Synthesis of diverse lactam carboxamides leading to the discovery of a new transcription-factor inhibitor

Angewandte Chemie - International Edition

Volumn 46, Issue 28, 2007, Pages 5352-5355

  Ng, Pui Yee ^a   Tang, Yuchen ^a   Knosp, Wendy M ^c   Stadler, H Scott ^b   Shaw, Jared T ^a,d  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Combinatorial chemistry; DNA; Gene expression; Lactams; Proteins

Indexed keywords

COMBINATORIAL CHEMISTRY; LACTAMS; PROTEIN-BIOPOLYMER INTERACTIONS;

BIOPOLYMERS; CELLS; DNA; ENZYME INHIBITION; GENE EXPRESSION; MOLECULAR INTERACTIONS; SYNTHESIS (CHEMICAL);

ORGANIC COMPOUNDS;

AMIDE; CARBOXYLIC ACID; DNA; HOMEOBOX PROTEIN HOXA13; HOMEODOMAIN PROTEIN; LACTAM; TRANSCRIPTION FACTOR;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; METABOLISM; STEREOISOMERISM; SYNTHESIS;

AMIDES; CARBOXYLIC ACIDS; DNA; HOMEODOMAIN PROTEINS; LACTAMS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; STEREOISOMERISM; TRANSCRIPTION FACTORS;

EID: 34447535439     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200700762     Document Type: Article

References (50)

1. For recent reviews on small-molecule modulation of biological processes, see: a) S. L. Schreiber, Nat. Chem. Biol. 2005, 1, 64-66;
2. b) P. Arya, R. Joseph, Z. Gan, B. Rakic, Chem. Biol. 2005, 12, 163-180;
3. c) D. R. Spring, Chem. Soc. Rev. 2005, 34, 472-482;
4. d) N. Tolliday, P. A. Clemons, P. Ferraiolo, A. N. Koehler, T. A. Lewis, X. Li, S. L. Schreiber, D. S. Gerhard, S. Eliasof, Cancer Res. 2006, 66, 8935-8942;
5. e) D. S. Tan, Nat. Chem. Biol. 2005, 1, 74-84.
6. For recent reviews on small-molecule disruption of protein-protein interactions, see: a) H. Yin, A. D. Hamilton, Angew. Chem. 2005, 117, 4200-4235;
7. Angew. Chem. Int. Ed. 2005, 44, 4130-4163;
8. b) M. R. Arkin, J. A. Wells, Nat. Rev. Drug Discovery 2004, 3, 301-317;
9. c) T. Berg, Angew. Chem. 2003, 115, 2566-2586;
10. Angew. Chem. Int. Ed. 2003, 42, 2462-2481; ;
11. d) D. L. Boger, J. Desharnais, K. Capps, Angew. Chem. 2003, 115, 4270-4309;
12. Angew. Chem. Int. Ed. 2003, 42, 4138-4176.
13. For recent reviews on small-molecule modulation of transcription factors, see: a) H.-D. Arndt, Angew. Chem. 2006, 118, 4664-4673;
14. Angew. Chem. Int. Ed. 2006, 45, 4552-4560;
15. b) A. K. Mapp, Org. Biomol. Chem. 2003, 1, 2217;
16. c) J. E. Darnell, Jr., Nat. Rev. Cancer 2002, 2, 740-749.
17. J. M. Mitchell, J. T. Shaw, Angew. Chem. 2006, 118, 1754-1758;
18. Angew. Chem. Int. Ed. 2006, 45, 1722-1726; ;
19. D. S. Tan, Nat. Chem. Biol. 2005, 1, 74-84.
20. R. Morgan, Trends Genet. 2006, 22, 67-69.
21. a) I. G. Maroulakou, D. D. Spyropoulos, Anticancer Res. 2003, 23, 2101-2110;
22. b) D. G. Grier, A. Thompson, A. Kwasniewska, G. J. McGonigle, H. L. Halliday, T. R. Lappin, J. Pathol. 2005, 205, 154-171.
23. C. E. Masse, P. Y. Ng, Y. Fukase, M. Sanchez-Rosello, J. T. Shaw, J. Comb. Chem. 2006, 8, 293-296.
24. P. Y. Ng, C. E. Masse, J. T. Shaw, Org. Lett. 2006, 8, 3999-4002.
25. a) M. Cushman, J. Gentry, F. W. Dekow, J. Org. Chem. 1977, 42, 1111-1116;
26. b) M. Cushman, E. J. Madaj, J. Org. Chem. 1987, 52, 907-915.
27. a) M. Cushman, L. Cheng, J. Org. Chem. 1978, 43, 286-288;
28. b) Y. P. Gupta, J. Am. Chem. Soc. 1983, 105, 2873-2879;
29. c) M. Cushman, M. Jayaraman, J. A. Vroman, A. K. Fukunaga, B. M. Fox, G. Kohlhagen, D. Strumberg, Y. Pommier, J. Med. Chem. 2000, 43, 3688-3698.
30. a) M. C. Griffith, C. T. Dooley, R. A. Houghten, J. S. Kiely, Mol. Diversity Comb. Chem.: Libr. Drug Discovery, Conf. 1996, pp. 50-57;
31. b) M. Lebl, V. Krchnak, G. Ibrahim, J. Pires, C. Burger, Y. Ni, Y. Chen, D. Podue, P. Mudra, V. Pokorny, P. Poncar, K. Zenisek, Synthesis 1999, 1971-1978;
32. c) Y. Ni, V. Krchnak, M. Lebl, Mol. Diversity 2000, 5, 153-161.
33. This high-throughput screen was conducted at the NCI's Initiative for Chemical Genetics (ICG) screening center at the Broad Institute of Harvard and MIT. The data has been deposited in ChemBank (http://chembank.broad.harvard.edu/ ), a freely available resource on the WWW.
34. A. K. Franz, P. D. Dreyfuss, S. L. Schreiber, J. Am. Chem. Soc. 2007, 129, 1020-1021.
35. V. Rishi, T. Potter, J. Laudeman, R. Reinhart, T. Silvers, M. Selby, T. Stevenson, P. Krosky, A. G. Stephen, A. Acharya, J. Moll, W. J. Oh, D. Scudiero, R. H. Shoemaker, C. Vinson, Anal. Biochem. 2005, 340, 259-271.
36. The details of the screen are included in the Supporting Information. The high-throughput screen included control experiments examining the changes in fluorescence polarization (FP) when DNA alone, that is, in the absence of HOXA13 binding domain, was treated with screening compounds. In the initial screen, no significant change in FP was observed when DNA alone was treated with 30 or 31.
37. a) H. S. Stadler, K. M. Higgins, M. R. Capecchi, Development 2001, 128, 4177-4188;
38. b) E. A. Morgan, S. B. Nguyen, V. Scott, H. S. Stadler, Development 2003, 130, 3095-3109;
39. c) W. Cheng, J. Liu, H. Yoshida, D. Rosen, H. Naora, Nat. Med. 2005, 11, 531-537.
40. W. M. Knosp, V. Scott, H. P. Bächinger, H. S. Stadler, Development 2004, 131, 4581-4592.
41. J. B. Le Pecq, D. Nguyen, C. Gosse, C. Paoletti, Proc. Natl. Acad. Sci. USA 1974, 71, 5078-5082.
42. 50 determination.
43. For an early example of a compound from an unbiased combinatorial library that disrupts protein-DNA binding, see S. Y. Stevens, B. A. Bunin, M. J. Plunkett, P. C. Swanson, J. A. Ellman, G. D. Glick, J. Am. Chem. Soc. 1996, 118, 10650-10651.
44. For examples of compounds that disrupt protein-DNA binding discovered by using NMR spectroscopy, see a) P. J. Hajduk, J. Dinges, G. F. Miknis, M. Merlock, T. Middleton, D. J. Kempf, D. A. Egan, K. A. Walter, T. S. Robins, S. B. Shuker, T. F. Holzman, S. W. Fesik, J. Med. Chem. 1997, 40, 3144-3150;
45. b) J. R. Huth, L. Yu, I. Collins, J. Mack, R. Mendoza, B. Isaac, D. T. Braddock, S. W. Muchmore, K. M. Comess, S. W. Fesik, G. M. Clore, D. Levens, P. J. Hajduk, J. Med. Chem. 2004, 47, 4851-4857.
46. For synthetic polyamides that disrupt or induce transcription-factor binding by targeting DNA, see a) N. R. Wurtz, J. L. Pomerantz, D. Baltimore, P. B. Dervan, Biochemistry 2002, 41, 7604-7609;
47. b) H.-D. Arndt, K. E. Hauschild, D. P. Sullivan, K. Lake, P. B. Dervan, A. Z. Ansari, J. Am. Chem. Soc. 2003, 125, 13322-13323;
48. c) D. H. Nguyen-Hackley, E. Ramm, C. M. Taylor, J. K. Joung, P. B. Dervan, C. O. Pabo, Biochemistry 2004, 43, 3880-3890;
49. d) K. E. Hauschild, R. E. Metzler, H.-D. Arndt, R. Moretti, M. Raffaelle, P. B. Dervan, A. Z. Ansari, Proc. Natl. Acad. Sci. USA 2005, 102, 5008-5013;
50. e) C. L. Warren, N. C. S. Kratochvil, K. E. Hauschild, S. Foister, M. L. Brezinski, P. B. Dervan, G. N. Phillips, Jr., A. Z. Ansari, Proc. Natl. Acad. Sci. USA 2006, 103, 867-872.