Structure-guided design of selective inhibitors of neuronal nitric oxide synthase

Journal of Medicinal Chemistry

Volumn 56, Issue 7, 2013, Pages 3024-3032

  Huang, He ^a   Li, Huiying ^b   Martásek, Pavel ^c,d   Roman, Linda J ^c   Poulos, Thomas L ^b   Silverman, Richard B ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^d CHARLES UNIVERSITY   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

3,5 BIS(2 (6 AMINO 4 METHYLPYRIDIN 2 YL)ETHYL)BENZONITRILE; ASPARAGINASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; INDUCIBLE NITRIC OXIDE SYNTHASE; ISOENZYME; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; DRUG BINDING; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY;

CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NITRIC OXIDE SYNTHASE TYPE I;

EID: 84876232647     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4000984     Document Type: Article

References (28)

1. Vallance, P.; Leiper, J. Blocking NO synthesis: How, where and why Nat. Rev. Drug Discovery 2002, 1, 939-950
2. Alderton, W. K.; Cooper, C. E.; Knowles, R. G. Nitric oxide synthases: Structure, function and inhibition Biochem. J. 2001, 357, 593-615
3. Rosen, G. M.; Tsai, P.; Pou, S. Mechanism of free-radical generation by nitric oxide synthase Chem. Rev. 2002, 102, 1191-1199
4. Granik, V. G.; Grigor'ev, N. A. Nitric oxide synthase inhibitors: Biology and chemistry Russ. Chem. Bull. 2002, 51, 1973-1995
5. Olesen, J. Nitric oxide-related drug targets in headache Neurotherapeutics 2010, 7, 183-190
6. Reif, D. W.; McCarthy, D. J.; Cregan, E.; MacDonald, J. E. Discovery and development of neuronal nitric oxide synthase inhibitors Free Radical Biol. Med. 2000, 28, 1470-1477
7. Villanueva, C.; Giulivi, C. Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease Free Radical Biol. Med. 2010, 49, 307-316
8. Aquilano, K.; Baldelli, S.; Rotilio, G.; Ciriolo, M. R. Role of nitric oxide synthases in Parkinson's disease: A review on the antioxidant and anti-inflammatory activity of polyphenols Neurochem. Res. 2008, 33, 2416-2426
9. Silverman, R. B. Design of selective neuronal nitric oxide synthase inhibitors Acc. Chem. Res. 2009, 42, 439-451
10. Maddaford, S.; Annedi, S. C.; Ramnauth, J.; Rakhit, S. Advancements in the development of nitric oxide synthase inhibitors Annu. Rep. Med. Chem. 2009, 44, 27-50
11. Oess, S.; Icking, A.; Fulton, D.; Govers, R.; Muller-Esterl, W. Subcellular targeting and trafficking of nitric oxide synthases Biochem. J. 2006, 396, 401-409
12. Annedi, S. C.; Ramnauth, J.; Maddaford, S. P.; Renton, P.; Rakhit, S.; Mladenova, G.; Dove, P.; Silverman, S.; Andrews, J. S.; Felice, M. D.; Porreca, F. Discovery of cis-N -(1-(4-(methylamino)cyclohexyl)indolin-6-yl)thiophene-2- carboximidamide: A 1,6-disubstituted indoline derivative as a highly selective inhibitor of human neuronal nitric oxide synthase (nNOS) without any cardiovascular liabilities J. Med. Chem. 2012, 55, 943-955
13. Ramnauth, J.; Renton, P.; Dove, P.; Annedi, S. C.; Speed, J.; Silverman, S.; Mladenova, G.; Maddaford, S. P.; Zinghini, S.; Rakhit, S.; Andrews, J.; Lee, D. K.; Zhang, D.; Porreca, F. 1,2,3,4-Tetrahydroquinoline-based selective human neuronal nitric oxide synthase (nNOS) inhibitors: Lead optimization studies resulting in the identification of N -(1-(2-(methylamino)ethyl)-1,2,3,4- tetrahydroquinolin-6-yl)thiophene-2-carboximi damide as a preclinical development candidate J. Med. Chem. 2012, 55, 2882-2893
14. Ji, H.; Delker, S. L.; Li, H.; Martasek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives J. Med. Chem. 2010, 53, 7804-7824
15. Huang, H.; Ji, H.; Li, H.; Jing, Q.; Jansen Labby, K.; Martasek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations J. Am. Chem. Soc. 2012, 134, 11559-11572
16. Xue, F.; Fang, J.; Delker, S. L.; Li, H.; Martasek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Symmetric double-headed aminopyridines, a novel strategy for potent and membrane-permeable inhibitors of neuronal nitric oxide synthase J. Med. Chem. 2011, 54, 2039-2048
17. Li, H.; Huang, H.; Zhang, X.; Luo, X.; Lin, L.; Jiang, H.; Ding, J.; Chen, K.; Liu, H. Discovering novel 3-nitroquinolines as a new class of anticancer agents Acta Pharmacol. Sin. 2008, 29, 1529
18. Hevel, J. M.; White, K. A.; Marletta, M. A. Purification of the inducible murine macrophage nitric oxide synthase. Identification as a flavoprotein J. Biol. Chem. 1991, 266, 22789-22791
19. Roman, L. J.; Sheta, E. A.; Martasek, P.; Gross, S. S.; Liu, Q.; Masters, B. S. S. High-level expression of functional rat neuronal nitric oxide synthase in Escherichia coli Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8428-8432
20. Martasek, P.; Liu, Q.; Liu, J. W.; Roman, L. J.; Gross, S. S.; Sessa, W. C.; Masters, B. S. S. Characterization of bovine endothelial nitric oxide synthase expressed in E. coli Biochem. Biophys. Res. Commun. 1996, 219, 359-365
21. Hevel, J. M.; Marletta, M. A. Nitric-oxide synthase assays Methods Enzymol. 1994, 233, 250-258
22. Li, H.; Shimizu, H.; Flinspach, M.; Jamal, J.; Yang, W.; Xian, M.; Cai, T.; Wen, E. Z.; Jia, Q.; Wang, P. G.; Poulos, T. L. The novel binding mode of N -Alkyl- N '-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis Biochemistry 2002, 41, 13868-13875
23. Flinspach, M. L.; Li, H.; Jamal, J.; Yang, W.; Huang, H.; Hah, J. M.; Gomez-Vidal, J. A.; Litzinger, E. A.; Silverman, R. B.; Poulos, T. L. Structural basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase Nat. Struct. Mol. Biol. 2004, 11, 54-59
24. McPhillips, T. M.; McPhillips, S. E.; Chiu, H. J.; Cohen, A. E.; Deacon, A. M.; Ellis, P. J.; Garman, E.; Gonzalez, A.; Sauter, N. K.; Phizackerley, R. P.; Soltis, S. M.; Kuhn, P. Blu-ice and the distributed control system: Software for data acquisition and instrument control at macromolecular crystallography beamlines J. Synchrotron Radiat. 2002, 9, 401-406
25. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode Methods Enzymol. 1997, 276, 307-326
26. Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method Acta Crystallogr. 1997, D53, 240-255
27. Emsley, P.; Cowtan, K. Coot: Model-building tools for molecular graphics Acta Crystallogr. 2004, D60, 2126-2132
28. Winn, M. D.; Isupov, M. N.; Murshudov, G. N. Use of TLS parameters to model anisotropic displacements in macromolecular refinement Acta Crystallogr. 2001, D57, 122-133