Inhibitors of nitric oxide synthase in inflammatory arthritis

IDrugs

Volumn 1, Issue 3, 1998, Pages 321-333

  Boughton Smith, Nigel K ^a   Tinker, Alan C ^a  

^a Astra Charnwood ^*  (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000255875     PISSN: 13697056     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (138)

1. Palmer, RMJ, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (1987) 327:524-526.
2. Furchgott RF, Zawadzski JV: The obligatory role of endothelial cell in the relaxation of arterial smooth muscle by acetylcholine. Nature (1980) 288:373-376.
3. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev (1991) 43:109-141.
4. Rees DD, Palmer RMJ, Schulz R, Hodson HF, Moncada S: Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol (1990) 101:746-752.
5. Calver A, Collier J, Vallance P: Nitric oxide and cardiovascular control. Exp Physiol (1993) 78:303-326.
6. Radomski MW, Moncada S: Regulation of vascular homeostasis by nitric oxide. Thromb Haem (1993) 70:36-41.
7. Snyder SH, Bredt DS: Nitric oxide as a neuronal messenger. TIPS (1991) 12:125-128.
8. Snyder SH: Nitric oxide: First in a new class of neurotransmitters? Science (1992) 257:494-496.
9. Garthwaite J, Charles SL, Chess-Williams R: Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature (London) (1988) 336:385-388.
10. Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM: Nitric oxide: A cytotoxic activated macrophage effector molecule. Biochem Biophys Res Comm (1988) 157:87-94.
11. Liew FY, Millot S, Parkinson C, Palmer RMJ, Moncada S: Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol (1990) 144:4794-4797.
12. Moncada S, Higgs EA: Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J (1995) 9:329-1330.
13. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA: Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial cell injury from nitric oxide. Proc Natl Acad Sci USA (1990) 87:1620-1624.
14. Halliwell B: Oxygen radicals, nitric oxide and human inflammatory joint disease. Ann Rheum Dis (1995) 54:505-510.
15. Darley-Usmar V, Wiseman H, Halliwell B: Nitric oxide and oxygen radicals: A question of balance. FEBS Lett (1995) 369:31-135.
16. Cochran FR, Selph J, Sherman P: Insights into the role of nitric oxide in inflammatory arthritis. Med Res Rev (1996) 16:547-563.
17. Boughton-Smith NK, Evans SM, Laszlo F, Whittle BJR, Moncada S: The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. Br J Pharmacol (1993) 110:1189-1195.
18. Ialenti A, Ianaro A, Moncada S, Di Rossa, M: Modulation of acute inflammation by endogenous nitric oxide Eur J Pharmacol (1992) 211:177-182.
19. Salvemini D, Manning PT, Zweifel BS, Seibert K, Connor J, Currie MG, Needleman P: Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors. J Clin Invest (1995) 96:301-308.
20. Salvemini D, Wang Z-Q, Wyatt PS, Bourden DM, Marino MH, Manning PT, Currie MG: Nitric oxide: A key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol (1996) 118:829-838.
21. Boughton-Smith NK, Ghelani A: Role of induced nitric oxide synthase and increased NO levels in zymosan peritonitis in the rat. Inflamm Res (1995) Suppl. 2: S149-S150.
22. Hibbs JB, Taintor RR, Vavrin Z: Macrophage cytotoxicity: Role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science (1987) 235:473-476.
23. Sakuma I, Stuehr DJ, Gross SS, Nathan C, Levi R: Identification of arginine as a precursor of endothelium derived relaxing factor. Proc Natl Acad Sci USA (1988) 85:8664-8667.
24. Stuehr DJ, Gross SS, Sakumo I, Levi R, Nathan CF: Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med (1989) 169:1011-1020.
25. Stuehr DJ, Kwon NS, Gross SS, Sakuma I, Thiel BA, Levi R, Nathan CF: Synthesis of nitrogen oxides from L-arginine by macrophage cytosol. Requirement for inducible and constitutive components. Biochem Biophys Res Comm (1989) 161:420-426.
26. Iyengar I, Stuehr DJ, Marietta MA: Macrophage synthesis of nitrate, nitrite and N-nitrosamines: Precursors and the role of the respiratory burst. Proc Natl Acad Sci USA (1987) 84:6369-6373.
27. McCall TB, Boughton-Smith NK, Palmer RMJ, Whittle BRJ, Moncada S: Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J (1989) 261:293-296.
28. G-methylarginine. Biochem Biophys Res Comm (1990) 170:96-103.
29. Lambert LE, Whitten JP, Baron BM, Cheng HC, Doherty NS, McDonald IA: Nitric oxide synthesis in the CNS, endothelium and macrophages differs in its sensitivity to inhibition by arginine analogs. Life Sci (1991) 48:69-75.
30. Lambert LE, French JF, Whitten JP, Barron BM, McDonald IA: Characterisation and cell selectivity of two novel inhibitors of nitric oxide synthase. Eur J Pharmacol (1992) 216:131-134.
31. G-cyclopropyl-L-arginine. Two novel inhibitors of macrophage nitric oxide synthase. J Med Chem (1992) 35:1137-1144.
32. Komori Y, Wallace GC, Fukuto JM: Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage by L-arginine analogs. Arch Biochem Biophys, (1994) 315:213-218.
33. 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) 339:572-575.
34. G-methyl-L-arginine. Biochem Biophys Res Comm (1991) 177:828-833.
35. G-methylarginine requires NADPH-dependent hydroxylation. J Med Chem (1993) 36:491-496.
36. Furfine ES, Harmon MF, Paith JE, Garvey EP: Selective inhibition of constitutive nitric oxide synthase by I-NG-nitroarginine. Biochemistry (1993) 32:8512-8517.
37. Narayanan K , Griffith OW: Synthesis of L-Thiocitrulline, L-Homothiocitrulline and S-Methyl-L-thiocitrulline: A new class of potent nitric oxide synthase inhibitors. J Med Chem (1994) 37:885-887.
38. Furfine ES, Harmon MF, Paith JE, Knowles RG, Salter M, Kiff RJ, Duffy C, Hazelwood R, Oplinger JA, Garvey EP: Potent and selective inhibition of human nitric oxide syntheses: Selective inhibition of neuronal nitric oxide synthase by S-methyl-L-thiocitrulline and S-ethyl-L-thiocitrulline. J Biol Chem (1994) 269:26677-26683.
39. McCall TB, Feelisch M, Palmer RMJ, Moncada S: Identification of N-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. Br J Pharmacol (1991) 102:234-238.
40. Moore WM, Webber RK, Jerome GM, Tjoeng FS, Misko TP, Currie MG: L-N′-(1-iminoethyl)lysine: A selective inhibitor of inducible nitric oxide synthase; J Med Chem (1994) 37:3886-3888.
41. Schmidt K, Klatt P, Mayer B: Uptake of nitric oxide synthase inhibitors by macrophage RAW 264.7 cells. Biochem J (1994) 301:313-316.
42. Baydoun AR, Mann GE: Selective targeting of nitric oxide synthase inhibitors to system y+ in activated macrophages. Biochem Biophys Res Comm (1994) 200:726-731.
43. Hasan K, Heesen BJ, Corbett JA, McDaniel ML, Chang K, Allison W, Wolfenbuttel BHR, Williamson JR, Tilton RG: Inhibition of nitric oxide formation by guanidines. Eur J Pharmacol (1993) 249:101
44. Southan GJ, Salzman AL, Szabó C: Mercaptoalkylguanidines: A novel class of inhibitors of the inducible isoform of nitric oxide synthase. FASEB J (1995) 9:A28.
45. Southan GJ, Zingarelli B, O'Connor M, Salzman AL, Szabo C: Spontaneous rearrangement of aminoalkylisothioureas into mercaptoalkyl-guanidines, a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform. Br J Pharmacol (1996) 117:619-632.
46. Cuzzocrea S, Zingarelli B, Hake P, Salzman AL, Szabo C: Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. Free Radic Biol Med (1998) 24:450-459.
47. Corbett A, Tilton RG and Chang K, Hasan, KS, Ido Y, Wang JL, Sweetland MA, Lancaster JR, Williamson JR, McDaniel ML: Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes (1992) 41:52-556.
48. Wolff DJ, Lubeskie A: Aminoguanidine is an isoform selective, mechanism based inactivator of nitric oxide synthase. Arch Biochem Biophys (1995) 316:290-301.
49. Wolff DJ, Gauld DS, Neulander MJ, Southan G: Inactivation of nitric oxide synthase by substituted aminoguanidines and aminoisothioureas. J Pharmacol Exp Ther (1997) 283:265-273.
50. Garvey EP, Oplinger JA, Tanoury GJ, Sherman PA, Fowler M, Marshall S, Harmon MF, Paith JE, Furfine ES: Potent and selective inhibition of human nitric oxide syntheses: inhibition by non-amino acid isothioureas. J Biol Chem (1994) 269:26669-26676.
51. Nakane M, Klinghofer V, Kuk JE, Donnelly JL, Budzik GP, Pollock JS, Basha F, Carter GW: Novel potent and selective inhibitors of inducible nitric oxide synthase. Mol Pharmacol (1995) 47:831-834.
52. Southan GJ, Szabó C, Thiemermann C: Isothioureas: Potent inhibitors of nitric oxide syntheses with variable isoform selectivity. Br J Pharmacol (1995) 114:510-516.
53. Southan GJ, Salzman AL, Szabo C: Potent inhibition of the inducible isoform of nitric oxide synthase by aminoethylisoselenourea and related compounds. Life Sci (1996) 58:1139-1148.
54. Stratman NC, Fici GJ, Sethy VH: U-19451A: A selective inducible nitric oxide synthase inhibitor. Life Sci (1996) 59:945-951.
55. th ACS Meeting (1997): MEDI 085.
56. Southan GJ, Szabó C, O'Connor MP, Salzman AL, Thiemermann C: Amidines are potent inhibitors of nitric oxide syntheses: Preferential inhibition of the inducible isoform. Eur J Pharmacol (1995) 291:311-318.
57. Moore WM, Webber RK, Fok KF, Jerome GM, Kommeier CM, Tjeong FS, Currie MG: Inhibitors of human nitric oxide synthase with the carbamidine moiety as a common structural element. Bioorg Med Chem (1996) 4:1559-1564.
58. Southan GJ, Gould D, Lubeskie A, Zingarelli B, Cuzzocrea S, Salzman AL, Szabó C, Wolff DJ: Inhibition of nitric oxide synthase with pyrazole-1-carboxamidine and related compounds. Biochem Pharmacol (1997) 54:409-417.
59. Garvey EP, Oplinger JA, Furfine ES, Kiff RJ, Laszlo F, Whittle BJR, Knowles RG: 1400W is a slow, tight binding inhibitor of inducible nitric oxide synthesis in vitro and in vivo. J Biol Chem (1997) 21:4959-4963.
60. Moore WM, Webber RK, Fok KF, Jerome GM, Connor JR, Manning PT, Wyatt PS, Misko TP, Tjeong FS, Currie MG: 2-iminopiperidines and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthesis isoforms. J Med Chem (1996) 39:669-672.
61. Webber RK, Metz S, Moore WM, Connor JR, Currie MG, Fok KF, Hagen TJ, Hansen DW, Jerome GM, Manning PT, Pitzele BS, Toth MV, Trivedi M, Zupek ME, Tjoeng FS: Substituted 2-iminopiperidines as inhibitors of nitric oxide synthase isoforms. J Med Chem (1998) 41:96-101.
62. Hansen DW, Peterson KB, Trivedi M, Webber RK, Tjeong FS, Moore WM, Jerome GM, Currie MG, Pitzele BS: Homopiperidine amidines as selective inhibitors of inducible nitric oxide synthase (iNOS). Portland Press Proc (1996) 10(Biology of Nitric Oxide Part 5):224.
63. Faraci WS, Nagel AA, Vedries KA, Vincent LA, Xu H, Nichols LE, Labasi JM, Salter ED, Pettipher ER: 2-Amino-4-methylpyridine as a potent inhibitor of inducible NO synthase activity in vitro and in vivo. Br J Pharmacol (1996) 119:1101-1108.
64. Southan GJ, Salzman AL, Szabó C: 2-Aminopyridines: Novel inhibitors of nitric oxide syntheses with potent pressor effects. Pharmacol Comm (1996) 7:275-286.
65. Sup SJ, Green BG, Grant SK: 2-iminobiotin is an inhibitor of nitric oxide syntheses. Biochem Biophys Res Comm (1994) 204:962-968.
66. Green BG, Chabin R, Grant SK: The natural product noformycin is an inhibitor of inducible nitric oxide synthase. Biochem Biophys Res Comm (1996) 225:621-626.
67. Grant SK, Green BG, Wang R, Pacholok SG, Kozarich JW: Characterization of inducible nitric oxide synthase by cytochrome P450 substrates and inhibitors. Inhibition by chlorzoxazone. J Biol Chem (1997) 272:977-983.
68. Shankaran K, Donnelly KL, Shah SK, Humes JL, Pacholok SG, Grant SK, Green BG, MacCoss M: Inhibition of inducible nitric oxide synthase by benzoxazolones. Bioorg Med Chem Lett (1997) 7:2887-2892.
69. Stuehr DJ, Fasehun OA, Kwon NS, Gross SS, Gonzalez JA, Levi R, Nathan CF: Inhibiton of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs. FASEB J (1991) 5:98-103.
70. Wolff DJ, Gribbin BJ: Interferon-γ-inducible murine macrophage nitric oxide synthase: Studies on the mechanism of inhibition by imidazole agents. Arch Biochem Biophys (1994) 311:293-299.
71. Wolff DJ, Gribbin BJ: The inhibition of constitutive and inducible nitric oxide synthase isoforms by indazole agents. Arch Biochem Biophys (1994) 311:300-306.
72. Wolff DJ, Lubeskie A, Umansky C: The inhibition of the constitutive bovine endothelial nitric oxide synthase by imidazole and indazole agents. Arch Biochem Biophys (1994) 314: 360-366.
73. Handy RLC, Moore PK: Mechanism of the inhibition of neuronal nitric oxide synthase by 1-(2-trifluoromethylphenyl)imidazole (TRIM). Life Sci (1997) 60:PL 389-394.
74. Hattori R, Inoue R, Sase K, Eizawa H, Kosuga K, Aoyama T, Masayasu H, Kawai C, Sasayama S, Yui Y: Preferential inhibition of inducible nitric oxide synthase by ebselen. Eur J Pharmacol (1994) 267:R1-R2.
75. Zembowicz A, Hatchett RJ, Radziszewski W, Gryglewski RJ: Inhibition of endothelial nitric oxide synthase by ebselen. Prevention by thiols suggests the inactivation by ebselen of a catalytic thiol essential for the catalytic activity of nitric oxide synthase. J Pharm Exp Ther (1993) 267:1112-1118.
76. Bland Ward PA, Pitcher A, Wallace P, Gaffen Z, Babbedge RC, and Moore PK: Isoform selectivity of indazole based nitric oxide synthase inhibitors. Br J Pharmacol (1994) 112 (Proc Suppl):351P.
77. Midorikawa K, Kumagai Y, Yoshikawa T, Homma-Takeda S, Shimojo N: Inhibition of nNOS by 6-amino-5,8-quinolinedione (LY-83583) a mechanism involved in the suppression of NO-dependent cGMP content. Jpn J Pharmacol (1997) 75(Suppl 1):29P.
78. Kumagai Y, Nakajima H, Hayashi T, Iguchi I, Homma-Takeda S, Shimojo N: The inhibition mechanism of nitric oxide formation by nNOS by phenanthraquinone. Jpn J Pharmacol (1997) 75(Suppl 1):29P.
79. Knowles RG, Salter M, Brooks SL, Moncada S: Antiinflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in lung, liver and aorta of the rat. Biochem Biophys Res Comm (1990) 172:1042-1048.
80. Di Rosa M, Radomski M, Camuccio R, Moncada S: Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem Biophys Res Comm (1990) 172:1246-1252.
81. Moncada S, Palmer RMJ: Inhibition of the induction of nitric oxide synthase by glucocorticoids: Yet another explanation for their antiinflammatory effects? Trends Pharmacol Sci (1991) 12: 130-131.
82. Farrell AJ, Blake DR, Palmer RMJ, Moncada S: Increased concentrations of nitrite in synovial fluid and serum samples suggests increase nitric oxide synthase in rheumatic disease. Ann Rheum Dis (1992) 51:1219-222.
83. Grabowski PS, England AJ, Dykhuizen R, Copland M, Benjamin N, Ried DM, Ralston SH: Elevated nitric oxide production in rheumatoid arthritis. Arthritis Rheum (1996) 39:643-647.
84. Stichtenoth DO, Fauler J, Zeidler H, Frolich JC: Urinary nitrate is increased in patients with rheumatoid arthritis and reduced by prednisolone. Ann Rheum Dis (1995) 54:820-824.
85. Kaur H, Halliwell B: Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett (1994) 350:9-12.
86. Palmer RJ, Hickery MS, Charles IG, Moncada S, Bayliss MT: Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Comm (1993) 193:398-405.
87. Palmer RJ, Andrews T, Foxwell NA, Moncada S: Glucocorticoids do not affect the induction of a novel calcium-dependent nitric oxide synthase in rabbit chondrocytes. Biochem Biophys Res Comm (1992) 188:209-215.
88. Stadler J, Stefanovic-Racic M, Billiar TR: Articular chondrocytes synthesise nitric oxide in response to cytokines and lipopolysaccharide. J Immunol (1991) 147:3915-3920.
89. McInnes IB, Leung BP, Field M, Wei XQ, Huang F-P, Sturrock RD, Kinninmonth A, Weidner J, Moumford R, Liew FY: Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritics. J Exp Med (1996) 184:1519-1524.
90. Sakurai H, Kohsaka H, Liu M-F, Higashiyama H, Hirata Y, Kanno K, Saito I, Miyasaka N: Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides. J Clin Invest (1995) 96:2357-2363.
91. Taskiran D, Stefanovic-Racic M, Georgescu H, Evans CH: Nitric oxide mediates suppression of cartilage proteoglycan synthesis by IL-1. Biochem Biophys Res Comm (1994) 200:142-148.
92. Blanco FJ, Geng Y, Lotz M: Differention-dependent effects of IL-1 and TGF-β on human chondrocyte proliferation are related to inducible nitric oxide synthase expression. J Immunol (1995) 154:4010-4026.
93. Blanco FJ, Ochs RL, Schwarz H, Lotz M: Chondrocyte apoptosis induced by nitric oxide. Am J Path (1995) 146:75-85.
94. Murell GA, Jang D, Williams RJ: Nitric oxide activates metalloprotease enzymes in articular cartilage. Biochem Biophys Res Comm (1995) 206: 15-21.
95. Grabowski PS, Macpherson H, Ralston SH: Nitric oxide in cells derived from the human joint. Br J Rheumatol (1996) 35:207-212.
96. Brandi ML, Hukkanen M, Umeda Y, Moradi-Bidendi N, Bianchi S, Gross SS, Polak JM, MacIntyre I: Biderectional regulation of osteoclast function be nitric oxide synthase isoforms. Ptoc Natl Acad Sci USA (1995) 92:2954-2958.
97. Ralston SH, Ho LP, Helfrich MH, Grabowski PS, Johnston PW, Benjamin N: Nitric oxide: A cytokine-induced regulator of bone resorption. J Bone Mineral Res (1995) 10:1040-1049.
98. Ialenti A, Moncada S, Di Rossa M: Modulation of adjuvant arthritis by endogenous nitric oxide. Br J Pharmacol (1993) 110:701-706.
99. Oyanagui Y: Nitric oxide and superoxide radical are involved in both initiation and development of adjuvant arthritis. Life Sci (1994) 54:285-289.
100. Stefanovic-Racic M, Meyers K, Meschter C, Coffey JW, Hoffman RA, Evans CH: N-monomethyl arginine, an inhibitor of the nitric oxide synthase suppresses the development of adjuvant arthritis. Arthritis Rheum (1994) 37:1062-1069.
101. Stefanovic-Racic M, Meyers K, Meschter C, Coffey JW, Hoffman RA, Evans CH: Comparison of the nitric oxide synthase inhibitors methylarginine and aminoguanidine as prophylactic and therapeutic agents in rat adjuvant arthritis. J Rheumatol (1995) 22:1922-1928.
102. McCartney-Frances N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, Wahl SH: Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med (1993) 178:749-754.
103. G- monomethyl-L-arginine. J Exp Med (1994) 179:651-660.
104. Connor RJ, Manning PT, Settle SL, Moore WM, Jerome GM, Webber RK, Siong Tjoeng F, Currie MG: Suppression of adjuvant - induced arthritis by selective inhibition of inducible nitric oxide synthase. Eur J Pharmacol (1995) 273:15-20.
105. Santos LL, Morland EF, Yang Y, Hutchinson P, Holdsworth SR: Suppression of adjuvant arthritis and synovial macrophage inducible nitric oxide synthase by N-iminoethyl-L-ornithine, a nitric oxide synthase inhibitor. Inflammation (1997) 21:299-311.
106. University of Texas and Cornell Research Foundation. (Kilbourn R, Gross S, Griffith R): Use of cardiotonic drugs and inhibitors of nitric oxide synthesis to alleviate pathologic hypotension. WO-09104024 (1991).
107. Merrell Dow Pharmaceuticals Inc (Whitten JP, Lambert LE, McDonald IA, Doherty NS): Inhibitors of nitric oxide biosynthesis. EP-00446699 (1991).
108. Washington University (Williamson JR, Corbett JA, McDaniel ML, Tilton RG): Method of inhibiting nitric oxide formation. EP-00558468 (1993).
109. GD Searie & Co (Hansen DW et al): Amidino derivatives useful as nitric oxide synthase inhibitors. WO-09511231 (1995).
110. Merck & Co Inc (Shah SK, Grant S, Maccoss M, Shankaran K, Guthikonda K): Substituted heterocycles as inhibitors of nitric oxide synthase. WO-09614842 (1996).
111. Hoechst AG (Strobel S et al): 2-Amino-1,3-thiazines as nitric oxide synthase inhibitors. EP-00713704 (1996).
112. Hoechst AG (Strobel S et al): 2-Amino-1,3-thiazepines and their use as inhibitors of the nitrogen oxide synthase. EP-00718294 (1996).
113. Japan Tobacco Inc (Yata S, Ozeki H, Watikani S): Thiazine or thiazepine derivatives which inhibit NOS. EP-00717040 (1996).
114. GD Searle & Co (Tjoeng FS, Fok KF, Webber RK) Amidino derivatives useful as nitric oxide synthase inhibitors. WO-09511014 (1995).
115. GD Searle & Co (Hansen DW et al): Cyclic amidino agents useful as nitric oxide synthase inhibitors. WO-09633175 (1996).
116. Merck & Co Inc (Guthikonda RN et al): Cyclic amidine analogs as inhibitors of nitric oxide synthase. WO-09614844 (1996).
117. Merck & Co Inc (Caldwell CG et al): Hexahydro-5-imino-1,4-heteroazepine derivatives as inhibitors of nitric oxide synthases.WO-09716430 (1996).
118. Ono Pharmaceutical Co (Taniguchi N, Obayashi K, Kusuta S): Nitric oxide synthase inhibitor. JP-09208562 (1997).
119. Ono Pharmaceutical Co (Taniguchi N, Kobayashi K, Murota M): Inhibitors of nitric oxide synthase. JP-09249655 (1997).
120. Merck & Co Inc (Esser CK et al): Substituted 2-aminopyridines as inhibitors of nitric oxide synthase. WO-09618616 (1996).
121. Japan Tobacco Inc (Araumi H, Yada S, Wakitani Y): 2-aminopyridine derivatives and nitric oxide synthetase inhibitors comprising them. JP-08311028 (1996).
122. Fujisawa Pharmaceutical Co Ltd (Iwamoto T et al): New use. JP-09077668 (1997).
123. Ono Pharmaceutical Co (Taniguchi N, Kobayashi K): Nitric oxide synthase inhibitors. JP-09132529 (1997).
124. Nippon Kayaku KK (Kawano E, Nagai M, Inubushi A): Nitrogen monoxide synthetase inhibitor comprising 2-aminopyridines as active ingredient. WO-09709982 (1997).
125. Pfizer Inc (Lowe JA, Whittle PJ): 6-Phenylpyridyl-2-amine derivatives. WO-09736871 (1997).
126. Schering AG (Holscher P et al): Imidazole derivatives and the use thereof as nitrogen monoxide synthase inhibitors. WO-09715555 (1997).
127. Roussel-Uclaf (Bloy C et al): Use of beta-naphthoquinone for accelerating the proliferation of endothelial cells and inhibiting NO syntheses. EP-00631776 (1995).
128. Otsuka Pharmaceutical Co (Moritoki N et al): Nitrogen monoxide synthesis inhibitor. WO-09510266 (1995).
129. Ontogen Corp (Mjalli AMM, Sarshar S, Zhang C): Nitric oxide synthase (NOS) inhibitors. WO-09705871 (1997).
130. Astra AB (Hamley PRJ et al): Pharmaceutically active quinazoline compounds. WO-09714686 (1997).
131. Astra AB (Hamley P et al): Aminoisoquinolines and aminothienopyridine derivatives and their use as antiinflammatory agents. WO-09738977 (1997).
132. Hoechst AG (Pfeiderer W, Schmidt H, Henning R): Use of tetrahydropteridine derivatives as NO synthase inhibitors. WO-09532203 (1995).
133. Hoechst AG (Pfeiderer W, Schmidt H, Henning R): Use of pteridine derivatives as NO-synthase inhibitors. WO-09531987 (1995).
134. Laboratoires Hoechst (Bernard D et al): Nouveaux derives nitro-ethyleniques soufres et leurs applications en tant qu'inhibiteurs de NO synthase. FR-02730733 (1996).
135. Fujisawa Pharmaceutical Co Ltd (Katsura Y, Nishino S, Tomishi T): Amidine derivatives. WO-09630350 (1996).
136. Fujisawa Pharmaceutical Co Ltd (Katsura Y, Nishino S, Tomishi T): Quinazoline derivatives. WO-09702254 (1997).
137. Fujisawa Pharmaceutical Co. Ltd (Itoh Y et al): New indolyl and benzofuranyl carboxamides as inhibitors of nitric oxide production. WO-09745425 (1997).
138. Takeda Chemical Industries Ltd (Ichimori Y et al): Suppressor against nitrogen monoxide formation and its screening. JP-08311050 (1996).