Letters
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 18 5647
gel angiogenesis model, crystal structure determination, and
refinement statistics, and synthetic procedures and charac-
terization for 3-32 are given. This material is available free
of charge via the Internet at http://pubs.acs.org.
(14) Lowther, W. T.; Zhang, Y.; Sampson, P. B.; Honek, J. F.;
Matthews, B. W. Insights into the Mechanism of Escherichia
coli Methionine Aminopeptidase from the Structural Analysis
of Reaction Products and Phosphorus-Based Transition-State
Analogues. Biochemistry 1999, 38, 14810-14819.
(
15) Kruger E. A.; Figg W. D. TNP-470: an Angiogenesis Inhibitor
References
in Clinical Development for Cancer. Expert Opin. Invest. Drugs
2
000, 9, 1383-96.
(
(
(
1) Folkman, J. Angiogenesis in Cancer, Vascular, Rheumatoid and
(
16) Logothetis, C. J.; Wu, K. K.; Finn, L. D.; Daliani, D.; Figg, W.;
Ghaddar, H.; Gutterman, J. U. Phase I Trial of the Angiogenesis
Inhibitor TNP-470 for Progressive Androgen-independent Pros-
tate Cancer. Clin. Cancer Res. 2001, 7, 1198-1203.
Other Disease. Nature Med. 1995, 1, 27-31.
2) Folkman, J. Tumor Angiogenesis: Therapeutic Implications.
New Eng. J. Med. 1971, 285, 1182-1186.
3) Ingber, D.; Fujita, T.; Kishimoto, S.; Sudo, K.; Kanamaru, T.;
Brem, H.; Folkman, J. Synthetic Analogs of Fumagillin that
Inhibit Angiogenesis and Suppress Tumor Growth. Nature 1990,
(
17) Bhargava P.; Marshall J. L.; Rizvi N.; Dahut W.; Yoe J.; Figuera
M.; Phipps K.; Ong V. S.; Kato A.; Hawkins M. J. A Phase I and
Pharmacokinetic Study of TNP-470 Administered Weekly to
Patients with Advanced Cancer. Clin. Cancer Res. 1999, 5,
348, 555-7.
(
(
(
4) Griffith E. C.; Su Z.; Turk B. E.; Chen S.; Chang Y. H.; Wu Z.;
Biemann K.; Liu J. O. Methionine Aminopeptidase (Type 2) is
the Common Target for Angiogenesis Inhibitors AGM-1470 and
Ovalicin. Chem. Biol. 1997, 4, 461-471.
1
989-95.
(
18) Zhou, G.; Tsai, C. W.; Liu, J. O. Fumagalone, a Reversible
Inhibitor of Type 2 Methionine Aminopeptidase and Angiogen-
esis. J. Med. Chem. 2003, 46, 3452-3454.
5) Sin, N.; Meng, L.; Wang, M. Q. W.; Wen, J. J.; Bornmann, W.
G.; Crews, C. M. The Anti-angiogenic Agent Fumagillin Co-
valently Binds and Inhibits the Methionine Aminopeptidase,
MetAP-2. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 6099-6103.
6) Lowther, W. T.; McMillen, D. A.; Orville, A. M.; Matthews, B.
W. The Anti-angiogenic Agent Fumagillin Covalently Modifies
a Conserved Active-site Histidine in the Escherichia coli Me-
thionine Aminopeptidase. Proc. Natl. Acad. Sci. U.S.A. 1998,
(
19) Sheppard, G. S.; Wang, J.; Kawai, M.; BaMaung, N. Y.; Craig,
R. A.; Erickson, S. A.; Lynch, L.; Patel, J.; Yang, F.; Searle, X.
B.; Lou, P.; Park, C.; Kim, K. H.; Henkin, J.; Lesniewski, R.
3
-Amino-2-hydroxyamides and Related Compounds as Inhibitors
of Methionine Aminopeptidase-2. Bioorg., Med. Chem. Lett. 2004,
4, 865-868.
1
(
20) Oefner, C.; Douangamath, A.; D’Arcy, A.; Hafeli, S.; Mareque,
D.; Sweeney, A. M.; Padilla, J.; Pierau, S.; Schulz, H.; Thormann,
M.; Wadman, S.; Dale, G. E. The 1.15 Å Crystal Structure of
the Staphylococcus Aureus Methionyl-aminpeptidase and Com-
plexes with Triazole Based Inhibitors. J. Mol. Biol. 2003, 332,
13-21.
95, 12153-12157.
(
7) Liu, S.; Widom, J.; Kemp, C. W.; Crews, C. M.; Clardy, J.
Structure of Human Methionine Aminopeptidase-2 Complexed
with Fumagillin. Science 1998, 282, 1324-1327.
(
8) Griffith, E. C.; Su, Z.; Niwayama, S.; Ramsay, C. A.; Chang, Y.-
H.; Liu, J. O. Molecular Recognition of Angiogenesis Inhibitors
Fumagillin and Ovalicin by Methionine Aminopeptidase 2. Proc.
Natl. Acad. Sci. U.S.A. 1998, 95, 15183-15188.
(21) Marino, J. P., Jr.; Thompson, S. K.; Veber, D. F. Substituted
Triazole Methionine Aminopeptidase Type 2 Inhibitors, Their
Preparation, and Their Therapeutic Use. Patent WO 2002078697,
2002.
(22) Marino, J. P., Jr.; Thompson, S. K.; Veber, D. F. Substituted
1,2,4-Triazole Methionine Aminopeptidase Type 2 Inhibitors,
Their Preparation, and Their Therapeutic Use. Patent WO
2002078696, 2002.
(
9) Turk, B. E.; Griffith, E. C.; Wolf, S.; Biemann, K.; Chang, Y.-
H.; Liu, J. O. Selective Inhibition of Amino-terminal Methionine
Processing by TNP-470 and Ovalicin in Endothelial Cells. Chem.
Biol. 1999, 6, 823-833.
(
10) Wang, J.; Quan, N.; Henkin, J. Proc. Am. Assoc. Cancer Res.
998, 39, 98 (abstract # 664).
1
(23) Mueller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J. An
Improved One-pot Procedure for the Synthesis of Alkynes from
Aldehydes. Synlett 1996, 6, 521-522.
(
11) Wang, J.; Sheppard, G. S.; Lou, P.; Kawai, M.; BaMaung, N.;
Erickson, S. A.; Tucker-Garcia, L.; Park, C.; Bouska, J.; Wang,
Y.-C.; Frost, D.; Tapang, P.; Albert, D. H.; Morgan, S. J.;
Morowitz, M.; Shusterman, S.; Maris, J. M.; Lesniewski, R.;
Henkin, J. Tumor Suppression by a Rationally Designed Revers-
ible Inhibitor of Methionine Aminopeptidase-2. Cancer Res.
(24) Tsuchiya, T.; Kato, M.; Sashida, H. Thermal intramolecular
cyclization of 2-ethynylpyridine N-ylides to indolizines and
cyclazines. Chem. Pharm. Bull. 1984, 32, 4666-9.
(25) Tanaka, Y.; Velen, S. R.; Miller, S. I. Syntheses and Properties
of 1,2,3-Triazoles. Tetrahedron 1973, 29, 3271-83.
(26) Koradi, R.; Billeter, M.; Wuethrich, K. MOLMOL: A Program
for Display and Analysis of Macromolecular Structures. J. Mol.
Graphics 1996, 14, 51-55.
(27) Passaniti, A.; Taylor, R. M.; Pili, R.; Guo, Y.; Long, P. V.; Haney,
J. A.; Pauly, R. R.; Grant, D. S.; Martin, G. R. A Simple,
Quantitative Method for Assessing Angiogenesis and Antian-
giogenic Agents Using Reconstituted Basement Membrane,
Heparin, and Fibroblast Growth Factor. Lab. Invest. 1992, 67,
519-528.
2
003, 63, 7861-7869.
(
12) Yang, G.; Kirkpatrick, R. B.; Ho, T.; Zhang, G.-F.; Liang, P.-H.;
Johanson, K. O.; Casper, D. J.; Doyle, M. L.; Marino, J. P., Jr.;
Thompson, S. K.; Chen, W.; Tew, D. G.; Meek, T. D. Steady-
State Kinetic Characterization of Substrates and Metal-Ion
Specificities of the Full-Length and N-Terminally Truncated
Recombinant Human Methionine Aminopeptidases (Type 2).
Biochemistry 2001, 40, 10645-10654.
13) Wang, J.; Sheppard, G. S.; Lou, P.; Kawai, M.; Park, C.; Egan,
D. A.; Schneider, A.; Bouska, J.; Lesniewski, R.; Henkin, J.
Physiologically Relevant Metal Cofactor for Methionine Ami-
nopeptidase-2 Is Manganese. Biochemistry 2003, 42, 5035-5042.
(
JM050408C