Therapeutic potential of sulfamides as enzymes inhibitors

Medicinal Research Reviews

Volumn 26, Issue 6, 2006, Pages 767-792

  Winum, Jean Yves ^a,b   Scozzafava, Andrea ^b   Montero, Jean Louis ^a   Supuran, Claudiu T ^b  

^a UNIV MONTPELLIER   (France)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

secretase; Carbonic anhydrase inhibitors; Carboxypeptidase A; Chymase; Elastase; Enzyme inhibitor adduct; HIV protease; Matrix metalloproteinase; Protease inhibitors; Steroid sulfatase inhibitors; Sulfamide; Thrombin; Tryptase

Indexed keywords

CARBONATE DEHYDRATASE; CARBONATE DEHYDRATASE INHIBITOR; CARBOXYPEPTIDASE A; CHYMASE; CHYMASE INHIBITOR; ELASTASE; ELASTASE INHIBITOR; ENZYME INHIBITOR; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; HYDROGEN; MATRIX METALLOPROTEINASE; MATRIX METALLOPROTEINASE INHIBITOR; METALLOPROTEINASE; METALLOPROTEINASE INHIBITOR; NITROGEN; PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; PROTEINASE; PROTEINASE INHIBITOR; SERINE PROTEINASE; SERINE PROTEINASE INHIBITOR; STERYL SULFATASE; SULFAMIDE DERIVATIVE; SULFONAMIDE; THROMBIN; THROMBIN INHIBITOR; TRYPTASE; TRYPTASE INHIBITOR; UNINDEXED DRUG;

ATOM; BINDING AFFINITY; CHEMICAL MODIFICATION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG SOLUBILITY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITION; HUMAN; MOLECULE; NONHUMAN; PHYSICAL CHEMISTRY; REVIEW;

CARBONIC ANHYDRASE INHIBITORS; ENZYME INHIBITORS; HUMANS; PROTEASE INHIBITORS; SULFONAMIDES;

EID: 33750935667     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/med.20068     Document Type: Review

References (107)

1. Supuran CT, Scozzafava A, Casini A. Carbonic anhydrase inhibitors. Med Res Rev 2003;23:146-189.
2. Supuran CT, Scozzafava A. Applications of carbonic anhydrase inhibitors and activators in therapy. Expert Opin Ther Pat 2002;12:217-242.
3. Supuran CT, Scozzafava A. Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opin Ther Pat 2000;10:575-600.
4. Scozzafava A, Owa T, Mastrolorenzo A, Supuran CT. Anticancer and antiviral sulfonamides. Curr Med Chem 2003;10:925-953.
5. Scozzafava A, Owa T, Mastrolorenzo A, Supuran CT. Modulation of carbonic anhydrase activity and its applications in therapy. Expert Opin Ther Pat 2004;14:667-702.
6. Supuran CT, Scozzafava A, Casini A. Development of sulfonamide carbonic anhydrase inhibitors (CAIs). In: Supuran CT, Scozzafava A, Conway J, editors. Carbonic anhydrase, its inhibitors and activators. Boca Raton, FL: CRC Press; 2004. pp 67-147.
7. Winum JY, Scozzafava A, Montera JL, Supuran CT. Sulfamates and their therapeutic potential. Med Res Rev 2005;25:186-228.
8. Abbate F, Supuran CT, Scozzafava A, Orioli P, Stubbs MT, Klebe G. Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: Role of hydrogen-bonding networks in ligand binding and drug design. J Med Chem 2002;45:3583-3587.
9. Winum JY, Scozzafava A, Montero JL, Supuran CT. Therapeutic applications of sulfamates. Expert Opin Ther Pat 2004;14:1273-1308.
10. Supuran CT, Scozzafava A, Conway J, editors. Carbonic anhydrase-Its inhibitors and activators. Boca Raton, FL: CRC Press; 2004. pp 1-363.
11. Pastorekova S, Parkkila S, Pastorek J, Supuran CT. Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects. J Enz Inhib Med Chem 2004;19:199-229.
12. Supuran CT, Scozzafava A. Carbonic anhydrase inhibitors. Curr Med Chem- Imm Endoc Metab Agents 2001;1:61-97.
13. Supuran CT. Carbonic anhydrase inhibitors in the treatment and prophylaxis of obesity. Expert Opin Ther Pat 2003;13:1545-1550.
14. Supuran CT. Indisulam: An anticancer sulfonamide in clinical development. Expert Opin Investig Drugs 2003;12:283-287.
15. Pastorekova S, Pastorek J. Cancer-related carbonic anhydrase isozymes and their inhibition. In: Supuran CT, Scozzafava A, Conway J, editors. Carbonic anhydrase-Its inhibitors and activators. Boca Raton, FL: CRC Press; 2004. pp 253-280.
16. Briganti F, Mangani S, Orioli P, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine. Biochemistry 1997;36:10384-10392.
17. Menchise V, De Simone G, Alterio V, Di Fiore A, Pedone C, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: Stacking with Phe131 determines active site binding region of inhibitors as exemplified by the X-ray crystal structure of a membrane-impermeant antitumor sulfonamide complexed with isozyme II. J Med Chem 2005;48:5721-5727.
18. De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, Scozzafava A, Wurl M, Supuran CT. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg Med Chem Lett 2005;15: 2315-2320.
19. Di Fiore A, De Simone G, Menchise V, Pedone C, Casini A, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: X-Ray crystal structure of a benzenesulfonamide strong CA II and CA IX inhibitor bearing a pentafluorophenylaminothioureido tail in complex with isozyme IT. Bioorg Med Chem Lett 2005;15:1937-1942.
20. Casini A, Antel J, Abbate F, Scozzafava A, David S, Waldeck H, Schäfer S, Supuran CT. Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg Med Chem Lett 2003;13:841-845.
21. Svastova E, Hulikova A, Rafajova M, Zatovicova M, Gibadulinova A, Casini A, Cecchi A, Scozzafava A, Supuran CT, Pastorek J, Pastorekova S. Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH. FEBS Letters 2004;577:439-445.
22. Briganti F, Pierattelli R, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors. Part 37. Novel classes of carbonic anhydrase inhibitors and their interaction with the native and cobalt-substituted enzyme: Kinetic and spectroscopic investigations. Eur J Med Chem 1996;31:1001-1010.
23. Scozzafava A, Banciu MD, Popescu A, Supuran CT. Carbonic anhydrase inhibitors. Inhibition of isozymes I, II and IV by sulfamide and sulfamic acid derivatives. J Enz Inhib 2000;15:443-453.
24. Casini A, Winum J-Y, Montera J-L, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: Inhibition of cytosolic isozymes I and II with sulfamide derivatives. Bioorg Med Chem Lett 2003;13:837-840.
25. Winum J-Y, Innocenti A, Nasr J, Montero J-L, Scozzafava A, Vullo D, Supuran CT. Carbonic anhydrase inhibitors: Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, IX and XII with N-hydroxy-sulfamides-A new zinc binding function in the design of inhibitors. Bioorg Med Chem Lett 2005;15:2353-2358.
26. Winum J-Y, Cecchi A, Montero J-L, Innocenti A, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors. Synthesis and inhibition of cytosolic/tumor- associated carbonic anhydrase isozymes I, II and IX with boron-containing sulfonamides, sulfamides and sulfamates: Towards agents for boron neutron capture therapy of hypoxic tumors. Bioorg Med Chem Lett 2005;15:3302-3306.
27. Leung D, Abbenante G, Fairlie DP. Protease inhibitors: Current status and future prospects. J Med Chem 2000;43:305-341.
28. Smith HJ, Simons C. Protease and peptidase inhibition-Recent potential target for drug development. Taylor & Francis, London and New-York. 2002. 1-412. and references cited therein.
29. Niestroj AJ, Demuth HU. Proteases. In: Smith J, Simons C, editors. Enzymes and their inhibition-Drug development. Boca Raton, FL: CRC Press; 2005. pp 88-117.
30. Supuran CT, Casini A, Scozzafava A. Protease inhibitors of the sulfonamide type: Anticancer, anti-inflammatory and antiviral agents. Med Res Rev 2003;23:535-558.
31. Supuran CT, Scozzafava A, Clare BW. Bacterial protease inhibitors. Med Res Rev 2002;22:329-372.
32. Ogden RC, Flexner CW. editors. Protease Inhibitors in AIDS Therapy. New York, Basel: Marcel Dekker; 2001. pp 1-310.
33. Erickson JW. HIV-1 protease as a target for AIDS therapy. In: Ogden RC, Flexner CW, editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekker; 2001. pp 1-25.
34. Schlechter I, Berger A. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun 1967;27:157-162.
35. Barbaro G, Scozzafava A, Mastrolorenzo A, Supuran CT. Highly active antiretroviral therapy: Current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome. Curr Pharm Des 2005;11:1805-1843.
36. Duncan IB, Redshaw S. Discovery and early development of saquinavir. In: Ogden RC, Flexner CW, editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekkerl; 2001. pp 27-47.
37. Kempf DJ. Discovery and early development of ritonavir and ABT-378. In: Ogden RC, Flexner CW, editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekker; 2001. pp 49-64.
38. Dorsey BD, Vacca JP. Discovery and early development of indinavir. In: Ogden RC, Flexner CW, editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekker; 2001. pp 65-83.
39. Reich SH. Discovery and early development of nelfmavir (Viracept). In: Ogden RC, Flexner CW, editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekker; 2001. pp 85-99.
40. Tung RD, Livingston DJ, Rao BG, Kim EE, Baker CT, Boger JS. Design and synthesis of amprenavir, a novel HIV protease inhibitor. In: Ogden RC, Flexner CW, editors. Protease inhibitors in AIDS therapy. New York: Marcel Dekker; 2001. pp 101-118.
41. Hulten J, Bonham NM, Nillroth U, Hansson T, Zuccarello G, Bouzide A. Cyclic HIV-1 protease inhibitors derived from mannitol: Synthesis, inhibitory potencies, and computational predictions of binding affinities. J Med Chem 1997;40:885-897.
42. Backbro K, Lowgren S, Osterlund K, Atepo J, Unge T, Hulten J. Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor. J Med Chem 1997;40:898-902.
43. Hulten J, Andersson HO, Schaal W, Danielson UH, Classon B, Kvarnstrom I. Inhibitors of the C(2)-symmetric HIV-1 protease: Nonsymmetric binding of a symmetric cyclic sulfamide with ketoxime groups in the P2/P2′ side chains. J Med Chem 1999;42:4054-4061.
44. Ala PJ, Chang CH. HIV aspartate proteinase: Resistance to inhibitors. In: Smith HJ, Simons C, editors. Proteinase and peptidase inhibition: Recent potential targets for drug development. London and New York: Taylor & Francis Publishing House; 2002. pp 367-382.
45. Schmidt B. Aspartic proteases involved in Alzheimer's disease. ChemBioChem 2003;4:366-378.
46. Pollack SJ, Lewis H. Secretase inhibitors for Alzheimer's disease: Challenges of a promiscuous protease. Curr Opin Invest Drugs 2005;6:35-47.
47. Tomita T, Iwatsubo T. The inhibition of γ-secretase as a therapeutic approach to Alzheimer's disease. Drug News Perspect 2004;17:321-325.
48. Tsai JY, Wolfe MS, Xia W. The search for γ-secretase and development of inhibitors. Curr Med Chem 2002;9:1087-1106.
49. Roberts SB. γ-secretase inhibitors and Alzheimer's disease. Adv Drug Deliv Rev 2002;54:1579-1588.
50. Wolfe MS. Secretase targets for Alzheimer's disease: Identification and therapeutic potential. J Med Chem 2001;44:2039-2060.
51. Sparey T, Beher D, Best J, Biba M, Castro JL, Clarke E, Hannam J, Harrison T, Lewis H. Cyclic sulfamide γ-secretase inhibitors. Bioorg Med Chem Lett 2005;15:4212-4216.
52. Merck, Sharp & Dohme. WO Patent 2005/014553. 2005.
53. Merck, Sharp & Dohme. WO Patent 2004/039370. 2004.
54. Merck, Sharp & Dohme. WO Patent 2004/039800. 2004.
55. Christianson DW, Lipscomb NW. Carboxypeptidase A. Acc Chem Res 1989;22:62-69.
56. Lipscomb NW, Strater N. Recent advances in zinc enzymology. Chem Rev 1996;96:2375-2433.
57. Kim DH. Chemistry-based design of inhibitors for carboxypeptidases A. Curr Top Med Chem 2004;4:1217-1226.
58. Park JD, Kim DH, Kim SJ, Woo JR, Ryu SE. Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition state analogue inhibitors for zinc proteases. J Med Chem 2002;45:5295-5302.
59. Park JD, Kim DH. Sulfamide derivatives as transition state analogue inhibitors for carboxypeptidase A. Bioorg Med Chem Lett 2004;12:2349-2356.
60. Supuran CT, Scozzafava A. Metalloproteinase-collagenase inhibitors examples. In: Smith HJ, Simons C, editors. Enzymes and their inhibition-Drug development. Boca Raton, FL: CRC Press; 2005. pp 292-300.
61. Supuran CT, Scozzafava A. Matrix metalloproteinase (MMPs). In: Smith HJ, Simons C, editors. Proteinase and peptidase inhibition-Recent potential target for drug development. London: Taylor & Francis; 2002. pp 35-61.
62. Kontogiorgis GA, Papaioannou P, Hadjipavlou LDJ. Matrix metalloproteinase inhibitors: A review on pharmacophore mapping and (Q)SARs results. Curr Med Chem 2005;12:339-355.
63. Matter H, Schudok M. Recent advances in the design of matrix metalloprotease inhibitors. Curr Opin Drug Discov Devel 2004;7:513-535.
64. Whittaker M, Floyd CD, Brown P, Gearing AJH. Design and therapeutic application of matrix metalloproteinase inhibitors. Chem Rev 1999;99:2735-2776.
65. Doherty TM, Asotra K, Pei D, Uzui H, Wilkin DJ, Shah PK, Rajavashisth TB. Therapeutic developments in matrix metalloproteinase inhibition. Expert Opin Ther Pat 2002;12:665-707.
66. Hoffmann-La Roche. WO. Patent 98/32748. 1998.
67. Ilies MA, Supuran CT, Scozzafava A. Therapeutic applications of serine protease inhibitors. Expert Opin Ther Pat 2002;12:1181-1214.
68. Zhong J, Groutas WC. Recent Developments in the design of mechanism-based and alternate substrate inhibitors of serine proteases. Curr Top Med Chem 2004;4:1203-1216.
69. Casini A, Scozzafava A, Supuran CT. Sulfonamide derivatives with protease inhibitory action as anticancer, antiinflammatory and antiviral agents. Expert Opin Ther Pat 2002;12:1307-1327.
70. Groutas WC, Epp JB, Kuang R, Ruan S, Chong LS, Venkataraman R, Tu J, He S, Yu H, Fu Q, Li YH, Truong TM, Vu NT. 1,2,5-thiadiazolidin-3-one 1,1-dioxide: A powerful scaffold for probing the S′ subsites of (chymo)trypsin-like serine protease. Arch Biochem Biophys 2001;385:162-169.
71. Groutas WC, He S, Kuang R, Ruan S, Tu J, Chan HK. Inhibition of serine protease by functionalized sulphonamide coupled to the 1,2,5-thiadiazolidin-3- one 1,1-dioxide scaffold. Bioorg Med Chem 2001;9:1543-1548.
72. Lai Z, Gan X, Wei L, Alliston KR, Yu H, Li YH, Groutas WC. Potent inhibition of human leukocyte elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide-based sulfonamide derivatives. Arch Biochem Biophys 2004;429:191-197.
73. Kuang R, Venkataraman R, Ruan S, Groutas WC. Use of the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffolds in the design of potent inhibitors of serine proteinase. Bioorg Med Chem Lett 1998;8:539-544.
74. Groutas WC, Kuang R, Ruan S, Epp JB, Venkataraman R, Truong TM. Potent and specific inhibition of human leukocyte elastase, cathepsin G and proteinase 3 by sulfone derivatives employing the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffold. Bioorg Med Chem 1998;6:661-671.
75. Kuang R, Epp JB, Ruan S, Chang LS, Venkataraman R, Tu J, He S, Truong TM, Groutas WC. Utilization of the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylate. Bioorg Med Chem 2000;8:1005-1016.
76. He S, Kuang R, Venkataraman R, Tu J, Truong TM, Chan HK, Groutas WC. Potent inhibition of serine protease by heterocyclic sulfide derivatives of 1,2,5-thiadiazolidin-3-one 1,1-dioxide. Bioorg Med Chem 2000; 1713-1717.
77. Zhong J, Gan X, Alliston KR, Groutas W. Design, synthesis and in vitro evaluation of inhibitors of human leukocyte elastase based on a functionalized cyclic sulfamide scaffold. Bioorg Med Chem Lett 2004;12:589-593.
78. Groutas WC, Kuang R. WO Patent 99/0997. 1999.
79. Groutas WC. WO Patent 2001/081561. 2001.
80. Zhong J, Gan X, Alliston KR, Lai Z, Yu H, Groutas CS, Wong T, Groutas WC. Potential protease inhibitors based on functionnalized cyclic sulfamide scaffold. J Comb Chem 2004;6:556-563.
81. Takai S, Jin D, Muramatsu M, Okamoto Y, Miyazaki M. Therapeutic applications of chymase inhibitors in cardiovascular diseases and fibrosis. Eur J Pharmacol 2004;501:1-8.
82. Doggrell SH, Wanstall JC. Vascular chymase: Pathophysiological role and therapeutic potential of inhibition. Cardiovascular Res 2004;61:653-662.
83. Takai S, Jin D, Muramatsu M, Miyazaki M. Chymase as a novel target for the prevention of vascular diseases. Trends Pharm Sci 2004;25:519-522.
84. Groutas WC, Schechter NM, He S, Yu H, Huang P, Tu J. Human chymase inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffold. Bioorg Med Chem Lett 1999;9:2199-2204.
85. Cairns JA. Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammation disorders. Pulmon Pharmacol Ther 2005;18:55-66.
86. Wong T, Groutas CS, Mohan S, Lai Z, Alliston KR, Vu N, Schechter NM, Groutas WC. 1,2,5-thiadiazolidin-3-one 1,1-dioxide-based heterocyclic sulfides are potent inhibitors of human tryptase. Arch Biochem Biophys 2005;436:1-7.
87. Vacca JP. New Advances in the Discovery of Thrombin and Factor Xa Inhibitors. Curr Opin Chem Biol 2000;25:369-383.
88. Steinmetzer T. Thrombin inhibitors. In: Smith HJ, Simons C, editors. Enzymes and their inhibition-Drug development. Boca Raton, FL: CRC Press; 2005. pp 254-268.
89. Srivastava S, Goswami LN, Dikshit DK. Progress in the design of low molecular weight thrombin inhibitors. Med Res Rev 2005;25:66-92.
90. Lee K, Jung WH, Park CW, Park HD, Lee SH, Kwon OH. Noncovalent tripeptidic thrombin inhibitors incorporating Amidrazone, Amine and Amidine Functions at P1. Bioorg Med Chem Lett 2002;12:1017-1022.
91. Lee K, Park CW, Jung WH, Park HD, Lee SH, Chung KH, Park SK, Kwon OH, Kang M, Park DH, Lee SK, Kim EE, Yoon SK, Kim A. Efficacious and orally bioavailable thrombin inhibitors bases on a 2,5-thienylamidine at the P1 position: Discovery of N-carboxymethyl-D-diphenylalanyl-L-prolyl-[(5-amidino-2- thienyl)methyl]amide. J Med Chem 2003;46:3612-3622.
92. Nussbaumer P, Billich A. Steroid sulfatase inhibitors. Expert Opin Ther Pat 2003;13:605-625.
93. Howarth NM, Purohit A, Reed MJ, Potter BVL. Estrone sulfamates: Potent inhibitors of estrone sulfatase with therapeutic potential. J Med Chem 1994;37:219-221.
94. Woo LWL, Purohit A, Reed MJ, Potter BVL. Active site directed inhibition of estrone sulfatase by nonsteroidal coumarin sulfamates. J Med Chem 1996;39:1349-1351.
95. Poirier D, Ciobanu LC, Maltais R. Steroid sulfatase inhibitors. Expert Opin Ther Pat: 1999;9:1083-1099.
96. Smith HJ, Nicholls PJ, Simons C, Le Lain R. Inhibitors of steroidogenesis as agents for the treatment of hormone-dependent cancers. Expert Opin Ther Pat 2001;11:789-824.
97. Purohit A, Woo LWL, Chander SK, Newman SP, Ireson C, Ho Y, Grasso A, Leese MP, Potter BVL, Reed MJ. Steroid sulphatase inhibitors for breast cancer therapy. J Steroid Biochem Mol Biol 2003;86:423-432.
98. Woo L, Lightowler M, Purohit A, Reed MJ, Potter BVL. Heteroatom- substituted analogues of the active site directed inhibitor. Estra-1,3,5(10)-trien-17-one-3-sulfamate inhibit estrone sulfatase by a different mechanism. J Steroid Biochem Mol Biol 1996;57:79-88.
99. NOVARTIS AG. WO 2003/0382842. 2003.
100. Supuran CT, Scozzafava A. Protein tyrosine kinase inhibitors as anticancer agents. Expert Opin Ther Pat 2004;14:25-53.
101. Dewang PM, Hsu NM, Peng SZ, Li WR. Protein tyrosine phosphatases and their inhibitors. Curr Med Chem 2005;12:l-22.
102. Pei Z, Liu G, Lubben TH, Szczepankiewicz BG. Inhibition of protein tyrosine phosphatase 1B as a potential treatment of diabetes and obesity. Curr Pharm Des 2004;10:3481-3504.
103. Taylor SD, Hill B. Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs 2004;13:199-214.
104. Dadke S, Chernoff J. Protein tyrosine phosphatase 1B as a potential drug target for obesity. Curr Drug Targets Imm Endocr Metab Disord 2003;3:299-304.
105. Black E, Breed J, Breeze AL, Embrey K, Garcia R, Gero TW, Godfrey L, Kenny PW, et al: Structure-based design of protein tyrosine phosphatase-1B inhibitors. Bioorg Med Chem Lett 2005;15:2503-2507.
106. NOVARTIS. US Patent 2004/0023974. 2004.
107. ASTRA ZENECA. WO Patent 2004/050646. 2004.