Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl] phenyl}-6,7-dimethoxy-2H-2-chromenone (AP2238) derivatives

Journal of Medicinal Chemistry

Volumn 50, Issue 17, 2007, Pages 4250-4254

  Piazzi, Lorna ^a   Cavalli, Andrea ^a   Belluti, Federica ^a   Bisi, Alessandra ^a   Gobbi, Silvia ^a   Rizzo, Stefano ^a   Bartolini, Manuela ^a   Andrisano, Vincenza ^a   Recanatini, Maurizio ^a   Rampa, Angela ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

3 [4 [(BENZYLMETHYLAMINO)METHYL]PHENYL] 6,7 DIMETHOXY 2H 2 CHROMENONE; 3 [4 [(BENZYLMETHYLAMINO)METHYL]PHENYL] 6,7 DIMETHOXYCHROMEN 2 ONE; 6 AMINO 3 [4 [(BENZYLMETHYLAMINO)METHYL]PHENYL]CHROMEN 2 ONE; ACETYLCHOLINESTERASE; AMINE; AMYLOID BETA PROTEIN; AP 2238; BENZENE DERIVATIVE; BENZYL DERIVATIVE; CHOLINESTERASE; CHROMENE DERIVATIVE; METHYL GROUP; UNCLASSIFIED DRUG;

ARTICLE; DENSITY FUNCTIONAL THEORY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME MECHANISM; IC 50; PROTEIN AGGREGATION; SIMULATION; STRUCTURE ACTIVITY RELATION;

ACETYLCHOLINESTERASE; BENZYLAMINES; BUTYRYLCHOLINESTERASE; CATALYTIC DOMAIN; CHOLINESTERASE INHIBITORS; COMPUTER SIMULATION; COUMARINS; HUMANS; MODELS, MOLECULAR; QUANTUM THEORY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34548133575     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070100g     Document Type: Article

References (16)

1. Goedert, M.; Spillantini, M. G. A century of Alzheimer's disease. Science 2006, 314, 777-781.
2. Terry, A. V., Jr.; Buccafusco, J. J. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: Recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther. 2003, 306, 821-827.
3. De Ferrari, G. V.; Canales, M. A.; Shin, I.; Weiner, L. M.; Silman, I.; Inestrosa, N. C. A Structural motif of acetylcholinesterase that promotes amyloid β-peptide fibril formation. Biochemistry 2001, 40, 10447-10457.
4. Piazzi, L.; Rampa, A.; Bisi, A.; Gobbi, S.; Belluti, F.; Cavalli, A.; Bartolini, M.; Andrisano, V.; Valenti, P.; Recanatini, M. 3-(4-{-[Benzyl(methyl) amino]methyl}-phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation: A dual function lead for Alzheimer's disease therapy. J. Med. Chem. 2003, 46, 2279-2281.
5. Ishihara, Y.; Goto, G.; Miyamoto, M. Central selective acetylcholinesterase inhibitor with neurotrophic activity: structure-activity relationships of TAK-147 and related compounds. Curr. Med. Chem. 2000, 7, 341-354.
6. Tumiatti, V.; Rosini, M.; Bartolini, M.; Cavalli, A.; Marucci, G.; Andrisano, V.; Angeli, P.; Banzi, R.; Minarini, A.; Recanatini, M.; Melchiorre, C. Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone. Role of the substituents on the phenyl ring and nitrogen atoms of caproctamine. J. Med. Chem. 2003, 46, 954-966.
7. Piazzi, L.; Belluti, F.; Bisi, A.; Gobbi, S.; Rizzo, S.; Bartolini, M.; Andrisano, V.; Recanatini, M.; Rampa, A. Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-ones. Bioorg. Med. Chem. 2007, 15, 575-585.
8. a) of basic acetylcholinesterase inhibitors by reversed-phase liquid chromatography. J. Chromatogr., A 2002, 958, 59-67.
9. Branduardi, D.; Gervasio, F. L.; Cavalli, A.; Recanatini, M.; Parrinello, M. The role of the peripheral anionic site and cation-pi interactions in the ligand penetration of the human AChE gorge. J. Am. Chem. Soc. 2005, 127, 9147-9155.
10. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727.
11. Bottegoni, G.; Cavalli, A.; Recanatini, M. A comparative study on the application of hierarchical-agglomerative clustering approaches to organize outputs of reiterated docking runs. J. Chem. Inf. Model. 2006, 46, 852-862.
12. Bottegoni, G.; Rocchia, W.; Recanatini, M.; Cavalli, A. AC1AP, Autonomous hierarchical agglomerative cluster analysis based protocol to partition conformational datasets. Bioinformatics 2006, 22, e58-65.
13. Olofsson, M.; Kalinin, S.; Zdunek, J.; Oliveberg, M.; Johansson, L. B. Tryptophan-BODIPY: A versatile donor-acceptor pair for probing generic changes of intraprotein distances. Phys. Chem. Chem. Phys. 2006, 8, 3130-3140.
14. Rampa, A.; Piazzi, L.; Belluti, F.; Gobbi, S.; Bisi, A.; Bartolini, M.; Andrisano, V. Cavrini, V.; Cavalli, A.; Recanatini, M.; Valenti, P. Acetylcholinesterase inhibitors: SAR and kinetic studies on ω-[N- methyl-N-(3alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl derivatives. J. Med. Chem. 2001, 44, 3810-3820.
15. Dickerson, T. J.; Beuscher IV, A. E.; Rogers, C. J.; Hixon, M. S.; Yamamoto, N.; Xu, Y.; Olson, A. J.; Janda, K. D. Discovery of acetylcholinesterase peripheral anionic site ligands through computational refinement of a directed library. Biochemistry 2005, 44, 14845-14853.
16. Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V. Beta-amyloid aggregation induced by human acetylcholinesterase: Inhibition studies. Biochem. Pharmacol. 2003, 65, 407-416.