Solid-phase synthesis of a focused library of trypanothione reductase inhibitors

Tetrahedron Letters

Volumn 44, Issue 15, 2003, Pages 3195-3197

  De Luca, Stefania ^a   Ulhaq, Saraj ^a   Dixon, Mark J ^a   Essex, Jonathan ^a   Bradley, Mark ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 METHOXYINDOLEACETIC ACID; ARGININE; BRIDGED COMPOUND; ENZYME INHIBITOR; TRYPANOTHIONE REDUCTASE; TRYPTOPHAN;

ARTICLE; PROTECTION; SOLID; SYNTHESIS;

EID: 0037424788     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00438-6     Document Type: Article

References (16)

1. Fairlamb A.H., Cerami A. Annu. Rev. Microbiol. 46:1992;695-729.
2. Augustyns K., Amssoms K., Yamani A., Rajan P.K., Haemers A. Curr. Pharm. Des. 7:2001;1117-1141.
3. For a review, see: Werbovetz K.A. Curr. Med. Chem. 7:2000;835-860.
4. Dumas C., Ouellette M., Tovar J., Cunningham M.L., Fairlamb A.H., Tamar S., Olivier M., Papadopoulou B. EMBO. 16:1997;2590-2598.
5. Smith H.K., Bradley M. J. Comb. Chem. 1:1999;326-332.
6. Houghton R.A. Proc. Natl. Acad. Sci. USA. 82:1985;5131-5135.
7. Nicolaou K.C., Xiao X.Y., Parandoosh Z., Senyei A., Nova M.P. Angew. Chem., Int. Ed. Engl. 34:1995;2289-2291.
8. Moran E.J., Sarshar S., Cargill J.F., Shahbaz M.M., Lio A., Mjalli A.M.M., Armstrong R.W. J. Am. Chem. Soc. 117:1995;10787-10788.
9. Avid PLC, East Sussex, TN22 3QY, UK (http://www.avidplc.com).
10. Marsh I.R., Bradley M. Tetrahedron. 53:1997;17317-17334.
11. Couplings were carried out using standard DIC/HOBT coupling conditions (see: König, W.; Geiger, R. Chem. Ber. 1970, 103, 788-798). Reactions were monitored using a qualitative ninhydrin test on a small quantity of resin (see: Sarin, V. K.; Kent, S. B. H.; Tam, J. P.; Merrifield, R. B. Anal. Biochem. 1981, 117, 147-157).
12. Couplings were carried out using standard DIC/HOBT coupling conditions (see: König, W.; Geiger, R. Chem. Ber. 1970, 103, 788-798). Reactions were monitored using a qualitative ninhydrin test on a small quantity of resin (see: Sarin, V. K.; Kent, S. B. H.; Tam, J. P.; Merrifield, R. B. Anal. Biochem. 1981, 117, 147-157).
13. 2) moiety were cleaved with 90% TFA in DCM for 1.5 h; compounds bearing the Arg(Tos) moiety were cleaved with 90% TFA in DCM for 1 h; compounds bearing the Arg(Mtr) and Arg(Mts) moieties were cleaved with 50% TFA in DCM for 15 min; compounds bearing the Arg(Pbf) and Arg(Pmc) moieties were cleaved with 20% TFA in DCM for 2×15 min.
14. -1, detected by ELS and UV at 220 nm. ES-MS data was obtained using a VG platform quadrupole electrospray ionisation mass spectrometer.
15. 4, 1 mM EDTA, pH 7.5), 100 μM NADPH and various known concentrations of trypanothione (16 μM to 150 μM). Initial rates were recorded at 340 nm, following addition of the substrate. Data was collected in triplicate and analysed using GraFit.
16. +.