Sequential nucleophilic substitution: A powerful strategy for the solid- phase production of diverse compound libraries

Angewandte Chemie - International Edition

Volumn 39, Issue 3, 2000, Pages 554-556

  Zaragoza, Florencio ^a   Stephensen, Henrik ^a  

^a NOVO NORDISK A S   (Denmark)

Author keywords

Combinatorial chemistry; Drug research; Nucleophilic additions; Solid phase synthesis

Indexed keywords

AMINE; BETA ALANINE; REAGENT; THIOL DERIVATIVE;

ACYLATION; ARTICLE; CHEMICAL REACTION KINETICS; CHEMICAL STRUCTURE; CRYSTALLIZATION; HYDROGEN BOND; NONHUMAN; PROTEIN BINDING; PROTON NUCLEAR MAGNETIC RESONANCE; SYNTHESIS;

EID: 0034603125     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3773(20000204)39:3<554::AID-ANIE554>3.0.CO;2-W     Document Type: Article

References (12)

1. E. M. Gordon, M. A. Gallop, D. V. Patel, Acc. Chem. Res. 1996, 29, 144-154; X. Williard, I. Pop, L. Bourel, D. Horvath, R. Baudelle, P. Melnyk, B. Deprez, A. Tartar, Eur. J. Med. Chem. 1996, 31, 87-98; N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki, J. Steele, Tetrahedron 1995, 51, 8135-8173; E. M. Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor, M. A. Gallop, J. Med. Chem. 1994, 37, 1385-1401.
2. E. M. Gordon, M. A. Gallop, D. V. Patel, Acc. Chem. Res. 1996, 29, 144-154; X. Williard, I. Pop, L. Bourel, D. Horvath, R. Baudelle, P. Melnyk, B. Deprez, A. Tartar, Eur. J. Med. Chem. 1996, 31, 87-98; N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki, J. Steele, Tetrahedron 1995, 51, 8135-8173; E. M. Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor, M. A. Gallop, J. Med. Chem. 1994, 37, 1385-1401.
3. E. M. Gordon, M. A. Gallop, D. V. Patel, Acc. Chem. Res. 1996, 29, 144-154; X. Williard, I. Pop, L. Bourel, D. Horvath, R. Baudelle, P. Melnyk, B. Deprez, A. Tartar, Eur. J. Med. Chem. 1996, 31, 87-98; N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki, J. Steele, Tetrahedron 1995, 51, 8135-8173; E. M. Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor, M. A. Gallop, J. Med. Chem. 1994, 37, 1385-1401.
4. E. M. Gordon, M. A. Gallop, D. V. Patel, Acc. Chem. Res. 1996, 29, 144-154; X. Williard, I. Pop, L. Bourel, D. Horvath, R. Baudelle, P. Melnyk, B. Deprez, A. Tartar, Eur. J. Med. Chem. 1996, 31, 87-98; N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki, J. Steele, Tetrahedron 1995, 51, 8135-8173; E. M. Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor, M. A. Gallop, J. Med. Chem. 1994, 37, 1385-1401.
5. A. M. Davis, S. J. Teague, Angew. Chem. 1999, 111, 778-792; Angew. Chem. Int. Ed. 1999, 38, 736-749.
6. A. M. Davis, S. J. Teague, Angew. Chem. 1999, 111, 778-792; Angew. Chem. Int. Ed. 1999, 38, 736-749.
7. 1).
8. As a model amine we used piperazine bound to the Wang resin as a carbamate: F. Zaragoza, S. V. Petersen, Tetrahedron 1996, 52, 10823-10826. Primary amines bound to polystyrene through backbone amide linkages can also be used, which expands the scope of this synthesis significantly.
9. The structure of resin 2 was confirmed by acidolytic cleavage from the support and analysis of the crude product by HPLC and LCMS.
10. B. L. Mylari, T. A. Beyer, T. W. Siegel, J. Med. Chem. 1991, 34, 1011-1018; J. F. Harris, J. Org. Chem. 1972, 37, 1340-1346.
11. B. L. Mylari, T. A. Beyer, T. W. Siegel, J. Med. Chem. 1991, 34, 1011- 1018; J. F. Harris, J. Org. Chem. 1972, 37, 1340-1346.
12. 1H NMR spectroscopy.