Highly potent, selective, and orally active phosphodiesterase 10A inhibitors

Journal of Medicinal Chemistry

Volumn 54, Issue 21, 2011, Pages 7621-7638

  Malamas, Michael S ^a   Ni, Yike ^a   Erdei, James ^a   Stange, Hans ^b   Schindler, Rudolf ^b   Lankau, Hans Joachim ^b   Grunwald, Christian ^b   Fan, Kristi Yi ^a,d   Parris, Kevin ^a   Langen, Barbara ^b   Egerland, Ute ^b   Hage, Thorsten ^b   Marquis, Karen L ^a   Grauer, Steve ^a   Brennan, Julie ^a   Navarra, Rachel ^a   Graf, Radka ^a   Harrison, Boyd L ^a   Robichaud, Albert ^a,c   Kronbach, Thomas ^b   Pangalos, Menelas N ^a,e   Hoefgen, Norbert ^b   Brandon, Nicholas J ^a   more..

^a PFIZER INC   (United States)

^b Biocrea Therapies GmbH   (Germany)

^c LUNDBECK RESEARCH USA   (United States)

^d Vitae Pharmaceuticals   (United States)

^e ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

8 FLUORO 6 METHOXY 3,4 DIMETHYL 1 (3 METHYLPYRIDIN 4 YL)IMIDAZO[1,5 A]QUINOXALINE; CYCLIC AMP; CYCLIC GMP; ISOENZYME; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE XA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; FEMALE; HYDROGEN BOND; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; MUTAGENICITY; NONHUMAN; PHARMACODYNAMICS; RAT;

ADMINISTRATION, ORAL; ANIMALS; ANTIPSYCHOTIC AGENTS; AVOIDANCE LEARNING; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; CYCLIC AMP; CYCLIC GMP; DOGS; FEMALE; HUMANS; HYDROLYSIS; HYPERKINESIS; ISOENZYMES; LIGANDS; MALE; MICE; MICROSOMES; MODELS, MOLECULAR; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PROTEIN CONFORMATION; PYRAZINES; RATS; RATS, SPRAGUE-DAWLEY; RATS, WISTAR; RECOMBINANT PROTEINS; STEREOISOMERISM; STEREOTYPED BEHAVIOR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 80455140545     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2009138     Document Type: Article

References (22)

1. Manallack, D. T.; Hughes, R. A.; Thompson, P. E. The next generation of phosphodiesterase inhibitors: structural clues to ligand and substrate selectivity of phosphodiesterases J. Med. Chem. 2005, 48, 3449-3462
2. Odingo, J. O. Inhibitors of PDE4: a review of recent patent literature Expert Opin. Ther. Pat. 2005, 15, 773-787
3. Rotella, D. Phosphodiesterase 5 inhibitors: current status and potential applications Nat. Rev. Drug Discovery 2002, 1, 674-682
4. Houslay, M. D.; Schafer, P.; Zhang, K. Y. Keynote review: phosphodiesterase-4 as a therapeutic target Drug Discovery Today 2005, 10, 1503-1519
5. Bender, A. T.; Beavo, J. A. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use Pharmacol. Rev. 2006, 58, 488-520
6. Loughney, K.; Snyder, P. B.; Uher, L.; Rosman, G. J.; Ferguson, K.; Florio, V. A. Isolation and characterization of PDE10A, a novel human 30, 50-cyclic nucleotide phosphodiesterase Gene 1999, 234, 109-117
7. Fujishige, K.; Kotera, J.; Omori, K. Striatum- and testis-specific phosphodiesterases PDE10A: isolation and characterization of a rat PDE10A Eur. J. Biochem. 1999, 266, 1118-1127
8. Fujishige, K.; Kotera, J.; Michibata, H.; Yuasa, K.; Takebayashi, S.; Okumura, K.; Omori, K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A) J. Biol. Chem. 1999, 274, 18438-18445
9. Soderling, S.; Bayuga, S. J.; Beavo, J. A. Isolation and characterization of a dualsubstrate phosphodiesterase gene family: PDE10A Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 7071-7076
10. Soderling, S.; Beavo, J. A. Phosphodiestarase inhibitors Curr. Opin. Cell Biol. 1999, 12, 174-179
11. Zhang, K.; Card, G.; Suzuki, Y.; Artis, R.; Fong, D.; Gillette, S.; Hsieh, D.; Neiman, J.; West, B.; Zhang, C.; Milburn, M.; Kim, S.-H.; Schlessinger, J.; Bollag, G. A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases Mol. Cell 2004, 15, 279-286
12. Seeger, T. F.; Bartlett, B.; Coskran, T. M.; Culp, J. S.; James, L. C.; Krull, D. L.; Lanfear, J.; Ryan, A. M.; Schmidt, C. J.; Strick, C. A.; Varghese, A. H.; Williams, R. D.; Wylie, P. G.; Menniti, F. S. Immunohistochemical localization of PDE10A in the rat brain Brain Res. 2003, 985, 113-126
13. Kaiya, H. Second messenger imbalance hypothesis of schizophrenia Prostaglandins, Leukotrienes Essent. Fatty Acids 1992, 46, 33-38
14. Muly, E. C.; Smith, Y.; Allen, P.; Greengard, P. Signal transduction abnormalities in schizophrenia: the cAMP system Psychopharmacol. Bull 2002, 36, 92-105
15. Garver, D. L.; Carl Johnson, C.; Kanter, D. R. Schizophrenia and reduced cyclic AMP production: evidence for the role of receptor-linked events Life Sci. 1982, 31, 1987-1992
16. Hoefgen, N.; Stange, H.; Rudolf Schindler, R.; Lankau, H.-J.; Grunwald, C.; Langen, B.; Egerland, U.; Tremmel, P.; Pangalos, M. N.; Marquis, K. L.; Hage, T.; Harrison, B. L.; Malamas, M. S.; Brandon, N. J.; Kronbach., T. Discovery of imidazo[1,5- a ]pyrido[3,2-e]pyrazines as a new class of phosphodiesterase 10A inhibitiors J. Med. Chem. 2010, 53, 4399-4411
17. Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds Chem. Rev. 1995, 95, 2457-2483
18. Grauer, S.; Pulito, V.; Navarra, R.; Kelly, M.; Kelley, C.; Graf, R.; Langen, B.; Logue, S.; Brennan, J.; Jiang, L.; Charych, E.; Egerland, U.; Liu, F.; Marquis, K.; Malamas, M. S.; Hage, T.; Comery, T.; Brandon, N. PDE10A inhibitors show anti-psychotic, pro-cognitive and negative symptom activities suggesting broad-spectrum utility for the treatment of schizophrenia J. Pharmacol. Exp. Ther. 2009, 331, 574-590
19. Andiné, P.; Widermark, N.; Axelsson, R.; Nyberg, G.; Olofsson, U.; Martensson, E.; Sandberg, M. Characterization of MK-801-induced behavior as a putative rat model of psychosis J. Pharmacol. Exp. Ther. 1999, 290, 1393-1408
20. SigmaStat, version 3.11; Systat Software, Inc.: Chicago, IL, 2004.
21. SigmaPlot, version 9.0; Systat Software, Inc.: Chicago, IL, 2004.
22. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions Protein Eng. 1995, 8, 127-134