In situ blood-brain barrier permeability of a C-10 paclitaxel carbamate

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 23, 2008, Pages 6119-6121

  Ballatore, Carlo ^a,b   Zhang, Bin ^a   Trojanowski, John Q ^a   Lee, Virginia M Y ^a   Smith III, Amos B ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Blood brain barrier; Mouse brain perfusion; Neurodegenerative diseases; Paclitaxel C 10 carbamate; Taxane

Indexed keywords

CNDR 29; GLYCOPROTEIN P; PACLITAXEL CARBAMATE; PACLITAXEL DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BLOOD BRAIN BARRIER; BRAIN PERFUSION; CONTROLLED STUDY; DRUG PENETRATION; DRUG STRUCTURE; DRUG SYNTHESIS; ISOTOPE LABELING; MOUSE; NONHUMAN;

ANIMALS; BLOOD-BRAIN BARRIER; BRAIN; CARBAMATES; CENTRAL NERVOUS SYSTEM; DISEASE MODELS, ANIMAL; MICE; MOLECULAR STRUCTURE; NEURODEGENERATIVE DISEASES; P-GLYCOPROTEIN; PACLITAXEL; PERMEABILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 55549101229     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.10.024     Document Type: Article

References (17)

1. Trojanowski J.Q., Smith III A.B., Huryn D., and Lee V.M.-Y. Expert Opin. Pharmacother. 6 (2005) 683
2. Rowinsky E.K., and Donehower R.C. N. Engl. J. Med. 332 (1995) 1004
3. Zhang B., Maiti A., Shively S., Lakhani F., McDonald-Jones G., Bruce J., Lee E.B., Xie S.X., Joyce S., Li C., Toleikis P.M., Lee V.M.-Y., and Trojanowski J.Q. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 227
4. Sparreboom A., van Asperen J., Mayer U., Schinkel A.H., Smit J.W., Meijer D.K.F., Borst P., Nooijen W.J., Beijnen J.H., and van Tellingen O. Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 2031
5. Girardin F. Dialogues Clin. Neurosci. 8 (2006) 311
6. Kemper E.M., van Zandbergen A.E., Cleypool C., Mos H.A., Boogerd W., Beijnen J.H., and van Tellingen O. Clin. Cancer Res. 9 (2003) 2849
7. Gallo J.M., Li S., Guo P., Reed K., and Ma J. Cancer Res. 63 (2003) 5114
8. Fricker G., and Miller D.S. Pharmacology 70 (2004) 169
9. Cirrito J.R., Deane R., Fagan A.M., Spinner M.L., Parsadanian M., Finn M.B., Jiang H., Prior J.L., Sagare A., Bales K.R., Paul S.M., Zlokovic B.V., Piwnica-Worms D., and Holtzman D.M. J. Clin. Invest. 115 (2005) 3285
10. Zlokovic B.V. Neuron 57 (2008) 178
11. Rice A., Liu Y., Michaelis M.L., Himes R.H., Georg G.I., and Audus K.L. J. Med. Chem. 48 (2005) 832
12. Ballatore C., Hyde E., Deiches R.F., Lee V.M.-Y., Trojanowski J.Q., Huryn D., and Smith III A.B. Bioorg. Med. Chem. Lett. 17 (2007) 3642
13. Yanbin Liu F., Ali S.M., Boge T.C., Georg G.I., Victory S., Zygmunt J., Marquez R.T., and Himes R.H. Comb. Chem. High Throughput Screen. 5 (2002) 39
14. Ballatore C., Aspland S.E., Castillo R., Desharnais J., Eustaquio T., Sun C., Castellino A.J., and Smith III A.B. Bioorg. Med. Chem. Lett. 15 (2005) 2477
15. 4 directly in the same scintillation vial used for the synthesis. The top organic layer is then collected with a Pasteur and transferred into a new scintillation vial. After removal of the volatiles via a stream of nitrogen the residue is re-dissolved in the minimal amount of dichloromethane/methyl alcohol 9:1 (ca. 100 μL). Finally, the compound is purified by preparative TLC (dichloromethane/methyl alcohol, 9:1) obtaining the desired compound (4.2 mg; 42% yield; 8.5 mCi/mmol).
16. 2 and incubation continued for an additional 30 min until discoloration. A 1 mL of brain sample was then added with 5 mL of Ultima Gold and the radioactivity measured in a scintillation counter.
17. Audus K., Rose J.M., Wang W., and Borchardt R.T. Brain microvessel endothelial cell culture systems. In: Pardridge W.M. (Ed). An Introduction to the Blood-Brain Barrier: Methodology and Biology (1998), Cambridge University, Cambridge 86-93