Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model

European Journal of Medicinal Chemistry

Volumn 47, Issue 1, 2012, Pages 175-185

  Redondo, Miriam ^a   Zarruk, Juan G ^b   Ceballos, Placido ^a   Pérez, Daniel I ^a   Pérez, Concepción ^a   Perez Castillo, Ana ^c   Moro, María A ^b   Brea, José ^d   Val, Cristina ^d   Cadavid, María I ^d   Loza, María I ^d   Campillo, Nuria E ^a   Martínez, Ana ^a   Gil, Carmen ^a  

^a INSTITUTO DE QUÍMICA MÉDICA   (Spain)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^c INSTITUTO DE INVESTIGACIONES BIOMÉDICAS ALBERTO SOLS   (Spain)

^d UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

Author keywords

Neuroprotection; PDE7 inhibitors; Quinazolines; Stroke

Indexed keywords

3 (2 BROMOPHENYL) 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 (2 BROMOPHENYL) 8 CHLORO 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 (2 BROMOPHENYL) 8 METHYL 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 (2 MORPHOLINOETHYL) 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 (2,6 DIFLUOROPHENYL) 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 (3 BROMOPHENYL) 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROPYRIDO (2,3 DEXTRO) PYRIMIDINE; 3 (4 BROMO 2 FLUOROPHENYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROQUINAZOLIN; 3 (4 METHOXYBENZYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO (2,3 DEXTRO) PYRIMIDINE; 3 (4 METHOXYBENZYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 (4 METHOXYPHENETHYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO (3,4 DEXTRO) PYRIMIDINE; 3 (4 METHOXYPHENETHYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 3 PHENYL 2,4 DITHIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 4 OXO 3 (PYRIDIN 3 YL) 2 THIOXO 1,2,3,4 TETRAHYDROPYRIDO (3,4 DEXTRO) PYRIMIDINE; 4 OXO 3 (PYRIDIN 3 YL) 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 4 OXO 3 [2 (PIPERIDIN 1 YL)ETHYL] 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 4 OXO 3 PHENYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIDO (2,3 DEXTRO) PYRIMIDINE; 4 OXO 3 PHENYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIDO (3,4 DEXTRO) PYRIMIDINE; 4 OXO 3 PHENYL 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 6 BROMO 3 (4 METHOXYPHENETHYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 6,7 DIMETHOXY 3 (2 MORPHOLINOETHYL) 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 6,7 DIMETHOXY 4 OXO 3 (2 (PIPERIDIN 1 YL)ETHYL) 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 6,7 DIMETHOXY 4 OXO 3 (PYRIDIN 3 YL) 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 6,7 DIMETHOXY 4 OXO 3 PHENYL 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 8 BROMO 6 METHYL 4 OXO 3 PHENYL 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; 8 CHLORO 3 (2,6 DIFLUOROPHENYL) 4 OXO 2 THIOXO 1,2,3,4 TETRAHYDROQUINAZOLINE; PHOSPHODIESTERASE VII; PHOSPHODIESTERASE VII INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CELL CULTURE; CONTROLLED STUDY; DRUG EFFICACY; DRUG PENETRATION; FEMALE; IN VITRO STUDY; IN VIVO STUDY; MIDDLE CEREBRAL ARTERY OCCLUSION; NERVE CELL; NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; STROKE; TREATMENT OUTCOME;

ANIMALS; BLOOD-BRAIN BARRIER; CELLS, CULTURED; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 7; DISEASE MODELS, ANIMAL; ENZYME INHIBITORS; INFARCTION, MIDDLE CEREBRAL ARTERY; MALE; MICE; NEUROPROTECTIVE AGENTS; PERMEABILITY; QUINAZOLINES; STROKE;

EID: 84855819970     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.10.040     Document Type: Article

References (40)

1. C. Lugnier Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents Pharmacol. Ther. 109 2006 366 398
2. K.H. Banner, and C.P. Page Theophylline and selective phosphodiesterase inhibitors as anti-inflammatory drugs in the treatment of bronchial asthma Eur. Respir. J. 8 1995 996 1000
3. D.M. Essayan Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation Biochem. Pharmacol. 57 1999 965 973
4. M. Kumar, and V. Bhattacharya Cilostazol: a new drug in the treatment intermittent claudication Recent Pat. Cardiovasc. Drug Discov. 2 2007 181 185
5. L.M. Fabbri, B. Beghe, U. Yasothan, and P. Kirkpatrick Roflumilast Nat. Rev. Drug Discov. 9 2010 761 762
6. K. Hatzimouratidis Sildenafil in the treatment of erectile dysfunction: an overview of the clinical evidence Clin. Interv. Aging 1 2006 403 414
7. F.S. Menniti, W.S. Faraci, and C.J. Schmidt Phosphodiesterases in the CNS: targets for drug development Nat. Rev. Drug Discov. 5 2006 660 670
8. N.J. Brandon, and D.P. Rotella Potential CNS applications for phosphodiesterase enzyme inhibitors Ann. Rep. Med. Chem. 42 2007 3 12
9. T.B. Halene, and S.J. Siegel PDE inhibitors in psychiatry-future options for dementia, depression and schizophrenia? Drug Discov. Today 12 2007 870 878
10. G.M. Rose, A. Hopper, M. De Vivo, and A. Tehim Phosphodiesterase inhibitors for cognitive enhancement Curr. Pharm. Des. 11 2005 3329 3334
11. L. Li, C. Yee, and J.A. Beavo C3- and CD28-dependent induction of PDE7 required for T cell activation Science 283 1999 848 851
12. M.A. Giembycz, and S.J. Smith Phosphodiesterase 7A: a new therapeutic target for alleviating chronic inflammation? Curr. Pharm. Des. 12 2006 3207 3220
13. M.A. Giembycz, and S.J. Smith Phosphodiesterase 7 (PDE7) as a therapeutic target Drugs Fut. 31 2006 207 229
14. I. Paterniti, E. Mazzon, C. Gil, D. Impllizzari, V. Palomo, M. Redondo, D.I. Perez, E. Esposito, A. Martinez, and S. Cuzzocrea PDE 7 inhibitors: new potential drugs for the therapy of spinal cord injury PLoS ONE 6 2011 e15937
15. J. Morales-Garcia, M. Redondo, C. Gil, S. Alonso-Gil, A. Martinez, A. Santos, and A. Perez-Castillo Phosphodiesterase 7 inhibition preserves dopaminergic neurons in cellular and rodent models of Parkinson disease PLoS ONE 6 2011 e17240
16. A. Martinez, A. Castro, C. Gil, M. Miralpeix, V. Segarra, T. Domenech, J. Beleta, J.M. Palacios, H. Ryder, X. Miro, C. Bonet, J.M. Casacuberta, F. Azorin, B. Piña, and P. Puigdomenech Benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]thiadiazine 2,2-dioxides: first phosphodiesterase 7 inhibitors J. Med. Chem. 43 2000 683 689
17. A. Castro, M.I. Abasolo, C. Gil, V. Segarra, and A. Martinez CoMFA of benzyl derivatives of 2,1,3-benzo and benzothieno[3,2-a]thiadiazine 2,2-dioxides: clues for the design of phosphodiesterase 7 inhibitors Eur. J. Med. Chem. 36 2001 333 338
18. C. Gil, N.E. Campillo, D.I. Perez, and A. Martinez Phosphodiesterase 7 (PDE7) inhibitors as new drugs for neurological and inflammatory disorders Expert Opin. Ther. Pat. 18 2008 1127 1139
19. ® v1.0 (revision 3).
20. A. Castro, M.J. Jerez, C. Gil, F. Calderon, T. Domenech, A. Nueda, and A. Martinez CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example Eur. J. Med. Chem. 43 2008 1349 1359
21. T. Castaño, H. Wang, N.E. Campillo, S. Ballester, C. Gonzalez-Garcia, J. Hernandez, C. Perez, J. Cuenca, A. Perez-Castillo, A. Martinez, O. Huertas, J.L. Gelpi, F.J. Luque, H. Ke, and C. Gil Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors ChemMedChem 4 2009 866 876
22. Z. Li, H. Huang, H. Sun, H. Jiang, and H. Liu Microwave-assisted efficient and convenient synthesis of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolines J. Comb. Chem. 10 2008 484 486
23. H.C. Wang, Y.D. Liu, Y.X. Chen, H. Robinson, and H.M. Ke Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide phosphodiesterases 4 and 7 J. Biol. Chem. 280 2005 30949 30955
24. N.A. Meanwell Synopsis of some recent tactical application of bioisosteres in drug design J. Med. Chem. 54 2011 2529 2591
25. M. Ishikawa, and Y. Hashimoto Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry J. Med. Chem. 54 2011 1539 1554
26. C. Bissantz, B. Kuhn, and M. Stahl A medicinal chemist's guide to molecular interactions J. Med. Chem. 53 2010 5061 5084
27. F.L. Cardoso, D. Brites, and M.A. Brito Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches Brain Res. Rev. 64 2010 328 363
28. L. Di, E.H. Kerns, and G.T. Carter Strategies to assess blood-brain barrier penetration Expert Opin. Drug Discov. 3 2008 677 687
29. K.H. Bleicher, H.J. Bohm, K. Muller, and A.I. Alanine Hit and lead generation: beyond high-throughput screening Nat. Rev. Drug Discov. 2 2003 369 378
30. L. Di, E.H. Kerns, K. Fan, O.J. McConnell, and G.T. Carter High throughput artificial membrane permeability assay for blood-brain barrier Eur. J. Med. Chem. 38 2003 223 232
31. P. Crivori, G. Cruciani, P.A. Carrupt, and B. Testa Predicting blood-brain barrier permeation from three-dimensional molecular structure J. Med. Chem. 43 2000 2204 2216
32. 1-antihistaminic agents Bioorg. Med. Chem. Lett. 15 2005 1877 1880
33. S. Muthusamy, and V.T. Ramakrishnan A facile photochemical-synthesis of 12H-benzothiazolo[2,3-b]quinazolin-12-ones Synth. Commun. 22 1992 519 533
34. N. Koay, and L.C. Campeau Efficient preparation of 3-substituted quinazolinediones directly from anthranilic acids and isocyanates J. Het. Chem. 48 2011 473 478
35. I.A. Rivero, K. Espinoza, and R. Somanathan Syntheses of quinazoline-2,4-dione alkaloids and analogues from Mexican Zanthoxylum species Molecules 9 2004 609 616
36. J. Garin, E. Melendez, F.L. Merchan, and T. Tejero Synthesis of pyridio[2,3-d]pyrimidines and fused tetracyclic derivatives from methyl N-aryldithiocarbamates Synthesis 1984 586 588
37. R. Luna-Medina, M. Cortes-Canteli, M. Alonso, A. Santos, A. Martinez, and A. Perez-Castillo Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation J. Biol. Chem. 280 2005 21453 21462
38. S.T. Chen, C.Y. Hsu, E.L. Hogan, H. Maricq, and J.D. Balentine A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction Stroke 17 1986 738 743
39. T.H. Liu, J.S. Beckman, B.A. Freeman, E.L. Hogan, and C.Y. Hsu Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury Am. J. Physiol. 256 1989 H589 H593
40. J. Chen, P.R. Sanberg, Y. Li, L. Wang, M. Lu, A.E. Willing, J. Sanchez-Ramos, and M. Chopp Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats Stroke 32 2001 2682 2688