake their optimization.
- The design of novel chemical drug delivery systems (prodrugs) based on non-toxic carriers that can: (i)
improve the physico-chemical properties that affect dissolution fenomena and passive membrane
permeation; (ii) target specific membrane transporters or activating enzymes and thus improve cell or
tissue selectivity.
- Study of structure-reactivity and structure-metabolism relationships as a tool to design drugs with
optimized reactivity and metabolism (e.g. when extensive drug metabolism leads to bioavailability
problems).
- Design and synthesis of peptidomimetics. This includes the development of novel synthetic methods as
well as the design of novel peptidomimetic scaffolds.
Outras competências/actividades
Other skills/activities
1)Expert in Chemistry and Pharmaceutical Sciences at the European Medicines Agency (EMEA) and
Portuguese Medicines Agency (INFARMED).
2)Expert in Chemistry and Patents at the Commercial Court of Lisbon
6. Experiência na orientação
6. Supervising experience
Pos-Doctoral
1. Maria Santos (from 2006)
2. Subhash Gosh (starting 2007)
Ph.D. Thesis
Concluded
1. Maria Eduarda Mendes. Concluded in 1998.
2. Teresa Calheiros e Menezes. Concluded in 1998.
3. Francisca Lopes. Concluded in 2000.
4. Paula Chambel. Concluded in 2006.
Running
5. Ana Bela Santana.
6. Luísa Martins.
7. Cláudia Valente.
8. Jalmira Mulchande
9. João Paulo Lavrado
10. Rita Capela
M.Sc. Thesis
1.
2.
3.
4.
5.
Emília Valente. Concluded in 1999.
Célia Fernandes. Concluded in 1999.
Graça Mata. Concluded in 1999.
Luísa Martins. Concluded in 2002.
João Paulo Lavrado. Concluded in 2006.
7. Participação em projectos
7. Participation in research projects
As project coordinator:
1. Desenvolvimento de Novos Sistemas Químicos de Cedência de Fármacos Antimaláricos.
JNICT/CEN/1084/92 (Concluded).
2. Desenvolvimento de Novos Sistemas Químicos de Cedência de Cefalosporinas e Penicilinas para
Modificação da Biodisponibilidade Oral. JNICT/SAU/1546/92 (Concluded)
3. Rational Design of Mechanism-Based Inhibitors of Serine Proteases Based on the b-Lactam Scaffold.
PRAXIS XXI/QUI710039/98 (Concluded).
4. A new approach to antimalarial therapy. Novel chemical delivery systems for primaquine and
amodiaquine. POCTI/FCB/39218/2001 (Running).
5. Introdução de métodos computacionais de modelização molecular e de técnicas de RMN na Faculdade de
Farmácia da Universidade de Lisboa para projectos de design de fármacos. Treaty of Windsor Programme
(Running).
8. Prémios e Distinções
8. Prizes and awards
Ano
Year
Nome do Prémio ou Distinção
Name of the prize or award
Nome da entidade promotora
Name of the granting entity
1985
Prémio Sociedade Lusitana
Ordem dos Farmacêuticos
9. Publicações
9. Publications
Teses / Thesis
3. R. Moreira, ‘Contribuição para o Desenvolvimento de Pró-Fármacos de Alguns Compostos com Actividade
Antitumoral’, 1991, Tese de Doutoramento (Ph.D. Thesis), Faculdade de Farmácia da Universidade de
Lisboa.
Artigos em revistas de circulação internacional com arbitragem científica / Papers in
international scientific periodicals with referees
1. J. Iley, R. Moreira, E. Rosa, ‘Triazene drug metabolites. Part 4. Kinetics and mechanism of the
decomposition of 1-aryl-3-benzoyloxymethyl-3-methyltriazenes in mixed aqueous organic solvents’, J.
Chem. Soc. Perkin Trans. 2, 1987, 1503.
2. J. Iley, R. Moreira, G. Ruecroft, E. Rosa, ‘Synthesis of N-Cysteinyl, S-(N-Acetylcysteinyl) and SGlutathionyl Conjugates of N-Hydroxymethyl-triazenes’, Tetrahedron Lett., 1988, 29, , 2707.
3. J. Iley, R. Moreira, E. Rosa, ‘Triazene drug metabolites. Part 10. Metal ion catalysed decomposition of
monoalkyltriazenes in ethanol solutions’, J. Chem. Soc. Perkin Trans 2, 1991, 81.
4. J. Iley, R. Moreira, E. Rosa, ‘Acyloxymethyl as a drug protecting group. Kinetics and mechanism of the
hydrolysis of N-acyloxymethylbenzamides’, J. Chem. Soc. Perkin Trans. 2, 1991, 563.
5. J. Iley, R. Moreira, E. Rosa, ‘Triazene drug metabolites. Part. 11. Synthesis of cysteinyl and related
derivatives of N-hydroxymethyltriazenes’, J. Chem. Soc. Perkin Trans 1, 1991, 3241.
7. R. Moreira, E. Mendes, T. Calheiros, M. J. Bacelo, J. Iley, ‘A new direct synthesis of tertiary Nacyloxymethylamide prodrugs of carboxylic acid drugs’, Tetrahedron Lett., 1994, 35, 7107.
8. T. Calheiros, J. Iley, F. Lopes, R. Moreira, ‘Acyloxymethyl as a drug protecting group. Synthesis and
reactivity of N-acyloxymethylsulfonamide prodrugs’, Bioorg. Med. Chem. Lett., 1995, 5, 937.
9. R. Moreira, T. Calheiros, J. Cabrita, E. Mendes, M. Pimentel, J. Iley, ‘Acyloxymethyl as a drug protecting
group. Part 3. Tertiary O-amidomethyl esters of penicillin G: chemical hydrolysis and anti-bacterial activity’.
Pharm. Res., 1996, 13, 70.
10. J. Iley, R. Moreira, T. Calheiros, E. Mendes, ‘Acyloxymethyl as a drug protecting group. Part 4. The
hydrolysis of tertiary amidomethyl ester prodrugs of carboxylic acid agents’, Pharm. Res., 1997, 14, 1634.
11. J. Iley, T. Calheiros, R. Moreira, ‘Phthalimidomethyl as a drug pro-moiety. probing its reactivity’, Bioorg.
Med. Chem. Lett., 1998, 8, 955.
12. F. Lopes, R. Moreira, J. Iley, ‘Acyloxymethyl as a drug protecting group. Part 5. Kinetics and mechanism
of the hydrolysis of tertiary N-acyloxymethylsulfonamides’, J. Chem. Soc. Perkin Trans. 2, 1999, 431.
13. M. J. Portela, R. Moreira, E. Valente, L. Constantino, J. Iley, J. Pinto, R. Rosa, P. Cravo and V. E. do
Rosário, ‘Dipeptide derivatives of primaquine as transmission-blocking antimalarials. Effect of aliphatic sidechain acylation on the gametocytocidal activity and on the formation of carboxyprimaquine in rat liver
homogenates’, Pharm. Res., 1999, 16, 949.
14. L. Constantino, P. Paixão, R. Moreira, M.J. Portela, V. E. do Rosário and J. Iley, ‘Metabolism of
primaquine by liver homogenate fractions. Evidence for monoamine oxidase and cytochrome P450
involvement in the oxidative deamination of primaquine to carboxyprimaquine’, Exp. Toxic. Pathol., 1999,
51, 299.
15. J. Iley, E. Mendes, R. Moreira, S. Souza, ‘Cleavage of tertiary amidomethyl ester prodrugs of carboxylic
acids by rat liver homogenates’, Eur. J. Pharm. Sci., 1999, 6, 201.
16. F. Lopes, R. Moreira, J. Iley, ‘Acyloxymethyl as a drug protecting group. Part 6. N-Acyloxymethyl- and
N-[(aminocarbonyloxy)methyl]sulfonamides as prodrugs of agents containing a secondary sulfonamide
group’, Bioorg. Med. Chem., 2000, 8, 707.
17. J. Iley, H. Barroso, R. Moreira, F. Lopes, T. Calheiros, ‘Acyloxymethyl as a drug protecting group. Part 7.
Tertiary sulfonamidomethyl ester prodrugs of benzylpenicillin: chemical hydrolysis and anti-bacterial
activity’, Bioorg. Med. Chem., 2000, 8, 1629
18. J. Iley, F. Lopes, R. Moreira, ‘Kinetics and mechanism of hydrolysis of N-amidomethylsulfonamides’, J.
Chem. Soc. Perkin Trans. 2, 2001, 749.
19. A. Clemente, A. Domingos, A.P.Grancho, J. Iley, R. Moreira, J. Neres, N. Palma, A.B. Santana, E.
Valente, ‘Design, synthesis and stability of N-acyloxymethyl- and N-aminocarbonyloxymethyl-2-azetidinones
as human leukocyte elastase inhibitors’, Bioorg. Med. Chem. Lett., 2001, 11, 1065.
20. T. Furtado, J. Iley, T. Jarvinen, E. Mendes, R. Moreira, J. Neres, J. Rautio, ‘Synthesis, stability and in
vitro dermal evaluation of aminocarbonyloxymethyl esters as prodrugs of carboxylic acid agents’, Bioorg.
Med. Chem., 2002, 10, 809.
21. P. Gomes, M.I. Santos, M.J. Trigo, R Castanheiro, R Moreira, ‘Improved synthesis of amino acid and
dipeptide chloromethyl esters using bromochloromethane’, Synthet.. Commun., 2003, 33, 1683.
22. P. Gomes, J.R.B. Gomes, M. Rodrigues, R. Moreira, ‘Amino acids as selective sulfonamide acylating
agents’, Tetrahedron, 2003, 59, 5473.
23. C. Fernandes, L. Patrício, R. Moreira, G. Cantinho, H. Pena, P. C. Campello, I. Santos, ‘Novel 3+1 mixedligand technetium-99m complexes carrying dipeptides as monodentate ligands’, Nucl. Med. Biol., 2004, 31,
139.
24. E. Valente, J.R.B. Gomes, R. Moreira, J. Iley, ‘Kinetics and mechanism of hydrolysis of N-acyloxymethyl
derivatives of azetidin-2-one’, J. Org. Chem., 2004, 69, 3359.
25. P. Gomes, M.J. Araújo, M. Rodrigues, N. Vale, Z. Azevedo, J. Iley, J. Morais, P. Chambel, R. Moreira,
‘Synthesis of imidazolidin-4-one and 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-dione derivatives of
primaquine: scope and limitations’, Tetrahedron., 2004, 60, 5551.
26. F. Lopes, R. Capela, J.O. Gonçaves, P.N. Horton, M.B. Hursthouse, J. Iley, C.M. Casimiro, J. Bom, R.
Moreira, ‘Amidomethylation of amodiaquine: antimalarial N-Mannich base derivatives ’, Tetrahedron Lett.,
2004, 45, 7663.
27. M. J. Araújo, J. Bom, R. Capela, C. Casimiro, P. Chambel, P. Gomes, J. Iley, F. Lopes, J. Morais, R.
Moreira, E. de Oliveira, V. do Rosário, N. Vale, ‘Imidazolidin-4-one derivatives of primaquine as novel
transmission-blocking antimalarials’, J. Med. Chem, 2005, 48, 888.
28. C. Santos, M. L. Mateus, A. P. dos Santos, R. Moreira, E. Oliveira, P. Gomes, ‘Cyclization-activated
prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamol’, Bioorg. Med. Chem. Lett.,
2005, 15, 1595.
29. R. Moreira, A. B. Santana, J. Iley, J. Neres, K. T. Douglas, P. N. Horton, M. B. Hursthouse, ‘Design,
synthesis and enzymatic evaluation of N1-acyloxyalkyl- and N1-oxazolidin-2,4-dion-5-yl-substituted blactams as novel inhibitors of human leukocyte elastase’, J. Med. Chem. 2005, 48, 4861.
30. Iley, J.; Moreira, R.; Martins L.; Guedes, R.C.; Soares, C.M. ‘The Bsmoc group as a novel scaffold for the
design of irreversible inhibitors of cysteine proteases’, Bioorg. Med. Chem. Lett., 2006, 16, 2738-2741.
31. Valente, C.; Moreira, R.; Iley, J.; Gut, J.; Rosenthal, P.J. ‘Dipeptide Vinyl Sultams: Synthesis via the
Wittig-Horner Reaction and Activity Against Papain, Falcipain-2 and Plasmodium falciparum’, Bioorg. Med.
Chem. Lett., 2006, 16, 4115-4119.
32. Chambel, P., Capela, R., Lopes, F., Iley, J., Morais, J., Gouveia, L., Gomes, J. R. B., Gomes, P., Moreira,
R. ‘Reactivity of imidazolidin-4-one derivatives of primaquine: implications for prodrug design’. Tetrahedron,
2006, 62, 9883-9891.
33. Ribeiro, L.; Silva, Nuno; Iley, J.; Rautio. J.; Jarvinen, T.; Filipe, H.; Moreira, R.; Mendes, E.
‘Aminocarbonyloxymethyl ester prodrugs of flufenamic acid and diclofenac: suppressing the rearrangement
pathway in aqueous media’. Archiv der Pharmazie- Chemistry in Life Science. 2007 (in press).
Artigos em revistas nacionais com arbitragem científica / Papers in national periodicals with
referees
6. E. Rosa, E. Carvalho, S.C. Chang, L. Fernandes, J. Iley, R. Moreira, A. Nunes, G. Ruecroft, ‘Triazenos
antitumorais: mecanismo de acção biológica e desenvolvimento de pró-fármacos’, Rev. Port. Farm., 1992,
61, 7.
Publicações em actas de encontros científicos / Papers in conference proceedings
1. J. Pinto, E. Valente, R. Rosa, P. Cravo, L. Constantino, V. E. do Rosário and R. Moreira, ‘Gametocytocidal
Activity of Some Dipeptide Derivatives of Primaquine’, Proceedings of the European Conference on Tropical
Medicine, Blackwell Science, Hamburg, 1995, 118.
2. R. Castanheiro, M. J. Araújo, R. Ferraz, R. Moreira and P. Gomes , ‘Peptide 4-imidazolidinones as
potential drug delivery systems’, Proceedings of the 27th European Peptide Symposium, Eds. E. Benedetti,
C. Pedone; Edizione Ziino, 2002, pp. 936.