Organic & Biomolecular Chemistry
Paper
pyrimidinones. The target compounds were prepared in most
cases under microwave irradiation and processed in a parallel
manner. These compounds have been tested in vitro as PDE7
inhibitors. For the most active compounds, corresponding to
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4-aminothieno[2,3-d]pyrimidine-6-carbonitrile
derivatives,
molecular modelling studies provided a rationale for the
improved PDE7 inhibitory activity and their selectivity over
PDE3 and PDE4 isoforms. The selectivity profile of 2az, 2ba
and 2be, all of which have a trimethoxyphenyl substituent on
the pyrimidine ring, makes these compounds the molecules of
choice for further development as selective PDE7 inhibitors.
On the other hand, 2bh containing a propargyl substituent on 10 G. L. Card, B. P. England, Y. Suzuki, D. Fong, B. Powell,
the amine position and a dimethoxybenzyl group on the pyri-
midine position is a nanomolar inhibitor of PDE7 and PDE3
but inhibits PDE4 poorly. Therefore this compound stands out
as a good candidate for a dual PDE7/3 inhibitor, which may be
B. Lee, C. Luu, M. Tabrizizad, S. Gillette, P. N. Ibrahim,
D. R. Artis, G. Bollag, M. V. Milburn, S. H. Kim,
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C. Gonzalez-Garcia, J. Hernandez, C. Perez, J. Cuenca,
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Acknowledgements
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Financial support from the Spanish Ministry of Economía y
Competitividad (project CTQ2011-24715 to J. J. V.), the 13 K. Gotanda, A. Shinbo, Y. Nakano, H. Kobayashi, M. Okada
Spanish Ministry of Science and Innovation (SAF2012-39760- and A. Asagarasu, PCT Int. Appl, WO 2006135080 A1, 2006.
C02-02 to F. G.), Comunidad de Madrid (S2010-BMD-2457 to 14 A. Castro, M. J. Jerez, C. Gil, F. Calderon, T. Domenech,
F. G.), Universidad de Alcalá (project UAH GC 2012-001 to
J. A. B.), Instituto de Salud Carlos III (Red de Investigación
A. Nueda and A. Martinez, Eur. J. Med. Chem., 2008, 43,
1349.
Renal, REDinREN, RD06/0016/0016 and RD12/0021/0014 to 15 M. Safavi, M. Baeeri and M. Abdollahi, Expert Opin. Drug
J. J. V.) and grants from Almirall Prodesfarma S.A. (to A. I. S.,
R. M., J. M. M. and A. N.) is gratefully acknowledged.
A. C. C. and F. F. are recipients of research scholarships
Discovery, 2013, 8, 733; A. Banerjee, P. S. Yadav, M. Bajpai,
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Spanish Ministry of Education.
E. Terricabras, V. M. Segarra Matamoros, J. Alvarez-Builla,
J. J. Vaquero and J. M. Minguez, PCT Int. Appl, WO
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