Abstract
Using solid phase synthesis, a library has been constructed of benzamidine-derived sulfonamides which have strong inhibitory activity against blood coagulant thrombin. The library compounds were obtained in good yield and high purity.
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1. For recent reviews see: a. Lam, K.S., Lebl, M. and Krchnak, V., The ‘one-bead-one-compound’ combinatorial library method, Chem. Rev., 97 (1997) 411–448.
Gallop, M.A., Barrett, R.W., Dower, W.J., Fodor, S.P.A. and Gordon, E.M., Application of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries, J. Med. Chem., 37 (1994) 1233–1251.
Thompson, L.A. and Ellman, J.A., Synthesis and application of small molecule libraries, Chem. Rev., 96 (1996) 555–600.
Nefzi, A., Ostresh, J.M. and Houghten, R.A., The current status of heterocyclic combinatorial libraries, Chem. Rev., 97 (1997) 449–472.
Gordon, E.M., Barrett, R.W., Dower, W.J., Fodor, S.P.A. and Gallop, M.A., Application of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and fucture directions, J.Med. Chem., 37 (1994) 1385–1401.
Desai, M.C., Zuckermann, R.N. and Moos, W.H., Recent advances in the generation of chemical diversity libraries, Drug Dev. Res., 33 (1994) 174–188.
Terrett, N.K., Gardner, M., Gordon, D.W., Kobylecki, R.J. and Steele, J., Combinatorial synthesis–the design of compound libraries and their application to drug discovery, Tetrahedron, 51 (1995) 8135–8173.
Balkenhohl, F., Bussche-Hunnefeld, C.V.D., Lansky, A. and Zechel, C., Combinatorial synthesis of small organic molecules, Angew. Chem. Int. Ed. Engl., 35 (1996) 2288–2337.
Still, W.C., Discovery of sequence-selective peptide binding by synthesis receptors using encoded combinatorial libraries, Acc. Chem. Res., 29 (1996) 155–163.
Jung, G. and Beck-Sickinger, A.G., Multiple peptide synthesis methods and their applications, Angew. Chem. Int. Ed. Engl., 1992, 31, 367–383.
Ruhland, B., Bhandari, A., Gordon, E.M. and Gallop, M.A., Solid-supported combinatorial synthesis of structurally diverse β-lactams, J. Am. Chem. Soc., 118 (1996) 253–254.
Boojamra, C.G., Burow, K.M., Thompson, L.A. and Ellman, J.A., Solid-phase synthesis of 1,4-benzodiazepine-2,5-diones. Library preparation and demonstration of synthesis generality, J. Org. Chem., 62 (1997) 1240–1256.
Buckman, B.O. and Mohan, R., Solid-phase synthesis of 1,3-dialkyl quinazoline-2,4-diones, Tetrahedron Lett., 37 (1996) 4439–4442.
Kim, S.W., Ahn, S.Y., Koh, J.S., Lee, J.H., Ro, S. and Cho, H.Y., Solid-phase synthesis of hydantoin library using a novel cyclization and traceless cleavage step, Tetrahedron Lett., 38 (1997) 4603–4606.
DeWitt, S.H., Kiely, J.S., Stankovic, C.J., Schroeder, M.C., Cody, D.M.R. and Pavia, M.R., ‘Diversomers’: An approach to nonpeptide, nonoligomeric chemical diversity, Proc. Natl. Acad. Sci. USA, 90 (1993) 6909–6913.
Sturzebecher, J., Markwardt, F., Voigt, B., Wagner, G. and Walsmann, P., Cyclic amides of N(alpha)-aryl-sulfonylaminoacylated 4-amidinophenyl-alanine-tight binding inhibitors of thrombin, Thromb. Res., 29 (1983) 635.
Banner, D.W. and Hadvary, P., Crystallographic analysis at 3.0-Å resolution of the binding to human thrombin of four active site-directed inhibitors, J. Biol. Chem., 266 (1991) 20085–20093.
Sturzebecher, J., Vieweg, H., Wikstroem, P. and Alder, C., Piperazides of substituted phenylalanine derivates as thrombin inhibitors, WO Patent 94/18185.
Edmunds, J.J. and Rapundalo, S.T., Thrombin and factor Xa inhibitor, Annu. Rep. Med. Chem., 31 (1996) 51–60.
Stone, S.R., Thrombin inhibitors. A new generation of antithrombotics, Trends Cardiovasc. Med., 5 (1995) 134–140.
Tapparelli, C., Metternich, R., Ehrhardty, C. and Cook, N.S., Synthetic low-molecular weight thrombin inhibitors: Molecular design and pharmacological profile, Trends Pharm. Sci., 14 (1993) 366–376.
Roussel, P., Bradley, M., Matthews, I. and Kane, P., A linker for amidines in solid phase synthesis, Tetrahedron Lett., 38 (1997) 4861–4864.
Furth, P.S., Reitman, M.S. and Cook, A.F., A novel formamidine linker for use in solid-phase synthesis, Tetrahedron Lett., 38 (1997) 5403–5406.
Wang, S.S., p-Alkoxybenzyl alcohol resin and p-alkoxybenzyl-oxycarbonylhydrazide resin for solid phase synthesis of protected peptide fragments, J. Am. Chem. Soc., 95 (1973) 1328–1333.
Wang resin (0.85 mmol/g) was purchased from Advanced ChemTech.
Oh, Y.S., Kim, S.S., Hwang, S.Y., Yun, M.K., Hwang, S.R., Hong, S.W., Lee, Y.H., Jeong, Y.N., Lee, K. and Shin, Y.S., Selective thrombin inhibitors, European Patent Application EP739886-A2, 1996.
Kim, S., Hwang, S.Y., Kim, Y.K., Yun, M.K. and Oh, Y.S., Rational design of selective thrombin inhibitors, Bioorg. Med. Chem. Lett., 7 (1997) 769–774.
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Kim, S.W., Hong, C.Y., Koh, J.S. et al. Solid phase synthesis of benzamidine-derived sulfonamide libraries. Mol Divers 3, 133–136 (1997). https://doi.org/10.1023/A:1009608400697
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DOI: https://doi.org/10.1023/A:1009608400697