3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 4, 2004, Pages 865-868

  Sheppard, George S ^a   Wang, Jieyi ^a   Kawai, Megumi ^a   BaMaung, Nwe Y ^a   Craig, Richard A ^a   Erickson, Scott A ^a   Lynch, Linda ^a   Patel, Jyoti ^a   Yang, Fan ^a   Searle, Xenia B ^a   Lou, Pingping ^a   Park, Chang ^a   Kim, Ki H ^a   Henkin, Jack ^a   Lesniewski, Richard ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; DIACYLHYDRAZINE; HYDRAZINE DERIVATIVE; ISOENZYME; METHIONYL AMINOPEPTIDASE; METHIONYL AMINOPEPTIDASE 2; UNCLASSIFIED DRUG;

ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFECT; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; STRUCTURE ACTIVITY RELATION;

EID: 10744228072     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.12.031     Document Type: Article

References (16)

1. Arfin S.M., Kendall R.L., Hall L., Weaver L.H., Stewart A.E., Matthews B.W., Bradshaw R.A. Proc. Natl. Acad. Sci. U.S.A. 92:1995;7714.
2. Sin N., Meng L., Wang M.Q., Wen J.J., Bornmann W.G., Crews C.M. Proc. Natl. Acad. Sci. U.S.A. 94:1997;6099.
3. Griffith E.C., Su Z., Turk B.E., Chen S., Chang Y.H., Wu Z., Biemann K., Liu J.O. Chem. Biol. 4:1997;461.
4. Liu S., Widom J., Kemp C.W., Crews C.M., Clardy J. Science. 282:1998;1324.
5. Ingber, D. In Cancer Therapeutics; Teicher, B. A., Ed.; Humana Press: Totowa, NJ, 1997; p 283.
6. Umezawa H., Aoyagi T., Suda H., Hamada M., Takeuchi T. J. Antibiot. 29:1976;97.
7. Aoyagi T., Tobe H., Kojima F., Hamada M., Takeuchi T., Umezawa H. J. Antibiot. 31:1978;636.
8. Keding, S. J.; Rich, D. H. In Peptides for the New Millennium; Fields, G. B., Tam, J. P., Barany, G., Eds.; Kluwer Academic Publishers: Dordrecht/Boston/London, 2000; p 431.
9. Marino, J. P., Jr.; Ryan, M. D.; Thompson, S. K.; Veber, D. F. PCT International Publication Number WO 01/36404.
10. Nishizawa R., Saino T., Takita T., Suda H., Aoyagi T., Umezawa H. J. Med. Chem. 20:1977;510.
11. Wang J., Sheppard G.S., Lou P., Kawai M., Park C., Egan D.A., Schneider A., Bouska J., Lesniewski R., Henkin J. Biochemistry. 42:2003;5035. A coupled-enzyme chromogenic assay was used to measure methionine aminopeptidase activity by monitoring production of free methionine with L-amino acid oxidase and horseradish peroxidase. Compounds in 10 mM DMSO stock solutions were serially diluted with 50 mM Hepes buffer pH 7.4 containing 150 mM NaCl and the solutions added to an enzyme-substrate mixture containing MetAP2 or MetAP1, MAS peptide, coupling enzymes and substrate. A450 was recorded every 20 seconds for 20 min at room temperature.
12. Syntheses described in: Craig, R. A.; Henkin, J.; Kawai, M.; Lynch, L. L.; Patel, J.; Sheppard, G. S.; Wang, J. U.S. Patent 6,242,494, June 5, 2001.
13. Craig, R. A.; Kawai, M.; Lynch, L. M.; Patel, J. R.; Sheppard, G. S.; Wang, J.; Yang, F.; BaMaung, N. Y. PCT International Publication Number WO 01/79157; U.S. Patent Application US2002002152.
14. Refined crystallographic coordinates for the structures of MetAP2 complexed with ligands 2l, 3t and 6n have been deposited with the Protein Data Bank ( www.rcsb.org ) with entry codes 1R58, 1R5G and 1R5H.
15. HMVEC proliferation was measured using MTS reagents after a period of 3 days in complete growth medium EGM2 containing a combination of growth factors (VEGF, bFGF, EGF, IGF) and FBS: Wang J., Lou P., Henkin J. Biochemistry. 77:2000;465.
16. Wang J., Sheppard G.S., Lou P., Kawai M., BaMaung N.Y., Erickson S.A., Tucker-Garcia L., Park C., Bouska J., Wang Y.-C., Frost D., Tapang P., Albert D., Morgan S., Morowitz M., Shusterman S., Maris J.M., Lesniewski R., Henkin J. Cancer Research. 63:2003;7861.