Water-soluble prodrugs of an Aurora kinase inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 5, 2009, Pages 1409-1412

  Oslob, Johan D ^a   Heumann, Stacey A ^a   Yu, Chul H ^a   Allen, Darin A ^a   Baskaran, Subramanian ^a   Bui, Minna ^a   Delarosa, Erlie ^a   Fung, Amy D ^a   Hashash, Ahmad ^a   Hau, Jonathan ^a   Ivy, Sheryl ^a   Jacobs, Jeffrey W ^a   Lew, Willard ^a   Maung, Jack ^a   McDowell, Robert S ^a   Ritchie, Sean ^a   Romanowski, Michael J ^a   Silverman, Jeffrey A ^a   Yang, Wenjin ^a   Zhong, Min ^a   Fuchs Knotts, Tarra ^a   more..

^a Sunesis Pharmaceuticals Inc   (United States)

Author keywords

Aurora; Inhibitor; Kinase; Prodrugs

Indexed keywords

AURORA KINASE INHIBITOR; ETHYLENE DERIVATIVE; PRODRUG; SNS 314; UNCLASSIFIED DRUG; WATER;

ALKYLATION; ANIMAL EXPERIMENT; AQUEOUS SOLUTION; ARTICLE; BIOTRANSFORMATION; CHEMICAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; MOUSE; NONHUMAN; RAT; RODENT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; THERMODYNAMICS;

ANIMALS; ANTINEOPLASTIC AGENTS; MALE; MICE; PHENYLUREA COMPOUNDS; PRODRUGS; PROTEIN-SERINE-THREONINE KINASES; RATS; RATS, SPRAGUE-DAWLEY; SOLUBILITY; THIAZOLES; WATER;

RODENTIA;

EID: 60449109522     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.01.043     Document Type: Article

References (27)

1. Gautschi O., Heighway J., Mack P.C., Purnell P.R., Lara Jr. P.N., and Gandara D.R. Clin. Cancer Res. 14 (2008) 1639
2. Carvajal R.D., Tse A., and Schwartz G.K. Clin. Cancer Res. 12 (2006) 6869
3. Naruganahalli K.S., Lakshmanan M., Dastidar S.G., and Ray A. Curr. Opin. Investig. Drugs 7 (2006) 1044
4. Gautschi O., Mack P.C., Davies A.M., Lara Jr. P.N., and Gandara D.R. Clin. Lung Cancer 8 (2006) 93
5. Mortlock A., Keen N.J., Jung F.H., Heron N.M., Foote K.M., Wilkinson R., and Green S. Curr. Top. Med. Chem. 5 (2005) 199
6. Andrews P.D. Oncogene 24 (2005) 5005
7. Wilkinson R.W., Odedra R., Heaton S.P., Wedge S.R., Keen N.J., Crafter C., Foster J.R., Brady M.C., Bigley A., Brown E., Byth K.F., Barrass N.C., Mundt K.E., Foote K.M., Heron N.M., Jung F.H., Mortlock A.A., Boyle F.T., and Green S. Clin. Cancer Res. 13 (2007) 3682
8. Manfredi M.G., Ecsedy J.A., Meetze K.A., Balani S.K., Burenkova O., Chen W., Galvin K.M., Hoar K.M., Huck J.J., LeRoy P.J., Ray E.T., Sells T.B., Stringer B., Stroud S.G., Vos T.J., Weatherhead G.S., Wysong D.R., Zhang M., Bolen J.B., and Claiborne C.F. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 4106
9. Soncini C., Carpinelli P., Gianellini L., Fancelli D., Vianello P., Rusconi L., Storici P., Zugnoni P., Pesenti E., Croci V., Ceruti R., Giorgini M.L., Cappella P., Ballinari D., Sola F., Varasi M., Bravo R., and Moll J. Clin. Cancer Res. 12 (2006) 4080
10. Harrington E.A., Bebbington D., Moore J., Rasmussen R.K., Ajose-Adeogun A.O., Nakayama T., Graham J.A., Demur C., Hercend T., Diu-Hercend A., Su M., Golec J.M., and Miller K.M. Nat. Med. 10 (2004) 262
11. Oslob J.D., Romanowski M.J., Allen D.A., Baskaran S., Bui M., Elling R.A., Flanagan W.M., Fung A.D., Hanan E.J., Harris S., Heumann S.A., Hoch U., Jacobs J.W., Lam J., Lawrence C.E., McDowell R.S., Nannini M.A., Shen W., Silverman J.A., Sopko M.M., Tangonan B.T., Teague J., Yoburn J.C., Yu C.H., Zhong M., Zimmerman K.M., O'Brien T., and Lew W. Bioorg. Med. Chem. Lett. 18 (2008) 4880
12. Taverna P., Hogan J., Kumer J., Arbitrario J., Hoch U., Silverman J., and Howlett A. Ann. Oncol. 18 (2007) 204
13. General procedure for determination of thermodynamic solubilities: The test compound was accurately weighed out in a suitable size screw cap glass vial followed by the addition of the appropriate media. The resulting slurry was sonicated for 20 min at room temperature, 10 min at 50 °C, and then another 10 min at room temperature. The slurry was then agitated for a minimum of two days at room temperature at the end of which they were inspected under polarized light microscope (Olympus BX51) for crystallinity of the residual solid. Additional time for equilibration was allowed if crystallinity was not observed. On the day of analysis, the slurry was aliquoted into 1.5 mL propylene centrifuge tubes and centrifuged at 15,000 rpm at 20 ± 2 °C for 20 min. The supernatant was analyzed for concentration by HPLC (Agilent 1100 binary pump and a Phenomenex Synergi Hydro-RP column (30 × 2 mm, 4 μm, 80 Å particle size)) and for pH by pH meter (where applicable). When mono-salts were prepared, sufficient volume of the aqueous solution of the base was added such that the molar ratio of the base to that of the drug is 1.05:1. When bis-salts were prepared, sufficient volume of the aqueous solution of the base was added such that the molar ratio of the base to that of the drug is 2.1:1.
14. Ettmayer P., Amidon G.L., Clement B., and Testa B. J. Med. Chem. 47 (2004) 2393
15. Rautio J., Kumpulainen H., Heimbach T., Oliyai R., Oh D., Jarvinen T., and Savolainen J. Nat. Rev. Drug Discov. 7 (2008) 255
16. The regio-chemical identity of the prodrugs was verified by NOE studies. For example, key enhancements observed for prodrug 2g: {A figure is presented}
17. Krise J.P., Zygmunt J., Georg G.I., and Stella V.J. J. Med. Chem. 42 (1999) 3094
18. Dumas J., Smith R.A., and Lowinger T.B. Curr. Opin. Drug Discov. Devel. 7 (2004) 600
19. Leppik I.E., Boucher B.A., Wilder B.J., Murthy V.S., Watridge C., Graves N.M., Rangel R.J., Rask C.A., and Turlapaty P. Neurology 40 (1990) 456
20. Luer M.S. Neurol. Res. 20 (1998) 178
21. Boucher B.A. Pharmacotherapy 16 (1996) 777
22. Yavas S., Lizdas D., Gravenstein N., and Lampotang S. Anesth. Analg. 106 (2008) 880 table of contents
23. Cohen L.B. Aliment. Pharmacol. Ther. 27 (2008) 597
24. Fechner J., Schwilden H., and Schuttler J. Handb. Exp. Pharmacol. (2008) 253
25. Hester E.K., Chandler H.V., and Sims K.M. Ann. Pharmacother. 40 (2006) 1301
26. Wire M.B., Shelton M.J., and Studenberg S. Clin. Pharmacokinet. 45 (2006) 137
27. Cho A. Ann. Rep. Med. Chem. 41 (2006) 395