OpenSourceMalaria:GSK Amino-thienopyrimidine Series

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Contents

GSK Thienopyrimidine Series

The first structure in this series, | TCMDC 135294, has the following structure:

GSK Thienopyrimidine Series: TCMDC 135294
GSK Thienopyrimidine Series: TCMDC 135294

| ChEMBL 581088 link.

| ChemSpider link.

SMILES: Nc1ncnc2cc(sc12)c3cccc(c3)S(=O)(=O)N

InChI=1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)

Synthesis

The proposed synthesis for this compound is below:

Proposed synthesis for the above compound
Proposed synthesis for the above compound

Additionally, the thiophene available from Sigma Aldrich for $159/10g can be made from the following synthesis.

Proposed synthesis for the above compound
Proposed synthesis for the above compound

Analogues

TCMDC 135294 is part of a series with one other member, | TCMDC 135255, shown below:

TCMDC 135255
TCMDC 135255

| ChEMBL639249 link.

| ChemSpider link.

SMILES: Nc1ncnc2cc(sc12)c3cccc(NC(=O)Nc4ccccc4)c3

InChI=1S/C19H15N5OS/c20-18-17-15(21-11-22-18)10-16(26-17)12-5-4-8-14(9-12)24-19(25)23-13-6-2-1-3-7-13/h1-11H,(H2,20,21,22)(H2,23,24,25)

Iain Wallace created a cytoscape file which details purchaseable compounds related to the two series that I am trying to make. The file can be found here, and Cytoscape can be downloaded for free here (one will need to activate the chemviz plugin, which can be activated from within Cytoscape). The results of this work, in the form of a list of purchaseable compounds, can be found here

References

| Barker, J. M.; Huddleston, P. R.; Wood, M. L., A RAPID CONVERSION OF 3-OXOTHIOLANES INTO 3-AMINOTHIOPHENES. Synthetic Communications 2002, 32 (16), 2565-2568.

| Baykal, A. T.; Kakalis, L.; Jordan, F., Electronic and nuclear magnetic resonance spectroscopic features of the 1 ',4 '-iminopyrimidine tautomeric form of thiamin diphosphate, a novel intermediate on enzymes requiring this coenzyme. Biochemistry 2006, 45 (24), 7522-7528.

Brown, G. B.; Baker, B. R.; Bernstein, S.; Safir, S. R., BIOTIN. II. 3,4-trans-DIAMINOTHIOPHANE. The Journal of Organic Chemistry 1947, 12 (1), 155-159.

Castenado, G.; Dotson, J.; Goldsmith, R.; Gunzo, J.; Heffron, T.; Mathieu, S.; Oliveo, A.; Staben, S.; Sutherlin, D.P.; Tsui, V.; Wang, S.; Zhu, B.; Bayliss, T.; Chuckowree, I.; Folkes, A.; Wan, N.C. (Genentech, Inc., USA; Piramed Limited). Thienopyrimidine and furopyrimidine derivatives as phosphoinositide 3-kinase inhibitor and their preparation, pharmaceutical compositions and use in the treatment of cancer. World Intellectual Property Organisation 2008073785 A2, 2008; SciFinder Scholar AN 2008:735944 (accessed 2/2/2012).

| Diel, B. N.; Han, M. C.; Kole, P. L.; Boaz, D. B., Synthesis of (C-13(6)-Ring-(U))-(+/-)-benzo(a)pyrene metabolites from (C-13(6)-Ring-(U))benzene. Journal of Labelled Compounds & Radiopharmaceuticals 2007, 50 (5-6), 551-553.

| F, Duus., A study of the tautomerism of 2- and 4-ethoxycarbonylthiolan-3-ones implicating stereochemical effects of ring-substitution. Tetrahedron 1981, 37 (15), 2633-2640.

Son, J.B.; Jung, S. H.; Choi, W.I.; Jung, Y.H.; Choi, J.Y.; Song, J.Y.; Lee, K.H.; Lee, J.C.; Kim, E.Y.; Ahn, Y.G.; Kim, M.S.; Choi, HG.; Sim, T.B.; Ham, Y.J.; Park, D.; Kim, H.; Kim, D. (Hanmi Holdings Co., Ltd., S. Korea; Korea Institute of Science and Technology; Catholic University Industry Academic Cooperation Foundation). Preparation of thienopyrimidine derivatives for use as protein kinase inhibitors. World Intellectual Property Organisation 2011093684 A2, 2011; SciFinder Scholar AN 2011:971406 (accessed 3/2/2012).

Woodward, R. B.; Eastman, R. H., Tetrahydrothiophene ("Thiophane") Derivatives. J. Am. Chem. Soc. 1946, 68 (11), 2229-2235.

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