Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of tacrine-pyrazolo[3, 4-b]pyridine hybrids. Issue 16 (15th August 2019)

• Record Type: Journal Article
• Authors: Pan, Tingting; Xie, Shishun; Zhou, Yan; Hu, Jinhui; Luo, Haibin; Li, Xingshu; Huang, Ling
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 16(2019)
• Page Start: 2150
• Page End: 2152
• Publication Date: 2019-08-15
• Subjects: Tacrine-pyrazolo[3, 4-b]pyridine hybrids -- Cholinesterase inhibitor -- PDE4D inhibitors -- Alzheimer's disease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.06.056
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of tacrine-pyrazolo[3, 4-b]pyridine hybrids were synthesised and evaluated as dual cholinesterase (ChE) and phosphodiesterase 4D (PDE4D) inhibitors for the treatment of Alzheimer's disease (AD). Compound 10j, which is tacrine linked with pyrazolo[3, 4-b]pyridine moiety by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) with IC50 value of 0.125 μM. Moreover, compound 10j provided a desired balance of AChE and butylcholinesterase (BuChE) and PDE4D inhibition activities, with IC50 value of 0.449 and 0.271 μM, respectively. The above results indicated that this hybrid was a promising dual functional agent for the treatment of AD.