Design and synthesis of a library of tetracyclic hydroazulenoisoindoles

Journal of Combinatorial Chemistry

Volumn 11, Issue 3, 2009, Pages 486-494

  Brummond, Kay M ^a   Mao, Shuli ^a   Shinde, Sunita N ^a   Johnston, Paul J ^a   Day, Billy W ^a,b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FUSED HETEROCYCLIC RINGS; GLUCOCORTICOID RECEPTOR; PALLADIUM; RHODIUM;

ANIMAL; ARTICLE; CATALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; COMBINATORIAL CHEMISTRY; DRUG EFFECT; HYDROGENATION; MOLECULAR LIBRARY; MOUSE; SYNTHESIS; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

ANIMALS; CATALYSIS; CELL LINE, TUMOR; COMBINATORIAL CHEMISTRY TECHNIQUES; CRYSTALLOGRAPHY, X-RAY; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HYDROGENATION; MICE; MOLECULAR STRUCTURE; PALLADIUM; RECEPTORS, GLUCOCORTICOID; RHODIUM; SMALL MOLECULE LIBRARIES;

EID: 66149128005     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc900024p     Document Type: Article

References (28)

1. Sauer, W. H. B.; Schwarz, M. K. J. Chem. Inf. Comput. Sci. 2003, 43, 987-1003.
2. Lipkus, A. H.; Yuan, Q.; Lucas, K. A.; Funk, S. A.; Bartelt III, W. F.; Schenck, R. J.; Trippe, A. J. J. Org. Chem. 2008, 73, 4443-4451.
3. For a review on a DOS planning strategy, see: (a) Burke, M. D.; Schreiber, S. L. Angew. Chem. Int. Ed 2004, 43, 46-58.
4. Lipinski, C.; Hopkins, A. Nature (London) 2004, 432, 855-86J.; The NIH Roadmap http://www.nihroadmap.nih.gov.
5. Brummond, K. M.; Mitasev, B. Org. Lett. 2004, 6, 2245-2248.
6. Nielsen, T. E.; Schreiber, S. L. Angew. Chem. Int. Ed 2008, 47, 48-56; building blocks are synthesized in the build phase, the intermolecular coupling reactions are carried out in the couple phase, and in the pair phase, intramolecular reactions are effected.
7. Beeler, A. B.; Su, S.; Singleton, C. A.; Porco, J. A., Jr. J. Am. Chem. Soc. 2007, 129, 1413-1419.
8. (a) Brummond, K. M.; Chen, D. Org. Lett. 2005, 7, 3473-3475.
9. (b) Brummond, K. M.; Chen, H.; Mitasev, B.; Casarez, A. D. Org. Lett. 2004, 6, 2161-2163.
10. (a) Werner, S.; Turner, D. M.; Chambers, P. G.; Brummond, K. M. Tetrahedron 2008, 64, 6997-7007.
11. (b) Brummond, K. M.; Yan, B. Synlett 2008, 15, 2303-2308.
12. (c) Mitasev, B.; Yan, B.; Brummond, K. M. Heterocycles 2006, 70, 367-388.
13. (d) Werner, S.; Iyer, P. S.; Fodor, M. D.; Coleman, C. M.; Twining, L. A.; Mitasev, B.; Brummond, K. M. J. Comb. Chem 2006, 8, 368-380.
14. (e) Brummond, K. M.; Curran, D. P.; Mitasev, B.; Fischer, S. J. Org. Chem. 2005, 70, 1745-1753.
15. Brummond, K. M.; Chen, D.; Painter, T. O.; Mao, S.; Seifried, D. D. Synlett 2008, 5, 759-764.
16. Davies, H. M. L.; Smith, H. D.; Korkor, O. Tetrahedron Lett. 1987, 28, 1853-1856.
17. Davies, H. M. L.; Clark, D. M.; Alligood, D. B.; Eiband, G. R. Tetrahedron 1987, 43, 4265-4270.
18. Davies, H. M. L.; Clark, T. J.; Smith, H. D. J. Org. Chem. 1991, 56, 3817-3824.
19. Davies, H. M. L. Tetrahedron 1993, 49, 5203-5223.
20. Mao, S.; Probst, D.; Werner, S.; Chen, J.; Xie, X.; Brummond, K. M. J. Comb. Chem 2008, 10, 235-246.
21. (a) QikProp 2.1; Schroedinger Inc.: New York, 2003. MW is the molecular weight of the molecule, volume is the total solvent-accessible volume in cubic angstroms using a probe with a 1.4 Å radius, SASA is the total solvent-accessible surface area in square angstroms using a probe with a 1.4 Å radius, HBD is the estimated number of hydrogen bonds that would be donated by the solute to water molecules in an aqueous solution, HBA is the estimated number of hydrogen bonds that would be accepted by the solute from water molecules in an aqueous solution, logP is the predicted octanol/water partition coefficient, logS is the predicted aqueous solubility (S in mol/L is the concentration of the solute in a saturated solution that is in equilibrium with the crystalline solid), rotatable bonds is the number of non-trivial (not CX3), non-hindered (not alkene, amide, small ring) rotatable bonds, logKhsa is the prediction of binding to human serum albumin, Caco-Perm. is the predicted apparent Caco-2 cell permeability in nm/s.
22. (b) Duffy, E. M.; Jorgensen, W. L. J. Am. Chem. Soc. 2000, 122, 2878-2888.
23. (c) Jorgensen, W. L.; Duffy, E. M. Adv. Drue Delivery Rev. 2002, 54, 355-366.
24. (d) Jorgensen, W. L. Science 2004, 303, 1813-1818.
25. (a) Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Adv. Drue Delivery Rev. 1997, 23, 3-25.
26. (b) Egan, W. J.; Merz, K. M., Jr.; Baldwin, J. J. J. Med. Chem. 2000, 43, 3867-3877.
27. (c) Veber, D. F.; Johnson, S. R.; Cheng, H.-Y.; Smith, B. R.; Ward, K. W.; Kopple, K. D. J. Med. Chem. 2002, 45, 2615-2623.
28. Walker, D.; Htun, H.; Hager, G. L. Methods 1999, 19, 386-393.