Arginine-based inhibitors of nitric oxide synthase: Therapeutic potential and challenges

Mediators of Inflammation

Volumn 2012, Issue , 2012, Pages

  Víteček, Jan ^a,b   Lojek, Antonín ^b   Valacchi, Giuseppe ^c,d   Kubala, Lukáš ^a,b  

^a ST ANNE S UNIVERSITY HOSPITAL   (Czech Republic)

^b INSTITUTE OF BIOPHYSICS   (Czech Republic)

^c UNIVERSITY OF FERRARA   (Italy)

^d Kyung Hee University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3 [[2 (ETHANIMIDOYLAMINO)ETHYL]SULFONYL]PROPANOIC ACID; 2 AMINO 4 [[2 (ETHANIMIDOYLAMINO)ETHYL]THIO]BUTANOIC ACID; ARGININE DERIVATIVE; GW 273629; N(G) METHYLARGININE; N(G) NITROARGININE; N(G) NITROARGININE METHYL ESTER; N(G) PROPYLARGININE; N(G),N(G) DIMETHYLARGININE; N5 (1 IMINOETHYL)ORNITHINE; N6 (1 IMINOETHYL)LYSINE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; S METHYLTHIOCITRULLINE; S [2 (1 IMINOETHYLAMINO)ETHYL]HOMOCYSTEINE; UNCLASSIFIED DRUG;

DRUG DESIGN; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 84867817981     PISSN: 09629351     EISSN: 14661861     Source Type: Journal    
DOI: 10.1155/2012/318087     Document Type: Review

References (179)

1. Alderton W. K., Cooper C. E., Knowles R. G., Nitric oxide synthases: structure, function and inhibition. Biochemical Journal 2001 357 3 593 615 2-s2.0-0035425503 10.1042/0264-6021:3570593 (Pubitemid 32735142)
2. Daff S., NO synthase: structures and mechanisms. Nitric Oxide 2010 23 1 1 11 2-s2.0-77952240774 10.1016/j.niox.2010.03.001
3. Ji H., Tan S., Igarashi J., Huiying L., Derrick M., Martásek P., Roman L. J., Vasquez-Vivar J., Poulos T. L., Silverman R. B., Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy. Annals of Neurology 2009 65 2 209 217 2-s2.0-62549102043 10.1002/ana.21555
4. Loscalzo J., Welch G., Nitric oxide and its role in the cardiovascular system. Progress in Cardiovascular Diseases 1995 38 2 87 104 2-s2.0-0029091366 10.1016/S0033-0620(05)80001-5
5. Jaffrey S. R., Snyder S. H., Nitric oxide: a neural messenger. Annual Review of Cell and Developmental Biology 1995 11 417 440 2-s2.0-0029619811 (Pubitemid 26019610)
6. Bogdan C., Nitric oxide and the immune response. Nature Immunology 2001 2 10 907 916 2-s2.0-0034769118 10.1038/ni1001-907 (Pubitemid 32976162)
7. Hobbs A. J., Higgs A., Moncada S., Inhibition of nitric oxide synthase as a potential therapeutic target. Annual Review of Pharmacology and Toxicology 1999 39 191 220 2-s2.0-0032948112 10.1146/annurev.pharmtox.39.1.191 (Pubitemid 29222557)
8. Tinker A. C., Wallace A. V., Selective inhibitors of inducible nitric oxide synthase: potential agents for the treatment of inflammatory diseases? Current Topics in Medicinal Chemistry 2006 6 2 77 92 2-s2.0-33646169337 10.2174/156802606775270297
9. Silverman R. B., Design of selective neuronal nitric oxide synthase inhibitors for the prevention and treatment of neurodegenerative diseases. Accounts of Chemical Research 2009 42 3 439 451 2-s2.0-65249163408 10.1021/ar800201v
10. Madaford S., Annedi S. C., Ramnauth J., Rakhit S., Macor J. E., Advancements in the development of nitric oxide synthase inhibitors. Annual Reports in Medicinal Chemistry 2009 Elsevier 27 50
11. Garcin E. D., Arvai A. S., Rosenfeld R. J., Kroeger M. D., Crane B. R., Andersson G., Andrews G., Hamley P. J., Mallinder P. R., Nicholls D. J., St-Gallay S. A., Tinker A. C., Gensmantel N. P., Mete A., Cheshire D. R., Connolly S., Stuehr D. J., Åberg A., Wallace A. V., Tainer J. A., Getzoff E. D., Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nature Chemical Biology 2008 4 11 700 707 2-s2.0-54249114838 10.1038/nchembio.115
12. Ji H., Li H., Martásek P., Roman L. J., Poulos T. L., Silverman R. B., Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping. Journal of Medicinal Chemistry 2009 52 3 779 797 2-s2.0-61449263657 10.1021/jm801220a
13. Bedford M. T., Clarke S. G., Protein arginine methylation in mammals: who, what, and why. Molecular Cell 2009 33 1 1 13 2-s2.0-58149295717 10.1016/j.molcel.2008.12.013
14. Palmer R. M. J., Rees D. D., Ashton D. S., Moncada S., L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochemical and Biophysical Research Communications 1988 153 3 1251 1256 2-s2.0-0024300153
15. Sakuma I., Stuehr D. J., Gross S. S., Nathan C., Levi R., Identification of arginine as a precursor of endothelium-derived relaxing factor. Proceedings of the National Academy of Sciences of the United States of America 1988 85 22 8664 8667 2-s2.0-0024259715 (Pubitemid 19025017)
16. Aisaka K., Gross S. S., Griffith O. W., Levi R., N(G)-methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochemical and Biophysical Research Communications 1989 160 2 881 886 2-s2.0-0024475102 (Pubitemid 19140604)
17. Lowenstein C. J., Dinerman J. L., Snyder S. H., Nitric oxide: a physiologic messenger. Annals of Internal Medicine 1994 120 3 227 237 2-s2.0-0028178506 (Pubitemid 24038808)
18. Calver A., Collier J., Vallance P., Nitric oxide and cardiovascular control. Experimental Physiology 1993 78 3 303 326 2-s2.0-0027276333 (Pubitemid 23179039)
19. Zhang J., Snyder S. H., Nitric-oxide in the nervous-system. Annual Review of Pharmacology and Toxicology 1995 35 213 233 10.1146/annurev.pa.35.040195. 001241
20. Reif D. W., McCreedy S. A., N-Nitro-L-arginine and N-monomethyl-L- arginine exhibit a different pattern of inactivation toward the three nitric oxide synthases. Archives of Biochemistry and Biophysics 1995 320 1 170 176 2-s2.0-0028978149 10.1006/abbi.1995.1356
21. Olken N. M., Osawa Y., Marletta M. A., Characterization of the inactivation of nitric oxide synthase by N(G)- methyl-L-arginine: evidence for heme loss. Biochemistry 1994 33 49 14784 14791 2-s2.0-0028567798 10.1021/bi00253a017
22. Griffith O. W., Kilbourn R. G., Kartsatos A. G., Nitric oxide synthase inhibitors: amino acids. Nitric Oxide, Part A: Sources and Detection of No; No Synthase 1996 268 San Diego Academic Press 375 392 Methods in Enzymology (Pubitemid 26286380)
23. McDonald K. K., Rouhani R., Handlogten M. E., Block E. R., Griffith O. W., Allison R. D., Kilberg M. S., Inhibition of endothelial cell amino acid transport System y+ by arginine analogs that inhibit nitric oxide synthase. Biochimica et Biophysica Acta. Biomembranes 1997 1324 1 133 141 2-s2.0-0031057320 10.1016/S0005-2736(96)00226-X (Pubitemid 27076769)
24. Schwartz S., Clare R., Devereux K., Fook Sheung C., Pharmacokinetics, disposition and metabolism of 546C88 (L-N(G)- methylarginine hydrochloride) in rat and dog. Xenobiotica 1997 27 12 1259 1271 2-s2.0-0031446854 10.1080/004982597239840 (Pubitemid 28060078)
25. Maurer T. S., Mishra Y., Fung H. L., Nonlinear pharmacokinetics of L-N-G-methyl-arginine in rats: characterization by an improved HPLC assay. Biopharmaceutics & Drug Disposition 1999 20 8 397 400 (Pubitemid 30449779)
26. Ueno S. I., Sano A., Kotani K., Kondoh K., Kakimoto Y., Distribution of free methylarginines in rat tissues and in the bovine brain. Journal of Neurochemistry 1992 59 6 2012 2016 2-s2.0-0026499647
27. Hussein Z., Beerahee M., Grover R., Jordan B., Jeffs R., Donaldson J., Zaccardelli D., Colice G., Guntupalli K., Watson D., Vincent J. L., Pharmacokinetics of the nitric oxide synthase inhibitor L-N(G)- methylarginine hydrochloride in patients with septic shock. Clinical Pharmacology and Therapeutics 1999 65 1 1 9 2-s2.0-0032892009 10.1016/S0009-9236(99)70116-5 (Pubitemid 29062023)
28. Umans J. G., Levi R., Nitric oxide in the regulation of blood flow and arterial pressure. Annual Review of Physiology 1995 57 771 790 2-s2.0-0028935790
29. Kilbourn R. G., Jubran A., Gross S. S., Griffith O. W., Levi R., Adams J., Lodato R. F., Reversal of endotoxin-mediated shock by N(G)-methyl-L- arginine, an inhibitor of nitric oxide synthesis. Biochemical and Biophysical Research Communications 1990 172 3 1132 1138 2-s2.0-0025242299 10.1016/0006-291X(90)91565-A
30. Kilbourn R. G., Gross S. S., Jubran A., Adams J., Griffith O. W., Levi R., Lodato R. F., N(G)-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proceedings of the National Academy of Sciences of the United States of America 1990 87 9 3629 3632 2-s2.0-0025195627 10.1073/pnas.87.9.3629 (Pubitemid 20173690)
31. Kilbourn R. G., Szabó C., Traber D. L., Beneficial versus detrimental effects of nitric oxide synthase inhibitors in circulatory shock: lessons learned from experimental and clinical studies. Shock 1997 7 4 235 246 2-s2.0-0031112190 (Pubitemid 127654274)
32. Haynes W. G., Noon J. P., Walker B. R., Webb D. J., Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. Journal of Hypertension 1993 11 12 1375 1380 2-s2.0-0027739308 (Pubitemid 24008485)
33. Stamler J. S., Loh E., Roddy M. A., Currie K. E., Creager M. A., Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 1994 89 5 2035 2040 2-s2.0-0028314525 (Pubitemid 24142778)
34. Nyberg M., Mortensen S. P., Saltin B., Hellsten Y., Bangsbo J., Low blood flow at onset of moderate-intensity exercise does not limit muscle oxygen uptake. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2010 298 3 R843 R848 2-s2.0-77749323238 10.1152/ajpregu.00730.2009
35. Petros A., Bennett D., Vallance P., Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 1991 338 8782-8783 1557 1558 2-s2.0-0026346162
36. Petros A., Lamb G., Leone A., Moncada S., Bennett D., Vallance P., Effects of a nitric oxide synthase inhibitor in human with septic shock. Cardiovascular Research 1994 28 1 34 39 2-s2.0-0028155913
37. Grover R., Zaccardelli D., Colice G., Guntupalli K., Watson D., Vincent J. L., An open-label dose escalation study of the nitric oxide synthase inhibitor, N(G)-methyl-L-arginine hydrochloride (546C88), in patients with septic shock. Critical Care Medicine 1999 27 5 913 922 2-s2.0-0032990946 10.1097/00003246-199905000-00025 (Pubitemid 29266008)
38. Bakker J., Grover R., McLuckie A., Holzapfel L., Andersson J., Lodato R., Watson D., Grossman S., Donaldson J., Takala J., Administration of the nitric oxide synthase inhibitor NG-methyl- L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Critical Care Medicine 2004 32 1 1 12 2-s2.0-9144220131 (Pubitemid 38125557)
39. Watson D., Grover R., Anzueto A., Lorente J., Smithies M., Bellomo R., Guntupalli K., Grossman S., Donaldson J., Le Gall J. R., Cardiovascular effects of the nitric oxide synthase inhibitor N G-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Critical Care Medicine 2004 32 1 13 20 2-s2.0-9144268892 (Pubitemid 38125558)
40. López A., Lorente J. A., Steingrub J., Bakker J., McLuckie A., Willatts S., Brockway M., Anzueto A., Holzapfel L., Breen D., Silverman M. S., Takala J., Donaldson J., Arneson C., Grove G., Grossman S., Grover R., Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Critical Care Medicine 2004 32 1 21 30 2-s2.0-4444273012 (Pubitemid 38125559)
41. Lassen L. H., Ashina M., Christiansen I., Ulrich V., Grover R., Donaldson J., Olesen J., Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks. Cephalalgia 1998 18 1 27 32 2-s2.0-0031907881 10.1046/j.1468-2982.1998.1801027.x (Pubitemid 28096515)
42. Ashina M., Lassen L. H., Bendtsen L., Jensen R., Olesen J., Effect of inhibition of nitric oxide synthase on chronic tension-type headache: a randomised crossover trial. Lancet 1999 353 9149 287 289 2-s2.0-0033026309 10.1016/S0140-6736(98)01079-4 (Pubitemid 29088122)
43. Lassen L. H., Christiansen I., Iversen H. K., Jansen-Olesen I., Olesen J., The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs. Cephalalgia 2003 23 9 877 886 2-s2.0-0242298670 10.1046/j.1468-2982.2003.00586.x (Pubitemid 37352624)
44. Hjorth Lassen L., Klingenberg Iversen H., Olesen J., A dose-response study of nitric oxide synthase inhibition in different vascular beds in man. European Journal of Clinical Pharmacology 2003 59 7 499 505 2-s2.0-0242266405 10.1007/s00228-003-0662-7 (Pubitemid 37363561)
45. Lassen L. H., Sperling B., Andersen A. R., Olesen J., The effect of i.v. L-NG methylarginine hydrochloride (L-NMMA: 546C88) on basal and acetazolamide (Diamox) induced changes of blood velocity in cerebral arteries and regional cerebral blood flow in man. Cephalalgia 2005 25 5 344 352 2-s2.0-17644363043 10.1111/j.1468-2982.2004.00862.x (Pubitemid 40559416)
46. Vallance P., Leone A., Calver A., Collier J., Moncada S., Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992 339 8793 572 575 2-s2.0-0026548912 10.1016/0140-6736(92)90865-Z
47. Vallance P., Leone A., Calver A., Collier J., Moncada S., Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. Journal of Cardiovascular Pharmacology 1992 20 12 S60 S62 2-s2.0-0027087177 (Pubitemid 23014109)
48. Böger R. H., Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor. Journal of Nutrition 2004 134 10 S2842 S2847 2-s2.0-4744339386
49. Komori Y., Wallace G. C., Fukuto J. M., Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage by L-arginine analogs. Archives of Biochemistry and Biophysics 1994 315 2 213 218 2-s2.0-0028110435 10.1006/abbi.1994.1492 (Pubitemid 24381536)
50. Cardounel A. J., Zweier J. L., Endogenous methylarginines regulate neuronal nitric-oxide synthase and prevent excitotoxic injury. Journal of Biological Chemistry 2002 277 37 33995 34002 2-s2.0-0037072804 10.1074/jbc.M108983200
51. Kielstein J. T., Zoccali C., Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age? American Journal of Kidney Diseases 2005 46 2 186 202 2-s2.0-22844442784 10.1053/j.ajkd.2005.05.009 (Pubitemid 41040347)
52. Böger R. H., The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor. Cardiovascular Research 2003 59 4 824 833 2-s2.0-0842347848 10.1016/S0008-6363(03)00500-5 (Pubitemid 38366238)
53. Teerlink T., Luo Z., Palm F., Wilcox C. S., Cellular ADMA: regulation and action. Pharmacological Research 2009 60 6 448 460 2-s2.0-70350048649 10.1016/j.phrs.2009.08.002
54. Vallance P., Leiper J., Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arteriosclerosis, Thrombosis, and Vascular Biology 2004 24 6 1023 1030 2-s2.0-2942577486 10.1161/01.ATV.0000128897.54893.26 (Pubitemid 38737826)
55. Wolf S. S., The protein arginine methyltransferase family: an update about function, new perspectives and the physiological role in humans. Cellular and Molecular Life Sciences 2009 66 13 2109 2121 2-s2.0-67649968054 10.1007/s00018-009-0010-x
56. Moore P. K., Al-Swayeh O. A., Chong N. W. S., Evans R. A., Gibson A., L-N(G)-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. British Journal of Pharmacology 1990 99 2 408 412 2-s2.0-0025194144 (Pubitemid 20147541)
57. Rees D. D., Palmer R. M. J., Schulz R., Hodson H. F., Moncada S., Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. British Journal of Pharmacology 1990 101 3 746 752 2-s2.0-0025011716 (Pubitemid 20357206)
58. Furfine E. S., Selective inhibition of constitutive nitric oxide synthase by L-NG-nitroarginine. Biochemistry 1993 32 33 8512 8517 2-s2.0-0027184034 (Pubitemid 23270433)
59. Moore W. M., Webber R. K., Fok K. F., Jerome G. M., Kornmeier C. M., Tjoeng F. S., Currie M. G., Inhibitors of human nitric oxide synthase isoforms with the carbamidine moiety as a common structural element. Bioorganic and Medicinal Chemistry 1996 4 9 1559 1564 2-s2.0-0029738974 10.1016/0968-0896(96) 00148-4 (Pubitemid 26320005)
60. Furfine E. S., Harmon M. F., Paith J. E., Knowles R. G., Salter M., Kiff R. J., Duffy C., Hazelwood R., Oplinger J. A., Garvey E. P., Potent and selective inhibition of human nitric oxide synthases. Selective inhibition of neuronal nitric oxide synthase by S-methyl-L-thiocitrulline and S-ethyl-L-thiocitrulline. Journal of Biological Chemistry 1994 269 43 26677 26683 2-s2.0-0027967765
61. Klatt P., Schmidt K., Brunner F., Mayer B., Inhibitors of brain nitric oxide synthase. Binding kinetics, metabolism, and enzyme inactivation. Journal of Biological Chemistry 1994 269 3 1674 1680 2-s2.0-0028140141
62. Schmidt K., Klatt P., Mayer B., Characterization of endothelial cell amino acid transport systems involved in the actions of nitric oxide synthase inhibitors. Molecular Pharmacology 1993 44 3 615 621 2-s2.0-0027268315 (Pubitemid 23280274)
63. Kubes P., Suzuki M., Granger D. N., Nitric oxide: an endogenous modulator of leukocyte adhesion. Proceedings of the National Academy of Sciences of the United States of America 1991 88 11 4651 4655 2-s2.0-0025731835 (Pubitemid 21914599)
64. Dawson V. L., Dawson T. M., Bartley D. A., Uhl G. R., Snyder S. H., Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. Journal of Neuroscience 1993 13 6 2651 2661 2-s2.0-0027178135 (Pubitemid 23151779)
65. Boje K. M., Arora P. K., Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Research 1992 587 2 250 256 2-s2.0-0026702955 10.1016/0006-8993(92)91004-X
66. Papapetropoulos A., García-Cardeña G., Madri J. A., Sessa W. C., Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. Journal of Clinical Investigation 1997 100 12 3131 3139 2-s2.0-2642597076 (Pubitemid 28022851)
67. Ziche M., Morbidelli L., Masini E., Amerini S., Granger H. J., Maggi C. A., Geppetti P., Ledda F., Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. Journal of Clinical Investigation 1994 94 5 2036 2044 2-s2.0-0028143547 (Pubitemid 24348244)
68. Balligand J. L., Kelly R. A., Marsden P. A., Smith T. W., Michel T., Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proceedings of the National Academy of Sciences of the United States of America 1993 90 1 347 351 2-s2.0-0027398455 10.1073/pnas.90.1.347 (Pubitemid 23010307)
69. Tabrizi-Fard M. A., Fung H. L., Pharmacokinetics and steady-state tissue distribution of L- and D-isomers of nitroarginine in rats. Drug Metabolism and Disposition 1996 24 11 1241 1246 2-s2.0-0030457690
70. Kidd E. J., Michel A. D., Humphrey P. P. A., Autoradiographic distribution of [3H]L-N(G)-Nitro-arginine binding in rat brain. Neuropharmacology 1995 34 1 63 73 2-s2.0-0028985893 10.1016/0028-3908(94)00132-C
71. Rao V. L. R., Butterworth R. F., Kinetics, pharmacology, and autoradiographic distribution of L-[3H]nitroarginine binding sites in rat cerebellum. Journal of Neurochemistry 1996 66 2 701 709 2-s2.0-0030039680
72. Pfeiffer S., Leopold E., Schmidt K., Brunner F., Mayer B., Inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME): requirement for bioactivation to the free acid, N(G)-nitro-L-arginine. British Journal of Pharmacology 1996 118 6 1433 1440 2-s2.0-0029888810 (Pubitemid 26248796)
73. Frandsen U., Bangsbo J., Sander M., Hüffner L., Betak A., Saltin B., Hellsten Y., Exercise-induced hyperaemia and leg oxygen uptake are not altered during effective inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester in humans. Journal of Physiology 2001 531 1 257 264 2-s2.0-0035865222 10.1111/j.1469-7793.2001.0257j.x (Pubitemid 32178042)
74. Avontuur J. A. M., Buijk S. L. C. E., Bruining H. A., Distribution and metabolism of N(G)-nitro-L-arginine methyl ester in patients with septic shock. European Journal of Clinical Pharmacology 1998 54 8 627 631 2-s2.0-0031795041 10.1007/s002280050525 (Pubitemid 28531424)
75. Zhang H. Q., Fast W., Marletta M. A., Martasek P., Silverman R. B., Potent and selective inhibition of neuronal nitric oxide synthase by N(ω)-propyl-L-arginine. Journal of Medicinal Chemistry 1997 40 24 3869 3870 2-s2.0-0030731240 10.1021/jm970550g (Pubitemid 27512303)
76. Zhang H. Q., Dixon R. P., Marletta M. A., Nikolic D., Van Breemen R., Silverman R. B., Mechanism of inactivation of neuronal nitric oxide synthase by N(ω)-allyl-L-arginine. Journal of the American Chemical Society 1997 119 45 10888 10902 2-s2.0-0030700932 10.1021/ja964160f (Pubitemid 27528834)
77. Olken N. M., Marietta M. A., NG-allyl- and NG-cyclopropyl-L-arginine: two novel inhibitors of macrophage nitric oxide synthase. Journal of Medicinal Chemistry 1992 35 6 1137 1144 2-s2.0-0026611295
78. Wolff D. J., Lubeskie A., Inactivation of nitric oxide synthase isoforms by diaminoguanidine and NG-amino-L-arginine. Archives of Biochemistry and Biophysics 1996 325 2 227 234 2-s2.0-0030053008 10.1006/abbi.1996.0028
79. Huang H., Martasek P., Roman L. J., Masters B. S. S., Silverman R. B., N(ω)-nitroarginine-containing dipeptide amides. Potent and highly selective inhibitors of neuronal nitric oxide synthase. Journal of Medicinal Chemistry 1999 42 16 3147 3153 2-s2.0-0033549862 10.1021/jm990111c (Pubitemid 29384050)
80. Silverman R. B., Huang H., Marletta M. A., Martasek P., Selective inhibition of neuronal nitric oxide synthase by N(ω)- nitroarginine- and phenylalanine-containing dipeptides and dipeptide esters. Journal of Medicinal Chemistry 1997 40 18 2813 2817 2-s2.0-0030773013 10.1021/jm970200u (Pubitemid 27382531)
81. Ji H., Gómez-Vidal J. A., Martásek P., Roman L. J., Silverman R. B., Conformationally restricted dipeptide amides as potent and selective neuronal nitric oxide synthase inhibitors. Journal of Medicinal Chemistry 2006 49 21 6254 6263 2-s2.0-33750121507 10.1021/jm0604124 (Pubitemid 44595202)
82. Hah J. M., Roman L. J., Martásek P., Silverman R. B., Reduced amide bond peptidomimetics. (4S)-N-(4-amino-5-[aminoalkyl]aminopentyl)-N′- nitroguanidines, potent and highly selective inhibitors of neuronal nitric oxide synthase. Journal of Medicinal Chemistry 2001 44 16 2667 2670 2-s2.0-0035797359 10.1021/jm0101491 (Pubitemid 32852155)
83. Hah J. M., Martásek P., Roman L. J., Silverman R. B., Aromatic reduced amide bond peptidomimetics as selective inhibitors of neuronal nitric oxide synthase. Journal of Medicinal Chemistry 2003 46 9 1661 1669 2-s2.0-0344088452 10.1021/jm0202932 (Pubitemid 36444219)
84. Park J. M., Higuchi T., Kikuchi K., Urano Y., Hori H., Nishino T., Aoki J., Inoue K., Nagano T., Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides. British Journal of Pharmacology 2001 132 8 1876 1882 2-s2.0-0035039121 (Pubitemid 32397980)
85. Babu B. R., Griffith O. W., N5-(1-imino-3-butenyl)-L-ornithine. A neuronal isoform selective mechanism-based inactivator of nitric oxide synthase. Journal of Biological Chemistry 1998 273 15 8882 8889 2-s2.0-0032502351 10.1074/jbc.273.15.8882 (Pubitemid 28176170)
86. Litzinger E. A., Martásek P., Roman L. J., Silverman R. B., Design, synthesis, and biological testing of potential heme-coordinating nitric oxide synthase inhibitors. Bioorganic and Medicinal Chemistry 2006 14 9 3185 3198 2-s2.0-33644979237 10.1016/j.bmc.2005.12.043
87. Young R. J., Beams R. M., Carter K., Clark H. A. R., Coe D. M., Chambers C. L., Davies P. I., Dawson J., Drysdale M. J., Franzman K. W., French C., Hodgson S. T., Hodson H. F., Kleanthous S., Rider P., Sanders D., Sawyer D. A., Scott K. J., Shearer B. G., Stocker R., Smith S., Tackley M. C., Knowles R. G., Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine. Bioorganic and Medicinal Chemistry Letters 2000 10 6 597 600 2-s2.0-0034689418 10.1016/S0960-894X(00)00055-X (Pubitemid 30162468)
88. Alderton W. K., Angell A. D. R., Craig C., Dawson J., Garvey E., Moncada S., Monkhouse J., Rees D., Russell L. J., Russell R. J., Schwartz S., Waslidge N., Knowles R. G., GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo. British Journal of Pharmacology 2005 145 3 301 312 2-s2.0-21244458471 10.1038/sj.bjp.0706168 (Pubitemid 40896075)
89. Ijuin R., Umezawa N., Higuchi T., Design, synthesis, and evaluation of new type of l-amino acids containing pyridine moiety as nitric oxide synthase inhibitor. Bioorganic and Medicinal Chemistry 2006 14 10 3563 3570 2-s2.0-33645861976 10.1016/j.bmc.2006.01.020
90. Ulhaq S., Chinje E. C., Naylor M. A., Jaffar M., Stratford I. J., Threadgill M. D., S-2-Amino-5-azolylpentanoic acids related to L-ornithine as inhibitors of the isoforms of nitric oxide synthase (NOS). Bioorganic and Medicinal Chemistry 1998 6 11 2139 2149 2-s2.0-0031791189 10.1016/S0968-0896(98) 00174-6 (Pubitemid 28540762)
91. Ulhaq S., Chinje E. C., Naylor M. A., Jaffar M., Stratford I. J., Threadgill M. D., Heterocyclic analogues of L-citrulline as inhibitors of the isoforms of nitric oxide synthase (NOS) and identification of N(δ)-(4,5-dihydrothiazol-2-yl)ornithine as a potent inhibitor. Bioorganic and Medicinal Chemistry 1999 7 9 1787 1796 2-s2.0-0032874388 10.1016/S0968-0896(99)00136-4 (Pubitemid 29457675)
92. Scheer M., Grote A., Chang A., Schomburg I., Munaretto C., Rother M., Söhngen C., Stelzer M., Thiele J., Schomburg D., BRENDA, the enzyme information system in 2011. Nucleic Acids Research 2011 39 1 D670 D676 2-s2.0-78651330012 10.1093/nar/gkq1089
93. Babu B. R., Griffith O. W., Design of isoform-selective inhibitors of nitric oxide synthase. Current Opinion in Chemical Biology 1998 2 4 491 500 2-s2.0-0032133353 (Pubitemid 128645702)
94. Garvey E. P., Oplinger J. A., Tanoury G. J., Sherman P. A., Fowler M., Marshall S., Harmon M. F., Paith J. E., Furfine E. S., Potent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas. Journal of Biological Chemistry 1994 269 43 26669 26676 2-s2.0-0028089793
95. Hagen T. J., Bergmanis A. A., Kramer S. W., Fok K. F., Schmelzer A. E., Pitzele B. S., Swenton L., Jerome G. M., Kornmeier C. M., Moore W. M., Branson L. F., Connor J. R., Manning P. T., Currie M. G., Hallinan E. A., 2-Iminopyrrolidines as potent and selective inhibitors of human inducible nitric oxide synthase. Journal of Medicinal Chemistry 1998 41 19 3675 3683 2-s2.0-15144344799 10.1021/jm970840x (Pubitemid 28449349)
96. Collins J. L., Shearer B. G., Oplinger J. A., Lee S., Garvey E. P., Salter M., Duffy C., Burnette T. C., Furfine E. S., N-phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity. Journal of Medicinal Chemistry 1998 41 15 2858 2871 2-s2.0-0031853450 10.1021/jm980072p (Pubitemid 28350350)
97. Seo J., Martásek P., Roman L. J., Silverman R. B., Selective l-nitroargininylaminopyrrolidine and l-nitroargininylaminopiperidine neuronal nitric oxide synthase inhibitors. Bioorganic and Medicinal Chemistry 2007 15 5 1928 1938 2-s2.0-33846562999 10.1016/j.bmc.2007.01.001 (Pubitemid 46176635)
98. Sonntag M., Deussen A., Schrader J., Role of nitric oxide in local blood flow control in the anaesthetized dog. Pflugers Archiv European Journal of Physiology 1992 420 2 194 199 2-s2.0-0026537663
99. Van Buren G. A., Yang D., Clark K. E., Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis. American Journal of Obstetrics and Gynecology 1992 167 3 828 833 2-s2.0-0026808863
100. Vials A., Burnstock G., Effects of nitric oxide synthase inhibitors, L-N(G)-nitroarginine and L-N(G)-nitroarginine methyl ester, on responses to vasodilators of the guinea-pig coronary vasculature. British Journal of Pharmacology 1992 107 2 604 609 2-s2.0-0026774775
101. Lorente J. A., Landin L., De Pablo R., Renes E., Liste D., L-arginine pathway in the sepsis syndrome. Critical Care Medicine 1993 21 9 1287 1295 2-s2.0-0027304372 (Pubitemid 23270497)
102. Avontuur J. A. M., Tutein Nolthenius R. P., Van Bodegom J. W., Bruining H. A., Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical study. Critical Care Medicine 1998 26 4 660 667 2-s2.0-0031892252 10.1097/00003246-199804000-00012 (Pubitemid 28201411)
103. Yates D. H., Kharitonov S. A., Thomas P. S., Barnes P. J., Endogenous nitric oxide is decreased in asthmatic patients by an inhibitor of inducible nitric oxide synthase. American Journal of Respiratory and Critical Care Medicine 1996 154 1 247 250 2-s2.0-0030017086 (Pubitemid 26255797)
104. Fast W., Levsky M. E., Marletta M. A., Silverman R. B., N(ω)-Propargyl-L-arginine and N(ω)-hydroxy-N(ω)-propargyl-L- arginine are inhibitors, but not activators, of neuronal and macrophage nitric oxide synthases. Bioorganic and Medicinal Chemistry 1997 5 8 1601 1608 2-s2.0-0030879495 10.1016/S0968-0896(97)00109-0 (Pubitemid 27389342)
105. Raoul C., Estévez A. G., Nishimune H., Cleveland D. W., DeLapeyrière O., Henderson C. E., Haase G., Pettmann B., Motoneuron death triggered by a specific pathway downstream of fas: potentiation by ALS-linked SOD1 mutations. Neuron 2002 35 6 1067 1083 2-s2.0-0037068836 10.1016/S0896-6273(02)00905-4 (Pubitemid 35279535)
106. Caron M. H., Alling C., Role of nitric oxide in ethanol-induced up-regulation of muscarinic acetylcholine receptors in SH-SY5Y cells. Alcoholism: Clinical and Experimental Research 2001 25 8 1107 1113 2-s2.0-0034878787 (Pubitemid 32758461)
107. Cooper G. R., Mialkowski K., Wolff D. J., Cellular and enzymatic studies of N(ω)-propyl-L-arginine and S-ethyl-N- [4-(trifluoromethyl)phenyl] isothiourea as reversible, slowly dissociating inhibitors selective for the neuronal nitric oxide synthase isoform. Archives of Biochemistry and Biophysics 2000 375 1 183 194 2-s2.0-0034161786 10.1006/abbi.1999.1658 (Pubitemid 30133638)
108. Oceandy D., Cartwright E. J., Emerson M., Prehar S., Baudoin F. M., Zi M., Alatwi N., Venetucci L., Schuh K., Williams J. C., Armesilla A. L., Neyses L., Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b. Circulation 2007 115 4 483 492 2-s2.0-33846605594 10.1161/CIRCULATIONAHA.106.643791 (Pubitemid 46184200)
109. Isaak A., Ellrich J., Neuronal nitric oxide synthase is involved in the induction of nerve growth factor-induced neck muscle nociception. Headache 2011 51 5 734 743 2-s2.0-79955480851 10.1111/j.1526-4610.2011.01854.x
110. Klamer D., Engel J. A., Svensson L., The neuronal selective nitric oxide synthase inhibitor, N ω -propyl-l-arginine, blocks the effects of phencyclidine on prepulse inhibition and locomotor activity in mice. European Journal of Pharmacology 2004 503 13 103 107 2-s2.0-7444263402 10.1016/j.ejphar.2004.09.042 (Pubitemid 39445949)
111. Kellogg D. L., Zhao J. L., Wu Y., Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans. Journal of Applied Physiology 2009 107 5 1438 1444 2-s2.0-72749109102 10.1152/japplphysiol.00690.2009
112. Fukuto J. M., Wood K. S., Byrns R. E., Ignarro L. J., N(G)-Amino-L-arginine: a new potent antagonist of L-arginine-mediated endothelium-dependent relaxation. Biochemical and Biophysical Research Communications 1990 168 2 458 465 2-s2.0-0025195583 10.1016/0006-291X(90)92343-X (Pubitemid 20164564)
113. Gross S. S., Stuehr D. J., Aisaka K., Jaffe E. A., Levi R., Griffith O. W., Macrophage and endothelial cell nitric oxide synthesis: cell-type selective inhibition by N(G)-aminoarginine, N(G)-nitroarginine and N(G)-methylarginine. Biochemical and Biophysical Research Communications 1990 170 1 96 103 2-s2.0-0025046968 10.1016/0006-291X(90)91245-N (Pubitemid 20249390)
114. Hecker M., Walsh D. T., Vane J. R., On the substrate specificity of nitric oxide synthase. FEBS Letters 1991 294 3 221 224 2-s2.0-0026060469 10.1016/0014-5793(91)81434-A
115. Silverman R. B., Huang H., Zhang H. Q., Inhibition of nitric oxide synthase by amino acids and dipeptides. USA patent US6274557B1, Northwestern University, Evanston, Ill, USA, 2001
116. Silverman R. B., Selective neuronal nitric oxide synthase inhibitors. USA patent WO03000198(A2), Northwestern University, 2003
117. Kobayashi N., Higuchi T., Hirobe M., Nagano T., Selective inhibitor for nitrogen monooxide synthase. Dainippon Pharmaceutical, Japan patent JP10237097(A), 1998
118. Kobayashi N., Higuchi T., Urano Y., Kikuchi K., Hirobe M., Nagano T., Dipeptides containing L-arginine analogs: new isozyme-selective inhibitors of nitric oxide synthase. Biological and Pharmaceutical Bulletin 1999 22 9 936 940 2-s2.0-0032820128 (Pubitemid 29482903)
119. Rogers N. E., Ignarro L. J., Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. Biochemical and Biophysical Research Communications 1992 189 1 242 249 2-s2.0-0027096817 10.1016/0006-291X(92)91550-A (Pubitemid 23030033)
120. Narayanan K., Griffith O. W., Synthesis of L-thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline: a new class of potent nitric oxide synthase inhibitors. Journal of Medicinal Chemistry 1994 37 7 885 887 2-s2.0-0028314083 (Pubitemid 24140857)
121. Frey C., Narayanan K., McMillan K., Spack L., Gross S. S., Masters B. S., Griffith O. W., L-thiocitrulline: a stereospecific, heme-binding inhibitor of nitric- oxide synthases. Journal of Biological Chemistry 1994 269 42 26083 26091 2-s2.0-0028172940
122. Narayanan K., Spack L., McMillan K., Kilbourn R. G., Hayward M. A., Masters B. S. S., Griffith O. W., S-alkyl-L-thiocitrullines. Potent stereoselective inhibitors of nitric oxide synthase with strong pressor activity in vivo. Journal of Biological Chemistry 1995 270 19 11103 11110 2-s2.0-0029078058 10.1074/jbc.270.19.11103
123. Ijuin R., Umezawa N., Nagai S. I., Higuchi T., Evaluation of 3-substituted arginine analogs as selective inhibitors of human nitric oxide synthase isozymes. Bioorganic and Medicinal Chemistry Letters 2005 15 11 2881 2885 2-s2.0-19544379712 10.1016/j.bmcl.2005.03.078 (Pubitemid 40732239)
124. Zhang J., Xu M., Dence C. S., Sherman E. L. C., McCarthy T. J., Welch M. J., Synthesis, in vivo evaluation and PET study of a carbon-11 -labeled neuronal nitric oxide synthase (nNOS) inhibitor S-Methyl-L-thiocitrulline. Journal of Nuclear Medicine 1997 38 8 1273 1278 2-s2.0-0030878787
125. Zanzinger J., Czachurski J., Seller H., Neuronal nitric oxide reduces sympathetic excitability by modulation of central glutamate effects in pigs. Circulation Research 1997 80 4 565 571 2-s2.0-0030898206 (Pubitemid 27137294)
126. Kelley J. B., Anderson K. L., Altmann S. L., Itzhak Y., Long-term memory of visually cued fear conditioning: roles of the neuronal nitric oxide synthase gene and cyclic AMP response element-binding protein. Neuroscience 2011 174 91 103 2-s2.0-78650956136 10.1016/j.neuroscience.2010.11.005
127. Ichihara A., Inscho E. W., Imig J. D., Navar L. G., Neuronal nitric oxide synthase modulates rat renal microvascular function. American Journal of Physiology, Renal Physiology 1998 274 3 F516 F524 2-s2.0-0031945589
128. Komers R., Oyama T. T., Chapman J. G., Allison K. M., Anderson S., Effects of systemic inhibition of neuronal nitric oxide synthase in diabetic rats. Hypertension 2000 35 2 655 661 2-s2.0-0033952017 (Pubitemid 30108164)
129. Komers R., Lindsley J. N., Oyama T. T., Allison K. M., Anderson S., Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes. American Journal of Physiology, Renal Physiology 2000 279 3 F573 F583 2-s2.0-0033829947
130. McCall T. B., Feelisch M., Palmer R. M. J., Moncada S., Identification of N-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. British Journal of Pharmacology 1991 102 1 234 238 2-s2.0-0025804605
131. Moore W. M., Webber R. K., Jerome G. M., Tjoeng F. S., Misko T. P., Currie M. G., L-N6-(1-Iminoethyl)lysine: a selective inhibitor of inducible nitric oxide synthase. Journal of Medicinal Chemistry 1994 37 23 3886 3888 2-s2.0-0028173010 (Pubitemid 24379677)
132. Hallinan E. A., Tsymbalov S., Dorn C. R., Pitzele B. S., Hansen D. W., Moore W. M., Jerome G. M., Connor J. R., Branson L. F., Widomski D. L., Zhang Y., Currie M. G., Manning P. T., Synthesis and biological characterization of L-N6-(1-iminoethyl)lysine 5-tetrazole-amide, a prodrug of a selective iNOS inhibitor. Journal of Medicinal Chemistry 2002 45 8 1686 1689 2-s2.0-0037061608 10.1021/jm010420e (Pubitemid 34293534)
133. Assreuy J., Cunha F. Q., Epperlein M., Noronha-Dutra A., O'Donnell C. A., Liew F. Y., Moncada S., Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major. European Journal of Immunology 1994 24 3 672 676 2-s2.0-0028222669 (Pubitemid 24076634)
134. De Graaf J. C., Banga J. D., Moncada S., Palmer R. M. J., De Groot P. G., Sixma J. J., Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation 1992 85 6 2284 2290 2-s2.0-0026639191
135. Jenkins D. C., Charles I. G., Thomsen L. L., Moss D. W., Holmes L. S., Baylis S. A., Rhodes P., Westmore K., Emson P. C., Moncada S., Roles of nitric oxide in tumor growth. Proceedings of the National Academy of Sciences of the United States of America 1995 92 10 4392 4396 2-s2.0-0029079394
136. Duffield J. S., Erwig L. P., Wei X. Q., Liew F. Y., Rees A. J., Savill J. S., Activated macrophages direct apoptosis and suppress mitosis of mesangial cells. Journal of Immunology 2000 164 4 2110 2119 2-s2.0-0034652020 (Pubitemid 30108770)
137. Brahmachari S., Fung Y. K., Pahan K., Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. Journal of Neuroscience 2006 26 18 4930 4939 2-s2.0-33646947850 10.1523/JNEUROSCI.5480-05.2006 (Pubitemid 44315335)
138. Zhang J. Y., Wang Y., Milton M. N., Kraus L., Breau A. P., Paulson S. K., Disposition and Pharmacokinetics of L-N6-(1-Iminoethyl)Lysine-5-Tetrazole- Amide, a Selective iNOS Inhibitor, in Rats. Journal of Pharmaceutical Sciences 2004 93 5 1229 1240 2-s2.0-1942530736 10.1002/jps.20048 (Pubitemid 38529696)
139. Zhang J. Y., Wang Y. F., Milton M. N., Beconi M., Chang M., Yin D., Breau A. P., Paulson S. K., Pharmacokinetics, metabolism and excretion of an inhibitor of inducible nitric oxide synthase, L-NIL-TA, in dog. Xenobiotica 2003 33 11 1159 1171 2-s2.0-0345491346 10.1080/00498250310001609183 (Pubitemid 37500172)
140. László F., Whittle B. J. R., Actions of isoform-selective and non-selective nitric oxide synthase inhibitors on endotoxin-induced vascular leakage in rat colon. European Journal of Pharmacology 1997 334 1 99 102 2-s2.0-0342378148 10.1016/S0014-2999(97)01163-1 (Pubitemid 27417815)
141. Connor J. R., Manning P. T., Settle S. L., Moore W. M., Jerome G. M., Webber R. K., Siong Tjoeng F., Currie M. G., Suppression of adjuvant-induced arthritis by selective inhibition of inducible nitric oxide synthase. European Journal of Pharmacology 1995 273 1-2 15 24 2-s2.0-0028959180 10.1016/0014-2999(94)00672-T
142. Macmicking J. D., North R. J., Lacourse R., Mudgett J. S., Shah S. K., Nathan C. F., Identification of nitric oxide synthase as a protective locus against tuberculosis. Proceedings of the National Academy of Sciences of the United States of America 1997 94 10 5243 5248 2-s2.0-0031010661 10.1073/pnas.94.10.5243 (Pubitemid 27214768)
143. Salvemini D., Wang Z. Q., Wyatt P. S., Bourdon D. M., Marino M. H., Manning P. T., Currie M. G., Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. British Journal of Pharmacology 1996 118 4 829 838 2-s2.0-0029763960 (Pubitemid 26261251)
144. Pelletier J. P., Jovanovic D., Fernandes J. C., Reduced progression of experimental osteoarthritis in vivo by selective inhibition of inducible nitric oxide synthase. Arthritis & Rheumatism 1998 41 7 1275 1286 10.1002/1529-0131(199807)41:7<1275::AID-ART19>3.0.CO;2-T (Pubitemid 28313431)
145. Dumont M., Wille E., Calingasan N. Y., Nathan C., Beal M. F., Lin M. T., N-iminoethyl-l-lysine improves memory and reduces amyloid pathology in a transgenic mouse model of amyloid deposition. Neurochemistry International 2010 56 2 345 351 2-s2.0-77149163015 10.1016/j.neuint.2009.11.006
146. Crowell J. A., Steele V. E., Sigman C. C., Fay J. R., Is inducible nitric oxide synthase a target for chemoprevention? Molecular Cancer Therapeutics 2003 2 8 815 823 2-s2.0-2942686015
147. Eynott P. R., Groneberg D. A., Caramori G., Adcock I. M., Donnelly L. E., Kharitonov S., Barnes P. L., Chung K. F., Role of nitric oxide in allergic inflammation and bronchial hyperresponsiveness. European Journal of Pharmacology 2002 452 1 123 133 2-s2.0-0037183779 10.1016/S0014-2999(02)02237-9 (Pubitemid 35248132)
148. Neufeld A. H., Kawai S. I., Das S., Vora S., Gachie E., Connor J. R., Manning P. T., Loss of retinal ganglion cells following retinal ischemia: the role of inducible nitric oxide synthase. Experimental Eye Research 2002 75 5 521 528 2-s2.0-0036453054 10.1006/exer.2002.2042 (Pubitemid 35435607)
149. Hansel T. T., Kharitonov S. A., Donnelly L. E., Erin E. M., Currie M. G., Moore W. M., Manning P. T., Recker D. P., Barnes P. J., A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics. The FASEB Journal 2003 17 10 1298 1300 2-s2.0-0038604348
150. Hodson H. F., Palmer R. M. J., Sawyer D. A., Enzyme inhibitors. US patent WO9534534(A1), 1995
151. Baydoun A. R., Bertran J., Thakur S., Dawson J., Palacín M., Knowles R. G., y+ LAT-1 mediates transport of the potent and selective iNOS inhibitor, GW274150, in control J774 macrophages. Amino Acids 2006 31 2 101 109 2-s2.0-33747145643 10.1007/s00726-005-0311-9 (Pubitemid 44222572)
152. O'Brien A. J., Wilson A. J., Sibbald R., Singer M., Clapp L. H., Temporal variation in endotoxin-induced vascular hyporeactivity in a rat mesenteric artery organ culture model. British Journal of Pharmacology 2001 133 3 351 360 2-s2.0-0034759952 (Pubitemid 33027771)
153. Mattiussi S., Lazzari C., Truffa S., Antonnini A., Soddu S., Capogrossi M. C., Gaetano C., Homeodomain interacting protein kinase 2 activation compromises endothelial cell response to laminar flow: protective role of p21waf1,cip1,sdi1. PLoS One 2009 4 8 2-s2.0-68749092860 10.1371/journal.pone. 0006603 e6603
154. Chatterjee P. K., Kvale E. O., Patel N. S. A., Thiemermann C., GW274150 inhibits nitric oxide production by primary cultures of rat proximal tubular cells. Medical Science Monitor 2003 9 10 BR357 BR362 2-s2.0-0142246337 (Pubitemid 37305245)
155. Arnhold S., Fabender A., Klinz F. J., Kruttwig K., Löhnig B., Andressen C., Addicks K., NOS-II is involved in early differentiation of murine cortical, retinal and ES cell-derived neurons-An immunocytochemical and functional approach. International Journal of Developmental Neuroscience 2002 20 2 83 92 2-s2.0-0036112431 10.1016/S0736-5748(02)00020-5 (Pubitemid 34553425)
156. De Alba J., Clayton N. M., Collins S. D., Colthup P., Chessell I., Knowles R. G., GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain. Pain 2006 120 1-2 170 181 2-s2.0-30444458848 10.1016/j.pain.2005.10.028 (Pubitemid 43077180)
157. McDonald M. C., Izumi M., Cuzzocrea S., Thiemermann C., A novel, potent and selective inhibitor of the activity of inducible nitric oxide synthase (GW274150) reduces the organ injury in hemorrhagic shock. Journal of Physiology and Pharmacology 2002 53 4 I 555 569 2-s2.0-0036908191 (Pubitemid 36014802)
158. Cuzzocrea S., Chatterjee P. K., Mazzon E., McDonald M. C., Dugo L., Di Paola R., Serraino I., Britti D., Caputi A. P., Thiemermann C., Beneficial effects of GW274150, a novel, potent and selective inhibitor of iNOS activity, in a rodent model of collagen-induced arthritis. European Journal of Pharmacology 2002 453 1 119 129 2-s2.0-0037130983 10.1016/S0014-2999(02)02338-5 (Pubitemid 35232462)
159. Chatterjee P. K., Patel N. S. A., Sivarajah A., Kvale E. O., Dugo L., Cuzzocrea S., Brown P. A. J., Stewart K. N., Mota-Filipe H., Britti D., Yaqoob M. M., Thiemermann C., GW274150, a potent and highly selective inhibitor of iNOS reduces experimental renal ischemia/reperfusion injury. Kidney International 2003 63 3 853 865 2-s2.0-0037337260 10.1046/j.1523-1755.2003.00802.x (Pubitemid 36315563)
160. Dugo L., Marzocco S., Mazzon E., Di Paola R., Genovese T., Caputi A. P., Cuzzocrea S., Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. British Journal of Pharmacology 2004 141 6 979 987 2-s2.0-1942472504 10.1038/sj.bjp.0705683 (Pubitemid 38510081)
161. Di Paola R., Mazzon E., Patel N. S. A., Genovese T., Muià C., Thiemermann C., De Sarro A., Cuzzocrea S., Beneficial effects of GW274150 treatment on the development of experimental colitis induced by dinitrobenzene sulfonic acid. European Journal of Pharmacology 2005 507 13 281 289 2-s2.0-12344320248 10.1016/j.ejphar.2004.11.041 (Pubitemid 40126865)
162. Broom L., Marinova-Mutafchieva L., Sadeghian M., Davis J. B., Medhurst A. D., Dexter D. T., Neuroprotection by the selective iNOS inhibitor GW274150 in a model of Parkinson disease. Free Radical Biology and Medicine 2011 50 5 633 640 2-s2.0-79551488606 10.1016/j.freeradbiomed.2010.12.026
163. Singh D., Richards D., Knowles R. G., Schwartz S., Woodcock A., Langley S., O'Connor B. J., Selective inducible nitric oxide synthase inhibition has no effect on allergen challenge in asthma. American Journal of Respiratory and Critical Care Medicine 2007 176 10 988 993 2-s2.0-36249008584 10.1164/rccm.200704-588OC (Pubitemid 350127842)
164. Palmer J. E., Guillard F. L., Laurijssens B. E., Wentz A. L., Dixon R. M., Williams P. M., A randomised, single-blind, placebo-controlled, adaptive clinical trial of GW274150, a selective iNOS inhibitor, in the treatment of acute migraine. Cephalalgia 2009 29 1 124
165. Hoivik H. O., Laurijssens B. E., Harnisch L. O., Twomey C. K., Dixon R. M., Kirkham A. J. T., Williams P. M., Wentz A. L., Lunnon M. W., Lack of efficacy of the selective iNOS inhibitor GW274150 in prophylaxis of migraine headache. Cephalalgia 2010 30 12 1458 1467 2-s2.0-79952460799 10.1177/0333102410370875
166. Rogerson T. D., Wilkinson C. F., Hetarski K., Steric factors in the inhibitory interaction of imidazoles with microsomal enzymes. Biochemical Pharmacology 1977 26 11 1039 1042 2-s2.0-0017687255 10.1016/0006-2952(77)90241-6 (Pubitemid 8107444)
167. Rees D. D., Palmer R. M. J., Moncada S., Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proceedings of the National Academy of Sciences of the United States of America 1989 86 9 3375 3378 2-s2.0-0001599370 (Pubitemid 19129614)
168. Cheshire D. R., Åberg A., Andersson G. M. K., Andrews G., Beaton H. G., Birkinshaw T. N., Boughton-Smith N., Connolly S., Cook T. R., Cooper A., Cooper S. L., Cox D., Dixon J., Gensmantel N., Hamley P. J., Harrison R., Hartopp P., Käck H., Leeson P. D., Luker T., Mete A., Millichip I., Nicholls D. J., Pimm A. D., St-Gallay S. A., Wallace A. V., The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS). Bioorganic and Medicinal Chemistry Letters 2011 21 8 2468 2471 2-s2.0-79953286166 10.1016/j.bmcl.2011.02.061
169. Fullmer T., Rethinking mechanisms of drug discovery. SciBX 2011 4 27
170. Huang H., Martásek P., Roman L. J., Silverman R. B., Synthesis and evaluation of peptidomimetics as selective inhibitors and active site probes of nitric oxide synthases. Journal of Medicinal Chemistry 2000 43 15 2938 2945 2-s2.0-0342647320 10.1021/jm000127z (Pubitemid 30599652)
171. Ekins S., Mestres J., Testa B., In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. British Journal of Pharmacology 2007 152 1 9 20 2-s2.0-34548304745 10.1038/sj.bjp.0707305 (Pubitemid 47339896)
172. Guido R. V. C., Oliva G., Andricopulo A. D., Virtual screening and its integration with modern drug design technologies. Current Medicinal Chemistry 2008 15 1 37 46 2-s2.0-39049094335 10.2174/092986708783330683 (Pubitemid 351234626)
173. Hoffer L., Renaud J. P., Horvath D., Fragment-based drug design: computational and experimental state of the art. Combinatorial Chemistry and High Throughput Screening 2011 14 6 500 520 2-s2.0-79958006210 10.2174/138620711795767884
174. Tinker A. C., Beaton H. G., Boughton-Smith N., Cook T. R., Cooper S. L., Fraser-Rae L., Hallam K., Hamley P., McInally T., Nicholls D. J., Pimm A. D., Wallace A. V., 1,2-Dihydro-4-quinazolinamines: potent, highly selective inhibitors of inducible nitric oxide synthase which show antiinflammatory activity in vivo. Journal of Medicinal Chemistry 2003 46 6 913 916 2-s2.0-0037435062 10.1021/jm0255926 (Pubitemid 36423137)
175. Ji H., Stanton B. Z., Igarashi J., Li H., Martásek P., Roman L. J., Poulos T. L., Silverman R. B., Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors. Journal of the American Chemical Society 2008 130 12 3900 3914 2-s2.0-41149145121 10.1021/ja0772041 (Pubitemid 351429856)
176. Ekins S., Mestres J., Testa B., In silico pharmacology for drug discovery: applications to targets and beyond. British Journal of Pharmacology 2007 152 1 21 37 2-s2.0-34548319111 10.1038/sj.bjp.0707306 (Pubitemid 47339897)
177. Ji H., Li H., Flinspach M., Poulos T. L., Silverman R. B., Computer modeling of selective regions in the active site of nitric oxide synthases: implication for the design of isoform-selective inhibitors. Journal of Medicinal Chemistry 2003 46 26 5700 5711 2-s2.0-0347626255 10.1021/jm030301u (Pubitemid 37543320)
178. Fröhlich L. G., Kotsonis P., Traub H., Taghavi-Moghadam S., Al-Masoudi N., Hofmann H., Strobel H., Matter H., Pfleiderer W., Schmidt H. H. H. W., Inhibition of neuronal nitric oxide synthase by 4-amino pteridine derivatives: structure-activity relationship of antagonists of (6R)-5,6,7,8- tetrahydrobiopterin cofactor. Journal of Medicinal Chemistry 1999 42 20 4108 4121 2-s2.0-0038210982 10.1021/jm981129a (Pubitemid 29483028)
179. Matter H., Kotsonis P., Klingler O., Strobel H., Fröhlich L. G., Frey A., Pfleiderer W., Schmid H. H. H. W., Structural requirements for inhibition of the neuronal nitric oxide synthase (NOS-I): 3D-QSAR analysis of 4-oxo- and 4-amino-pteridine-based inhibitors. Journal of Medicinal Chemistry 2002 45 14 2923 2941 2-s2.0-0037019267 10.1021/jm020074g (Pubitemid 34721516)