The synthesis and structure-activity relationship of substituted N-phenyl anthranilic acid analogs as amyloid aggregation inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 3, 2009, Pages 654-657

  Simons, Lloyd J ^a   Caprathe, Bradley W ^a   Callahan, Michael ^a   Graham, James M ^a   Kimura, Takenori ^b   Lai, Yingjie ^a   LeVine III, Harry ^a   Lipinski, William ^a   Sakkab, Annette T ^a   Tasaki, Yoshikazu ^b   Walker, Lary C ^a   Yasunaga, Tomoyuki ^b   Ye, Yuyang ^a   Zhuang, Nian ^a   Augelli Szafran, Corinne E ^a  

^a PFIZER INC   (United States)

^b ASTELLAS PHARMA INC   (Japan)

Author keywords

Alzheimer's disease; Amyloid aggregation; Amyloid aggregation inhibitors; Amyloid plaques; Analogs; Beta amyloid; Hsiao mouse model; N Phenyl anthranilic acid; Tg2576 mice

Indexed keywords

AMYLOID BETA PROTEIN; ANTHRANILIC ACID DERIVATIVE; BENZENE DERIVATIVE; PD 0118057; PD 0202091; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG SYNTHESIS; IC 50; IN VIVO STUDY; MOUSE; NONHUMAN; SENILE PLAQUE; STRUCTURE ACTIVITY RELATION;

ALZHEIMER DISEASE; AMYLOID; ANIMALS; CHEMISTRY, PHARMACEUTICAL; DISEASE MODELS, ANIMAL; DRUG DESIGN; ENZYME INHIBITORS; FENAMATES; HUMANS; MICE; MICROSCOPY, ATOMIC FORCE; MODELS, CHEMICAL; MOLECULAR STRUCTURE; PEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS;

EID: 58549114656     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.12.049     Document Type: Article

References (9)

1. Selkoe D.J., and Haass C. Nat. Rev. Mol. Cell Biol. 8 (2007) 101
2. Augelli-Szafran C.E., Walker L.C., and LeVine III H. Annu. Rep. Med. Chem. 34 (1999) 21
3. Augelli-Szafran, C. E.; Bian, F.; Callahan, M. J.; Feng, R.; Iwai, A.; Lai, Y., LeVine, III, H.; Lipinski, W.; Walker, L. C.; Yasunaga, T. Abstracts of Papers, 228th National Meeting of the American Chemical Society, Philadelphia, PA; American Chemical Society: Washington, DC, 2004; Abstract MEDI-315.
4. LeVine III H., and Scholten J.D. Meth. Enzymol. 309 (1999) 467
5. LeVine III H. Meth. Enzymol. 309 (1999) 278
6. Callahan M.J., Lipinski W.J., Bian F., Durham R.A., Pack A., and Walker L.C. Am. J. Pathol. 158 (2001) 1173
7. Plaque reduction for 14 and 57 seems to be at maximum effect expected in this model: 14 (200 mg/kg/day, PO: 7 months (n = 15, 44% reduction); 57 (60 mg/kg/day, PO: 7 months (n = 14, 47% reduction) and 3 months (n = 16, 45% reduction).
8. Thank you to P. Lansbury/J. Harper for AFM studies and J. Kelly/H. Lashuel for the analytical ultracentrifugation studies.
9. Unpublished results.