Benzimidazole derivatives as arginine mimetics in 1,4-benzodiazepine nonpeptide vitronectin receptor (αvβ3) antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 22, 1998, Pages 3165-3170

  Keenan, Richard M ^a   Miller, William H ^a   Lago, M Amparo ^a   Ali, Fadia E ^b   Bondinell, William E ^a   Callahan, James F ^a   Calvo, Raul R ^a   Cousins, Russell D ^a   Hwang, Shing Mei ^b   Jakas, Dalia R ^a   Ku, Thomas W ^a   Kwon, Chet ^a   Nguyen, Thomas T ^a   Reader, Valerie A ^a   Rieman, David J ^b   Ross, Steven T ^b   Takata, Dennis T ^a   Uzinskas, Irene N ^a   Yuan, Catherine C K ^a   Smith, Brian R ^b  

^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; BENZIMIDAZOLE DERIVATIVE; SB 223245; UNCLASSIFIED DRUG; VITRONECTIN RECEPTOR; VITRONECTIN RECEPTOR ANTAGONIST;

ANGIOGENESIS; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; OSTEOPOROSIS; RAT; RESTENOSIS; STRUCTURE ACTIVITY RELATION; TUMOR VASCULARIZATION;

ANIMALIA;

EID: 0032542046     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00555-1     Document Type: Article

References (12)

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2. 2. 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.; Huffinan, W. F. J. Med. Chem. 1997, 40, 2289.
3. 3. Samanen, J. Annu. Rep. Med. Chem. 1996, 31, 91.
4. 4. Keenan, R. M.; Lago, M. A.; Miller, W. H.; Ali, F. E.; Cousins, R. D.; Hall, L. B.; Hwang, S.-M.; Jakas, D. R.; Kwon, C.; Louden, C.; Nguyen, T.; Ohlstein, E.; Rieman, D. S.; Ross, S. T.; Samanen, J. M.; Smith, B. R.; Stadel, J. M.; Takata, D. T.; Vickery, L.; Yuan, C. C. K.; Yue, T.-L. Bioorg. Med. Chem. Lett. 1998, 8, following paper in this issue.
5. 5. (a) Miller, W. H.; Ku, T. W.; Ali, F. E.; Bondinell, W. E.; Calvo, R. R.; Davis, L. D.; Erhard, K. F.; Hall, L. B.; Huffman, W. F.; Keenan, R. M.; Kwon, C.; Newlander, K. A.; Ross, S. T.; Samanen, J. M.; Takata, D. T.; Yuan, C.-K. Tetrahedron Lett. 1995, 36, 9433.
6. (b) Ku, T. W.; Ali, F. E.; Bondinell, W. E.; Erhard, K. F.; Huffman, W. F.; Venslavsky, J. W.; Yuan, C. C.-K. Tetrahedron Lett. 1997, 38, 3131.
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8. 7. Ku, T. W.; Miller, W. H.; Bondinell, W. E.; Keenan, R. M.; Nichols, A. J.; Peishoff, C. E.; Samanen, J. M.; Wong, A. S.; Huffman, W. F. J. Med. Chem. 1995, 38, 9.
9. i 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.
10. i values represent the means of values determined in two to three separate experiments. Typical assay variability was ±10%. See Ali, F. E.; Bennett, D. B.; Calvo, R. R.; Elliott, J. D.; Hwang, S.-M.; Ku, T. W.; Lago, M. A.; Nichols, A. J.; Romoff, T. T.; Shah, D. H.; Vasko, J. A.; Wong, A. S.; Yellin, T. O.; Yuan, C.-K.; Samanen, J. M. J. Med. Chem. 1994, 37, 769.
11. 50 values for the HEK293 cell adhesion assay were determined in two experiments of triplicates with compound 29 as 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.
12. 1/2 = 9-16 min.; plasma clearance = 35 mL/min/kg.