An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing Src SH2 ligand

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 21, 1999, Pages 3109-3112

  Shakespeare, William C ^a   Bohacek, Regine S ^a   Narula, Surinder S ^a   Azimioara, Mihai D ^a,b   Yuan, Ruth W ^a   Dalgarno, David C ^a   Madden, Laura ^a   Botfield, Martyn C ^a,c   Holt, Dennis A ^a  

^a ARIAD PHARMACEUTICALS INC   (United States)

^b Tanabe Research Laboratories   (United States)

^c VERTEX PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; FUNCTIONAL GROUP; LIGAND; PALLADIUM; PEPTIDE; PHENYLALANINE DERIVATIVE; PHOSPHOTYROSINE;

ARTICLE; CATALYSIS; PROTEIN DOMAIN; PROTEIN MODIFICATION; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

BINDING SITES; CYSTEINE; FLUORINE COMPOUNDS; LIGANDS; MOLECULAR STRUCTURE; PHENYLALANINE; PHOSPHONIC ACIDS; PROTEIN BINDING; PROTEIN-TYROSINE KINASES; SRC HOMOLOGY DOMAINS;

EID: 0033229786     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00545-4     Document Type: Article

References (25)

1. Charifson, P. S.; Shewchuk, L. M.; Rocque, W.; Hummel, C. W.; Jordan, S. R.; Mohr, C.; Pacofsky, G. J.; Peel, M. R.; Rodriguez, M.; Sternbach, D. D.; Counsler, T. G. Biochemistry 1997, 36, 6283.
2. Alligwood, K. J.; Charifson, P. S.; R. Crosby, T. G. C.; Feldman, P. L.; Gampe, R. T.; Gilmer, T. M.; Jordan, S. R.; Milstead, M. W.; Mohr, C.; Peel, M. R.; Rocque, W.; Rodriguez, M.; Rusnak, D. W.; Shewchuk, L. M.; Sternbach, D. D. Bioorg. Med. Chem. Lett. 1998, 8, 1189.
3. Holt, D. A.; Veber, D. F.; Yamashita, D. S. PCT Int. Appl. WO9840093 1998.
4. Shaw, E. J. Protein Chem. 1984, 3, 109.
5. Shaw, E. Adv. Enzymol. Relat. Area Mol. Biol. 1990, 63, 271.
6. Rich, D. H. Proteinase Inhibitors; Elsevier: Amsterdam, 1986; pp 153-178.
7. Otto, H.-H.; Schirmeister, T. Chem. Rev. 1997, 97, 133.
8. Singer, A. U.; Forman-Kay, J. D. Protein Sci. 1997, 6, 1910.
9. Smyth, M. S.; Ford, H.; Burke, T. R. Tetrahedron Lett. 1992, 33, 4137.
10. Burke, T. R.; Smyth, M. S.; Otaka, A.; Roller, P. R. Tetrahedron Lett. 1993, 34, 4125.
11. Wrobel, J.; Dietrich, A. Tetrahedron Lett. 1993, 34, 3543.
12. Tstomu, Y.; Murano, T.; Suemune, K.; Shibuya, S. Tetrahedron 1997, 53, 815.
13. Sakamoto, T.; Kondo, Y.; Yasuhara, A.; Yamanaka, H. Heterocycles 1990, 31, 219.
14. Sarma, K. D.; Maitra, U. Tetrahedron 1998, 54, 4965.
15. Bates, R. W.; Rama-Devi, T. Synlett 1995, 1151.
16. Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. J. Heterocyclic Chem. 1995, 32, 1261.
17. Volhardt, K. P. C. Pure & Appl. Chem. 1993, 65, 153.
18. Smyth, M. S.; Burke, T. R. Tetrahedron Lett. 1994, 35, 551.
19. Shahripour, A.; Para, K. S.; Plummer, M. S.; Lunney, E. A.; Holland, D. R.; Rubin, J. R.; Humblet, C.; Fergus, J. H.; Marks, J. S.; Saltiel, A. R.; Sawyer, T. K. Bioorg. Med. Chem. Lett. 1997, 7, 1107.
20. Stankovic, C. J.; Surendran, N.; Lunney, E. A.; Plummer, M. S.; Para, K. S.; Shahripour, A.; Fergus, J. H.; Marks, J. S.; Herrera, R.; Hubbel, S. E.; Humblet, C.; Saltiel, A. R.; Stewart, B. H.; Sawyer, T. K. Bioorg. Med. Chem. Lett. 1997, 7, 1909.
21. 50, = 1.5 μM in this assay.
22. Unpublished results.
23. Tong, L.; Warren, T. C.; King, J.; Betageri, R.; Rose, J.; Jakes, S. Unpublished results.
24. McMartin, C.; Bohacek, R. S. J. Comput. Aided Mol. Design 1997, 11, 333.
25. The 25 lowest energy conformations are retained and compared to the conformation pYEEI adopts in the crystal structure of pYEEI bound to Lck SH2. Compounds that engage Cys188 adopt a conformation very similar to that of pYEEI without significant van der Waals repulsion with binding site atoms while retaining a reasonable ligand strain energy (e.g., less than 40 kJ). Compounds that do not engage Cys188 display significant shifts in the position of the tyrosine ring or can only adopt the pYEEI conformation at the expense of high internal energy (i.e., large ligand strain energy).