Discovery of an imidazopyridine-containing 1,4-benzodiazepine nonpeptide vitronectin receptor (αvβ3) antagonist with efficacy in a restenosis model

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 22, 1998, Pages 3171-3176

  Keenan, Richard M ^a   Lago, M Amparo ^a   Miller, William H ^a   Ali, Fadia E ^a   Cousins, Russell D ^a   Hall, Leon B ^b   Hwang, Shing Mei ^b   Jakas, Dalia R ^a   Kwon, Chet ^a   Louden, Calvert ^b   Nguyen, Thomas T ^a   Ohlstein, Eliot H ^b   Rieman, David J ^b   Ross, Steven T ^b   Samanen, James M ^a   Smith, Brian R ^b   Stadel, Jeffrey ^b   Takata, Dennis T ^a   Vickery, Lynne ^b   Yuan, Catherine C K ^a   Yue, Tian Li ^b   more..

^a GLAXOSMITHKLINE   (United Kingdom)

^b NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 OXO 1,4 BENZODIAZEPINE 2 ACETIC ACID DERIVATIVE; ARGININE; IMIDAZOPYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; VITRONECTIN RECEPTOR; VITRONECTIN RECEPTOR DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA MEDIA; ARTICLE; CELL ADHESION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; INTRAVENOUS DRUG ADMINISTRATION; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; RESTENOSIS; THROMBOCYTE; TRANSLUMINAL CORONARY ANGIOPLASTY;

ANIMALIA;

EID: 0032542076     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00556-3     Document Type: Article

References (16)

1. 1. Yue, T. L.; Wang, X. K.; Stadel, J. M.; Feuerstein, G. Z. In Coronary Restenosis: From Genes to Therapeutics; Feuerstein, G., Ed.; Marcel Dekker: New York, 1996, pp 69-84. For a recent review of αvβ3 and restenosis, see: Samanen, J.; Jonak, Z.; Rieman, D.; Yue, T.-L. Curr. Pharmaceut. Design 1997, 3, 545.
2. 1. Yue, T. L.; Wang, X. K.; Stadel, J. M.; Feuerstein, G. Z. In Coronary Restenosis: From Genes to Therapeutics; Feuerstein, G., Ed.; Marcel Dekker: New York, 1996, pp 69-84. For a recent review of αvβ3 and restenosis, see: Samanen, J.; Jonak, Z.; Rieman, D.; Yue, T.-L. Curr. Pharmaceut. Design 1997, 3, 545.
3. 2. O'Brien, E. R.; Schwartz, S. M. Trends Cardiovasc. Med. 1994, 4, 169.
4. 3. Yue, T. L.; McKenna, P. J.; Ohlstein, E. H.; Farach-Carson, M. C.; Butler, W. T.; Johanson, K.; McDevitt, P.; Feuerstein, G. Z.; Stadel, J. M.; Exp. Cell Res. 1994, 214, 459.
5. 4. Liaw, L.; Almeida, M.; Hart, C. E.; Schwartz, S. M.; Giachalli, C. M. Circ. Res. 1994, 74, 214.
6. 5. Choi, E. T.; Engel, L.; Callow, A. D.; Sun, S.; Trachtenberg, J.; Santoro, S.; Ryan, U. S. J. Vasc. Surg. 1994, 19, 125.
7. 6. Matsuno, H.; Stassen, J. M.; Vermylen, J.; Deckmyn, H. Circulation 1994, 90, 2203.
8. 7. EPIC 1994; Topol, E. J.; Califf, R. M.; Weisman, H. F.; Ellis, S. G.; Tcheng, J. E.; Worley, S.; Ivanhoe R.; George, B. S.; Fintel, D.; Weston, M.; Sigmon, K.; Anderson, K. M.; Lee, K. L.; Willerson, J. T. Lancet 1994, 343, 881.
9. 8. Lefkovits J.; Topol E. J. Eur. Heart J. 1996, 17, 9.
10. 9. Keenan, R. M.; Miller, W. H.; Kwon, C.; Ali, F. E.; Callahan, J. F.; Calvo, R. R.; Hwang, S.-M.; Kopple, K. D.; Peishoff, C. E.; Samanen, J. M.; Wong, A. S.; Yuan, C.-K.; Huffman, W. F. J. Med. Chem. 1997, 40, 2289.
11. 10. Keenan, R. M.; Miller, W. H.; Lago, M. A.; Ali, F. E.; Bondinell, W. E.; Callahan, J. F.; Calvo, R. R.; Cousins, R. D.; Hwang, S.-M.; Jakas, D. R.; Ku, T. W.; Kwon, C.; Nguyen, T. T.; Reader, V. A.; Rieman, D. S.; Ross, S. T.; Takata, D. T.; Uzinskas, I. N.; Yuan, C. C. K.; Smith, B. R. Bioorg Med Chem Lett. 1998, 8, preceding paper in this issue.
12. 11. Binding affinity for human αvβ3 was determined in a competitive binding assay employing a tritiated RGD peptide as the displaced ligand. The Ki values represent the means of values determined in two to three separate experiments. Typical assay variability was ±10%. See Wong, A.; Hwang, S. M.; McDevitt, P.; McNulty, D.; Stadel, J. M.; Johanson, K. Mol. Pharm. 1996, 50, 529.
13. 50 values for the HEK293 cell adhesion assay were determined in two experiments of triplicates with compound 29 from reference 10 as an internal standard. Typical assay variability was ±20%. For a description of the assay, see: Kumar, C. S.; James, I. E.; Wong, A.; Mwang, V.; Feild, J. A.; Nuthulaganti, P.; Connor, J. R.; Eichman, C.; Ali, F.; Hwang, S. M.; Rieman, D.; Drake, F. H.; Gowen, M. J. Biol. Chem. 1997, 272, 16390.
14. 13. Yue, T. L.; Wang, X. K.; Sung, C. P.; Olson, B.; McKenna, P. J.; Gu, J. L.; Feuerstein, G. Z. Circ. Res. 1994, 75, 1.
15. 14. Ohlstein, H. E.; Douglas, S. A.; Sung, C. P.; Yue, T. L.; Louden, C.; Arleth, A.; Poste, G.; Ruffolo, R. R.; Feuerstein, G. Z. Proc. Nat. Acad. Sci. U.S.A. 1993, 90, 6189.
16. 15. A preliminary account of this work was presented at the 5th Chemical Congress of North America, Cancun, Mexico, November 11-15, 1996.