Parallel synthesis and biological evaluation of 5,6,7,8- tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one cytotoxic agents selective for p21-deficient cells

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 21, 2005, Pages 4731-4735

  Jennings, Lee D ^a   Kincaid, Scott L ^a   Wang, Yanong D ^a   Krishnamurthy, Girija ^a   Beyer, Carl F ^a   McGinnis, John P ^a   Miranda, Miriam ^a   Discafani, Carolyn M ^a   Rabindran, Sridhar K ^a  

^a WYETH RESEARCH   (United States)

Author keywords

Inhibitors of cell cycle progression; Parallel synthesis; Tubulin binding

Indexed keywords

2 (1,4 DIBENZODIOXANE) DERIVATIVE; CHECKPOINT KINASE 1; CYTOTOXIC AGENT; PROTEIN P21; PYRIMIDINONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BIOLOGICAL ACTIVITY; CANCER CELL; CELL CYCLE; CELL LINE; CELL PROLIFERATION; DRUG DESIGN; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; MOLECULE;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; HUMANS; INHIBITORY CONCENTRATION 50; PYRIMIDINONES; STRUCTURE-ACTIVITY RELATIONSHIP; TUBULIN;

EID: 25144431934     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.07.072     Document Type: Article

References (22)

1. A.G. Paulovich, D.P. Toczyski, and L.H. Hartwell Cell 88 1997 315
2. D. Hanahan, and R.A. Weinberg Cell 100 2000 57
3. C.J. Torrance, V. Agrawal, B. Vogelstein, and K.W. Kinzler Nature Biotechol. 19 2001 940
4. G.C. Prendergast Nature Biotech. 19 2001 919
5. A.J. Levine Cell 88 1997 323
6. Z.A. Stewart, and J.A. Pietenpol Chem. Res. Toxicol. 14 2001 243
7. B. Vogelstein, D. Lane, and A.J. Levine Nature 408 2000 307
8. Z.A. Stewart, S.D. Leach, and J.A. Pietenpol Mol. Cell. Biol. 19 1999 205
9. T. Waldman, K.W. Kinzler, and B. Vogelstein Cancer Res. 55 1995 5187
10. T. Waldman, C. Lengaur, K.W. Kinzler, and B. Vogelstein Nature 381 1996 713
11. A. Gopalsamy, J.W. Ellingboe, H.-R. Tsou, N. Zhang, D. Wang, E. Honores, S. Johnson, D. Powell, M. Miranda, J.P. McGinnis, and S.K. Rabindran Bioorg. Med. Chem. Lett. 5 6 2005 591
12. A. Cruceyra, V. Gomez Parra, and R. Madronero Anales de Quimica (1968-1979) 71 1975 103 The authors actually reported the preparation of 2-(3,4,5-trimethoxyphenyl)-2,3,5,6,7,8-hexahydro-1H-benzo[4,5]thieno[2,3-d] pyrimidin-4-one (CAS # 37556-33-5) but probably, in fact, synthesized the tetrahydrothieno pyrimidinone 2
13. Y.D. Wang, S. Johnson, D. Powell, J. McGinnis, M. Miranda, and S.K. Rabindran Bioorg. Med. Chem. Lett. 15 2005 3763
14. K. Gerwald, E. Schinke, and H. Bottcher Chem. Ber. 99 1966 94
15. E.J. Martin, J.M. Blaney, M.A. Siani, D.C. Spellmeyer, A.K. Wong, and W.H. Moos J. Med. Chem. 38 1995 1431
16. L. Eriksson, E. Johanasson, N. Kettaneh-Wold, and S. Wold Introduction to Multi- and Megavariate Data Analysis Using Projection Methods (PCA % PLS) 1999 Umetrics AB Umea, Sweden Calculations performed using software product SIMPCA-P (Umetrics AB, Umea, Sweden)
17. meta substituent.
18. 4OH buffer, at 22.5 mL/min).
19. 50 > 20 μM on 80S14, as well as HCT116 cell lines.
20. 50 > 10 μM on 80S14 as well as HCT116 cell lines.
21. 50s shown represent the mean value.
22. G. Krishnamurthy, W. Cheng, M.-C. Lo, A. Aulabaugh, V. Raznikov, W. Ding, F. Loganzo, A. Zask, and G. Ellestad Biochemistry 42 2003 13484