Synthesis and biological evaluation of new conformationally biased integrin ligands based on a tetrahydroazoninone scaffold

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 5, 2007, Pages 1341-1345

  Banfi, Luca ^a   Basso, Andrea ^a   Damonte, Gianluca ^a   Pellegrini, Federico De ^a   Galatini, Andrea ^a   Guanti, Giuseppe ^a   Monfardini, Ilaria ^a   Riva, Renata ^a   Scapolla, Carlo ^a  

^a UNIVERSITY OF GENOA   (Italy)

Author keywords

Angiogenesis; Azoninones; Integrin ligands; Peptidomimetics

Indexed keywords

ARGINYLGLYCYLASPARTIC ACID; BETA3 INTEGRIN; CD51 ANTIGEN; INTEGRIN; LIGAND; PENTAPEPTIDE; TETRAHYDROAZONINONE; UNCLASSIFIED DRUG;

ARTICLE; CONFORMATION; DRUG ACTIVITY; ENANTIOMER; RING CLOSING METATHESIS; SAPONIFICATION; STEREOCHEMISTRY; SYNTHESIS;

AZO COMPOUNDS; HUMANS; INTEGRIN ALPHAVBETA3; INTEGRINS; LIGANDS; MOLECULAR CONFORMATION; OLIGOPEPTIDES; PEPTIDES, CYCLIC; RECEPTORS, VITRONECTIN; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 33846897471     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.11.085     Document Type: Article

References (29)

1. Gadek T.R., and Nicholas J.B. Biochem. Pharmacol. 65 (2003) 1
2. Yin H., and Hamilton A.D. Angew. Chem. Int. Ed. Engl. 44 (2005) 4130
3. Souers A.J., and Ellman J.A. Tetrahedron 57 (2001) 7431
4. Marinelli L., Lavecchia A., Gottschalk K.-E., Novellino E., and Kessler H. J. Med. Chem. 46 (2003) 4393
5. Gottschalk K.-E., and Kessler H. Angew. Chem. Int. Ed. Engl. 41 (2002) 3767
6. Dechantsreiter M.A., Planker E., Matha B., Lohof E., Hoelzemann G., Jonczyk A., Goodman S.L., and Kessler H. J. Med. Chem. 42 (1999) 3033
7. Casiraghi G., Rassu G., Auzzas L., Burreddu P., Gaetani E., Battistini L., Zanardi F., Curti C., Nicastro G., Belvisi L., Motto I., Castorina M., Giannini G., and Pisano C. J. Med. Chem. 48 (2005) 7675
8. Creighton C.J., Du Y., Santulli R.J., Tounge B.A., and Reitz A.B. Bioorg. Med. Chem. Lett. 16 (2006) 3971
9. Belvisi L., Bernardi A., Manzoni L., Potenza D., and Scolastico C. Eur. J. Org. Chem. (2000) 2563
10. Belvisi L., Bernardi A., Checchia A., Manzoni L., Potenza D., Scolastico C., Castorina M., Cupelli A., Giannini G., Carminati P., and Pisano C. Org. Lett. 3 (2001) 1001
11. Belvisi L., Bernardi A., Colombo M., Manzoni L., Potenza D., Scolastico C., Giannini G., Marcellini M., Riccioni T., Castorina M., LoGiudice P., and Pisano C. Bioorg. Med. Chem. 14 (2006) 169
12. Banfi L., Basso A., Guanti G., and Riva R. Tetrahedron Lett. 44 (2003) 7655
13. Surprenant S., and Lubell W.D. Org. Lett. 8 (2006) 2851
14. Anthoine-Dietrich S., Banfi L., Basso A., Damonte G., Guanti G., and Riva R. Org. Biomol. Chem. 3 (2005) 97
15. We have not been able to determine the relative configurations of these two isomers. In this paper, we will designate with a the isomers derived from the crystalline Ugi adduct.
16. Abbreviations used in this paper: Grubbs 1st gen. cat.: benzylidene-bis(tricyclohexylphosphine)ruthenium dichloride. Bop = (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate. HOBT = N-Hydroxybenzotriazole. TBTU = O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate. HATU = O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate. Mtr = 4-methoxy-2,3,6-trimethylbenzene-1-sulfonyl. Pbf = 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl.
17. Hebach C., and Kazmaier U. Chem. Commun. (2003) 596
18. 11,13
19. We had indeed already established that the trans isomers were not well suited for the assembly of a pentapeptide due to the excessively high distance between the two handles (Ref. 13).
20. Simoneau C.A., George E.A., and Ganem B. Tetrahedron Lett. 47 (2006) 1205
21. Pick R., Bauer M., Kazmaier U., and Hebach C. Synlett (2005) 757
22. In the case of 12b we carried out the synthesis up to 18b on the 66:34 cis:trans mixture of 12b and 13b. During the final cyclization, the trans isomer gave the cyclopeptide in less than 10% yield and it could be separated at this stage by chromatography. The yield reported in the Scheme is calculated on the cis isomer only. In the case of 14a,b we carried out the synthesis up to 3a,b without separating the two diastereoisomers.
23. 2NH lowered the yields of coupling with the scaffold.
24. In this series, the conditions used for methyl ester saponification led to partial decomposition. Thus, we preferred the mild conditions of deblocking of the 2-chlorotrityl linker.
25. 13
26. 50 = 1.4 nM under these conditions. The assays were done essentially as described in Refs. 7 or 10a.
27. Wermuth J., Goodman S.L., Jonczyk A., and Kessler H. J. Am. Chem. Soc. 119 (1997) 1328
28. 50 values for competitive binding for vitronectin.
29. Marinelli L., Meyer A., Heckmann D., Lavecchia A., Novellino E., and Kessler H. J. Med. Chem. 48 (2005) 4204