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Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors.
Eur J Med Chem. 2013 May; 63:95-103.EJ

Abstract

2,6-Disubstituted pyridazinone 4 was identified by HTS as a novel acetylcholinesterase (AChE) inhibitor. Under SAR development, compound 17e stood out as displaying high AChE inhibitory activity and AChE/butyrylcholinesterase (BuChE) selectivity in vitro. Docking studies revealed that 17e might interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) simultaneously. Based on this novel binding information, 6-ortho-tolylamino and N-ethyl-N-isopropylacetamide substituted piperidine were disclosed as new PAS and CAS binders.

Authors+Show Affiliations

State Key Laboratory of Drug Research, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23466605

Citation

Xing, Weiqiang, et al. "Discovery of Novel 2,6-disubstituted Pyridazinone Derivatives as Acetylcholinesterase Inhibitors." European Journal of Medicinal Chemistry, vol. 63, 2013, pp. 95-103.
Xing W, Fu Y, Shi Z, et al. Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors. Eur J Med Chem. 2013;63:95-103.
Xing, W., Fu, Y., Shi, Z., Lu, D., Zhang, H., & Hu, Y. (2013). Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors. European Journal of Medicinal Chemistry, 63, 95-103. https://doi.org/10.1016/j.ejmech.2013.01.056
Xing W, et al. Discovery of Novel 2,6-disubstituted Pyridazinone Derivatives as Acetylcholinesterase Inhibitors. Eur J Med Chem. 2013;63:95-103. PubMed PMID: 23466605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors. AU - Xing,Weiqiang, AU - Fu,Yan, AU - Shi,Zhangxing, AU - Lu,Dong, AU - Zhang,Haiyan, AU - Hu,Youhong, Y1 - 2013/02/08/ PY - 2012/11/03/received PY - 2013/01/24/revised PY - 2013/01/27/accepted PY - 2013/3/8/entrez PY - 2013/3/8/pubmed PY - 2013/12/16/medline SP - 95 EP - 103 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 63 N2 - 2,6-Disubstituted pyridazinone 4 was identified by HTS as a novel acetylcholinesterase (AChE) inhibitor. Under SAR development, compound 17e stood out as displaying high AChE inhibitory activity and AChE/butyrylcholinesterase (BuChE) selectivity in vitro. Docking studies revealed that 17e might interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) simultaneously. Based on this novel binding information, 6-ortho-tolylamino and N-ethyl-N-isopropylacetamide substituted piperidine were disclosed as new PAS and CAS binders. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/23466605/Discovery_of_novel_26_disubstituted_pyridazinone_derivatives_as_acetylcholinesterase_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(13)00084-6 DB - PRIME DP - Unbound Medicine ER -