The search for new COX-2 inhibitors: A review of 2002 - 2008 patents

Expert Opinion on Therapeutic Patents

Volumn 19, Issue 9, 2009, Pages 1193-1228

  Ramalho, Teodorico C ^a   Rocha, Marcus V J ^a   Da Cunha, Elaine F F ^a   Freitas, Matheus P ^a  

^a FEDERAL UNIVERSITY OF LAVRAS   (Brazil)

Author keywords

Anti inflammatory drugs; COX 2; NSAIDs; Patents

Indexed keywords

ACETYLSALICYLIC ACID; BENZOPYRAN DERIVATIVE; BIPHENYL DERIVATIVE; BLX 1002; CELECOXIB; CYCLOOXYGENASE 2 INHIBITOR; DERACOXIB; DICLOFENAC; ETORICOXIB; GW 406381; IBUPROFEN; INDOLE DERIVATIVE; INDOMETACIN; ISOXAZOLE DERIVATIVE; LUMIRACOXIB; MORPHINE; NAPHTHALENE DERIVATIVE; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; OCID 2065; PARECOXIB; PC 406; PC 407; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; ROFECOXIB; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALDECOXIB;

ACUTE ABDOMEN; ACUTE HEART INFARCTION; ANTIINFLAMMATORY ACTIVITY; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; DRUG SAFETY; DRUG SYNTHESIS; GASTROINTESTINAL SYMPTOM; HEART INFARCTION; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LOW BACK PAIN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OSTEOARTHRITIS; PAW EDEMA; POSTOPERATIVE PAIN; REVIEW; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION;

ANALGESICS; ANIMALS; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; DRUG DELIVERY SYSTEMS; HUMANS; INFLAMMATION; PAIN; PATENTS AS TOPIC;

EID: 69949150537     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543770903059125     Document Type: Review

References (107)

1. Pillai AD, Rathod PD, Xavier FP, et al. Tetra substituted thiophenes as anti-inflammatory agents: exploitation of analogue-based drug design. Bioorg Med Chem 2005;13(24):6685-6692
2. Wilson LM. In: Price SA, Wilson LM, editors, Pathophysiology: clinical concepts of disease processes, Mosby St. Louis, Missouri. 2003. p. 44-61
3. Cicconetti A, Bartoli MDA, Ripari FDDS, Ripari A. Cox-2 selective inhibitors: a literature review of analgesic efficacy and safety in oral-maxillofacial surgery. Oral Srug Med Oral Pathol 2004;97(2):139-146
4. Radi ZA, Khan NK. Effects of cyclooxygenase inhibition on the gastrointestinal tract. Exp Toxicol Pathol 2006;58:163-173 (Pubitemid 44635152)
5. Kiefer JR, Pawlitz JL, Moreland KT, et al. Structural insights into the stereochemistry of the cyclooxygenase reaction. Nature 2000;405(6782):97-101
6. Capone ML, Tacconelli S, Di Francesco L, et al. Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat 2007;82 Special Issue:85-94
7. Patrignani P, Tacconelli S, Sciulli MG, Capone ML. New insights into COX-2 biology and inhibition. Brain Res Rev 2005;48:352-359 (Pubitemid 40585766)
8. GD Searle & Co. Substituted pyrazolyl benzenesulfonamides. US5466823; 1993
9. Merck Frosst Canada & Co. Phenyl heterocycles as cyclooxygenase-2 inhibitors. WO09500501; 1995
10. Penning TD, Talley JJ, Bertenshaw SR, et al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-58635, Celecoxib). J Med Chem 1997;40(9):1347-1365
11. Chan CC, Boyce C, Brideau C, Charleson S, et al. Rofecoxib [Vioxx, MK-0966; 4-(49-Methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther 1999;290:551-560 (Pubitemid 29344546)
12. Available from: http.://www.vioxx.com.
13. Talley J, Brown DL, Nagarajan S, Carter JS, et al. Substituted isoxazoles for the treatment of inflammation. US5633272; 1997
14. Fricke J, Varkalis J, Zwillich SAM, et al. Valdecoxib is more efficacious than rofecoxib in relieving pain associated with oral surgery. J Ther 2002;9(2):89-97
15. Jain KK. Evaluation of intravenous parecoxib for the relief of acute post-surgical pain. Expert Opin Invest Drugs 2000;9(11):2717-2723
16. Cochrane DJ, Jarvis B, Keating GM. Etoricoxib. Drugs 2002;62(18):2637- 2651
17. Bannwarth B, Bérenbaum F. Lumiracoxib in the management of osteoarthritis and acute pain. Expert Opin Pharmacother 2007;8:1551-1564 (Pubitemid 47082703)
18. Karnik PS, Johnston S, Ward D, et al. The effects of epidural deracoxib on the ground reaction forces in an acute stifle synovitis model. Vet Surg 2006;35:34-42
19. Tacconelli S, Capone ML, Patrignani P. Clinical pharmacology of novel selective COX-2 inhibitors. Curr Pharm Des 2004;10:589-601 (Pubitemid 38292386)
20. Rahme E, Nedjar H. Risks and benefits of COX-2 inhibitors vs non-selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study. Rheumatology 2007;46:435-438 (Pubitemid 46344654)
21. Warner TD, Mitchell JA. COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet 2008;371:270-273
22. Kulmacz RJ, Wang LH. Comparison of hydroperoxide initiator requirements for the cyclooxygenase activities of prostaglandin H synthase-1 and -2. J Biol Chem 1995;270:24019-24023
23. Ueno N, Murakami M, Tanioka T, et al. Coupling between cyclooxygenase, terminal prostanoid synthase, and phospholipase A2. J Biol Chem 2001;276:34918-34927 (Pubitemid 37384495)
24. Dajani EZ, Islam K. Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man. J Physiol Pharmacol 2008;59(Suppl 2):117-133
25. Huntjens DR, Danhof M, Della Pasqua OE. Pharmacokinetic-pharmacodynamic correlations and biomarkers in the development of COX-2 inhibitors. Rheumatology (Oxford) 2005;44:846-859 (Pubitemid 41511177)
26. Solomon SD, Mcmurray JJ, Pfeffer MA. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071-1080 (Pubitemid 40365348)
27. Andersohn F, Suissa S, Garbe E. Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation 2006;113:1950-1957 (Pubitemid 43754197)
28. Garcia Rodriguez LA, Gonzalez-Perez A. Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. BMC Med 2005;3:17-21
29. Marnett LJ, Rowlinson SW, Goodwin DC, et al. Arachidonic acid oxygenation by COX-1 and COX-2: mechanisms of catalysis and inhibition. J Biol Chem 1999;274:22903-22906 (Pubitemid 129529112)
30. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000;343:1520-1528 (Pubitemid 30844348)
31. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005;352:1081-1091
32. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005;352:1092-1102 (Pubitemid 40365350)
33. Dixon DA, Kaplan CD, Mcintyre TM, et al. Post-transcriptional control of cyclooxygenase-2 gene expression: the role of the 3-untranslated region. J Biol Chem 2000;275:11750-11757 (Pubitemid 30237739)
34. Murphey LJ, Williams MK, Sanchez SC, et al. Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal Biochem 2004;334:266-275
35. Cheng Y, Wang M, Yu Y, et al. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 2006;116:1391-1399
36. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthitis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthitis Safety Study. JAMA 2000;284:1247-1255
37. Moreau A, Chen QH, Rao PNP, Knaus EE. Design, synthesis, and biological evaluation of (E)-3-(4-methanesulfonylphenyl)-2-(aryl)acrylic acids as dual inhibitors of cyclooxygenases and lipoxygenases. Bioorg Med Chem 2006;14:7716-7727 (Pubitemid 44584724)
38. Weir MR, Sperling RS, Reicin A, et al. Selective COX-2 inhibition and cardiovascular effects: a review of the rofecoxib development program. Am Heart J 2003;146:591-604 (Pubitemid 37281702)
39. Lu ZH, Xiong X, Zhang BL, et al. Evaluation of 2 celecoxib derivatives: analgesic effect and selectivity to cyclooxygenase-2/11. Acta Pharmacol Sin 2005;26(12):1505-1511 (Pubitemid 41789541)
40. Navidpour L, Amini M, Shafaroodi H, et al. Design and synthesis of new water-soluble tetrazolide derivatives of celecoxib and rofecoxib as selective cyclooxygenase-2 (COX-2) inhibitors. Bioorg Med Chem Lett 2006;16:4483-4487 (Pubitemid 44094087)
41. Liu H, Huang XQ, Shen JH, et al. Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1: molecular docking and 3D QSAR analyses. J Med Chem 2002;45:4816-4827 (Pubitemid 35192771)
42. Singh SK, Saibaba V, Sprinivasa RK, et al. Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore. Eur J Med Chem 2005;40:977-990 (Pubitemid 41421103)
43. Pharmacia Corporation. Stabilized oral pharmaceutical composition. WO02102376; 2002
44. Pharmacia Corporation. Novel arylsulfonamide prodrugs of COX-2 inhibitors. WO02083655; 2002
45. Young DV, Cochran ED, Dhawan V, et al. A comparison of the cyclooxygenase inhibitor-NO donors (CINOD), NMI-1182 and AZD3582, using in vitro biochemical and pharmacological methods. Biochem Pharm 2005;70:1343-1351 (Pubitemid 41383470)
46. NitroMed, Inc. Novel substituted benzene compounds as COX-2 inhibitors useful for the treatment of gastrointestinal disorders, inflammation, pain, fever and neoplasia. WO04010945; 2004
47. NitroMed, Inc. Novel oxime- and/or hydrazone-containing nitrosated and/or nitrosylated selective COX-2 inhibitors, useful for the treatment of inflammation. WO04002420; 2004
48. NitroMed, Inc. Novel nitrosated or nitrosylated 3-phenylpyrazole derivatives with COX-2-inhib-iting and NO-donating activities, useful for the treatment of inflammation. WO04002409; 2004
49. Ranatunge RR, Augustyniak M, Bandarage UK, et al. Synthesis and selective cyclooxygenase-2 inhibitory activity of a series of novel, nitric oxide donor-containing pyrazoles. J Med Chem 2004;47:2180-2193 (Pubitemid 38478842)
50. Merck Frosst Canada & Co. New nitric oxide releasing compounds are selective cyclooxygenase 2 inhibitors - useful for the treatment of inflammatory disease. WO04037798; 2004
51. Whitehead AJ, Ward RA, Jones MF. Efficient synthesis of the selective COX-2 inhibitor GW406381X. Tetrahedron Lett 2007;48:911-913 (Pubitemid 46072997)
52. Bingham S, Beswick PJ, Bountra C, et al. The cyclooxygenase-2 inhibitor GW406381X [2-(4-Ethoxyphenyl)-3-[4-(methylsulfonyl)phenyl]-pyrazolo [1,5-b]pyridazine] is effective in animal models of neuropathic pain and central sensitization. J Pharmacol Exp Ther 2005;312:1161-1169
53. CJ Corp. Novel bipyridinyl derivatives useful as selective COX-2 inhibitors. WO03055874; 2003
54. CJ Corp. Novel diaryl 1,2,4-triazole derivatives useful as selective COX-2 inhibitors. WO03055875; 2003
55. CJ Corp. Use of 1,2,4-triazole derivatives as COX-2 inhibitors - for the prevention and treatment e.g. of fever, pain, inflammation, gastric ulcers and rheumatoid arthritis. WO04048347; 2004
56. CJ Corp. Novel COX-2-inhibiting 1,2,4-triazole derivatives useful for the treatment of fever, pain, inflammation, cancer and dementia. WO04014878; 2004
57. CJ Corp. New 1-(3-fluoro-4-methylsulfonyl-phenyl)-5-aryl- 3-trifluoromethyl-1,2,4-triazole derivatives are selective COX-2 inhibitors - useful for the treatment of fever, pain, inflammation, cancer and dementia. WO04046121; 2004
58. Navidpour L, Shafaroodi H, Abdi K, et al. Design, synthesis, and biological evaluation of substituted 3-alkylthio-4, 5-diaryl-4H-1,2,4-triazoles as selective COX-2 inhibitors. Bioorg Med Chem 2006;14:2507-2517
59. CJ Corp. 1H-indoles as a highly selective cyclooxygenase-2 inhibitors. WO03031409; 2003
60. NitroMed, Inc. New 2-methylindole derivatives are selective COX-2 inhibitors - useful for the treatment of inflammation, pain, fever, gastrointestinal disorders, wound healing and diseases resulting from elevated levels of COX-2. WO06099416; 2006
61. Sedgwick D, Lees P. Studies of eicosanoid production in the air pouch model of synovial inflammation. Agents Actions 1986;18:429-438 (Pubitemid 16040731)
62. Masferrer JL, Zweifel BS, Manning PT, et al. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. PNAS USA 1994;91:3228-3232
63. University of Liege. Pyridinic sulfonamide derivatives, method of production and use thereof. WO03029217; 2003
64. Orchid Research Laboratories Ltd. New pyrimidine carboxamides are TNF-α inhibitors - useful for the treatment of eg pain, inflammation, rheumatoid arthritis, osteoporosis, leukemia, atherosclerosis and cancer. WO07031829; 2007
65. CJ Corp. 3,4-dihydro-1H-naphthalene derivatives as a highly selective cyclooxygenase-2 inhibitor. WO03031418; 2003
66. Pharmacia & Upjohn Co. New benzopyran carboxylate derivatives are COX-2 inhibitors - useful for the treatment of inflammation and other conditions. WO06040676; 2006
67. GD Searle & Co. Dihydrobenzopyrans, dihydrobenzothiopyrans, and tetrahydroquinolines for the treatment of cox-2-mediated disorders. US50010050; 2005
68. Carter J, Brown D, Xing L, Aston K, et al. Benzopyran compounds for use in the treatment and prevention of inflammation related conditions. US50148627; 2005
69. CJ Corp. 4′-methanesulfonyl-biphenyl derivatives as a highly selective cyclooxygenase-2 inhibitor. WO03031398; 2003
70. CJ Corp. New thione derivatives are cyclooxygenase-2 inhibitors - useful for the treatment of fever, pain and inflammation. WO05051941; 2005
71. Universita di Bari. New 3, 4-bis-arylisoxazole derivatives are cyclooxygenase inhibitors - useful for the treatment of pain, infllammation and cancer. WO05068442; 2005
72. Di Nunno L, Vitale P, Scilimati A, et al. Novel synthesis of 3,4-diarylisoxazole analogues of valdecoxib: reversal cyclooxygenase-2 selectivity by sulfonamide group removal. J Med Chem 2004;47:4881-4891 (Pubitemid 39238263)
73. Gedeon Richter Ltd. New N-hydroxy-4-(3-phenyl-5-methyl-isoxazole-4-yl)- benzenesulfonamide solvates are COX-2 inhibitors - useful for the treatment of arthritis and pain. WO05007620; 2005
74. Toyokuni T, Dillep KJS, Walsh JC, et al. Synthesis of 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl)-benzenesulfonamide, a new [18]F]fluorinated analogue of valdecoxib, as a potential radiotracer for imaging cyclooxygenase-2 with positron emission tomography. Bioorg Med Chem Lett 2005;15:4699-4702
75. Biava M, Porretta GC, Poce G, et al. Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents. Bioorg Med Chem 2008;16:8072-8081
76. Anzini M, Rovini M, Cappelli A, et al. Synthesis, biological evaluation, and enzyme docking simulations of 1,5-diarylpyrrole-3-alkoxyethyl ethers as selective cyclooxygenase-2 inhibitors endowed with anti-inflammatory and antinociceptive activity. J Med Chem 2008;51:4476-4481
77. Swinney DC, Mak AY, Barnett J, Ramesha CS. Differential allosteric regulation of prostaglandin H synthase-1 and -2 by arachidonic acid. J. Biol. Chem 1997;272:12393-12398 (Pubitemid 27203326)
78. Merck Frosst Canada & Co. Synthesis of 4-[(5-substituted or unsubstituted phenyl)-3-substituted-1H-pyrazol -1-yl] benzenesulfonamides. WO00042021; 2000
79. Generics (UK) Ltd. Novel crystalline adducts of celecoxib with organic solvents, providing improved handling properties. WO03091221; 2003
80. Generics (UK) Ltd. Novel crystalline forms of celecoxib and other compounds. WO03090730; 2003
81. Hetero Drugs Ltd. New crystalline form of celecoxib DMF solvate - comprising an N,N-dimethylformamide content of about 4-12% of the weight of the celecoxib DMF solvate. WO05014546; 2005
82. Pharmacia & Upjohn Co. Crystalline Form IV of celecoxib - useful for the treatment of pain and inflammation. WO06079923; 2006
83. Pharmacia Corporation. Novel crystalline form of parecoxib sodium useful for treating inflammation, pain, fever and arthritis. WO03078408; 2003
84. Pharmacia Corporation. Oral dosage form of a sulfonamide prodrug such as parecoxib. WO03041705; 2003
85. Pharmacia Corporation. New metal salts of parecoxib are prodrugs of valdecoxib - useful for treating inflammation, fever and pain. WO05065684; 2005
86. Pharmacia Corporation. Transdermal formulations of COX-2 inhibitors. WO02096435; 2002
87. St John MAR, Abemayor E, Wong DTW. Recent new approaches to the treatment of head and neck cancer. Anti Cancer Drugs 2006;17(4):365-375 (Pubitemid 44309978)
88. Sooriakumaran P, Langley SEM, Laing RW. COX-2 inhibition: a possible role in the management of prostate cancer? J Chemotherapy 2007;19(1):21-32
89. Gonzalez-Periz A, Claria J. New approaches to the modulation of the cyclooxygenase-2 and 5-lipoxygenase pathways. Curr Topics Med Chem 2007;7(3):297-309 (Pubitemid 46358663)
90. Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acid Res 2000;28:235-242
91. Kiefer JR, Pawlitz JL, Moreland KT, et al. Structural insights into the stereochemistry of the cyclooxygenase reaction. Nature 2000;405:97-101
92. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, et al. A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem 2003;278(46):45763-45769
93. Sakya SM, Cheng HM, DeMello KML, et al. 5-heteroatom-substituted pyrazoles as canine COX-2 inhibitors: part 2. Structure-activity relationship studies of 5-alkylethers and 5-thioethers. Bioorg Med Chem Lett 2006;16(5):1202-1206
94. Sakya SM, DeMello KML, Minich ML, et al. 5-Heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part 1: structure-activity relationship studies of 5-alkylamino pyrazoles and discovery of a potent, selective, and orally active analog. Bioorg Med Chem Lett 2006;16(2):288-292
95. Shahapurkar S, Pandya T, Kawathekar N. Quantitative structure activity relationship studies of diaryl furanones as selective COX-2 inhibitors. Eur J Med Chem 2004;39:899-904 (Pubitemid 38457032)
96. Ranatunge RR, Augustyniak M, Bandarage UK. Synthesis and selective cyclooxygenase-2 inhibitory activity of a series of novel, nitric oxide donor-containing pyrazoles. J Med Chem 2004;47(9):2180-2193 (Pubitemid 38478842)
97. Ranatunge RR, Garvey DS, Janero DR. Synthesis and selective cyclooxygenase-2 (COX-2) inhibitory activity of a series of novel bicyclic pyrazoles. Bioorg Med Chem 2004;12(6):1357-1366 (Pubitemid 38296526)
98. Ranatunge RR, Earl RA, Garvey DS. 3-(2-methoxytetrahydrofuran-2-yl) pyrazoles: a novel class of potent, selective cyclooxygenase-2 (COX-2) inhibitors. Bioorg Med Chem Lett 2004;14(24):6049-6052 (Pubitemid 39531269)
99. Chen QH, Rao PNP, Knaus EE. Design, synthesis, and biological evaluation of N-acetyl-2-carboxybenzenesulfonamides: a novel class of cyclooxygenase-2 (COX-2) inhibitors. Bioorg Med Chem 2005;13:2459-2468 (Pubitemid 40341650)
100. Abouzid K, Bekhit SA. Novel anti-inflammatory agents based on pyridazinone scaffold; design, synthesis and in vivo activity. Bioorg Med Chem 2008;16:5547-5556 (Pubitemid 351694476)
101. Singh P, Mittal A. Current status of COX-2 inhibitors. Mini Rev Med Chem 2008;8:73-90
102. Chowdhury MA, Dong Y, Chen QH. Synthesis and cyclooxygenase inhibitory activities of linear 1-(methanesulfonylphenyl or benzenesulfonamido)-2(pyridyl) acetylene regioisomers. Bioorg Med Chem 2008;16:1948-1956
103. Da Cunha EFF, Albuquerque MG, Antunes OAC. 4D-QSAR models of HOE/BAY-793 analogues as HIV-1 protease inhihitors. QSAR Comb Sci 2005;24(2):240-253
104. Da Cunha EFF, Ramalho TC, De Alencastro RB. Interactions of 5-deazapteridine derivatives with Mycobacterium tuberculosis and with human dihydrofolate reductases. J Biomol Struct Dyn 2004;22(2):119-130
105. Da Cunha EFF, Martins RCA, Albuquerque MG. LIV-3D-QSAR model for estrogen receptor ligands. J Mol Mod 2004;10(4):297-304
106. Da Cunha EFF, Ramanlho TC, Mala ER, De Alencastro RB. The search for new DHFR inhibitors: a review of patents, January 2001 February 2005. Expert Opin Ther Patents 2005;15(8):967-986
107. Araujo LF, Soeiro AM, Fernandes JL, Serrano Júnior. Cardiovascular events: a class effect by COX-2 inhibitors. Arq Bras Cardiol 2005;85(3):222-229 (Pubitemid 41345487)