Solid-phase synthesis of substituted imidazoline-tethered 2,3-diketopiperazines, cyclic ureas, and cyclic thioureas

Journal of Combinatorial Chemistry

Volumn 3, Issue 6, 2001, Pages 612-623

  Acharya, Achyuta N ^a   Ostresh, John M ^a   Houghten, Richard A ^a  

^a TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; HETEROCYCLIC COMPOUND; IMIDAZOLE DERIVATIVE; PIPERAZINE DERIVATIVE; PIPERAZINEDIONE; RESIN; THIOUREA; UREA;

ARTICLE; CHEMISTRY; COMBINATORIAL CHEMISTRY; CYCLIZATION; SYNTHESIS;

COMBINATORIAL CHEMISTRY TECHNIQUES; CYCLIZATION; ENZYME INHIBITORS; HETEROCYCLIC COMPOUNDS; IMIDAZOLES; PIPERAZINES; RESINS, SYNTHETIC; THIOUREA; UREA;

EID: 0035512309     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc010030d     Document Type: Article

References (40)

1. (a) Houghten, R. A.; Pinilla, C.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Eichler, J.; Nefzi, A.; Ostresh, J. M. Mixture-Based Synthetic Combinatorial Libraries. J. Med. Chem. 1999, 42, 3743-3778.
2. (b) Franzen, R. G. Recent Advances in the Preparation of Heterocycles on Solid Support: A Review of the Literature. J. Comb. Chem. 2000, 2, 195-214.
3. (c) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. The Current Status of Heterocyclic Combinatorial Libraries. Chem. Rev. 1997, 97, 449-472.
4. (d) Thompson, L. A.; Ellman, J. A. Synthesis and Application of Small Molecule Libraries. Chem. Rev. 1996, 96, 555-600.
5. (e) Gordon, E. M.; Barret, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions. J. Med Chem. 1994, 37, 1385-1401.
6. (a) Cui C.-B.; Kakeya, H.; Osada, H. Novel Mammalian Cell Cycle Inhibitors, Spirotryprostatins A and B, Produced by Aspergillus fumigates, Which Inhibit Mammalian Cell Cycle at G2/M Phase 1. Tetrahedron 1996, 52, 12651-12666.
7. (b) Alvarez, M. E.; Houck, D. R.; White, C. B.; Brownell, J. E.; Bobko, M. A.; Rodger, C. A.; Stawicki, M. B.; Sun, H. H.; Gillum, A. M.; Cooper, R. J. Antibiot. 1994, 47, 1195-1201.
8. Cui, C.-B.; Kakeya, H.; Osada, H. Novel Mammalian Cell Cycle Inhibitors, Tryprostatins A, B and Other Diketopiperazines Produced by Aspergillus fumigatus. II. Physico-Chemical Properties and Structures. J. Antibiot. 1996, 49, 534-540.
9. Funabashi, Y.; Horiguchi, T.; Iinum, S.; Tanida, S.; Harada, S. TAN-1496 A, C and E, Diketopiperazine Antibiotics with Inhibitory Activity Against Mammalian DNA Topoisomerase I. J. Antibiot. 1994, 47, 1202-1218.
10. (a) Szardenings, A. K.; Antonenko, V.; Campbell, D. A.; DeFrancisco, N.; Ida, S.; Shi, L. H.; Sharkov, N.; Tien, D.; Wang, Y. W.; Navre, M. Identification of Highly Selective Inhibitors of Collagenase-1 from Combinatorial Libraries of Diketopiperazines. J. Med. Chem. 1999, 42, 1348-1357.
11. (b) Szardenings, A. K.; Harris, D.; Lam, S.; Shi, L.; Tien, D.; Wang, Y.; Patel, D. V.; Nevre, M.; Campbell, D. A. Rational Design and Combinatorial Evaluation of Enzyme Inhibitor Scaffolds: Identification of Novel Inhibitors of Matrix Metalloproteinases. J. Med. Chem. 1998, 41, 2194-2200.
12. Baures, P. W.; Ojala, W. H.; Costain, W. J.; Ott, M. C.; Pradhan, A.; Gleason, W. B.; Mishra, R. K.; Johnson, R. L. Design, Synthesis, and Dopamine Receptor Modulating Activity of Diketopiperazine Peptidomimetics of L-Propyl-L-leucylglycinamide. J. Med. Chem 1997, 40, 3594-3600.
13. Bryant, S. D.; Balboni, G.; Guerrini, R.; Salvadori, S.; Tomatis, R.; Lazarus, L. H. Opioid Diketopiperazines: Refinement of the δ Opioid Antagonist Pharmacophore. Biol. Chem. 1997, 378, 107-114.
14. Jullian, V.; Shepherd, E.; Gelbrich, T.; Hrusthouse, M. B.; Kilburn, J. D. New Macrobicyclic Receptors of Amino Acids. Tetrahedron Lett. 2000, 41, 3963-3966.
15. Benito, J. M.; Garcia, M. G-.; Blanco, J. L. J.; Mettet, C. O.; Fernandez, J. M. G. Carbohydrate-Based Receptors with Multiple Thiourea Binding Sites. Multipoint Hydrogen Bond Recognition of Dicarboxylates and Monosaccharides. J. Org. Chem. 2001, 66, 1366-1372.
16. Lam, P. Y. S.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Chang, C.-H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Viitanen, S. E. Rational Design of Potent, Bioavailable, Nonpeptide Cyclic Ureas as HIV Protease Inhibitors. Science 1994, 263, 380-384.
17. Bihan, G. L.; Rondu, F.; Tounian, A. P.; Wang, X.; Lidy, S.; Touboul, E.; Lamouri, A.; Dive, G.; Huet, J.; Pfeiffer, B.; Renard, P.; Lemaitre, B. G.; Manechez, D.; Penicaud, L.; Ktorza, A.; Godfroid, J.-J. Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 2. Syntheses and Biological Activities of 1,4-Dialkyl-, 1,4-Dibenzyl-, and 1-Benzyl-4-alkyl-2-(4′,5′-dihydro-1′H-imidazol-2′yl) piperazines and Isosteric Analogues of Imidazoline. J. Med. Chem 1999, 42, 1587-1603.
18. Gilman, A. G.; Goodman, L. S. In The Pharmacological Basis of Therapeutics, 5th ed.; Macmillan & Co.: New York, 1980; p 710.
19. (a) Nefzi, A.; Giulianotti, M. A.; Houghten, R. A. Solid-Phase Synthesis of Bis-Heterocyclic Compounds from Resin-Bound Orthogonally Protected Lysine. J. Comb. Chem. 2001, 3, 68-70.
20. (b) Nefzi, A.; Giulianotti, M. A.; Houghten, R. A. Solid-Phase Synthesis of Substituted 2,3-Diketopiperazines from Reduced Polyamides. Tetrahedron, 2000, 56, 3319-3326.
21. (c) Nefzi, A.; Giulianotti, M. A.; Houghten, R. A. Solid-Phase Synthesis of of 1,6-Disubstituted 2,3-Diketopiperazines and 1,2-Disubstituted Piperazines from N-Acylated Amino Acids. Tetrahedron. Lett. 1999, 40, 8539-8542.
22. (a) Bianco, A.; Sonksen, C. P.; Roepstorff, P.; Briand, J.-P. Solid-Phase Synthesis and Structural Characterization of Highly Substituted Hydroxyproline Based 2,5-Diketopiperazines. J. Org. Chem. 2000, 65, 2179-2187.
23. (b) Del Fresno, M.; Alsina, J.; Royo, M.; Barany, G.; Albericio, F. Solid-Phase Synthesis of Diketopiperazines. Useful Scaffolds for Combinatorial Chemistry. Tetrahedron Lett. 1998, 39, 2639-2642.
24. (c) Sabatino, G.; Chelli, M.; Mazzucco, S.; Ginanneschi, M.; Papini, A. M. Cyclisation of Histidine Containing Peptides in the Solid-Phase by Anchoring the Imidazole Ring to Trityl Resin. Tetrahedron Lett. 1999, 40, 809-812.
25. (a) Nefzi, A.; Ostresh, J. M.; Giulianotti, M.; Houghten, R. A. Solid-Phase Synthesis of Trisubstituted 2-Imidazolidones and 2-Imidazolidinethiones. J. Comb. Chem. 1999, 1, 195-198.
26. (b) Goff, D. The Synthesis of 2-Imidazolidones on Solid Support by Tandem Aminoacylation/Michael Addition. Tetrahedron Lett. 1996, 37, 5309-5312.
27. Ostresh, J. M.; Husar, G. M.; Blondelle, S. E.; Dorner, B.; Weber, P. A.; Houghten, R. A. "Libraries from Libraries": Chemical Transformation of Combinatorial Libraries To Extend the Range and Repertoire of Chemical Diversity. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11138-11142.
28. Ostresh, J. M.; Schoner, C. C.; Hamashin, V. T.; Nefzi, A.; Meyer, J.-P.; Houghten, R. A. Solid-Phase Synthesis of Trisubstituted Bicyclic Guanidines via Cyclicization of Reduced N-Acylated Dipeptides. J. Org. Chem. 1998, 63, 8622-8623.
29. Acharya, A. N.; Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Tethered Libraries: Solid-Phase Synthesis of Substituted Urea-Linked Bicyclic Guanidines. J. Comb. Chem. 2001, 3, 189-195.
30. Johnson, T.; Quibell, M.; Owen, D.; Sheppard, R. C. A Reversible Protecting Group for the Amide Bond in Peptides. Use in the Synthesis of "Difficult Sequences". J. Chem. Soc., Chem. Commun. 1993, 369-372.
31. Iwanowicz, E. J.; Poss, M. A.; Lin, J. Preparation of N,N′-Bis-tert-butoxycarbonylthiourea. Synth. Commun. 1993, 23, 1443-1445.
32. Wang, F.; Manku, S.; Hall, D. G. Solid Phase Syntheses of Polyamine Toxins HO-416b and PhTX-433. Use of an Efficient Polyamide Reduction Strategy That Facilitates Access to Branched Analogues. Org. Lett. 2000, 2, 1581-1583.
33. Merrifield, R. B. Peptide Synthesis. 1. The Synthesis of a Tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149-2154.
34. (a) Fodor, G.; Nagubandi, S. Correlation of the Von Braun, Ritter, Bischler-Napieralski, Beckmann and Schmidt Reactions via Nitrilium Salt Intermediates. Tetrahedron 1980, 36, 1279-1300.
35. (b) Whaley, W. M.; Govindachari, T. R. The Preparation of 3,4-Dihydroisoquinolines and Related Compounds by the Bischler-Napieralski Reaction. Org. React. 1951, 6, 74-82.
36. Huheey, J. E. In Inorganic Chemistry; Harper and Row: New York, 1983; p 289.
37. Cuervo, J. H.; Weitl, F.; Ostresh, J. M.; Hamashin, V. T.; Hannah, A. L.; Houghten, R. A. Polyalkylamine Chemical Combinatorial Libraries. In Peptides 94: Proceedings of the 23rd European Peptide Symposium; Maia, H. L. S., Ed.; ESCOM: Leiden, The Netherlands, 1995; pp 465-466.
38. Houghten, R. A. General Method for the Rapid Solid-Phase Synthesis of Large Numbers of Peptides: Specificity of Antigen-Antibody Interaction at the Level of Individual Amino Acids. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 5131-5135.
39. Kaiser, E. T.; Colescott, R. L.; Blossinger, C. D.; Cook, P. I. Color Test for Detection of Free Terminal Amino Groups in the Solid-Phase Synthesis of Peptides. Anal. Biochem. 1970, 34, 595-598.
40. Houghten, R. A.; Bray, M. K.; DeGraw, S. T.; Kirby, C. J. Simplified Procedure for Carrying Out Simultaneous Multiple Hydrogen Fluoride Cleavages of Protected Peptide Resins. Int. J. Pept. Protein Res. 1986, 27, 673-678.