Construction of a family of biphenyl combinatorial libraries: Structure- activity studies utilizing libraries of mixtures

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 17, 1998, Pages 2395-2398

  Neustadt, Bernard R ^a   Smith, Elizabeth M ^a   Lindo, Neil ^a   Nechuta, Terry ^a   Bronnenkant, Alan ^a   Wu, Arthur ^a   Armstrong, Lydia ^a   Kumar, Chandra ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; BIPHENYL DERIVATIVE; PHENANTHRIDINE DERIVATIVE; VITRONECTIN; VITRONECTIN RECEPTOR;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CYCLIZATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NITRATION; SOLID PHASE EXTRACTION; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

BIPHENYL COMPOUNDS; DATABASES; DRUG DESIGN; ISOMERISM; KINETICS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; RECEPTORS, VITRONECTIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032497431     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00433-8     Document Type: Article

References (18)

1. 1. Recent reviews on combinatorial chemistry and applications in drug discovery: (a) Bristol, J. A., Ed. Tetrahedron 1997, 53, 6573;
2. (b) Szostak, J., Ed. Chemical Rev. 1997, 97, 347;
3. (c) Beutel, B. A. Ann. Reports Med. Chem. 1997, 32, 261;
4. (d) Plunkett, M. J.; Ellman, J. A. Scientific American 1997, 276, 68.
5. 2. Pavia, M. R.; Cohen, M. P.; Dilley, M. J.; Dubuc, G. R.; Durgin, T. L.; Forman, F. W.; Hediger, M. E.; Milot, G.; Powers, T. S.; Sucholeiki, I.; Zhou, S.; Hangauer, D. G. Bioorg. Med. Chem. 1996, 4, 659.
6. 3. Migachev, G. I. J. Org. Chem. USSR (Enlish translation) 1979, 15 , 503.
7. 4. Glover, S. A.; Golding, S. L.; Goosen, A.; McCleland, C. W. J. Chem. Soc. Perkin Trans. 1 1981, 842.
8. 5. Grieve, W. S. M.; Hey, D. H. J. Chem. Soc. 1933, 968.
9. 6. For 9, 3-nitrobenzeneboronic acid + ethyl bromobenzoates; for 10, benzeneboronic acid + ethyl 3-bromobenzoate, then nitration; for 11, 2-methylbenzeneboronic acid + ethyl bromobenzoates, then NBS.
10. 7. A dialkoxybenzyl alcohol resin obtained from BACHEM: Mergler, M.; Tanner, R.; Gosteli, J.; Grogg, P. Tetrahedron Lett. 1988, 29, 4005.
11. 8. Knorr, R.; Trzeciak, A.; Bannwarth, W.; Gillessen, D. Tetrahedron Lett. 1989, 30, 1927.
12. 9. Houghten, R. A.; Pinilla, C.; Blondelle, S. E.; Appel, J. R.; Dooley, C. T.; Cuervo, J. H. Nature (London) 1991, 354, 84.
13. 10. Furka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. Int. J. Peptide Protein Res. 1991, 37, 487.
14. 11. Kumar, C. C.; Nie, H.; Rogers, C. P.; Malkowski, M.; Maxwell, E.; Catino, J. J.; Armstrong L. J. Pharm. Exp. Biol. 1997, 283, 843.
15. 12. The analogs of 24 and 25 with terminal glutamic acid were much less active (repeat assay).
16. 13. Stepwise truncation was examined prior to iterative optimization (such as employed by Houghten), since a smaller molecule, if active, would be preferred for the drug development process.
17. 14. Samanen, J.; Jonak, Z.; Yuie, T-L. Current Pharmaceutical Design, 1997, 3, 545.
18. 15. All concentration-response curves were run in duplicate, with at least one repeat pair of assays.