Design, synthesis and evaluation of 3-(2-Aminoheterocycle)-4- benzyloxyphenylbenzamide derivatives as BACE-1 inhibitors

Molecules

Volumn 18, Issue 3, 2013, Pages 3577-3594

  Shangguan, Shihao ^a   Wang, Fei ^a   Liao, Yong ^a   Yu, Haiping ^b   Li, Jia ^b   Huang, Wenhai ^a,c   Hu, Haihong ^a   Yu, Lushan ^a   Hu, Yongzhou ^a   Sheng, Rong ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b National Center for Drug Screening   (China)

^c INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

2 amino 6H 1,3,4 thiadizine; BACE 1 inhibitor; Blood brain barrier permeability

Indexed keywords

ASPARTIC PROTEINASE; BACE1 PROTEIN, HUMAN; MULTIDRUG RESISTANCE PROTEIN; N (3 (2 AMINO 6H 1,3,4 THIADIAZIN 5 YL) 4 (BENZYLOXY)PHENYL) 1 NAPHTHAMIDE HYDROBROMIDE; N-(3-(2-AMINO-6H-1,3,4-THIADIAZIN-5-YL)-4-(BENZYLOXY)PHENYL)-1-NAPHTHAMIDE HYDROBROMIDE; NAPHTHALENE DERIVATIVE; PROTEINASE INHIBITOR; SECRETASE; THIADIAZINE DERIVATIVE;

ANIMAL; ARTICLE; BLOOD BRAIN BARRIER; CELL LINE; CHEMISTRY; DOG; DRUG ANTAGONISM; DRUG DESIGN; DRUG SCREENING; HUMAN; METABOLISM; PERMEABILITY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; ANTAGONISTS AND INHIBITORS;

AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; BLOOD-BRAIN BARRIER; CELL LINE; DOGS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; NAPHTHALENES; P-GLYCOPROTEIN; PERMEABILITY; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; THIADIAZINES;

EID: 84875614780     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules18033577     Document Type: Article

References (21)

1. Dinusson, J.; Knopman, D. Pharmacoeconomics in Alzheimer's disease. Neurologist 2000, 6, 116-125.
2. Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002, 297, 353-356.
3. Luo, Y.; Bolon, B.; Kahn, S.; Bennett, B.D.; Babu-Khan, S.; Denis, P.; Fan, W.; Kha, H.; Zhang, J.; Gong, Y.; et al. Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat. Neurosci. 2001, 4, 2001-2003.
4. Vassar, R.; Kovacs, D.M.; Yan, R.; Wong, P.C. The β-secretase enzyme BACE in health and Alzheimer's disease: Regulation, cell biology, function, and therapeutic potential. J. Neurosci. 2009, 29, 12787-12794.
5. Taleb, H.A.; Mohammad, H.S.; Raed, A.A.; Marco, F.S.; Raafat, E.; Mustafa, A.; Rania, Z.; Shashidhar, N.R.; Omar, E. Design, synthesis, and qualitative structure-activity evaluations of novel β-secretase inhibitors as potential Alzheimer's drug leads. J. Med. Chem. 2011, 54, 8373-8385.
6. Efremov, V.I.; Vajdos, F.F.; Borzilleri, K.A.; Capetta, S.; Chen, H.; Dorff, P.H.; Dutra, J.K.; Goldstein, S.W.; Mansour, M.; McColl, A.; et al. Discovery and optimization of a novel spiropyrrolidine inhibitor of β-secretase (BACE1) through fragment-based drug design. J. Med. Chem. 2012, 55, 9069-9088.
7. Huang, W.H.; Sheng, R.; Hu, Y.Z. Progress in the development of nonpeptidomimetic BACE 1 inhibitors for Alzheimers disease. Curr. Med. Chem. 2009, 16, 1806-1820.
8. Ghosh, A.K.; Brindisi, M.; Tang, J.J. Developing β-secretase inhibitors for treatment of Alzheimer's disease. J. Neurochem. 2012, 120, 71-83.
9. Probst, G.; Xu, Y. Small-molecule BACE1 inhibitors: A patent literature review (2006-2011). Expert. Opin. Ther. Pat. 2012, 22, 511-540.
10. Malamas, M.S.; Erdei, J.; Gunawan, I.; Barnes, K.; Johnson, M.; Hui, Y.; Turner, J.; Hu, Y.; Wagner, E.; Fan, K.; et al. Amino-imidazoles as Potent and Selective Human β-Secretase (BACE1) Inhibitors. J. Med. Chem. 2009, 52, 6314-6323.
11. Swahn, B.M.; Holenz, J.; Kihlstr, J.; Kolmodin, K.; Lindstrom, J.; Plobeck, N.; Rotticci, D.; Sehgelmeble, F.; Sundstrom, M.; von Berg, S.; et al. Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy. Bioorg. Med. Chem. Lett. 2012, 22, 1854-1859.
12. Chiriano, G.; Simone, A.; Mancini, F.; Perez, D.I.; Cavalli, A.; Bolognesi, M.L.; Legname, G.; Martinez, A.; Andrisano, V.; Carloni, P.; et al. A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation. Eur. J. Med. Chem. 2012, 48, 206-213.
13. Congreve, M.; Aharony, D.; Albert, J.; Callaghan, O.; Campbell, J.; Carr, R.A.E.; Chessari, G.; Cowan, S.; Edwards, P.D.; Frederickson, M.; et al. Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of β-secretase. J. Med. Chem. 2007, 50, 1124-1132.
14. Stachel, S.J.; Coburn, C.A.; Rush, D.; Jones, K.; Zhu, H.; Rajapakse, H.; Graham, S.L.; Simon, A.; Holloway, M.K.; Allison, T.J.; et al. Discovery of aminoheterocycles as a novel β-secretase inhibitor class: pH dependence on binding activity part 1. Bioorg. Med. Chem. Lett. 2009, 19, 2977-2980.
15. Huang, W.H.; Tang, L.; Shi, Y.; Huang, S.F.; Xu, L.; Sheng, R.; Wu, P.; Li, J.; Zhou, N.M.; Hu, Y.Z. Discovery of quinoxaline-based hybrid compounds with AChE, H3R and BACE 1 inhibitory activities. Bioorg. Med. Chem. 2011, 19, 7158-7167.
16. Huang, W.H.; Lv, D.; Yu, H.; Sheng, R.; Kim, S.C.; Wu, P.; Luo, K.; Li, J.; Hu, Y.Z. Dual-target-directed 1, 3-diphenylurea derivatives: BACE 1 inhibitor and metal chelator against Alzheimer's disease. Bioorg. Med. Chem. 2010, 18, 5610-5615.
17. Hussain, I.; Hawkins, J.; Harrison, D.; Hille, C.; Wayne, G.; Cutler, L.; Buck, T.; Walter, D.; Demont, E.; Howes, C.; et al. Oral administration of a potent and selective non-peptidic BACE-1 inhibitor decreases β-cleavage of amyloid precursor protein and amyloid precursor protein and amyloid-β production in vivo. J. Neurochem. 2006, 100, 802-809.
18. Wang, Q.; Rager, J.D.; Weinstein, K.; Kardos, P.S.; Dobson, G.L.; Li, J.; Hidalgo, I. Evaluation of the MDR-MDCK cell line as a permeability screen for the blood-brain barrier. Int. J. Pharm. 2005, 288, 349-359.
19. Sun, S.Y.; Chen, Z.; Li, L.; Sun, D.; Tian, Y.; Pan, H.; Bi, H.C.; Huang, M.; Zeng, S.; Jiang, H.D. The two enantiomers of tetrahydropalmatine are inhibitors of P-gp, but not inhibitors of MRP1 or BCRP. Xenobiotica 2012, 42, 1-9.
20. Bruice, T.C.; Schmir, G.L. Imidazole catalysis. I. The catalysis of the hydrolysis of phenyl acetates by imidazole. J. Am. Chem. Soc. 1957, 79, 1663-1667.
21. Matsumura, E.; Ariga, M.; Tohda, Y. A ring transformation of 1-substituted 3,5-dinitro-2-pyridones. Tetrahedron Lett. 1979, 16, 1393-1396.