Discovery of novel pyridinopolyamines with potent antimicrobial activity: Deconvolution of mixtures synthesized by solution-phase combinatorial chemistry

Journal of Medicinal Chemistry

Volumn 41, Issue 5, 1998, Pages 706-716

  An, Haoyun ^a   Haly, Becky D ^a   Dan Cook, P ^a  

^a ISIS PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; ANTIINFECTIVE AGENT; CIPROFLOXACIN; POLYAMINE DERIVATIVE; PYRIDINE DERIVATIVE;

ANTIBACTERIAL ACTIVITY; ARTICLE; CHEMISTRY; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENTEROCOCCUS FAECALIS; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; STREPTOCOCCUS PYOGENES; STREPTOMYCES;

ANTI-BACTERIAL AGENTS; ANTI-INFECTIVE AGENTS; CANDIDA ALBICANS; DRUG DESIGN; ENTEROCOCCUS FAECALIS; ESCHERICHIA COLI; KLEBSIELLA PNEUMONIAE; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; POLYAMINES; PROTEUS VULGARIS; PSEUDOMONAS AERUGINOSA; PYRIDINES; STREPTOCOCCUS; STREPTOCOCCUS PYOGENES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032567987     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970598u     Document Type: Article

References (44)

1. Sim, M. M.; Ganesan, A. Solution-Phase Synthesis of a Combinatorial Thiohydantoin Library. J. Org. Chem. 1997, 62, 3230-3235.
2. (a) Shipps, G. W., Jr.; Spitz, U. P.; Rebek, J., Jr. Solution-Phase Generation of Tetraurea Libraries. Bioorg. Med. Chem. 1996, 4, 655-657.
3. (b) Carell, T.; Wintner, E. A.; Bashir-Hashemi, A.; Rebek, J., Jr. A Novel Procedure for the Synthesis of Libraries Containing Small Organic Molecules. Angew, Chem., Int. Ed. Engl. 1994, 33, 2059-2061.
4. (a) Cheng, S.; Comer, D. D.; Williams, J. P.; Myers, P. I.; Boger, D. L. Novel Solution Phase Strategy for the Synthesis of Chemical Libraries Containing Small Organic Molecules. J. Am. Chem. Soc. 1996, 118, 2567-2573.
5. (b) Cheng, S.; Tarby, C. M.; Comer, D. D.; Williams, J. P.; Caporale, L. H.; Mayers, P. L.; Boger, D. L. A Solution-Phase Strategy for the Synthesis of Chemical Libraries Containing Small Organic Molecules: A Universal and Dipeptide Mimetic Template. Bioorg. Med. Chem. 1996, 4, 727-737.
6. (c) Boger, D. L.; Tarby, C. M.; Myers, P. L.; Caporale, L. H. Generalized Dipeptidomimetic Template: Solution Phase Parallel Synthesis of Combinatorial Libraries. J. Am. Chem. Soc. 1996, 118, 2109-2110.
7. (a) McDevitt, J. P.; Lansbury, P. T., Jr. Glycosamino Acids: New Building Blocks for Combinatorial Synthesis. J. Am. Chem. Soc. 1996, 118, 3818-3828.
8. (b) Pirrung, M. C.; Chen, J. Preparation and Screening against Acetylcholinesterase of a Non-Peptide "Indexed" Combinatorial Library. J. Am. Chem. Soc. 1995, 117, 1240-1245.
9. (c) Smith, P. W.; Lai, J. Y. Q.; Whittington, A. R.; Cox, B.; Houston, J. G.; Stylli, C. H.; Banks, M. N.; Tiller, P. R. Synthesis and Biological Evaluation of a Library Containing Potentially 1600 Amides/Esters. A Strategy for Rapid Compound Generation and Screening. Bioorg. Med. Chem. Lett. 1994, 4, 2821-2824.
10. (a) Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Use of Solid Supported Nucleophiles and Electrophiles for the Purification of Non-Peptide Small Molecule Libraries. Tetrahedron Lett. 1996, 37, 7193-7196.
11. (b) Kaldor, S. W.; Fritz, J. E.; Tang, J.; Mckinney, E. R. Discovery of Antirhinoviral Leads by Screening a Combinatorial Library of Ureas Prepared Using Covalent Scavengers, Bioorg. Med. Chem. Lett. 1996, 6, 3041-3044.
12. (a) Booth, R. J.; Hodges, J. C. Polymer-supported Quenching Reagents for Parallel Purification. J. Am. Chem. Soc. 1997, 119, 4882-4886.
13. (b) Flynn, D. L.; Crich, J. Z.; Devraj, R. V.; Hockerman, S. L.; Parlow, J. J.; South, M. S.; Woodard, S. Chemical Library Purification Strategies Based on Principles of Complementary Molecular Reactivity and Molecular Recognition. J. Am. Chem. Soc. 1997, 119, 4874-4881.
14. (a) Balkenhohl, F.; von dem Hussche-Hünnefeld, C.; Lansky, A.; Zechel, C. Combinatorial Synthesis of Small Organic Molecules. Angew. Chem., Int. Ed. Engl. 1996, 35, 2288-2337.
15. (b) Lam, K. S.; Lebl, M.; Krchnak, V. The "One-Bead-One-Compound" Combinatorial Library Methodology. Chem. Rev. (Washington, D.C.) 1997, 97, 411-448.
16. (a) Pirrung, M. C. Spatially Addressable Combinatorial Libraries. Chem. Rev. (Washington, D.C.) 1997, 97, 473-488.
17. (b) Ding, Y.; Labbe, J.; Kanie, O.; Hindsgaul, O. Toward Oligosaccharide Libraries: A Study of the Random Galactosylation of Unprotected N-Acetylglucosamine. Bioorg. Med. Chem. 1996, 4, 683-692.
18. (a) Ellman, J. A. Design, Synthesis, and Evaluation of Small-Molecule Libraries. Acc. Chem. Res. 1996, 29, 132-143.
19. (b) Thompson, L. A.; Ellman, J. A. Synthesis and Applications of Small Molecule Libraries. Chem. Rev. (Washington, D.C.) 1996, 96, 555-600.
20. (c) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. The Current Status of Heterocyclic Combinatorial Libraries. Chem. Rev. (Washington, D.C.) 1997, 97, 449-472.
21. An, H.; Cook, P. D. Solution Phase Combinatorial Chemistry I. Synthesis of Polyazacyclophane Scaffolds and Tertiary Amine Libraries. Tetrahedron Lett. 1996, 37, 7233-7236.
22. An, H.; Cummins, L. L.; Griffey, R. H.; Bharadwaj, R.; Haly, B. D.; Fraser, A. S.; Wilson-Lingardo, L.; Risen, L. M.; Wyatt, J. R.; Cook, P. D. Solution Phase Combinatorial Chemistry. Discovery of Novel Polyazapyridinophanes with potent Antibacterial Activity by a Solution Phase Simultaneous Addition of Functionalities Approach. J. Am. Chem. Soc. 1997, 119, 3696-3708.
23. An, H.; Haly, B. D.; Fraser, A. S.; Guinosso, C. J.; Cook, P. D. Solution Phase Combinatorial Chemistry. Synthesis of Novel Linear Pyridinopolyamine Libraries with Potent Antibacterial Activity. J. Org. Chem. 1997, 62, 5156-5164.
24. (a) Blondelle, S. E.; Takahashi, E.; Houghten, R. A.; Perez-Paya, E. Rapid Identification of Compounds with Enhanced Antimicrobial Activity by Using Conformationally Defined Combinatorial Libraries. Biochem. J. 1996, 313, 141-147.
25. (b) Kurth, M. J.; Randall, L. A. A.; Takenouchi, K. Solid-Phase Combinatorial Synthesis of Polyisoxazolines: A Two-Reaction Iterative Protocol. J. Org. Chem. 1996, 61, 8755-8761.
26. (c) Look, G. C.; Schullek, J. R.; Holmes, C. P.; Chinn, J. P.; Gordon, E. M.; Gallop, M. A. The Identification of Cyclooxygenase-1 Inhibitors from 4-Thiazolidinone Combinatorial Libraries. Bioorg. Med. Chem. Lett. 1996, 6, 707-712.
27. (d) Janda, K. D. Tagged versus Untagged Libraries: Methods for the Generation and Screening of Combinatorial Chemical Libraries. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 10779-10785.
28. (a) Erb, E.; Janda, K. D.; Brenner, S. Recursive Deconvolution of Combinatorial Libraries. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11422-11426.
29. (b) Han, H.; Wolfe, M. M.; Brenner, S.; Janda, K. D. Liquid-Phase Combinatorial Synthesis. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 6419-6423.
30. (a) Freier, S. M.; Konings, D. A. M.; Wyatt, J. R.; Ecker, D. J. 'Mutational SURF': A Strategy for Improving Lead Compounds Identified from Combinatorial Libraries. Bioorg. Med. Chem. 1996, 4, 717-725.
31. (b) Konings, D. A. M.; Wyatt, J. R.; Ecker, D. J.; Freier, S. M. Deconvolution of Combinatorial Libraries for Drug Discovery: Theoretical Comparison of Pooling Strategies. J. Med. Chem. 1996, 39, 2710-2719.
32. (c) Wilson-Lingardo, L.; Davis, P. W.; Ecker, D. J.; Hebert, N.; Acevedo, O.; Sprankle, K.; Brennan, T.; Schwarcz, L.; Freier, S. M.; Wyatt, J. R. Deconvolution of Combinatorial Libraries for Drug Discovery: Experimental Comparison of Pooling Strategies. J. Med. Chem. 1996, 39, 2720-2726.
33. (d) Freier, S. M.; Konings, D. A. M.; Wyatt, J. R.; Ecker, D. J. Deconvolution of Combinatorial Libraries for Drug Discovery: A Model System. J. Med. Chem. 1995, 38, 344-352.
34. Deprez, B.; Williard, X.; Bourel, L.; Coste, H.; Hyafil, F.; Tartar, A. Orthogonal Combinatorial Chemical Libraries. J. Am. Chem. Soc. 1995, 117, 5405-5406.
35. Blake, J.; Litzi-Davis, L. Evaluation of Peptide Libraries: An Iterative Strategy To Analyze the Reactivity of Peptide Mixtures with Antibodies. Bioconjugate Chem. 1992, 3, 510-513.
36. (a) Pinilla, C.; Appel, J. R.; Blanc, P.; Houghten, R. A. Rapid Identification of High Affinity Peptide Ligands Using Positional Scanning Synthetic Peptide Combinatorial Libraries. BioTechniques 1992, 13, 901-905.
37. (b) Pinilla, C.; Buencamino, J.; Appel, J. R.; Hopp, T. P.; Houghten, R. A. Mapping the Detailed Specificity of a Calcium-Dependent Monoclonal Antibody Through the Use of Soluble Positional Scanning Combinatorial Libraries: Identification of Potent Calcium-Independent Antigens. Mol. Diver. 1995, 1, 21-28.
38. (c) Spatola, A. F.; Crozet, Y.; Dewit, D.; Yanagisawa, M. Rediscovering an Endothelin Antagonist (BQ-123): A Self-Deconvoluting Cyclic Pentapeptide Library. J. Med. Chem. 1996, 39, 3842-3846.
39. (a) Carell, T.; Wintner, E. A.; Rebek, J., Jr. A Solution-Phase Screening Procedure for the Isolation of Active Compounds form a Library of Molecules. Angew. Chem., Int. Ed. Engl. 1994, 33, 2061-2064.
40. (b) Carell, T.; Wintner, E. A.; Sutherland, A. J.; Rebek, J., Jr.; Dunayevskiy, Y. M.; Vouros, P. New Promise in Combinatorial Chemistry: Synthesis, Characterization, and Screening of Small-Molecule Libraries in Solution. Chem. Biol. 1995, 2, 171-183.
41. (2-1)(6 + 1)]/2 = 21 compounds.
42. Fukuyama, T.; Jow, C. K.; Chung, M. 2- and 4-Nitrobenzene-sulfonamides: Exceptionally Versatile Means for Preparation of Secondary Amines and Protection of Amines. Tetrahedron Lett. 1995, 36, 6373-6374.
43. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; NCCLS Document M7-A3; NCCLS: Villanova, PA, 1993; Vol. 13.
44. Benson, S. A.; Misra, R.; Sampson, B. A. Identification and Characterization of a New Gene of Escherichia coli K-12 Involved in Outer Membrane Permeability. Genetics 1989, 122, 491-501.