Synthesis of 4-[(diethylamino)methyl]-phenol derivatives as novel cholinesterase inhibitors with selectivity towards butyrylcholinesterase

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 11, 2010, Pages 3254-3258

  Yu, Liang ^a   Cao, Rihui ^a   Yi, Wei ^a   Yan, Qin ^a   Chen, Zhiyong ^a   Ma, Lin ^a   Peng, Wenlie ^a   Song, Huacan ^a  

^a SUN YAT SEN UNIVERSITY   (China)

Author keywords

Alzheimer's disease; Cholinesterase; Inhibitors; Kinetics analysis; p Hydroxybenzaldehyde

Indexed keywords

4 [(DIETHYLAMINO)METHYL]PHENOL DERIVATIVE; AMINE; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG INHIBITION; DRUG POTENCY; DRUG SYNTHESIS; IC 50;

BUTYRYLCHOLINESTERASE; CHOLINESTERASE INHIBITORS; PHENOLS;

EID: 77953285226     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.04.059     Document Type: Article

References (23)

1. McDowell I. Aging (Milano) 13 (2001) 143
2. Terry A.V., and Buccafusco J.J. J. Pharmacol. Exp. Ther. 306 (2003) 821
3. Silman I., and Sussman J.L. Curr. Opin. Pharmacol. 5 (2005) 293
4. Nachon F., Nicolet Y., and Masson P. Ann. Pharm. Fr. 63 (2005) 194
5. Greig N.H., Sambamurti K., Yu Q.S., Brossi A., Bruinsma G.B., and Lahiri D.K. Curr. Alzheimer Res. 2 (2005) 1307
6. Lahiri D.K., Farlow M.R., Hintz N., Utsuki T., and Greig N.H. Acta Neurol. Scand. Suppl. 176 (2000) 60-67
7. Giacobini E. In: Buccafusco J.J. (Ed). Cognitive Enhancing Drugs (2004), Birkhäuser, Basel, Boston, Berlin 11-36
8. Sussman J.L., Harel M., Frolow F., Oefner C., Goldman A., Toker L., and Silman I. Science 253 (1991) 872
9. Harel M., Schalk I., Ehret-Sabatier L., Bouet F., Goeldner M., Hirth C., Axelsen P.H., Silman I., and Sussman J.L. Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 9031
10. Wen H., Lin C.L., Que L., Peng W.L., Wang Z.H., and Song H.C. Eur. J. Med. Chem. 43 (2008) 166
11. Wen H., Zhou Y.Y., Lin C.L., and Song H.C. Bioorg. Med. Chem. Lett. 17 (2007) 2123
12. Sheng R., Lin X., Li J.Y., and Hu Y.Z. Bioorg. Med. Chem. Lett. 15 (2005) 3834
13. Tang H., Wei Y.B., Zhang C., Ning F.X., Qiao W., Huang S.L., Ma L., Huang Z.S., and Gu L.Q. Eur. J. Med. Chem. 44 (2009) 2523
14. Tang H., Ning F.X., Wei Y.B., Huang S.L., Huang Z.S., Albert Sun-Chi Chan A.S.C., and Gu L.Q. Bioorg. Med. Chem. Lett. 17 (2007) 3765
15. Markmee S., Ruchirawat S., Prachyawarakorn V., Ingkaninan K., and Khorana N. Bioorg. Med. Chem. Lett. 16 (2006) 2170
16. Piazzi L., Belluti F., Bisi A., Gobbi S., and Rampa A. Bioorg. Med. Chem. 15 (2007) 575
17. 3, 300 MHz) δ, ppm: 9.86 (s, 1H, CHO), 7.82 (d, J = 8.8 Hz, 2H, ArH), 6.99 (d, J = 8.7 Hz, 2H, ArH), 4.04 (t, J = 6.5 Hz, 2H, H1), 3.20 (t, J = 7.0 Hz, 2H, H8), 1.88-1.78 (m, 4H, H7, H2), 1.42-1.30 (m, 8H, H3, H4, H5, H6).
18. Abdel-Magid A., Carson K., and Harris B. J. Org. Chem. 61 (1996) 3849
19. 3).
20. 3).
21. Ellman G.L., Courtney K.D., Andres V., and Featherstone R.M. Biochem. Pharmacol. 7 (1961) 88
22. Assay of the AChE and BChE inhibitory activity. The assay was performed as described in the following procedure. Five different concentration of each compound were measured at 412 nm for 1 min, each concentration in triplicate. For buffer preparation, 0.1 M dipotassium hydrogen phosphate was adjusted to pH 8.0 with 1 M potassium dihydrogen phosphate. Enzyme solutions were prepared to give 2.5 units/mL in 1.5 mL aliquots. Furthermore, 0.01 M DTNB solution, 0.075 M ATC, and BTC solutions, respectively, were used. A cuvette containing 880 μL of phosphate buffer, 10 μL of the respective enzyme, 50 μL of DTNB, and 20 μL of the test compound solution was allowed to pre-incubate for 15 min at 37 °C, and the reaction was started by addition of 40 μL of the substrate solution (ATC/BTC). The reaction was monitored by measuring the absorbance at 412 nm. For the reference value, 20 μL of DMSO replaced the test compound solution. For determining the blank value, additionally 10 μL of buffer replaced the enzyme solution.
23. Pang Y.P., Quiram P., Jelacic T., Hong F., and Brimijoin S. J. Biol. Chem. 271 (1996) 23646