Design and synthesis of sialyl Lewisx mimics as E- and P-selectin inhibitors

Medicinal Research Reviews

Volumn 22, Issue 6, 2002, Pages 566-601

  Kaila, Neelu ^a   Thomas IV, Bert E ^a  

^a PFIZER INC   (United States)

Author keywords

Antagonist; Inflammation; Selectins; Structural biology

Indexed keywords

ANTIINFLAMMATORY AGENT; BIMOSIAMOSE; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; EPIDERMAL GROWTH FACTOR; GLUTAMIC ACID; MANNOSE BINDING PROTEIN; P SELECTIN GLYCOPROTEIN LIGAND 1; PADGEM PROTEIN; PROTEIN INHIBITOR; SELECTIN ANTAGONIST; SIALIC ACID; SIALYL LEWIS X ANTIGEN;

ANTIGEN BINDING; ANTIINFLAMMATORY ACTIVITY; ASTHMA; CELL ADHESION; CELL INTERACTION; CLINICAL TRIAL; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG DESIGN; DRUG SYNTHESIS; ENDOTHELIUM CELL; HEART INFARCTION; HUMAN; LEUKOCYTE; MOLECULAR MIMICRY; MOLECULAR MODEL; MOLECULAR WEIGHT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN STRUCTURE; REVIEW;

ANIMALS; CARBOHYDRATE SEQUENCE; CELL ADHESION; DRUG DESIGN; E-SELECTIN; HUMANS; MOLECULAR MIMICRY; MOLECULAR SEQUENCE DATA; OLIGOSACCHARIDES; P-SELECTIN;

EID: 0036846759     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/med.10018     Document Type: Review

References (179)

1. Geng JG, Bevilacqua MP, Moore KL, McIntyre TM, Prescott SM, Kim JM, Bliss GA, Zimmerman GA, Mcever RP. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature 1990;343:757-760.
2. Hattori R, Hamilton KK, Fugate RD, McEver RP, Sims PJ. Stimulated secretion of endothelium von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 1989;264:7768-7771.
3. Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA Jr. Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci USA 1987;84:9238-9242.
4. Gallatin WM, Weissman IL, Butcher EC. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature 1983;304:30-34.
5. Lewinsohn DM, Bargatze RF, Butcher EC. Leukocyte-endothelial cell recognition: Evidence of a common molecular mechanism shared by neutrophils, lymphocytes, and other leukocytes. J Immunol 1987;138:4313-4321.
6. Jung U, Norman KE, Ramos CL, Scharffetter-Kochanek K, Beaudet AL, Ley K. Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo. J Clin Invest 1998;102:1526-1533.
7. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994;76:301-314.
8. Vestweber D, Blanks JE. Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 1999;79:181-213.
9. Pouyani T, Seed B. PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus. Cell 1995;83:333-343.
10. Sako D, Comess KM, Barone KM, Camphausen RT, Cumming DA, Shaw GD. A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding. Cell 1995;83:323-331.
11. Wilkins PP, Moore KL, McEver RP, Cummings RD. Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin. J Biol Chem 1995;270:22677-22680.
12. Ley K, Bullard DC, Arbones ML, Bosse R, Vestweber D, Tedder TF, Beaudet AL. Sequential contribution of L- and P-selectin to leukocyte rolling in vivo. J Exp Med 1995;181:669-675.
13. Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severly compromised in P-selectindeficient mice. Cell 1993;74:541-554.
14. Bullard DC, Kunkel EJ, Kubo H, Hicks MJ, Lorenzo I, Doyle NA, Doerschuk CM, Ley K, Beaudet AL. Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice. J Exp Med 1996;183:2329-2336.
15. Frenette PS, Mayadas TN, Rayburn H, Hynes RO, Wagner DD. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 1996;84:563-574.
16. Klaus L. Functions of selectins. Results Probl Cell Differ 2000;33:177-200. (For recent reviews in the area of selectins see references 8, 16-19.)
17. Simanek EE, McGarvey GJ, Jablonowski JA, Wong C-H. Selectin-carbohydrate interactions: From natural ligands to designed mimics. Chem Rev 1998;98:833-862.
18. Ebnet K, Vestweber D. Molecular mechanisms that control leukocyte extravasation: The selectins and the chemokines. Histochem Cell Biol 1999;112:1-23.
19. Dasgupta F. Selectin Antagonists. High Throughput Screening for Novel Anti-inflammatories 2000;123-144.
20. x and PSGL-1. Cell 2000;103:467-479.
21. Erbe DV, Wolitzky BA, Presta LG, Norton CR, Ramos RJ, Burns DK, Rumberger JM, Rao BNN, Foxall CR, Brandley BH, Lasky LA. Identification of an E-selectin region critical for carbohydrate recognition and cell adhesion. J Cell Biol 1992;119:215-227.
22. Siegelman MH, Cheng IC, Weissman IL, Wakeland EK. The mouse lymph node homing receptor is identical with the lymphocyte cell surface marker Ly-22: Role of the EGF domain in endothelial binding. Cell 1990;61:611-622.
23. Watson SR, Imai Y, Fennie C, Geoffrey J, Singer M, Rosen SD, Lasky LA. The complement binding-like domains of the murine homing receptor facilitate lectin activity. J Cell Biol 1991;115:235-243.
24. Kansas GS, Saunders KB, Ley K, Zakrzewicz A, Gibson RM, Furie BC, Furie B, Tedder TF. A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion. J Cell Biol 1994;124:609-618.
25. Li SH, Burns DK, Rumberger JM, Presky DH, Wilkinson VL, Anostario M Jr, Wolitzky BA, Norton CR, Familleti PC, Kim KJ, Goldstein AL, Cox DC, Huang K-S. Consensus repeat domains of E-selectin enhance ligand binding. J Biol Chem 1994;269:4431-4437.
26. Bartgatze RF, Kurk S, Watts G, Kishimoto TK, Speer CA, Jutila MA. In vivo and in vitro functional examination of a conserved epitope of L- and E-selectin crucial for leukocyte-endothelial cell interactions. J Immunol 1994;152:5814-5825.
27. Gibson RM, Kansas GS, Tedder TF, Furie B, Furie BC. Lectin and epidermal growth factor domains of P-selectin at physiologic density are the recognition unit for leukocyte binding. Blood 1995;85:151-158.
28. Kolbinger F, Patton JT, Geisenhoff G, Aenis A, Li X, Katopodis AG. The carbohydrate-recognition domain of E-selectin is sufficient for ligand binding under both static and flow conditions. Biochemistry 1996;35:6385-6392.
29. Weis WI, Drickamer K, Hendrickson WA. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 1992;360:127-134.
30. Wright CS. Refinement of the crystal structure of wheat germ agglutinin isolectin 2 at 1.8 A resolution. J Mol Biol 1987;194:501-529.
31. Bourne Y, Rouge P, Cambillau C. X-ray structure of a (alpha-Man(1-3)beta-Man(1-4)GlcNAc)-lectin complex at 2.1-A resolution. The role of water in sugar-lectin interaction. J Biol Chem 1990;265:18161-18165.
32. Shaanan B, Lis H, Sharon N. Structure of a legume lectin with an ordered N-linked carbohydrate in complex with lactose. Science 1991;254:862-866.
33. Naismith JH, Emmerich C, Habash J, Harop SJ, Helliwell JR, Hunter WN, Rafetery J, Kalb AJ, Yariv J. Refined structure of concanavalin A complexed with methyl α-D-mannopyranoside at 2.0. ANG, resolution and comparison with the saccharide-free structure. Acta Crystallogr 1994;D50:847-858.
34. Graves BJ, Crowther RL, Chandram C, Rumberger JM, Li S, Huang K-S, Presky DH, Familletti PC, Wolitzky BA, Burns DK. Insight into e-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains. Nature 1994;367:532-538.
35. x oligosaccharides. Biochemistry 1997;36:979-988.
36. Ramphal JY, Zheng Z-L, Perez C, Walker LE, DeFrees SA, Gaeta FCA. Structure-activity relationships of sialyl lewis x-containing oligosaccharides. 1. Effect of modifications of the fucose moiety. J Med Chem 1994;37:3459-3463.
37. Brandley BK, Kiso M, Abbas S, Nikrad P, Srivasatava O, Foxall C, Oda Y, Hasegawa A. Structure-function studies on selectin carbohydrate ligands. Modifications to fucose, sialic acid, and sulphate as a sialic acid replacement. Glycobiology 1993;3:633-639.
38. Henrichsen D, Ernst B, Magnani JL, Wang W-T, Meyer B, Peters T. Bioaffinity NMR spectroscopy: Identification of an E-selectin antagonist in a substance mixture by transfer NOE. Angew Chem Int Ed Engl 1999;38:98-102.
39. x analogues. Potential selectin antagonists. Angew Chem Int Ed Engl 1994;22:2096-2098.
40. x mimics. Modifications of the 6-position of galactose. Bio Med Chem Lett 2001;11:459-462.
41. Tyrrell D, James P, Rao N, Foxall C, Abbas S, Dasgupta F, Nashed M, Hasegawa A, Kiso M, Asa D, Kidd J, Brandley BK. Structural requirements for the carbohydrate ligand of E-selectin. Proc Natl Acad Sci USA 1991;88:10372-10376.
42. x analogs. J Med Chem 1996;39:1339-1343.
43. DeFrees SA, Gaeta FCA, Lin YC, Ichikawa Y, Wong C-H. Ligand recognition by E-selectin: Analysis of conformation and activity of synthetic monomeric and bivalent sialyl Lewis X analogs. J Am Chem Soc 1993;115:7549-7550.
44. x recognition site of P-selectin. J Med Chem 1996;39:4547-4553.
45. Wada Y, Saito T, Matsuda N, Ihmoto H, Yoshino K, Ohashi M, Kondo H, Ishida H, Kiso M, Hasegawa A. Studies on selectin blockers. 2. Novel selectin blocker as potential therapeutics for inflammatory disorders. J Med Chem 1996;39:2055-2059.
46. Ball GE, O'Neill RA, Schultz JE, Lowe JB, Weston BW, Nagy JO, Brown EG, Hobbs CJ, Bednarski MD. Synthesis and structural analysis using 2-D NMR of sialyl Lewis X (SLex) and Lewis X (Lex) oligosaccharides: Ligands related to E-selectin [ELAM-1] binding. J Am Chem Soc 1992;114:5449-5451.
47. Ichikawa Y, Lin C-Y, Dumas DP, Shen G-J, Garcia-Junceda E, Williams MA, Bayer R, Ketcham C, Walker LE, Paulson JC, Wong C-H. Chemical-enzymatic synthesis and conformational analysis of sialyl Lewis X and derivatives. J Am Chem Soc 1992;114:9283-9298.
48. Lin C-Y, Hummel CW, Huang D-H, Ichikawa Y, Nicolaou KC, Wong C-H. Conformational studies of sialyl Lewis X in aqueous solution. J Am Chem Soc 1992;114:5452-5454.
49. x ligand changes upon binding to E-selectin. Biochemistry 1994;33:10591-10596.
50. Rutherford TJ, Spackman DG, Simpson, PJ, Homans SW. 5 Nanosecond molecular dynamics and NMR study of conformational transitions in the sialyl-Lewis X antigen. Glycobiology 1994;4:59-68.
51. x tetrasaccharide, free in solution, and bound to E-, P-, and L-selectin. J Am Chem Soc 1997;119:1727-1736.
52. x in solution and bound to E-selectin. J Am Chem Soc 1999;121:2546-2551.
53. Hensley P, McDervitt PJ, Brooks I, Trill JJ, Field JA, McNulty DE, Connor JR, Griswold DE, Kumar NV, Kopple KD, Carr SA, Dalton BJ, Johanson KJ. The soluble form of E-selectin is an asymmetric monomer. Expression, purification, and characterization of the recombinant protein. J Biol Chem 1994;269:23949-23958.
54. x complex. Angew Chem Int Ed Engl 1995;34:1841-1844.
55. x bound to E-selectin. Biomol NMR 1997;9:423-436.
56. Kogan TP, Revelle BM, Tapp S, Scott D, Beck PJ. A single amino acid residue can determine the ligand specificity of E-selectin. J Biol Chem 1995;270:14047-14055.
57. Ernst B, Dragic Z, Marti S, Müller C, Wagner B, Jahnke W, Magnani JL, Norman KE, Oehrlein R, Peters T, Kolb HC. Design and synthesis of E-selectin antagonists. Chimia 2001;55:268-274.
58. Kolb HC, Ernst B. Development of tools for the design of selectin antagonists. Chem Eur J 1997;3:1571-1578.
59. Kolb HC, Ernst B. Recent progress in the glycodrug area. Pure Applied Chem 1997;69:1879-1884.
60. Kolb HC. Design and synthesis of a macrocyclic E-selectin antagonist. Bio Med Chem Lett 1997;7:2629-2634.
61. Hiramatsu Y, Tsukida T, Nakai Y, Inoue Y, Kondo H. Study on selectin blocker. 8. Lead discovery of a non-sugar antagonist using a 3D-pharmacophore model. J Med Chem 2000;43:1476-1483.
62. x mimics derived from a pharmacophore search are selectin inhibitors with anti-inflammatory activity. J Biol Chem 1994;269:19663-19666.
63. Kogan TP, Dupre B, Keller, KM, Scott IL, Bui H, Market RV, Beck PJ, Voytus JA, Revelle BM, Scott D. Rational design and synthesis of small molecule, non-oligosaccharide selectin inhibitors: (α-D-mannosepyranosyloxy)biphenyl-substituted carboxylic acids. J Med Chem 1995;38:4976-4984.
64. Tsujishita H, Hiramatsu Y, Kondo N, Ohmoto H, Kondo H, Kiso M, Hasegawa A. Selectin-ligand interactions revealed by molecular dynamics simulation in solution. J Med Chem 1997;40:362-369.
65. x mimetics based on modified serine-glutamic acid dipeptides. J Med Chem 1997;40:3534-3541.
66. x mimetics based on modified ser-glu dipeptides. J Med Chem 1998;41:4279-4287.
67. Hiramatsu Y, Moriyama H, Kiyoi T, Tsukida T, Inoue Y, Kondo H. Studies on selectin blockers. 6. Discovery of homologous fucose sugar unit necessary for E-selectin binding. J Med Chem 1998;41:2302-2307.
68. x. Bio Med Chem Lett 1998;6:2421-2439.
69. x mimetic: How selective are the selectin receptors? Bio Med Chem Lett 2001;11:1109-1112.
70. Slee DH, Romano S, Yu J, Nguyen TN, John JK, Raheja NK, Axe FU, Jones TK, Ripka WC. Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with anti-inflammatory activity. J Med Chem 2001;44:2094-2107.
71. x mimics as E-selectin inhibitors. Bio Med Chem Lett 2001;11:151-155.
72. x analogues as inhibitors of cellular adhesion. Unites States Patent 5604207. 1997. (See reference 17 and for recent references see 79-86.)
73. x derivative having activity of inhibiting selectin cell adhesion and its intermediates. Jpn Kokai Tokkyo Koho JP 09052902 A2. 1997.
74. x mimetics and their relevance to P-selectin. Bioorg Med Chem Lett 1998;8:2803-2808.
75. x mimetics as selectin inhibitors. PCT Int Appl WO9910359. 1999.
76. Matta KL, Jain RK. Synthetic core 2-like branched structures as ligands for selectins. European Patent 0919563A2. 1999.
77. Xia J, Alderfer JL, Matta KL. Chemical Synthesis of a core 2 branched pentasaccharide containing a carboxylate group. Bioorg Med Chem Lett 2000;10:2485-2487.
78. x tetrasaccharides with high affinity for E- and P-selectin. J Prakt Chem 2000;342:745-752.
79. Lefer DJ. Pharmacology of selectin inhibitors in ischemia/reperfusion states. Ann Rev Pharmacol Toxicol 2000;40:283-294.
80. a. J Biol Chem 1994;269:1595-1598.
81. Koenig A, Jain R, Vig R, Norgard-Sumnicht KE, Matta KL, Varki A. Selectin inhibition: Synthesis and evaluation of novel sialylated, sulfated and fucosylated oligosaccharides, including the major capping group of GlyCAM-1. Glycobiology 1997;7:79-93.
82. Singh K, Fernandez-Mayoralas A, Martin-Lomas M. Synthesis of oligosaccharides structurally related to E-selectin ligands. J Chem Soc Chem Commun 1994;775-776.
83. Abbas SA, Falguni D, Darwin A, Musser JH, Nashed MA. Substituted lactose derivatives. United States Patent 5591835. 1997.
84. Manning DD, Bertozzi CR, Pohl NL, Rosen SD, Kiessling LL. Selectin-saccharide interactions: Revealing structure-function relationships with chemical synthesis. J Org Chem 1995;60:6254-6255.
85. x analogs. J Med Chem 1996;39:1339-1343.
86. Imazaki N, Koike H, Miyauchi H, Hayashi M. Stereoselective synthesis of Lewis-associated trisaccharides as E-selectin inhibitors. Bioorg Med Chem Lett 1996;6:2043-2048.
87. x analogue. Tetrahedron Lett 1999;40:3639-3642.
88. x tetrasaccharide. Tetrahedron: Assym 2000;11:549-566.
89. a analog. Tetrahedron Lett 1996;37:1953-1956.
90. Musser JH, Rao N, Nashed M, Dasgupta F, Abbas S, Nematalla A, Date V, Foxall C, Asa D. (Trends in drug research, Chapter 3.) Pharmacochem Libr 1993;20:33-40.
91. x. J Org Chem 1996;61:514-524.
92. Thoma G, Kinzy W, Bums C, Patton JT, Magnani JL, Banteli R. Synthesis and biological evaluation of a potent E-selectin antagonist. J Med Chem 1999;42:4909-4913.
93. Bantelli R, Herold P, Bruns C, Patton JT, Magnani JL, Thoma G. Potent E-selectin antagonists. Helv Chim Acta 2000;83:2893-2907.
94. x mimic with significantly improved E-selectin inhibition. Bioorg Med Chem Lett 2001;11:923-925.
95. x and a, in which the natural neuraminic acid residue and the natural N-acetylglucosamine monomer are replaced. Intenational Patent WO 06730. 1998.
96. x mimetics based on carbocyclic scaffolds derived from (-) quinic acid. Bioorg Med Chem Lett 1997;7:2729-2734.
97. x determinant. Tetrahedron Lett 1995;36:9161-9164.
98. x. Bioorg Med Chem Lett 1994;4:2563-2566.
99. x mimetics. J Am Chem Soc 1995;117:5395-5396.
100. x mimetics. J Org Chem 1995;60:3100-3106.
101. Uchiyama T, Woltering TJ, Wong W, Lin C-C, Kajimoto T, Takebayashi M, Weitz-Schmidt G, Asakura T, Noda M, Wong C-H. Design and synthesis of C-linked fucosides as inhibitors of E-selectin. Bioorg Med Chem 1996;4:1149-1165.
102. x. Tetrahedron Lett 1995;36:2339-2342.
103. 2-symmetric 1,2-diols. Bioorg Med Chem 1996;4:793-801.
104. x analogues with reduced carbohydrate character. Bioorg Med Chem Lett 1996;6:239-244.
105. x and sialyl Lewis a. International Patent WO 01569. 1997.
106. x mimetic, CGP69669A, disrupt E-selectin-dependent leukocyte rolling in vivo. Blood 1998;91:475-483.
107. x in binding to E-selectin. J Am Chem Soc 1996;118:9265-9270.
108. Cheng X, Khan N, Mootoo DR. Synthesis of the C-glycoside analogue of a novel sialyl Lewis X mimetic. J Org Chem 2000;65:2544-2547.
109. x tetrasaccharide. Tetrahedron 1998;54:15781-15792.
110. x antigen: Investigation of the effect of carboxyl group orientation on P-selectin inhibition. J Org Chem 2000;65:2393-2398.
111. x ligand for E-selectin. Synlett 1994;868-870.
112. x analogues. J Carbohydrate Chem 1996;15(4):383-398.
113. Dasgupta F, Musser JH, Levy DE, Tang PC. Sialic acid/fucose based medicaments. United States Patent 5658880. 1997.
114. x mimics. Tetrahedron Lett 1995;36:5503-5506.
115. x mimic. Bioorg Med Chem Lett 1995;5:2637-2642.
116. x determinant. Tetrahedron Lett 1993;34:3945-3948.
117. x determinant. Tetrahedron: Asymmetry 1994;5:2061-2076.
118. x mimetics. Bioorg Med Chem Lett 1997;7:1317-1322.
119. x mimetics. Bioorg Med Chem Lett 1997;7:1311-1316.
120. Toepfer A, Kretzschmar G, Schoelkens B, Klemm P, Huels C, Seiffge D. Carbohydrate conjugates of piperidine and pyrrolidine derivatives as leukocyte adhesion inhibitors. Ger Offen. DE 19537334 A1. 1997.
121. Liu A, Dillon K, Cmpbell RM, Cox DC, Huryn DM. Synthesis of E-selectin inhibitors: Use of an arylcyclohexyl ether as a disaccharide scaffold. Tetrahedron Lett 1996;37:3785-3788.
122. x mimics: Replacement of galactose by aromatic spacers. Tetrahedron Lett 1997;38:4059-4062.
123. x mimetics: Use of O-a-Fucosyl-(1R,2R)-2-aminocyclohexanol. Terahedron Lett 1996;37:5427-5430. (This class of compounds are discussed in detail in reference 17.)
124. x mimetics and related structures using the glycosyl phosphite methodology and evaluation of E-selectin inhibition. J Am Chem Soc 1996;118:6826-6840.
125. x mimetics. Bioorg Med Chem Lett 1996;6:2755-2760.
126. x mimetics. Angew Chem Int Ed 1996;35:88-90.
127. x mimetics on a solid phase: Access to a library of fucopeptides. Angew Chem Int Ed 1998;37:1707-1711.
128. Wong C-H, Lampe TFJ. Fucopeptides mimetics. United States Patent 6111084. 2000.
129. x mimetics incorporating fucopeptides. United States Patent 5962660. 1999.
130. x mimetics. Bioorg Med Chem 1997;5:283-296.
131. Tsukida T, Kiyoi T, Achiha T, Moriyama H, Kurokawa K, Ohmoto H, Nakamura K, Kondo H, Wada Y, Saito T, Fucose derivatives, drugs containing the same as active ingredient, and intermediates for producing the same. International patent WO97/15585. 1997.
132. x mimetics containing flavanoid backbones. International patent WO97/31007. 1997.
133. x mimetics containing phenyl backbones. International patent WO97/30984. 1997.
134. x mimetics containing naphthyl backbones. United States patent 5837689. 1998.
135. Manallack DT, Montana JG, Murphy PV, Hubbard RE, Taylor RJK. Design, synthesis, and testing of novel inhibitors of cell adhesion. Mol Model Predict Bioact 2000;371-372.
136. Rao N, Tang PC, Musser JH. Anthraquinone and anthracene derivatives as inhibitors of the cell-adhesion molecules of the immune system. International Patent WO94/18189. 1994.
137. Dupre B, Bui H, Scott IL, Market RV, Keller KM, Beck PJ, Kogan TP. Glycomimetic selectin inhibitors: (α-D-mannopyranosyloxy)methylbiphenyls. Bioorg Med Chem Lett 1996;6:569-572.
138. Patel TP, Goelz SE, Lobb RR, Parekh RB. Isolation and characterization of natural protein-associated carbohydrate ligands for E-selectin. Biochemistry 1994;33:14815-14824.
139. Kogan TP, Dupre B, Bui H, McAbee KL, Kassir JA, Scott IL, Xin H. Novel synthetic inhibitors of selectin-mediated cell adhesion: Synthesis of 1,6-Bis[3-(3-carboxymethylphenyl)-4-(2α-D-mannopyr-anosyloxy) phenyl]hexane(TBC1269). J Med Chem 1998;41:1099-1111.
140. Pardella L. TBC-1269 Texas biotechnology corp. Anti-inflammatory immunomodulatory Invest. Drugs 1999;1:56-60.
141. x mimetics as selectin inhibitors by enzymatic aldol condensation reactions. Bioorg Med Chem 1999;7:425-433.
142. x tetrasaccharide as selectin inhibition: A remarkable enhancement of inhibition by additional negative charge and/or hydrophobic group. J Am Chem Soc 1997;119:8152-8158.
143. x mimetics using the Ugi four-component reaction. Bioorg Med Chem Lett 1998;8:2333-2338.
144. x mimetics: A remarkanle enhancement of inhibition by pre-organizing all essential functional groups. Terahedron Lett. 2000;41:9499-9503.
145. Sutherlin DP, Stark TM, Hughes R, Armstrong RW. Generation of C-glycoside peptide ligands for cell surface carbohydrate receptors using a four-component condensation on solid support. J Org Chem 1996;61:8350-8354.
146. Schmidt W, Sprengard U, Kretzschmer G, Kunz H. Preparation of glycomimetics as selectin antagonists and anti-inflammatory agents. Eur Pat Appl EP761661 A1. 1997.
147. x glycomimetics as selectin antagonists. Tetrahedron 1998;54:3765-3780.
148. x. Bioorg Med Chem Lett 1998;8:3307-3310.
149. x and sialyl Lewis a glycomimetics. International Patent WO99/29705. 1999.
150. Sato S, Shinozuka T, Ito K. Preparation of benzyl C-glycosides as selectin inhibitors. Jpn Kokai Tokkyo Koho JP 11302272 A2. 1999.
151. Ito M, Imazaki N, Mihauchi H. Preparation of aryl-c-glycosides as selectin inhibitors. Jpn Kokai Tokkyo Koho JP 11269162 A2. 1999.
152. Kretzschmar G, Toepfer A. Preparation and use of benzoic acid derivatives as selectin antagonists and cell-adhesion inhibitors. Ger Often DE 19648681 A1. 1998.
153. Schmidt W, Sprengard U, Kretzschmar G, Klein R, Kunz H. New glycomimetics as selectin antagonists and antiinflammation pharmaceutical compositions. European Patent EP0771795 A1. 1997.
154. Imazaki N, Miyauchi H, Goto N, Hashimoto K, Tojo S. Preparation of N-hydroxyaminoalkyl C-glycosides derivatives as selectin inhibitors. Pct Int Appl WO9929681. 1999.
155. Yuri M, Miyauchi H. Quinic acid derivatives, pharmaceutical compositions containing them, and cyclohexane deivatives as their intermediates. Jpn Kokai Tokkyo Koho JP 11246503 A2. 1999.
156. Roche D, Bantelli R, Winkler T, Casset F, Ernst B. Synthesis of benzylated (R)- and (S)-aminoethyl-C-α-D-mannosides as conformationally restricted building blocks for the preparation of E- and P-selectin antagonists. Tetrahedron Lett 1998;39:2545-2548.
157. x. Tetrahedron Lett 1996;37:9037-9040.
158. x-polysaccharide conjugates: Targeting inflammatory lesions. Bioorg Med Chem Lett 1998;8:2783-2786.
159. Sears P, Wong C-H. Carbohydrate mimetics: A new strategy for tackling the problem of carbohydrate-mediated biological recognition. Angew Chem Int Ed 1999;38:2300-2324.
160. Thoma G, Patton JT, Magnani JL, Ernst B, Ohrlein R, Duthaler RO. Versatile functionalization of polyysine: Synthesis, characterization, and use of neoglycoconjugates. J Am Chem Soc 1999;12:5919-5929.
161. x ligands of definite structures as inhibitors of E-selectin mediated cell adhesion. Gycobiology 1998;8:311-319.
162. Roy R. Syntheses and some applications of chemically defined multivalent glycoconjugates. Curr Opin Struct Biol 1996;6:692-702.
163. Kiessling LL, Pohl NL. Strength in numbers: Non-natural polyvalent carbohydrate derivatives. Chem Biol 1996;3:71-77.
164. Mammen M, Choi S-K, Whitesides GM. Polyvalent interactions in biological systems: Implications for design and use of multivalent ligands and inhibitors. Angew Chem Int Ed 1998;37:2754-2794.
165. Gardiner JM. The therapeutic potential of synthetic multivalent carbohydrates. Exp Opin Invest Drugs 1998;7:405-410.
166. Golik J, Dickey JK, Todderud G, Lee D, Alford J, Huang S, Klohr S, Eustice D, Aruffo A, Agler ML. Isolation and structure determination of sufonoquinovosyl dipalmitoyl glyceride, a P-selectin receptor inhibitor from the Alga Dictyochloris Fragrans. J Nat Prod 1997;60:387-389.
167. Woltering TJ, Weitz-Schmidt G, Wong C-H. Tetrahedron Lett 1996;37:9033-9036.
168. Manning DD, Hu X, Beck P, Kiessling LL. J Am Chem Soc 1997;119:3161-3162.
169. Kretzschmar G, Toepfer A, Sonnentag M Short synthesis of sulfatide- and SQDG-Mimetics as small molecular weight selectin inhibitors. Tetrahedron 1998;54:15189-15198.
170. x. Bioorg Med Chem Lett 2000;10:1827-1830.
171. Bruehl RE, Dasgupta F, Katsumoto TR, Tan JH, Bertozzi CR, Spevak W, Ahn DJ, Rosen SD, Nagy JO. Polymerized liposome assemblies: Bifunctional macromolecular selectin inhibitors mimicking physiological selectin ligands. Biochemistry 2001;40:5964-5974.
172. x: Design, synthesis, and biological activity of a series of 2- and 3-malonate substituted galactoconjugates. Bioorg Med Chem 2001;9:1395-1427.
173. x-Polysaccharide conjugates. Chem Pharm Bull 2000;48:1256-1263.
174. Thoma G, Duthaler RO, Magnani JL, Patton JT. Nanomolar E-selectin inhibitors: 700-fold potentiation of affinity by multivalent ligand presentation. J Am Chem Soc 2001;123:10113-10114.
175. x-dependent lung colonization of tumor cells. Cancer Res 2000;60:450-456.
176. x with anti-inflammatory activity. Biochem Biophys Res Comm 2000;268:106-111.
177. Kim M-K, Brandley BK, Anderson MB, Bochner BS. Anatogonism of selectin-dependent adhesion of human eosinophils and neutrophils by glycomimetics and oligosaccharide compounds. Am J Respir Cell Mol Biol 1998;19:836-841.
178. Kaila N, Chen L, Thomas IV BE, Tsao D, Tam S, Bedard PW, Camphausen RT, Alvarez JC, Ullas G. β-C-mannosides as selectin inhibitors. J Med Chem 2002;45:1563-1566.
179. x mimetics as potential selectin antagonists. Tetrahedron 1997;53:2485-2494.