Novel halogenated nitrobenzylthioinosine analogs as es nucleoside transporter inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 9, 2004, Pages 2257-2260

  Gupte, Amol ^a   Buolamwini, John K ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (4 IODOBENZYL) 6 THIOINOSINE; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; DIPYRIDAMOLE; FLUORESCEIN; NITROBENZYLTHIOINOSINE; NUCLEOSIDE TRANSPORTER; NUCLEOSIDE TRANSPORTER INHIBITOR; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CYTOMETRY; DRUG BINDING; DRUG MECHANISM; DRUG POTENCY; DRUG SCREENING; HALOGENATION; HEART PROTECTION; HUMAN; HUMAN CELL; HYDROPHOBICITY; NEUROPROTECTION; PHARMACODYNAMICS; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION;

FLOW CYTOMETRY; MEMBRANE TRANSPORT MODULATORS; MEMBRANE TRANSPORT PROTEINS; NUCLEOSIDES; THIOINOSINE;

EID: 1842790913     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.02.016     Document Type: Article

References (16)

1. Cass C.E. Georgopapadakou N.H. Drug Transport in Antimicrobial and Anticancer Chemotherapy. 1995;403-451 Marcel Dekker, New York.
2. Young J.D., Cheeseman C.I., Mackey J.R., Cass C.E., Baldwin S.A. Barrett K.E., Donowitz M. Current Topics in Membranes. Vol. 50:2000;329-378 Academic, San Diego, CA.
3. Buolamwini J.K. Curr. Med. Chem. 4:1997;35.
4. Hyde R.J., Cass C.E., Young J.D., Baldwin S.A. Mol. Membr. Biol. 18:2001;53.
5. Baldwin S.A., Beal P.R., Yao S.Y., King A.E., Cass C.E., Young J.D. Pflugers Arch. 2003;. June 28 web publication.
6. Ohta A., Stkovski M. Nature. 414:2001;916.
7. Abd-Elfattah A.S., Wechsler A.S. J. Card. Surg. 9:1994;387.
8. Abd-Elfattah A.S.A., Hoehner J., Wechsler A.S. Mol. Cell. Biochem. 180:1998;105.
9. Van Belle H. Cardiovasc. Res. 27:1993;68.
10. Deckert J., Morgan P.F., Marangos P.J. Life Sci. 42:1988;1331.
11. Geiger J.D., Parkinson F.E., Kowaluk E.A. Jacobson K.A., Jarvis M.F. Purinergic Approaches in Experimental Therapeutics. 1997;55-84 Wiley-Liss, New York.
12. Robins M.J., Asakura J., Kaneko M., Shibuya S., Jakobs E.S., Agbanyo F.R., Cass C.E., Paterson A.R.P. Nucleos. Nucleot. 13:1994;1627.
13. Buolamwini J.K., Wiley J.S., Robins M.J., Craik J.D., Cass C.E., Gati W.P., Paterson A.R.P. Nucleos. Nucleot. 13:1994;737.
14. To a solution of 6-mercaptopurine riboside (200 mg, 0.70 mmol) in DMF (2.5 mL) was added the corresponding halogen substituted benzyl halides (0.84 mmol) and potassium carbonate (1 g, 7.23 mmol). The mixture was stirred overnight at ambient temperature. The mixture was evaporated in vacuo at a temperature below 45°C to remove the DMF. The residue was dissolved in water and extracted with three 75 mL portions of ethyl acetate. The combined organic layer was washed once with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude product was purified using silica gel chromatography followed by recrystallization from methanol, to afford the pure compounds.
15. f, is the es transporter-specific fluorescence of the SAENTA-fluorescein ligand standard in mean channel numbers. The results obtained were entered in the PRISM program (GraphPad, San Diego, CA) to derive the concentration dependent curves (examples are shown in Fig. 1.
16. Zhu Z., Furr J., Buolamwini J.K. J. Med. Chem. 46:2003;831.