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Nitric oxide synthase inhibitors: biology and chemistry

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Abstract

The review is devoted to the problems related to inhibition of the generation of nitric oxide, a versatile regulator of cell metabolism, whose excessive production is responsible for various pathologies. The approaches to the preparation of inhibitors are discussed and the prospects for the synthesis of inhibitors selective with respect to various NO-synthase isoforms are considered; these aspects largely determine the possibility of using these compounds in medicine. The structures of some classes of inhibitors are presented and their biological properties and the main applications for arresting pathological states are discussed.

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References

  1. V. G. Granik, S. Yu. Ryabova, and N. B. Grigor´ev, Usp. Khim., 1997, 66, 792 [Russ. Chem. Rev., 1997, 66 (Engl. Transl.)].

    Google Scholar 

  2. V. G. Granik, and N. B. Grigor´ev, Izv. Akad. Nauk, Ser. Khim., 2002, 51, 1268 [Russ. Chem. Bull., Int. Ed., 2002, 51, 1375].

    Google Scholar 

  3. A. J. Hobbs, A. Higgs, and S. Moncada, Annu. Rev. Pharmacol. Toxicol., 1999, 39, 191.

    Google Scholar 

  4. A. R. Seminara, J. S. Krumenasker, and F. Murad, in Nitric Oxide, Basic Research and Clinical Applications, Eds. R. J. Gryglewski and P. Minuz, IOS Press, Amsterdam-Berlin-Oxford-Tokyo-Washington, DC, 2000, 5.

    Google Scholar 

  5. J. M. Fukuto and G. Chaudhuri, Annu. Rev. Pharmacol. Toxicol., 1995, 35, 165.

    Google Scholar 

  6. M. D. Mashkovskii, Lekarstvennye sredstva, Posobie dlya vrachei [Drugs. Doctors´ Textbook], issue 13, Khar´kov, Torgsin, 1997, 1, 543 pp.; 2, 592 pp. (in Russian).

  7. M. D. Mashkovskii, Lekarstva XX veka [XX Century Drugs], Novaya volna, Moscow, 1998, 319 pp. (in Russian).

  8. R. B. Barlow, Introduction to Chemical Pharmacology, J. Wiley and Sons, London-New York, 1954. Granik and Grigor´ev 1994 Russ.Chem.Bull., Int.Ed., Vol. 51, No. 11, November, 2002

    Google Scholar 

  9. A. L. Lehninger, Principles of Biochemistry, Worth Publishers, Inc., New York, 1982.

    Google Scholar 

  10. D. A. Kharkevich, Farmakologiya [Pharmacology], Moscow, Meditsina, 1999, 661 pp. (in Russian).

    Google Scholar 

  11. A. Albert, Selective Toxicity. Physico-Chemical Basis of Therapy, Chapman and Hall, London-New York, 1985.

    Google Scholar 

  12. J. G. Cannon, Pharmacology for Chemists, Oxford University Press, New York, Oxford, 1999, 272 p.

    Google Scholar 

  13. G. I. Zhungietu and V. G. Granik, Osnovnye printsipy konstruirovaniya lekarstv [Main Principles of Drug Design], IPK Gos. univ. Moldovy, Kishinev, 2000, 300 pp.

    Google Scholar 

  14. V. G. Granik, Lekarstva, farmakologicheskii, biokhimicheskii i khimicheskii aspekty [Drugs. Pharmacological, Biochemical, and Chemical Aspects]. Vuzovskaya kniga, Moscow, 2001, 408 pp. (in Russian).

    Google Scholar 

  15. V. G. Granik, Osnovy meditsinskoi khimii [Foundations of Medicinal Chemistry],Vuzovskaya kniga, Moscow, 2001, 384 pp. (in Russian).

    Google Scholar 

  16. Nitric Oxide: Brain and Immune System, Eds. S. Moncada, G. Nistico, and E. A. Higgs, Portland Press, London-Chapel Hill, 1993, 293 p.

    Google Scholar 

  17. S. Moncada and A. Higgs, FASEB J., 1995, 9, 1315

    Google Scholar 

  18. O. W. Griffith and S. S. Gross, Methods in Nitric Oxide Research, Eds. M. Feelish and J. S. Stamler, Wiley, Chichester, 1996, p. 187.

    Google Scholar 

  19. J. T. Groves and C. C.-Y. Wang, Current Opinion Chem. Biol., 2000, 4, 687.

    Google Scholar 

  20. Y. Su, M. Couch and E. R. Block, Nitric Oxide: Biology and Chemistry, 1997, 1, 469.

    Google Scholar 

  21. S. Pfeifer, E. Leopold, K. Schmidt, F. Brunner, and B. Mayer, Br. J. Pharmacol., 1996, 118, 1433.

    Google Scholar 

  22. N. M. Olken and M. A. Marletta, Biochemistry, 1993, 32, 9677.

    Google Scholar 

  23. N. M. Olken, Y. Osawa, and M. A. Marletta, Biochemistry, 1994, 33, 14784.

    Google Scholar 

  24. P. Klatt, K. Shmidt, F. Brunner, and B. Mayer, J. Biol. Chem., 1994, 269, 1674.

    Google Scholar 

  25. O. W. Griffith and D. J. Stuehr, Annu. Rev. Physiol., 1995, 57, 707.

    Google Scholar 

  26. K. Narayanan, L. Spack, M. Hayward, and O. W. Griffith, FASEB J., 1994, 8, A360.

    Google Scholar 

  27. N. M. Olken and M. A. Marletta, J. Med. Chem., 1992, 35, 1137.

    Google Scholar 

  28. J.-Mi Hah, L. J. Roman, and R. B. Silverman, Bioorg. Med. Chem., 2000, 8, 1931.

    Google Scholar 

  29. M.-X. Wang, D. F. Murrell, C. Szabo, R. F. Warren, M. Sarris, and G. A. C. Murrell, Nitric Oxide: Biology and Chemistry, 2001, 5, 219.

    Google Scholar 

  30. G. Marechal and P. Gailly, Cell Mol. Life Sci., 1999, 55, 1088.

    Google Scholar 

  31. S. Pfeiffer, E. Leopold, K. Schmidt, F. Brunner, and B. Mayer, Br. J. Pharmacol., 1996, 118, 1433.

    Google Scholar 

  32. S. A. Lipton, N. J. Sucher, P. K. Kaiser, and E. B. Dreyer, Neuron, 1991, 7, 111.

    Google Scholar 

  33. S. Moncada, R. H. J. Palmer, and E. A. Higgs, Pharmacol. Rev., 1991, 43, 109.

    Google Scholar 

  34. M. A. Marletta, J. Biol. Chem., 1993, 268, 1223.

    Google Scholar 

  35. J. F. Kerwin and M. Heller, Med. Res. Rev., 1994, 14, 23.

    Google Scholar 

  36. J. L. Collins, J. A. Oplinger, S. Lee, E. P. Garvey, M. Sulter, C. Duffy, T. C. Burnette, and E. S. Furfine, J. Med. Chem., 1998, 41, 2858.

    Google Scholar 

  37. P. L. Feldman, O. W. Griffith, H. Hong, and D. J. Stuehr, J. Med. Chem., 1993, 36, 491.

    Google Scholar 

  38. S. Cellek and S. Moncada, Nitric Oxide: Biology and Chemistry, 1997, 1, 204.

    Google Scholar 

  39. J.-Mi Hah, L. J. Roman, P. Martasek, and R. B. Silverman, J. Med. Chem., 2001, 44, 2667.

    Google Scholar 

  40. H. Huang, P. Martasek, L. J. Roman, R. S. S. Masters, and R. B. Silverman, J. Med. Chem., 1999, 42, 3147.

    Google Scholar 

  41. H. Huang, P. Martasek, L. J. Roman, and R. B. Silverman, J. Med. Chem., 2000, 43, 2938.

    Google Scholar 

  42. Annual Drug Data Rep.,* 1996, 18, (a) 681; (b) 144; (c) 1017; (d) 527; (e) 786; (f) 785; (g) 887; (h) 873; (i) 697; (j) 967.

  43. Annual Drug Data Rep., 1995, 17, (a) 257; (b) 535; (c) 555; (d) 914; (e) 135; (f) 565; (g) 707; (h) 820; (i) 530; (j) 444; (k) 707.

  44. Annual Drug Data Rep., 1998, 20, (a) 45; (b) 210; (c) 46; (d) 134; (e) 301; (f) 404; (g) 706; (h) 978; (i) 935; (j) 160; (k) 934; (l) 310; (m) 403; (n) 669; (o) 29; (p) 404.

  45. J. Prous, T. Wroblewski, and T. Gastacer, Drug Future, 1998, 23, No. 2, 123.

    Google Scholar 

  46. K. Narayanan, L. Spack, M. Hayward, and O. W. Griffith, FASEB J., 1994, 8, A360.

    Google Scholar 

  47. K. Naraynan and O. W. Griffith, J. Med. Chem., 1994, 37, 885.

    Google Scholar 

  48. E. S. Furfine, M. F. Harmon, J. E. Paith, R. G. Knowles, M. Salter, R. J. Kiff, C. Duffy, R. Haselwood, J. A. Oplinger, and E. P. Garvey, J. Biol. Chem., 1994, 269, 26677.

    Google Scholar 

  49. W. N. Moore, R. K. Weber, G. M. Jerome, F. S. Tjoeng, T. P. Misco, and M. G. Currie, J. Med. Chem., 1994, 37, 3886.

    Google Scholar 

  50. Annual Drug Data Rep., 1999, 21, (a) 663; (b) 320; (c) 976; (d) 528; (e) 587; (f) 967; (g) 28; (h) 123; (i) 124; (j) 966; (k) 392; (l) 495; (m) 663.

  51. J. Ou, T. M. Carlos, S. C. Watkins, J. E. Saavedra, J. K. Keefer, Y.-M. Kim, R. G. Harbrecht, and T. R. Billear, Nitric Oxide: Biology and Chemistry, 1997, 1, 404.

    Google Scholar 

  52. Annual Drug Data Rep., 1994, 16, (a) 731; (b) 459; (c) 923; (d) 219.

  53. Annual Drug Data Rep., 2000, 22, (a) 177; (b) 199; (c) 775; (d) 132; (e) 147; (f) 999.

  54. Y. Lee, P. Martasek, L. J. Roman, B. S. Siler Master, and R. B. Silverman, Bioorg. Med. Chem., 1999, 7, 1941.

    Google Scholar 

  55. J. Prous, A. Graul, and J. Castacer, Drug Future, 1994, 19, 740.

    Google Scholar 

  56. T. Tabatabaie, K. L. Graham, A. M. Vasques, R. A. Floyd, and Y. Katake, Nitric Oxide: Biology and Chemistry, 2000, 4, 157.

    Google Scholar 

  57. H. Ruetten and C. Thiemermann, Br. J. Pharmacol., 1996, 119, 479.

    Google Scholar 

  58. Annual Drug Data Rep., 1997, 19, (a) 548; (b) 77; (c) 328; (d) 622; (e) 737; (f) 701; (g) 236; (h) 549; (i) 217; (j) 43.

  59. G. L. Southan, C. Szabo, M. P. O´Connor, A. L. Salzman, and C. Thiemermann, Europ. J. Pharmacol., 1995, 291, 311.

    Google Scholar 

  60. G. L. Southan, C. Szabo, and C. Thiemermann, Br. J. Pharmacol., 1995, 114, 510.

    Google Scholar 

  61. C. Szabo, G. L. Southan, and C. Thiemermann, Proc. Natl. Acad. Sci. USA, 1994, 91, 12472.

    Google Scholar 

  62. L. H. Wei, N. Arabolos, and L. J. Ignarro, Nitric Oxide: Biology and Chemistry, 1998, 2, 155.

    Google Scholar 

  63. S. Ulhag, E. C. Chinje, M. A. Naylor, M. Jaffer, J. J. Stafford, and M. D. Threadgill, Bioorg. Med. Chem., 1999, 7, 1941.

    Google Scholar 

  64. D. W. Chow, Proc. Natl. Acad. Sci. USA, 1993, 90, 9741.

    Google Scholar 

  65. T. M. Dowson, V. L. Dowson, and S. H. Snyder, Ann. Neurol., 1992, 32, 297

    Google Scholar 

  66. E. P. Garvey, J. V. Title, R. K. Covinton, B. H. Merrill, E. R. Wood, S. A. Baylis, and S. A. Charles, Arch. Biochem. Biophys., 1994, 311, 235.

    Google Scholar 

  67. E. P. Garvey, J. A. Oplinger, E. S. Furfine, R. J. Kiff, F. Laszlo, B. J. R. Whittle, and R. C. Knowles, J. Biol. Chem., 1997, 272, 4959.

    Google Scholar 

  68. F. N. Fastier, Pharmacol. Rev., 1962, 14, 37.

    Google Scholar 

  69. D. J. Wolf, G. A. Datto, A. Samatovicz, and R. A. Tempsick, J. Biol. Chem., 1993, 268, 9425.

    Google Scholar 

  70. D. J. Wolf, A. Libesski, and S. C. Umansky, Arch. Biochem. Biophys., 1994, 311, 360.

    Google Scholar 

  71. D. J. Wolf and B. J. Gribin, Arch. Biochem. Biophys., 1994, 311, 293.

    Google Scholar 

  72. R. L. C. Handy and P. K. Moore, Life Sci., 1997, 60, 389.

    Google Scholar 

  73. V. Sorrenti, C. D. Giacomo, L. Salerno, M. A. Siracusa, F. Guerrera, and A. Vanella, Nitric Oxide: Biology and Chemistry, 2001, 5, 32.

    Google Scholar 

  74. D. I. Metelitsa, Aktivatsiya kisloroda fermentnymi sistemami [Oxygen Activation by Enzyme Systems], Nauka, Moscow, 1982, 255 pp. (in Russian).

    Google Scholar 

  75. J. M. Quintella, C. Peinador, L. M. Gonzalez, R. Riguera, I. Rioja, M. C. Terencio, A. Ubeda, and M. J. Alkarez, J. Med. Chem., 1999, 42, 4720

    Google Scholar 

  76. G. Yue, F. F. Sun, C. Dunn, K. Yin, and P. Y. K. Wong, J. Pharmacol. Exp. Theor., 1996, 276, 265.

    Google Scholar 

  77. T. Honda, B. V. Rounds, F. G. Favaloro, G. W. Gribble, N. Suh, X. Wang, and M. B. Sporn, Bioorg. Med. Chem. Lett., 1999, 9, 3429.

    Google Scholar 

  78. Y.-X. Wang, C. I. Poon, K. S. Poon, and C. C. Y. Pang, Br. J. Pharmacol., 1993, 110, 1232.

    Google Scholar 

  79. C. Szabo, New Horiz., 1995, 3, 2.

    Google Scholar 

  80. B. S. Teilor, L. Kh. Alarson, and T. R. Billiar, Biokhimiya, 1998, 63, 905 [Biochemistry (Moscow), 1998, 63 (Engl. Transl.)].

    Google Scholar 

  81. L. Laudet, A. Rosselet, M. D. Schaller, M. Markert, C. Perret, and F. Feihl, J. Infect. Dis., 1998, 177, 127.

    Google Scholar 

  82. S. Bergamini, C. Rota, R. Canali, M. Staffieri, F. Daneri, A. Bini, F. Giovannini, A. Tomasi, and A. Jannone, Nitric Oxide: Biology and Chemistry, 2001, 5, 349.

    Google Scholar 

  83. F. Squadrito, D. Altavilla, G. Squadritta, G. M. Campo, M. Ioculano, P. Canale, F. Rossi, A. Saitta, and A. P. Caputi, Br. J. Pharmacol., 1996, 119, 23.

    Google Scholar 

  84. J. A. Corbett, G. Kwon, T. P. Mesko, C. P. Rody, and M. L. McDunuel, Am. J. Physiol., 1994, 267, 48.

    Google Scholar 

  85. R. E. Malmstrom, Acta. Physiol. Scand., 1997, 160, Suppl. 636, 1.

    Google Scholar 

  86. R. E. Malmstrom, H. Bjorne, K. Alving, E. Weitzberg, and J. O. N. Lundberg, Nitric Oxide: Biology and Chemistry, 2001, 5, 98.

    Google Scholar 

  87. M. R. Hynes, H. Dong, and S. P. Duckles, Life Sci., 1987, 42, 357.

    Google Scholar 

  88. T. M. Cocks and J. A. Angus, Nature, 1983, 305, 627.

    Google Scholar 

  89. C. Egleme, T. Godfraind, and R. C. Miller, Br. J. Pharmacol., 1984, 81, 16.

    Google Scholar 

  90. K. P. Konrad and S. L. Whittemore, Am. J. Physiol., 1992, 262, R1137.

    Google Scholar 

  91. S. Ito, C. S. Johnston, and O. A. Carretero, J. Clin. Invest., 1991, 87, 1656.

    Google Scholar 

  92. J.-C. Preiser, H. Zhang, B. Vray, A. Hrabak, and J.-L. Vincent, Nitric Oxide: Biology and Chemistry, 2001, 5, 208.

    Google Scholar 

  93. H. Inoue, K. Ando, N. Wakisaka, K.-I. Matsuzaki, M. Aihara, and N. Kumagai, Nitric Oxide: Biology and Chemistry, 2001, 5, 334.

    Google Scholar 

  94. T. Sozumi, Ann. Plast. Surg., 1997, 39, 272.

    Google Scholar 

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  1. Federal State Unitary Enterprise State Scientific Center “Scientific Research Institute of Organic Intermediates and Dyes”, 4 ul. Bolshaya Sadovaya, 103787, Moscow, Russian Federation

    V. G. Granik & N. B. Grigor"ev

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Granik, V.G., Grigor"ev, N.B. Nitric oxide synthase inhibitors: biology and chemistry. Russian Chemical Bulletin 51, 1973–1995 (2002). https://doi.org/10.1023/A:1021611422169

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